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Contents 7 Editorial Photo Essay 73 9 11 Madhu Karna Remembrance Focus I 75 ndustry News Dysfunctional Tear Syndrome 77 Cornea / Ocular Surface Disease 19 Deep Anterior Lamellar Keratoplasty: Big Bubble Technique 81 Automated Lamellar Therapeutic Keratoplasty Case 1 - Ophthalmoplegia-Looking Beyond the Obvious Sandeep Bhuttan, Suma Ganesh, Manish Sharma, Archana Gupta Namrata Sharma, Jeewan S. Titiyal, Rasik B. Vajpayee 29 Abstracts Clinical Monthly Meeting Descemet’s Stripping Automated Endothelial Keratoplasty Massimo Busin 25 Congenital Midline Facial Swellings 87 Jeewan S. Titiyal, Namrata Sharma, Rasik B. Vajpayee Case 2 - Bevacizumab (Avastin) in Management of Neovascular Glaucoma Suneeta Dubey, M. Agarwal, Monica Gandhi, Gourav Sood, A.P. Pandey, Julie Pegu Refractive Surgery 33 91 Gaurav Sood, Suneeta Dubey, Monica Gandhi, Julie Pegu Sub-Bowman’s Keratomileusis Stephen G. Slade, Daniel S. Durrie Retina 39 Columns 99 DOS Quiz Saurabh Sawhney, Ashima Agarwal Central Serous Retinopathy Bhuvan Chanana, Raj Vardhan Azad 102 Forthcoming Events 105 Membership Form Ocular Tumours 45 Clinical Talk-Determining Progression of Glaucoma on Perimetry Current Concepts in Retinoblastoma Santosh G. Honavar Neurophthalmology 65 Analyzing Disc Edema Rohit Saxena, Munish Dhawan Tearsheet 109 Intraocular Lens (IOL) Designs Sanjay Ahuja, Rishi Mohan, Aditi Gupta Delhi Ophthalmological Society Website www.dosonline.org The DOS Website (www.dosonline.org), features a new look with a re– designed Members Corner. You can now access the Updated Members Directory, Submit your Query and communicate easily with other fellow members. You can also update your membership details in real time! Forthcoming Events, Trade Directory, Details on the DOS Conferences and the latest DOS Times & Delhi Journal of Ophthalmology are available for download. To Test Drive the DOS Website, login with your Membership No. & Password today. We welcome your comments and suggestions on the DOS Web Site. Please mail your opinions to [email protected]. 6 Editorial Component Surgery of Cornea We have moved from a world of overkill therapeutics where the diseased corneal tissue was replaced either with a full thickness graft (penetrating keratoplasty) or a partial thickness graft (lamellar keratoplasty). The corneal surgeons have cleverly taken advantage of the layered structure of the cornea. For superficial corneal opacities there is an option of phototherapeutic keratectomy; for corneal opacities involving upto mid stroma, automated lamellar therapeutic keratoplasty or a manual lamellar keratoplasty can be done. Opacification of the cornea involving up to the posterior stroma and sparing the descemet’s membrane are dealt with the technique of deep anterior lamellar keratoplasty which can be done either using Anwar’s big bubble technique or Melles technique which nearly but not exactly and always reaches up to the Descemet’s membrane. In cases where the endothelium is diseased, but the stromal layers are not involved Francis Price technique of Descemet’s Stripping endothelial keratoplasty may be undertaken. In cases of corneo-iridic cars and leucomatous corneal opacities penetrating keratoplasty should be done. These subset of patients contribute to quite a substantial number of our corneal pathologies unlike in the western countries. The concept of component surgery of cornea is not only beneficial from the patient point of view but also for the Eye Banks. One tissue may be used for several procedures and surgeries may be planned accordingly. However, strict quality control should be observed in these cases. At this point, we mourn the sudden and untimely demise of our dear friend Dr. G. Sitalakshmi a renowned corneal surgeon from Sankara Nethralaya. She had a keen interest in the subjects of “Ocular Surface Disorders” and “Infectious Keratitis” and was the pioneer of “Osteoodontokeratoprosthesis” in India. This is a huge loss to the community and to the entire ophthalmic fraternity. On behalf of all the members of Delhi Ophthalmological Society we bid her farewell and pray that her family gathers strength to face this. It is ironical that she very recently contributed to the article on “Modified Osteoodontokeratoprosthesis” in the July issue of DOS Times this year. Coincidentally this issue’s theme is Component surgery of Cornea. It is indeed ironical that we last met in Frankfurt her parting words that I remember were, Life is too short. I want to do more and more of OOKPs as these are the patients who no one wants to operate upon and so I am concentrating more on this surgery now. Life was indeed too short for her ….. Namrata Sharma Secretary, Delhi Ophthalmological Society 7 8 DOS Times - Vol. 13, No.4, October 2007 Ajay Dave MS Dr. G. Sitalakshmi, 48 years , ophthalmologist, researcher and a dear colleague passed away recently after a brief illness, at Chennai. She is survived by her husband, Dr. Tarun Sharma and son , Abhishek, who is currently studying in USA. Dr. Sitalakshmi was working at Sankara Nethralaya for almost 16 years. She had done her Diploma in Ophthalmology from Madras University and subsequently at Sankara Nethralaya. She completed her Fellowship training at Sankara Nethralaya and became a Consultant in the field of Cornea at the same institution. She also met and married Dr. Tarun Sharma, a vitreo-retinal surgeon. Both complemented each other and brought their respective fields to global standards. When I joined Sankara Nethralaya in 1989 as a Fellow & Consultant, I received an unstinted support from her. Cornea at that stage was fledgling and Eye Banking was yet to be organised. Her unbridled enthusiasm and effort put Cornea at an important level at the institution. She was a pleasant Remembrance Dr. G. Sitalakshmi personality who did outstandingly well with her patients and colleagues, alike. In a short span of her career, she performed over 16000 cataract surgeries. Her effort in forwarding the work in Osteo-odontal Keratoprosthesis was crowned with the inaugural of MOOKP Centre at Sankara Nethralaya by Dr. G. Falicinelli. Dr. G. Sitalakshmi In her recognition of work in Eye Banking and Cornea Donation, 8th September has been declared as 'Dr. G. Sitalakshmi Day' I am sad at the loss of a friend and colleague. On behalf of fraternity of Delhi Ophthalmological Society we extend our heartfelt grief to Dr.Tarun Sharma and his family. 838/2, SFS Flats, Saket, New Delhi-17 www.dosonline.org 9 Madan Mohan MS, FACS, FAMS Gobinda Mukherjee DOMS, MD, FICS Ritu Arora MD Jeewan S. Titiyal MD Focus Dysfunctional Tear Syndrome Radhika Tandon MD, DNB, FRCS (Ed), FRCOpth Dry eye syndrome or keratoconjunctivitis sicca is among the most common and problematic conditions reported to ophthalmologists worldwide. 2007 International Dry Eye Work Shop -DEWS defined Dry eye as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. The changing pathophysiology, diagnostic paradigms, management pearls were discussed with eminent cornea specialists, the excerpts of which are being presented here. Dr. Madan Mohan (MM), Chairman, M.M. Eye Tech, New Delhi. Dr. Gobinda Mukherjee (GM), Senior Consultant of Ophthalmology, Mukherjee Eye Klinik, New Delhi. Dr. Ritu Arora (RA), Professor, Guru Nanak Eye Centre & Maulana Azad Medical College, New Delhi. Dr. Jeewan Singh Titiyal (JST) Professor, Cornea & Refractive Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. Dr. Radhika Tandon (RT) Professor, Cornea & Refractive Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. Dr. Noopur Gupta (NG) MS, DNB, Senior Research Associate (Pool Officer) at Cornea & Refractive Services, Rajendra Prasad Centre forOphthalmic Sciences, All India Institute of Medical Sciences, New Delhi, interviewed them on the current status of Dry eye. NG: MM: Primary dry eye disease in my practice is about 5-10%. Another 15-20% of my patients present with symptoms suggestive of dry eyes, which either coexist with other ocular pathologies or are secondary to other ocular diseases or due to local or systemic medication. Unusual presentations - Yes. Some patients can present with watering as a complaint, which is paradoxical, since they have underlying dry eye disease. GM: RA: I have encountered unusual presentations of dry eye eg. when patients have presented with filamentary keratitis or silent inferior corneal perforations due to dry eye or just presented with microbial keratitis. I have also seen patients with peripheral cataract wound melts where the surgeon had missed the dry eye and patient was also receiving topical diclofenac or topical ketorolac and patients in the post operative period. What percentage of patients in your clinical practice present with dry eye? Have you come across any unusual presentations of dry eye? In my clinical practice I see about 14-18 % cases of mild to moderate dry eye, and about 3-4 % of severe dry eyes. Out of these 60 -65 % cases are females over the age of 45 years. I have noticed an increasing incidence of dry eye in the younger age group patients with long working hours, associated with prolonged use of computers in airconditioned environment. There are some patients, who along with dry eye, may often present with recurrent corneal erosions, pterygium and Salzman’s nodular degeneration. I encounter 20-30% of my patients with mild to moderate dry eye usually related to prolonged working in front of computers, associated with allergic findings. As I am also working with HIV patients, the incidence of concomitant dry eye is higher in them perse because of disease or due to Anti Retroviral Therapy. www.dosonline.org JST: It all depends on the type of institution or practice one is in. I see more of cornea and cataract patients. In my clinical practice, dry eye patients make up around 10% of all cases. Most of them are middle-aged and older, while some patients are young specially those with associated allergic disease. RT: I predominantly get referral cases related to cornea and external diseases of the eye. Dry eye forms a large proportion of the disease pathologies. Approximately 40% cases have dry eye of varying degrees. NG: What percentage of patients have dry eye secondary to local ocular pathology like concomitant meibomianitis, blepharitis or allergic disease? Does a significant number of your dry eye patients have an associated systemic disease? MM: About 30% of patients have aqueous tear deficiency due to local ocular pathology; 4-5% are associated with rheumatoid arthritis and other collagen disorders, atopy, asthma etc. The rest two thirds are associated with 11 Meibomian Gland Disease (MGD), chronic trachoma, Blepharitis etc. GM: Nearly 40-45% case of dry eye are secondary to concomitant ocular diseases. Mebomian gland disease (MGD) perhaps is the major culprit in this group. A good number of cases present with healed trachoma or with sequeale of trachoma more so in the older age groups. 5-7% cases of dry eye have associated systemic diseases like rheumatoid arthritis Stevens Johnsons Syndrome (SJS), Sjogrens Syndrome, Ocular Pemphigoid etc. Approximately half of the patients (50%) have an identifiable local pathology (VKC, trachoma, meibomianitis, blepharitis, etc.) Approximately 30% have an associated systemic disease and 20% are idiopathic RA: JST: RT: NG: Yes a large percentage of my patients have dry eye secondary to local ocular pathology. Important being Vernal KeratoConjunctivitis and other allergic eye disorders and secondary to usage of topical antivirals and antiglaucoma medications. Post LASIK dry eye being commoner too. I do see a lot of dry eye patients with chemical –chuna burns, in children with vitamin A deficiency, post exanthematous fever etc. I also have large number of dry eye patients with associated RA or other collagen vascular disorders. Also 510% of my patients have typical sicca syndrome with associated dry mouth. Oculomuco cutaneous syndromes also form a significant subgroup. Most patients presenting to us especially younger patients have an associated ocular pathology i.e. VKC, blepharitis etc. The older patients have associated lid and/or meibomian dysfunction. Females above 45 years of age may have associated systemic disease like rheumatoid arthritis or menopausal hormonal disbalance. Other group of patients who have infectious or inflammatory disorder are also present. Approximately half of the patients (50%) have an identifiable local pathology (VKC, trachoma, meibomianitis, blepharitis, etc.) Approximately 30% have an associated systemic disease and 20% are idiopathic. What baseline investigations do you perform in a patient of dry eye? Do you perform Schirmer’s test, phonel red thread test, tear pH, osmolality, Break up time (BUT), Fluorescein staining-all or any 2-3 tests. Which test do you think is most reliable? Any other tests that you recommend? MM: Schirmer's I/II are routinely performed. In addition we check the tear pH, Tear Break up time, Fluorescein & 12 Lissamine Green staining lid margin and tear meniscus height. To confirm the diagnosis and for monitoring, 3-4 of these tests are usually performed. GM: Proper evaluation of symptoms and clinical examination of lid margin, tear meniscus, blinking reflex, overall assessment of ocular surface and non invasive TBUT gives the diagnosis. Primarily TBUT, Schirmers test (with and with anesthetic), Fluorescein staining are my routine investigations for Dry Eye cases. Additionally I may do the Rose Bengal and Lissamine green staining tests if the need arises. RA: My baseline investigations are Schirmer’s test, careful evaluation of the tear film meniscus, tear film height, BUT and fluorescein staining. I have started depending more and more on the tear film meniscus and decrease in the tear film height as the basic parameters in my practice, mainly because of the load of patients one has to evaluate in the OPD but Schirmer’s test in unanasthetized corneas gives reasonably clear diagnosis. Also corneal surface should be evaluated carefully for any irregularity which can be picked up by indirect or retroillumination method. JST: The first most important thing is clinical examination. Investigations are only needed to authenticate the diagnosis. The first test should be recording of visual acuity both for distance and near. Then I will go for Non-invasive BUT, if possible. The tear meniscus and corneal staining may then be examined and subsequently followed by Schirmer's test. Rose Bengal and Lissamine green staining may then be carried out if needed. The most reliable test in terms of therapeutic and diagnostic value can be diminished BUT and corneal staining. RT: I perform Schirmer’s test, Break up time and fluorescein staining in all cases of dry eye. Other tests that I recommend are Lissamine green Rose Bengal staining and tear function Index. Larger percentage of our patients have dry eye secondary to local ocular pathology NG: In which cases of dry eye do you carry out impression cytology? MM: At our clinic, we do not perform impression cytology for dry eye evaluation. The history, symptoms, clinical findings & other tests are sufficient to diagnose and monitor the condition. GM: To know the status of of the surface epithelium and goblet cells, impression cytology is a good tool. But I feel this is more academic and routinely I would not order for this. RA: Only if there is some study or for confirmation of stem cell disease. JST: Basically, is cases where we suspect mucin deficient dry eye or a decreased goblet cell count and in cases of limbal stem cell deficiency. DOS Times - Vol. 13, No.4, October 2007 RT: I carry out impression cytology in cases where limbal stem cell deficiency is suspected and limbal stem cell transplantation is planned. NG: Do you use preserved or non-preserved tear substituteswhich class of tear substitute (HPMC, PVA+Povidone, CMC, Na Hyaluronate) do you prefer? Any specific class of tear substitute for a specific disease? MM: Routinely I prefer to use transiently preserved tear substitutes. In some instances, to keep down the cost of treatment, I do advise tear substitute with preservatives particularly when frequency of instillation is less than 3-4 times a day. In such cases where the tear substitutes have to be used more frequently, and those who are on multiple drug Non preserved tear substitutes are preferred to reduce the epitheliotoxic effects of the preservatives. Cost and maintenance are the limiting factors therapy, for other local eye diseases, I prefer to prescribe non-preserved tear substitutes. In mild cases, I start with HPMC or CMC as my first choice. For moderate dry eye cases, I prescribe PVA- Povidone and CMC, to be used alternately. I give Na-Hyaluronate as additional therapy in moderate to severe eye cases. I prefer the substituted - Cellulose ethers (HPMC, CMC) for primary dry eye conditions. GM: RA: JST: I would advice tear substitutes without preservatives in case the patient is either going to use the drops more than four times a day or if the patient has been using the tear drops for more than 6 months. Apart from this all cases with compromised stem cell and corneal epithelium problems should be using preservative free tear substitutes. In mild to moderate dry eyes I tend to suggest PVA along with Povidone or CMC. But in Severe dry eyes I resort to CMC or Sodium Hyaluronate. I prefer non preserved tear substitutes to reduce the epitheliotoxic effects of the preservatives. Cost and maintenance are the limiting factors. I commonly use topical CMC or HPMC. Prefer sod. hyaluronate only in severe dry eyes to reduce the frequency of use of conventional tear substitutes. I also use gel preparations commonly as they spread uniformly over the ocular surface thus reducing the need for tear drops to be used frequently. HPMC in the gel form for all my post corneal transplant patients. I normally prefer non- preserved tear substitutes if the patient can afford. Otherwise, I use artificial tears which are transiently preserved. If there is aqueous deficiency, then HPMC or CMC may be used. In cases of decreased BUT, I'll prefer CMC because of longer retention time. I prefer sodium hyaluronate in contact lens related dry eye. www.dosonline.org RT: If the frequency of tear substitute prescribed is less than 4 times a day, I use preserved formulations like polyvinyl alcohol+povidone, and I use non-preserved preparations like carboxymethyl cellulose if the frequency is more than 6 times per day. In mucin –deficient dry eye, I use povidone. NG: Any role of electrolyte supplementation in artificial tears? MM: The presence of essential electrolytes in the tear substitute definitely gives better results. The preparation however, should not be hyperosmotic. GM: Electrolyte supplementation in tear substitutes definitely have a role in maintaining the stability of the ocular surface. Electrolytes take care of the osmotic balance of the surface epithelial cells and thereby add to the therapeutic value of artificial tears. RA: Can’t say but of late, role of compatible solutes in the form of glycerin, certain AAs and Glycols is being talked about as osmoprotective agents and better than hypotonic agents in maintaining the health of corneal epithelial cells thus reducing the release of pro -inflammatory agents. JST: It is again a debatable issue. It may not work in all patients unless the patient has increased osmolality of the tears. Usually, it does not last that long , so the benefit is not as expected. In fact we should have a tear substitute which should act at the cellular level and corrects the osmotic imbalance at that level. RT: I am not aware of any well documented clinical evidence so far. I do not think there is any specific role and would reserve my opinion in this issue till a properly designed randomized, controlled trial is performed. NG: Do you use cyclosporine eyedrops in dry eye-if yes, what is the indication and which patient is a suitable candidate? What is the concentration and frequency of cyclosporine drops you use? Which type of preparation (aqueous or oil based) do you prefer ? MM: I prescribe cyclosporin eye drops, in select cases of moderate to severe dry eye conditions. I try to assess whether the patient will be able to afford it for prolonged use. I use 0.05% cyclosporine is indicated when associated with chronic inflammatory component or ongoing immune inflammation e.g. severe VKC, some cases of autoimmune diseases related to dry eye and Steven Johnson syndrome. cyclosporin 0.05% in aqueous base, twice daily to start and taper it only after 6 months to 1 year. GM: Yes, I use topical cyclosporine as a 0.05% aqueous base formulations for cases of moderate to severe dry eye. In addition I would not hesitate to add cyclosporine at any 13 stage of dry eye if there is any element of ocular surface inflammation. RA: JST: RT: NG: Yes I do use topical cyclsporine eye drops in certain cases of dry eyes. Use in moderate cases of dry eyes has lead to decrease in the frequency of use of tear substitutes. I have found them very useful in patients with dry eyes with immunological problems esp. associated RA. Cases with inflammatory origin of dry eyes do best with topical .05% CsA in bid dose. Am not sure of its role in post LASIK dry eye, though have encountered the prescription from refractive surgeons. I prefer aqueous base CsA because of less stinging though cost factor is important. We do use cyclosporine in many of our dry eye patients when they have an associated inflammatory component. We normally start with available commercial preparation i.e. 0.05% twice a day (aqueous based). Since the response does not start immediately, surface acting steroids to control the inflammation may need to be added. In patients with chronic inflammation and allergy e.g. SJS , 1-2% cyclosporine drops in aqueous base or dissolved in artificial tears may be used. Yes. 0.05% cyclosporine is indicated when associated with chronic inflammatory component or ongoing immune inflammation e.g. severe VKC, some cases of autoimmune diseases related to dry eye and Steven Johnson syndrome. Oil based formulation available is expensive and if the price is not an issue, oil- based formulation is better in cases of dry eye. When do you expect a significant response with cyclosporine (CsA) drops-do you use steroids in conjunction? Any adverse events to watch out for! MM: It takes 4-8 weeks for cyclosporine drops to offer a significant relief. I do use diluted steroids and other surface acting mild steroids such as fluorometholone and keep these patients under close observation for any increase in IOP or increase in ocular surface staining. GM: RA: 14 I have noticed the onset of the beneficial effect of topical cyclosporine between 3 to 6 weeks of initiation of treatment. In case of ocular surface inflammation I prefer to add topical fluromethalone, three to four times a day, which I gradually taper off in 3 to 4 weeks. Except burning and irritation in some patients, I have not had any other problems with topical cyclosporine therapy. side effects noted by patients are those of ocular burning. JST: Normally it takes 4-8 weeks to take effect. There are only minor side effects seen with cyclosporine drops like stinging, burning and redness noticed in some patients. There have been no major adverse effects noted by us with the routinely used concentration of the drug. The burning sensation disappears within few days of use and can be overcome with artificial tears. . RT: A significant response is only expected when the drug is instilled for at least 3 months. Steroids are used in conjunction only if active inflammation is present as in VKC. The adverse events to look out for are irritation, burning, stinging and secondary infection. NG: How do you taper or stop cyclosporine drops in your patients-whether stopped totally or not? MM: Cyclosporin once started needs to be continued for many years and at best it may be possible to reduce the frequency to once a day. Its total stoppage may revert the condition to the original state. GM: After evaluation if there is a improvement in the dry eye status and ocular surface condition, I would consider tapering off topical cyclosporine, after 4 to 6 months. RA: I usually stop cyclosporine drops 6-8 months after initiation of the therapy. Also these patients may be receiving concomitant systemic steroids for the associated systemic conditions which then take over. JST: The minimum duration of cyclosporine therapy in any case of inflammatory dry eye who is tolerant to therapy is 4-6 months. The patients' response is then adjudged and the drug may be continued for another 6 months. On completion of therapy, it need not be tapered and may be stopped immediately. RT: I stop the cyclosporine drops 6-12 months after use or sooner if the patient is intolerant to them. I do not taper them. NG: What is the compliance and response of the patients to cyclosporine drops? MM: Affordability of this mode of therapy is of vital consideration. The Indian preparation costs the patients roughly Rs. 5/- per day in comparison to imported drug, which is 4-5 times more expensive. The long term compliance of this treatment is very vital and it needs to be stressed, since patients often stop treatment or switch over to other modalities, after a few months, due to high cost of treatment. Significant response with CsA is not observed before 6 weeks of the institution of therapy. Proper counselling of the patient is needed Significant response is not observed before 6 weeks of the institution of therapy. Proper counselling of the patients started on topical CsA is essential to expect the improvement in dry eye state only some time later in the course of treatment. I sometimes add topical diluted steroids in symptomatic cases in the early period of the initiation of topical CsA to reduce the symptoms like stinging and irritation arising from inflammation. Major GM: About 80–85 % tolerate the drug pretty well, and after 3 to 6 weeks of therapy most of the patients are symptomatically much better off. RA: Compliance is usually good, if counselled well for the stinging sensation. BID dose instillation is also convenient. DOS Times - Vol. 13, No.4, October 2007 Cost is the major hitch. Usually these patients also receive concomitant tear substitutes. It is important to gauge the expectation of patient and work accordingly. They are of little value in severe dry eye patients. JST: It all depends on proper case selection. If case selection is appropriate, then compliance and response is good. RT: I have often experienced that economic considerations do drive the patients to request a switch from a more expensive brand to a cheaper substitute. This must be interpreted in the context of a large government hospital practice and may not be generalized to more affluent sectors of the society. NG: GM: In dry eyes associated with systemic diseases, the relief of symptom is often delayed, more so if the underlying systemic condition if not taken care of. These are the patients I would refer to an internist for management of their systemic condition, after starting them on topical drops. RA: Yes, dry eye associated with systemic disease responds differently from that without any systemic disorder. Those with associated systemic disorders sometimes improve once put on systemic steroids or immunosuppresants. There may be decrease in the need for topical tear substitutes. I also add systemic Pilocarpine 5mg tds in some of my patients to increase the tear secretion. Caution them for diarrhoea or sweating arising out of this treatment. Some patients do tolerate this form of therapy also. Not to be used for dry eye associated with SJS. Generally surface acting topical steroids like fluoromethalone are used 4-6 times a day for 1-2 weeks and then tapered. At the outset, a warning and counseling regarding the potential harmful effects like glaucoma and infection Do you prescribe topical steroids to your patients-if yes, how frequently and indications? JST: As far as dry eye in relation to local ocular pathology is concerned, presentation is early and treatment is simpler. In patients with associated systemic disease, presentation is usually late and more severe. They may present with peripheral corneal thinning without any preliminary symptoms of dry eye. Management of these cases is related to control of the systemic disease alongwith local support. RT: Peripheral corneal involvement is more common in systemic disease. It is usually non-responsive to conventional therapy and may require to systemic immuno-supression. NG: Do you use punctal plugs/cautery-if yes, indications? MM: Fluorometholone drops 2-3 times daily to start with is my drug of choice for the treatment of severe dry eye disease particularly when dry eyes are associated with allergic disease or moderate to severe inflammation. GM: RA: JST: In case of ocular surface inflammation I prefer to add topical flurome-thalone, three to four times a day, which I gradually taper off in 3 to 4 weeks. I do add topical loteprednelol in some of my immune mediated dry eyes or in patients not able to afford cyclosporine eye drops. I use them in qid dosage for short term use to suppress an acute flare up of the surface inflammation. Caution to be used when proposed for long term use, for cataracts, glaucoma, peripheral corneal thinning etc. Yes, we do prescribe topical steroids in dry eye patients with associated conjunctival and/or corneal inflammatory component. They are used in conjunction with artificial tears with frequent follow-ups to watch out for ocular complications of topical steroids. They are usually prescribed for a short duration until some other antiinflammatory agent takes over. RT: Sometimes in VKC. Generally surface acting topical steroids like fluoromethalone are used 4-6 times a day for 1-2 weeks and then tapered. At the outset, a warning and counseling regarding the potential harmful effects like glaucoma and infection. NG: Do you think that dry eye associated with and without systemic disease presents or responds differently? MM: Yes, dry eye associated with and without systemic disease presents and responds differently. There is often corneal involvement and associated dryness of the mouth etc. Dry eyes associated with systemic diseases are slow to show improvement and symptomatic relief. www.dosonline.org MM: Yes, in moderate degree of dry eye disease, when patients needs tear substitute more than 4-5times a day. Punctal plugs are very helpful in these cases. GM: I would advice punctual occlusion in all cases of severe dry eyes, and in some moderate dry eye states. Initially I would use temporary punctal plugs, and then finally after the patient is convinced and feels better I would use a permanent punctual plug. I do not advocate punctal cautery. RA: I use punctal plugs in moderate dry eye patients. Always try temporary collagen plugs before permanent ones. Sometimes dry eye worsens after the use of punctal plugs because of the collection of tears with all the inflammatory agents making the symptoms worse esp. in cases with inflammatory dry eye. JST: We do use punctal plugs quite often, especially in evaporative variety of dry eye or when there is aqueous deficiency. Collagen plugs are first tried to assess the patient's response and if successful, permanent punctal plugs are inserted in the inferior puncta. RT: If puncta are open and patient is refractory to maximal tear supplementation, then plugs may be applied and follow-up with cautery, if needed. 15 NG: Do you use autologous serum-yes or no? RA: I do prescribe oral omega 3 fatty acids but easy availability in the market is not there. I do encourage the patients to consume fish products. JST: Not in any of my patients till date. RT: Not yet. NG: What is the future of dry eye therapy and diagnosis? MM: Autologous serum - I don't use it any more. GM: I have no personal experience of using autologous serum drops. RA: Only as an adjunct in nonhealing epithelial disorders associated with dry eye as topical 20%serum drops improve the health of corneal epithelium. I have not used topical We need to find good tear stimulants, at the same time continue our search for better tear substitute with lasting effect. A lot of hope is there on androgens, evaporation retardants and newer polymers MM: We need to find good tear stimulants, at the same time continue our search for better tear substitute with lasting effect. A lot of hope is there on androgens, evaporation retardants and newer polymers. GM: (i) Better diagnostic techniques which can access the specific flaw in the tear film and ocular surface. (ii) Further understanding of the path-mechanisms of dry eye condition. (iii) Availability of tear substitutes which can specifically replace or supplement the deficient layer. (iv) Availability of drugs like Omega 6 fatty acids and PGEI (tear specific anti inflammatory prostaglandin) RA: Future of dry eye therapy: Development of P2Y2 receptor agonist to increase aqueous tear volume and stimulate mucin secretion, Androgen/ estrogen supplementation, nutritional support, osmoprotective tears, tears with polymer like HP guar to reinforce the structural integrity of the ocular surface environment. Development of secretagouges may be helpful. JST: The future of dry eye will involve 2-3 aspects: (i) Education of public regarding injudicious use of systemic and topical medications. (ii) Education of dry eye patients (iii) Availability of a medication which will give prolonged and long-lasting effect or a device with sustained release of artificial tears e.g. inserts. (iv) In severe cases like SJS where the ocular surface is damaged, some long-lasting technology which could rejuvenate or regenerate the ocular surface is foreseen. RT: Future will be tear inserts, omega -3 fatty acids, and secretagogues like rebamipide. serum drops in isolation for the treatment of dry eye. Caution for infection is a must when using these drops. I have used them for peripheral thinning disorders with equivocal results. Can be tried when other modalities fail in the management of dry eyes. JST: To be very frank, I have not used autologous serum. There have been some studies in our centre to evaluate the efficacy of autologous serum in severe cases of dry eye. The preparation and maintenance of serum is difficult. But in some desperate cases e.g. Steven Johnson's syndrome (SJS), its use might be considered. RT: Occasionally. I use autologous serum only in cases of persistent epithelial defect not responsive to conventional therapy. NG: Do you prescribe oral Omega-3 fatty acids for dry eye? MM: Yes. I use them for chronic cases only. These are good adjuncts to other treatments. GM: Yes I have used oral Omega 3 fatty acids therapy in dry eye patients. I feel these patient on oral Omega 3 fatty acids symptomatically tend to do better than others. DOS Correspondent Noopur Gupta MS, DNB 16 DOS Times - Vol. 13, No.4, October 2007 Cornea Descemet’s Stripping Automated Endothelial Keratoplasty Massimo Busin MD1,2 D SAEK derives itself from the continuous improvement of the initial endokeratoplasty procedure, which we introduced in 1996. This technique included peeling of the Descemet, preparation of a donor lamella of deep stroma, Descemet and endothelium; insertion of the graft into the anterior chamber through a clear-cornea tunnel; and fixation of the graft onto the bare posterior corneal surface by means of trans-corneal sutures (Figure 1). The tip of a 25 gauge needle mounted on a 2.5 cc empty syringe is bent upwards (Figure 3) before it is introduced into the anterior chamber at the 12 o'clock position. Results in the rabbit model were not encouraging, as the postoperative course was complicated by frequent misplacement of the donor lenticule and high endothelial cell loss, thus making the use of this technique in humans unreasonable (Figure 1, right part) Then the needle is retracted and an ordinary 25 gauge cannula is mounted on the syringe and re-inserted through the same puncture site. The cannula is employed to sweep away Descemet and endothelium, usually in a single piece (Figure 5). In 1999 Melles demonstrated that corneal layers can adhere to each other permanently with no need for sutures and contributed substantially to the development of new posterior lamellar keratoplasty techniques. However, Melles and other surgeons employed hand dissection for the preparation of both donor tissue and recipient bed, and surfaces obtained with this type of dissection create an interface with an the optical quality which is very rarely compatible with 20/20 vision. More recently, Price and Gorovoy have substantially improved the optical quality of the interface by introducing the microkeratome-assisted dissection of donor tissue. Excellent visual results, comparable, if not superior to those of conventional penetrating keratoplasty (PK), have been reported by both authors. Nonetheless, the same complications encountered with the original endokeratoplasty procedure (graft displacement and, especially, endothelial cell loss up to 40-50% one year after surgery) still seem to complicate the postoperative course of DSAEK in a relatively high number of patients. The modified surgical technique presented below was developed with the purpose of eliminating the major draw-backs of the present DSAEK technique, while retaining the major advantages of a relatively simple, reproducible and safe procedure. Results obtained 1 year after DSAEK surgery modified according to the technique presented below have shown that endothelial cell loss is comparable to that recorded after conventional PK. Surgical Technique A marker, usually 9 mm in diameter, is used at the beginning of the procedure to outline the limit of the internal surface, from which the endothelium will be peeled off (Figure 2). 1. "Villa Serena" Hospital, Department of Ophthalmology, Forlì, Italy 2. University of "Magna Graecia", www.dosonline.org Aqueous (about 0.2-0.4 cc) is aspirated and air is injected, filling up the anterior chamber. The tip of the needle is used to cut through the endothelium and Descemet membrane following the contour of the superficial mark (Figure 4). As it is blunt, damage to the posterior stromal bare surface is avoided. Whenever air is lost through the entrance site of the needle/cannula, the anterior chamber is reformed by injecting new air with the syringe. Performing the whole manoeuvre under air allows perfect visualization of Descemet membrane and endothelium and eliminates the need for any type of dye or, much more importantly, for any viscoelastic substance in the anterior chamber. In fact, if the viscoelastic substance is removed incompletely before insertion of the graft, it may reach the interface space, preventing adhesion of the donor tissue to the stromal surface and causing the procedure to fail. A clear-cornea tunnel, 1 mm in length and 5 mm in width is prepared nasally (Figure 6). The dimensions of the tunnel are critical for the uneventful insertion of the graft into the anterior chamber. If the tunnel is too long the donor tissue may remain partly trapped during insertion, while a too narrow tunnel may cause an increase in endothelial cell loss through pronounced deformation of the graft. After coating the endothelial side with viscoelastic substance, the donor cornea is mounted on the artificial anterior chamber of the ALTK system and most of the anterior stroma is removed by means of the microkeratome with a 300 micron head, which usually cuts lamellae with a thickness between 350 and 400 micron (Figure 7). The same marker used to mark the corneal surface is employed to mark the stromal side of the remaining tissue (usually with a thickness between 100 and 200 micron), which is then punched to the desired size (8 to 9 mm) (Figure 8). As opposed to what is done by most surgeons, the donor tissue is not folded and inserted into the anterior chamber with the socalled "taco" technique. Instead, a specially designed glide is loaded with the donor lamella, endothelial side up and crocodile vitreous forceps are used to grasp the donor button and pull it into the glide opening (Figure 9). A side entry is created temporally. The glide is then inverted and positioned at the entrance of the nasal clear corneal tunnel. The 19 Figure 1. Schematic (left part) and rabbit pictures (right part) of the original design of endokeratoplasty Figure 2. Circular mark, 9.0 mm in diameter, outlining the extension of Descemet stripping. Figure 3. 25 G needle bent both proximally and at its tip used to perform Descemetorhexis. 20 Figure 4. Descemetorhexis performed under air bubble, using a 25 Gauge needle Figure 5. Blunt 25 G cannula used to remove in a single piece Descemet membrane and endothelium under air bubble DOS Times - Vol. 13, No.4, October 2007 Figure 6. Clear-cornea nasal tunnel prepared with a keratome. Figure 9. The donor tissue is pulled into the glide opening by means of crocodile vitreous forceps Figure 7. Microkeratome assisted removal of the anterior stroma from the donor cornea mounted on the artificial anterior chamber Figure 10. Insertion of the graft into the anterior chamber with the "pull through" technique, using vitreous forceps and tissue glide. Figure 8. Donor cornea mounted in the artificial anterior chamber after microkeratome-assisted removall of the anterior stroma (using the 300 µm head). The area to be punched out is marked within the area of stromal removal and an additional mark is made peripherally to identify the stromal and endothelial sides. Figure 11. Air is injected into the anterior chamber through a side entry to attach the donor tissue to the posterior corneal surface. www.dosonline.org 21 crocodile forceps are inserted through the side entry and passed across the anterior chamber, exiting through the clear-cornea tunnel to grab the graft and drag it into the anterior chamber (Figure 10). The donor lamella is allowed to unfold spontaneously under continuous irrigation .Gentle tapping at the inferior limbus may facilitate centring of the graft. The whole manoeuvre is performed with the aid of continuous irrigation with an anterior chamber maintainer inserted at the limbus at the 12 o'clock position. An iridectomy is performed, if not already present, in order to prevent papillary block and Urrets-Zavalia syndrome, secondary to filling of the anterior chamber with air at the end of surgery. The graft is finally attached to the posterior stromal surface by means of air (Figure 11). Both the clear-cornea tunnel and the side entry are sutured watertight with 10-0 nylon stitches. Triamcinolone acetonide and gentamicin are injected subconjunctivally at the end of the procedure. The eye is patched and the patient is required to lie on his back for the next 6-8 hours. Author Massimo Busin MD Required A Research Officer for the ICMR Project Entitled "Evaluation of Cyclosporin in Control of Ocular Inflammation in Acute Steven Johnson's Syndrome" under Dr. Namrata Sharma for Three Years. Applications with Detailed Curriculum Vitae and copies of Degrees/Certificates may be submitted by 20th October, 2007 in the office of Dr. Namrata Sharma, Room No. 474, 4th Floor, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029 22 DOS Times - Vol. 13, No.4, October 2007 1 Cornea Deep Anterior Lamellar Keratoplasty: Big Bubble Technique Namrata Sharma MD, 1Jeewan S. Titiyal MD, 2Rasik B Vajpayee, MS, FRCSEd, FRANZCO he surgical considerations for DALK technique will be discussed under anesthesia, instrumentation and the surgical technique. T Descemet’s membrane removal Anesthesia Suturing We prefer to perform this technique under general anesthesia, although other surgeons have undertaken this technique under peribulbar anesthesia. Lims forceps / Pierce Hoskins forceps, Needle Holder and 10-0 monofilament suture help in suturing the donor graft to the recipient bed In our experience, general anesthesia is preferable as this minimizes intraoperative upthrust and hence prevents an inadvertent descemet’s membrane tear which may occur due to suboptimal akinesia which occurs when the patient is given local anesthesia. Surgical Technique The Trypan blue dye is used to attain the membrane and this is removed with the non-toothed forceps / Dry Merocel Sponge Informed consent should be obtained from all patients. A lid speculum should be used to expose the palpebral aperture. The criteria for quality of donor tissue are not very stringent and a donor cornea with suboptimal quality may be used to perform the lamellar graft. However, an optical quality donor corneal tissue should always be kept in reserve in the event of a perforation when DALK may have to be converted to a penetrating keratoplasty. The steps of the surgical technique include the recipient dissection, donor preparation and graft host apposition. Trephination Recipient Dissection A caliberated guided trephine system (Krumeich, Rhein Medical) which can be set to any depth is preferred . The Hanna suction trephine (Moria) is also accurate but can be set to 100 microns steps only. The Hessburg-Barron vacuum trephine is less precise but is disposable and can be used easily. A superior and inferior recti bridle sutures are applied. Instrumentation The following instruments are required for DALK surgery. Exposure of palpebral aperture Big bubble Injection A 27- or 30- gauge needle attached to a 3mL to 5mL syringe which is bent approximately 5.0mm from its tip so that the terminal segment angles up approximately 60 degrees. Side port creation A Hessburg Barron (JedMed Instrument Co, St Louis, Missouri, USA) suction trephine (7.00 mm to 7.5 mm) is used for partialthickness trephination of the host cornea up to an approximate depth of 300 microns depth or 60 to 80% of the pre-operative corneal thickness. (Figure 1). A 27-gauge disposable needle attached to a 5-ml syringe, bent at 60 degrees, bevel down , is advanced in the paracentral stroma, and air is injected into the corneal stromal tissue, which forms a large air bubble between the descemet’s membrane and the host’s A MVR blade can be used to create the side port or paracentesis. Anterior Keratectomy/Corneal debulking A crescent blade 2.25 mm ( Alcon, Fortworth, Texas ) or a #69 Beaver blade ( Becton Dickinson Co. &) . Penetration of anterior stromal layers A30 degree ophthalmic knife (Alcon, Fortworth, Texas) or a blade braker. Quadrantic Splitting of anterior stromal layers Quadrantic splitting of the anterior stromal layers can be done with the helps of a blunted microscissors or Vannas scissors. 1. Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 2. Centre for Eye Research Australia Department of Ophthalmology University of Melbourne 32, Gisborne Street, East Melbourne, Victoria 3002, Australia www.dosonline.org Figure 1. Partial thickness trephination of the host 25 Figure 2. Formation of Big Bubble by Air Injection Figure 3. Anterior debulking after air injection Figure 4. Removal of residual stroma Figure 5. Suturing the donor cornea to the host corneal stroma (Figure 2). The needle is advanced to about 2 to 3 mm in a plane almost parallel to the corneal surface so as to avoid perforation of the descemet’ s membrane. Subsequently, debulking of the anterior two-thirds of the superficial corneal stroma is performed using a crescent blade (Alcon Surgical, Fort Worth, Texas, USA) leaving a very thin layer of corneal stromal tissue over the large air bubble (Figure 3). A paracentesis is then created using a 15-degree blade (Alcon Surgical) at the 10-o’clock position to lower the intraocular pressure of the eye so that the descemet’s membrane falls posteriorly. A small opening is created in the stromal tissue overlying the air bubble using a 15-degree blade (Alcon Surgical). This site of this incision is marked with the help of a marking pen /genitan violet stained sinskey hook prior to making an actual nick in the stromal layers. This mark helps to identify the exact site of incision which may get obscured due to the inadequately split stromal fibres . Following egression of the air bubble from the incision site, 2% hydroxypropyl methylcellulose (Visilon, Shah & Shah, Mumbai, India) is injected through the opening to maintain the space between the overlying corneal stromal tissue and the descemet’s membrane. 26 A curved Vannas scissors is then inserted inside and a nick is given on the stromal layers.Visocoelastic is then instilled again and this nick is extended distally as well as proximally which divides the stromal layers into two hemi-sections. A cut is also made towards the nasal and the temporal side of this vertical incision so that the overlying stromal layers are divided into four quadrants and each quadrant is then excised baring the decemet’s membrane completely ( Figure 4). Caution is required while giving nicks in the stromal tissue and this should preferably be done under the viscoelastic cushion, taking care that the pressure is applied upwards towards the stromal layers and not downwards towards the descemet’s membrane . While removing these quadrants from the trephinated edges, a posterior ledge usually forms all around circumferentially which occurs inadvertently as the surgeon avoids going very close to the descemet’s membrane. Donor Preparation Full-thickness donor corneal tissue stored in McCarey-Kaufman medium may be used for transplantation. Circular trephine blades (Storz Ophthalmics, St Louis, Missouri, USA) ranging from 7.5 DOS Times - Vol. 13, No.4, October 2007 Follow –up visits Patients are followed up just as in conventional lamellar keratoplasty. Follow-up visits are scheduled at 1, 7, and 14 days and then monthly for 12 months. Additional visits are scheduled in cases of complications or problems. Post operative Parameters A record of the following parameters should be kept at each visit: Visual Acuity Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA) and best corrected visual acuity (BCVA) should be noted at each visit. Contrast Sensitivity and glare Figure 6. Final post-op picture Although it is not mandatory to do these investigations in all cases, contrast sensitivity and glare acuity may be assessed, if such facilities are available. Slit Lamp Examination mm to 8.00 mm in diameter are used to punch the donor lenticule from the endothelial side of the corneoscleral button. The Descemet membrane of the donor corneal button is scraped off after staining it with 0.06% trypan blue dye (Visiblue, Shah & Shah) using a Descemet stripper. Alternatively a dry merocel sponge may be used to separate the stained Descemet’s membrane. The descemet’s membrane comes out quiet easily. The posterior corneal surface was thoroughly irrigated with BSS. Graft Host Apposition The host graft disparity should be 0.25 mm with donor graft being larger than the host. In cases of keratoconus same sized donor may be used to decrease myopia. The donor lenticule is placed on the recipient bed. Four cardinal sutures are passed first. The edge of the needle is passed just above the circumferential posterior stromal ledge which was created previously. The posterior ledge acts as a guide and any inadvertent microperforation is avoided as the edge of the needle is kept above this ledge (Figure 5). Rest of the 14 interrupted sutures are then passed using 10-0 monofilament nylon suture ( Figure 6). Alternatively, following the application of cardinal sutures a single continuous suture may be applied. Post Operative Evaluation and followup Post-operative Evaluation and follow-up Ostoperative follow up and evaluation includes the post-operative regime as well as the investigations which may be required routinely or in special cases. A detailed slit lamp evaluation should be done at each follow-up. The graft clarity, status of the graft host junction and anterior chamber status should be noted at each visit. If there is any evidence, of formation of double anterior chamber, remedial measures should be taken immediately. Any suture related problem such as a loose suture, broken suture or tight suture should be removed and replaced in the early post-operative period. Corneal Pachymetry Ultrasonic corneal pachymetry may be done in these cases at 1, 3, 6 and 12 months. Corneal Curvature Videokeratography should be done in all cases to assess the amount of post-operative astigmatism. Specular Microscopy Specular microscopy may be undertaken in these cases at 1, 3, 6 and 12 months. Suture Removal Selective suture removal should be performed for any suturerelated problems and for control of astigmatism from one month onwards. To control astigmatism interrupted sutures are removed gradually from the third to the sixth month, beginning with the tightest suture, revealed by tangential topography as a localized steepening. The continuous may be generally removed after 5 to 6 months or when it becomes loose. Post-Operative Regime Post-operatively the patients are given a regime similar to that of a conventional lamellar graft. Patients receive topical antibiotic drops such as 0.3% ciprofloxacin hydrochloride four times a day, topical corticosteroid drops such as 1% prednisolone acetate eye drops four times day, and preservative-free artificial tears every two hours for the first month, which were subsequently tapered over the next six months. www.dosonline.org First Author Namrata Sharma MD 27 Jeewan S. Titiyal MD, Namrata Sharma MD, Rasik B Vajpayee, MS, FRCSEd, FRANZCO L amellar keratoplasty with an automated microkeratome is a recent modification of the manual lamellar keratoplasty. This technique uses a microkeratome to excise the pathological part of the host cornea upto a particular depth and later a healthy donor cornea, which is also, cut using an automated microkeratome and artificial chamber is sutured in its place. This new lamellar grafting eliminates several disadvantages associated with conventional LK including difficult surgical manual technique. The automated micro keratome helps in achieving a regular, smooth recipient bed and optimal recipient graft opposition. Indications for Automated Lamellar Therapeutic Keratoplasty The indications for automated therapeutic lamellar keratoplasty (ALTK) include patients having diseases involving the anterior to mid-stromal part of the cornea with normal endothelium including superficial dystrophies, keratoconus, superficial chemical bums, posttraumatic scars, postinfections leucomas, trachoma, herpes and postrefractive surgery corneal haze related to the cap complications. Cornea Automated Lamellar Therapeutic Keratoplasty (or 0.5 mm undersized) and thickness as the donor disc. Once the disc is removed, the recipient bed is washed with balanced salt solution and dried with the sponge. Preparation of the Donor Lenticule The donor lenticule may be obtained from a corneoscleral rim. The corneoscleral rim should be at least 4 mm wide as the frill of the corneoscleral rim has to be positioned on the artificial anterior chamber maintainer. The artificial anterior chamber consists of a stainless steel structure with 3 screw type safety rings. The lower ring sustains a metal device that covers the superficial sclera and maintains a tight fit on the metal base of the chamber to avoid leakage. A second ring in an intermediate position approximates the chamber on the former structure to tighten the sclera from above. A third ring located superiorily is adjusted to modify the height of the microkeratome plate. This plate is a gearless track to Contraindications for Automated Lamellar Therapeutic Keratoplasty The contraindications for ALTK include patients with disorders of lids including ectropion, entropion, trichiasis, lagophthalmos, dry eye, keratoconjunctivitis sicca, severe blepharitis, uncontrolled uveitis, glaucoma and dense cataract. Any posterior segment pathology of the eye that may preclude attainment of good visual acuity after ALTK, immunocompromized patients where wound healing may be impaired, collagen vascular disorders and history of abnormal wound healing, e.g. keloid formation are other contraindications of ALTK. Preoperative Evaluation Figure 1. Automated Microkeratome The preoperative evaluation of a patient undergoing AUK is similar to that of a routine manually dissected lamellar keratoplasty. Pachymetry is of special relevance as the depth of the dissection is dictated by the depth of the pathology as well as the micro keratome head available. Surgical Technique Preparation of the Recipient Bed The recipient lamellar bed is prepared using a suction ring and an automated microkeratome in a manner just as one does in laserin-situ keratomileusis (Figure 1 & 2). The automated microkeratome is used as a cutting instrument. The instrument has a suction ring, which allows the surgeon to obtain a lenticule of a specific size. It has various range of heads such as 120, 180, 250 and 350 mm which can used depending on the desired depth of the lamellar cut. The goal is to cut a disc with the same diameter Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi www.dosonline.org Figure 2. ALTK surgical trolley 29 Figure 3a. Preoperative case of nebulomacular corneal opacity (Healed Keratitis) guide the micro keratome head translation at a constant height along the corneal pass. Depending on the height at which this plate is positioned, more (lower position) or less (higher position) of the cornea is exposed, resulting in a larger or smaller lenticule diameter, respectively. The chamber is connected to the infusion system with a reservoir of saline solution, placed 1.2 m above the chamber level. An expansion air chamber is located within the infusion line at the 10.0 cm of the connection to the chamber. without any sutures, we prefer to put at least 8 interrupted sutures with 10-0 monofilament nylon. The eye is than patched for 24 hours. Postoperatively, the patient receives topical antibiotics, diluted corticosteroids and artificial tears, which are then subsequently tapered. Advantages We use LSK micro keratome (Moria) to perform automated lamellar keratoplasty may be used to cut the corneas. It consists of a single piece metal head connected to a nitrogen-gas-driven hand piece. The blade oscillates at a rate of 15000 oscillations / min with an orientation of 25 degrees to the cut plane. The grooves on the base plate of the artificial anterior chamber are designed to fit into the microkeratome head, hence its pass along the cornea is uniform. An automated micro keratome allows the surgeon to obtain corneallenticules with parallel faces that are almost identical in the donor and the recipient corneas. These factors result in optical and refractive results that are better than those obtained with the manual techniques. The cut made by the microkeratome is regular and homogeneous. This prevents the irregular astigmatis that occurs, with a manual procedure because of the horizontal adherence of the disc to the donor tissue. Further, the surgical time is shortened fewer sutures are required for shorter periods of time, which reduces suture related complications. To reduce the number of air bubbles beneath the cornea, rims are placed on the chamber base after the infusion is released. Once the cornea is stabilized and centered and the absence of air bubbles is confirmed, the infusion is closed, the superior metal support is placed and locked by turning the first ring clockwise, and the second ring is turned anticlockwise to elevate the chamber height and tighten the scleral skirt between the support and chamber. There are several things surgeon should consider when using this technique. It is important to obtain lenticules with same diameter and thickness so that the fit is perfect and the future epithelial in growth is avoided. The epithelium of the donor should be kept intact as far as possible. The donor epithelium is replaced by the recipient epithelium during the first week. The applanation lens is then placed on the cornea to determine the plate height for the desired diameter, turning the second ring counter clockwise or clockwise depending on the guiding circle marks on the lenses,. Drops of saline solution are placed on the cornea and keratectomy is performed by passing the microkeratome head with its oscillating bade at a relatively constant speed along the plate. Behrens et al report that the precision and accuracy of this system varies according to the attempted thickness and diameter. Greater precision is obtained if the diameter of the cut is ~ 8 mm or if the flaps are thinner. 2 Donor Recipient Apposition The donor lenticule is placed on the recipient bed. Although some surgeons leave the donor lenticule adhered to the recipient bed 30 Figure 3b. Operated automated lamellar therapeutic keratoplasty for patient as in Figure 3a Outcome of ALTK Out of a total of 9 eyes that underwent ALTK at our center, 5 patients had nebulomacular corneal opacity (superficial corneal scars), (Figure 3a) 3 had Salzmann nodular degeneration, and one had keratoconus. Five patients were males and 4 were females, with age ranging from 5 years to 65 years. The donor button size ranged from 8.5 mm to 10 mm (thickness 350 mm) and the host cut size ranged from 8 mm to 9.5 mm (thickness 250 mm). Sixteen to twenty four interrupted sutures with 10-0 monofilament were applied (Figure 3b). The mean central corneal thickness was 503 mm. From a preoperative visual acuity of <2/60 in all eyes, a postoperative visual acuity of >6/24 was achieved in 8 out of 9 patients. All grafts epithelized within first week of surgery. No cases of interface scarring were seen after a follow-up of 6 months. DOS Times - Vol. 13, No.4, October 2007 However, the long-term problems of interface scarring needs to be ascertained. to penetrating keratoplasty especially in the treatment of anterior corneal opacities. Although we did not encounter any major complications, there are risks of postoperative complications, which include delays or defects in epithelization, epithelial in growth in the interface, fibrosis and even vascularization. Edema or melting of the lenticule may also occur. Although an endothelial rejection will not occur, an epithelial and stromal rejection may occur. Finally the original disease may recur. Optical lamellar keratoplasty, performed with an automated micro keratome, is an easy, simple, and accurate technique. It produces good visual results and is a good alternative References 1. Jimenez-Alfaro I, Perez-Santonja J J, Telleria G G, Palcin B, Puy P. Therapeutic lamellar keratoplasty with an automated microkeratome. J Cataract Surg 27: 1161-1165, 2001. 2. Behrens A, Dolorico AMT, Kara DT, Novick LH, McDonnell PJ, Chao LC, et al. Precision and accuracy of an artificial anterior chamber system in obtaining corneal lenticules for lamellar keratoplasty. J Cataract Refract Surg 27: 1679-1687, 2001. First Author Jeewan S. Titiyal MD Delhi Ophthalmological Society Monthly Clinical Meeting, October 2007 Venue: Main Auditoriam, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi-110002 Date and Time : 28th October, 2007 (Sunday), Clinical Session : 11.00 a.m. to 1.00 p.m. Tea & Snacks : 10.30 a.m. to 11.00 a.m. Clinical Cases: 1. An unusual presentation of a common systemic disease : Pankaj Vats P.K. Pandey 10 mins. : Pooja Dhama Sushil Kumar 10 mins. : Ritu Arora 15 mins. Discussion 2. Orbital SOL - How close are we to clinical diagnosis Discussion Clinical Talk: HIV and Ocular manifestations (Pre and Post HAART era) GNEC-LNJP-MAMC experience Symposium: Pediatric Teasers Chairman: P.K. Pandey Co-Chairman: Sushil Kumar, J.L. Goyal • • • Is age a bar to IOL implantation Valves in childhood glaucoma Unusual presentation of common pediatric ocular tumors : : : Anju Rastogi Usha Yadava Usha K. Raina 15 mins. 15 mins. 15 mins. To be followed by Lunch www.dosonline.org 31 Stephen G. Slade MD, Daniel S. Durrie MD W hile laser in situ keratomileusis (LASIK) surgery has the advantages of superior visual results, efficiency and patient friendliness, the procedure can lead to dry eye, flap complications and, arguably, an increased risk of corneal ectasia. The biomechanical stability of ablation at the outer surface of the cornea in photorefractive keratectomy (PRK) resolves this issue; the procedure leads to better correction of high-order aberrations (HOAs), better quality of contrast sensitivity and night vision, and fewer complaints of dry eye. But the PRK procedure is more painful, particularly in the immediate post-operative period, and has slower visual recovery, with increased risk of haze. In order to resolve this dilemma, LASIK and PRK can be combined to create one procedure that reaps the best of both; the visual recovery and painlessness of LASIK and the safety and stability of PRK. This new technique, sub-Bowman’s keratomileusis (SBK), involves the creation of a customized corneal flap that has a diameter based on the requirements of the individual patient, in addition to the type of excimer laser. Ectasia and other problems following LASIK procedures has become an increasing concern, particularly following the biomechanical research on the procedure by Marshall, Alio and others. Consequently many refractive surgeons are returning to surface ablation techniques, which, although maintaining biomechanical stability, carry the disadvantages of pain, haze and slower visual recovery. With regards to safety, surface ablation offers superior results in comparison to LASIK, but the visual results and patient satisfaction of PRK are not on par with those of LASIK. Creating Customized Corneal Flaps The Femtosecond Laser vs. the Mechanical Microkeratome The use of the femtosecond laser for LASIK has increased substantially since it was first introduced in 2002. A market study has shown that approximately 30% of LASIK procedures were performed using a femtosecond laser by the end of 2006. 1 Literature suggests that the creation of a thinner flap (±100 µm), with a diameter based on the maximum ablation zone of the excimer laser, is more effective. To carry out customized flap creation, the use of the femtosecond laser is crucial, as it is the only keratome that allows surgeons to manipulate the flap depth, as well as flap diameter. While the mechanical microkeratome creates corneal dissection using its metal blade, the femtosecond laser uses microphotodisruption to achieve dissection, at a predetermined depth using 1-mm pulses in either a raster or spiral pattern across the surface, thus creating a flap that is almost completely planar.2 As femtosecond-laser flaps have an even thickness across the entire Slade & Baker Vision Center 3900 Essex Lane, Suite 101 Houston, TX 77027 www.dosonline.org Refractive Surgery Sub-Bowman’s Keratomileusis surface, they have a significant advantage over mechanicalmicrokeratome flaps, which tend to have a more meniscus shape, being thicker in the periphery and shallower in the center, resulting in less predictable flap thickness. The evolution of the femtosecond laser saw the introduction of the 60-kHz laser in 2006, which allowed the laser to create corneal flaps about as quickly as the mechanical keratome, as well as requiring less energy for flap creation and enabling closer separation of spots and lines. The incidence of opaque bubble layers, which can form during the photodisruption process, is also reduced using the 60 kHz, which can make corneal flap-lifting an easier task. Corneal flap creation using the femtosecond laser is considered superior to flap creation using mechanical microkeratomes in various published studies.3,4,5 Using the femtosecond laser to create corneal flaps means a lower standard deviation in the central thickness of the cornea and good visual results in the early post-operative period. One of the first comparative studies that evaluated results with the femtosecond laser versus results with a mechanical microkeratome concluded that flap thickness predictability was better achieved with the femtosecond laser.6 Flaps of less than 150 µm can be created using a mechanical microkeratome, but flap predictably becomes an issue. Kezirian and Stonecipher compared two mechanical microkeratomes with the IntraLase Femtosecond Laser, showing that the mean flap thickness for the laser flaps was 114 ± 14 µm (SD) with an intended thickness of 130 µm. With the Hansatome microkeratome, the mean flap thickness was 156 ± 29 µm with a 130 µm head, and with the CB microkeratome, the mean flap thickness was 153 ± 26 µm, also with a 130 µm head. Recent biomechanical studies that compare the corneal response to different types of laser refractive procedures suggest that corneal flaps created using a femtosecond laser are the most stable. The study also proved that there was less surgically-induced astigmatism in the eyes treated with the femtosecond laser, and that there were fewer complications overall. In a prospective, contralateral eye study comparing the femtosecond laser and the Hansatome Microkeratome, Durrie and Kezirian showed that uncorrected visual acuity (UCVA) and manifest refractive outcomes were better with the femtosecond laser.7 Tran et al, studied induced aberrations following flap creation using the femtosecond laser and the Hansatome, and concluded that HOAs increased significantly in microkeratome eyes, which was not the case for eyes treated with the femtosecond laser.8 Marshall et al, carried out a study on cadaver eyes, observing wound healing and corneal biomechanics following PRK, epiLASIK, mechanical microkeratome-assisted LASIK and femtosecond laser-assisted LASIK. With the use of confocal specular microscopy, electron microscopy, Shearing interferometry and histology, the study concluded that the strongest part of the cornea was the first 150 µm, and out in the periphery where the 33 lamellae were packed tightly. Consequently, the corneas treated with PRK, epi-LASIK and femtosecond laser-created flaps of ±100 µm resulted in the greatest biomechanical stability and better corneal transparency.9 Dupps and Wilson demonstrate that the interweaving of the lamellae provides a significant structural foundation for shear (gliding) resistance, whereby the circumferential cutting of the central lamellae causes relaxation of the lamellae out in the periphery, leading to peripheral stromal thickening.10 The depth of the lamellar cut is one of the most important factors in a LASIK flap, and that corneal behavior is largely dependent on collagen fibrin distribution.11,12 Out of the five layers of the cornea, Bowman’s layer and the stroma are the only layers that contain collagen fibrils, which means that these layers have the most tensile strength.13 Comparative results can also be found in a study by Alio et al., which suggests that the biomechanical effect of LASIK with the femtosecond laser is equivalent to the effects of surface ablation.14 Stronger flaps are also a biomechanical advantage, and published literature suggests that using flaps created using the femtosecond laser are stronger than those created with a mechanical microkeratome. Kim et al. studied the amount of force required to re-lift flaps created by a femtosecond laser and a mechanical microkeratome, and concluded that a significantly greater amount of strength was needed to re-lift the femtosecond-laser flaps at 3 months post-operatively (P<0.05).3 An hypothesis by Marshall suggests that it is the manner in which the femtosecond laser creates the flap that results in a stronger flap, whereby microphotodisruption creates a surface that enables better adhesion between the corneal flap and the stromal bed.15 When using the metal blade of a mechanical microkeratome, a smooth corneal flap and stromal bed is created. Subsequently, the two surfaces may slip against each other once the flap has been replaced, which can delay wound healing. SBK: The best of LASIK and PRK While the LASIK procedure and PRK both have significant advantages, they are hindered by significant disadvantages. We created a procedure that combined the visual results and painless experience of the LASIK with the biomechanical stability of surface ablation, and called it sub-Bowman’s keratomileusis. Many surgeons already perform laser vision correction with a femtosecond laser or a mechanical microkeratome, with flaps of d”100 µm, but the SBK procedure boasts customized corneal flap creation. The key to this technique is to create a corneal flap that is planar. Some mechanical microkeratomes can create a 100-µm flap, but the shape is more typically meniscus, which is why we have a preference for corneal flap creation using the femtosecond laser.16 With the SBK procedure the diameter of the flap is based on the requirements of the individual patient and the type of excimer laser used, with an intended thickness of between 90 and 110 µm. In the clinical study we conducted to evaluate SBK vs. PRK, it was necessary to standardize the flap thickness and diameter to an intended flap thickness of 100 µm and a diameter of 8.5 mm. The approach allows the preservation of as much Bowman’s membrane as possible, as well as avoiding disruption of the lamellae in the periphery of the cornea. In our experience, with these thinner, 34 smaller flaps, patients who undergo the SBK procedure have less dry eye and less inflammation, as they help to protect the lamellae in the periphery of the cornea. For surgeons, these flaps are easier to handle and position, with minimal striae or flap slips. SBK enables the creation of a predictable, thin flap, quicker visual recover, with minimal pain, and superior visual results, especially in the first 3 months. Post-operatively, the SBK procedure shows reduced incidence of dry eye, minimal biomechanical changes with fewer HOAs and a decrease in loss of corneal sensitivity. SBK Methods With LASIK, flaps tend to be created as large as possible (9.5-10 mm) to compensate for any decentration. As the flap in the SBK procedure is smaller, it is crucial that the flap is centered over the optical zone. It is important to practice centration of the suction ring when using the femtosecond laser, using the pupil as the fixation point. It is also important that the suction ring is centered on the computer screen of the laser prior to flap creation. Flap diameter should be based on the type of excimer laser used. With the Alcon LADARVision CustomCornea Excimer Laser (Alcon, Ft Worth, Texas, USA), the maximum ablation zone is 6 mm, and the typical flap diameter ranges from 7-7.5 mm. With the Bausch & Lomb Zyoptix Excimer Laser (Bausch & Lomb, Rochester, New York, USA), the typical flap diameter is 7.5 -8 mm. Although careful handling is required, which is the case with any corneal flap, smaller corneal flaps tend to be easier to handle than flaps of 9 -10 mm, as they are less likely to tear or buttonhole. SBK vs. PRK Clinical Study We initiated a clinical study to evaluate SBK and compare it to PRK. In this contralateral study, 100 eyes of 50 patients were treated; one eye of each patient underwent femtosecond-laser assisted LASIK (with an intended flap thickness of 100 µm), and the fellow eye underwent PRK. The study took place at two centers, with 25 patients treated at Kansas City and 25 patients treated at Houston. Informed consent was obtained from all patients. The mean age of the patients was 33.24 ± 6.97 (range of 22 to 48) with 42% (n = 21) males and 58% (n = 29) females enrolled. Criteria for inclusion included spherical myopia of -2 to -6.00 D, with up to -3.50 D refractive astigmatism; stable refraction for 1 year; a BSCVA of at least 20/20 in each eye; and an average central corneal thickness e” 500 µm in each eye. As it was a contralateral study, the two groups were almost equal in terms of pre-operative mean refractive error: the femtosecond laser group was -3.64 D (-2.00 to -5.75 D) (SD = 0.97) with a mean manifest cylindrical refraction of -0.63 D (0 to -3.00 D), while the PRK group was -3.68 D (-2.00 to -5.75 D) (SD = 1.06) with a mean manifest cylindrical refraction of -0.64 D (0 to -2.75 D). Both groups had a mean pre-operative BSCVA of 20/17 with a range of 20/12 to 20/20 (SD = 2.47). Pre-operative UCVA ranged from 20/80 to count fingers in both groups. All patients underwent correction for myopia, with or without astigmatism, using the Alcon LADARVision 4000 Excimer Laser (Alcon Laboratories, Ft. Worth, TX) with a customized wavefront treatment. For the SBK eyes, we used a small flap diameter (8.5 mm) and a thin flap (d”100 µm). All flaps in this procedure were created using the 60-kHz femtosecond laser (IntraLase FS Femtosecond Laser, Advanced Medical Optics, Irvine, CA), using a raster pattern with the hinge located in the superior position. DOS Times - Vol. 13, No.4, October 2007 The hinge angle was set at 50º and the side-cut angle was 75º. The incidence of dense bubbles in the interface was decreased by enabling the e- “pocket” software. OCT measurements revealed that the femtosecond-laser flaps had a planar thickness with a mean of 112 ± 5 µm (range 87 to 118 µm), with the average standard deviation in flap thickness at 4 µm. All patients received customized ablation. The PRK procedure was performed with an 8.5-mm trephine placed on the eye, the application of 20% ethanol for 25 seconds, followed by irrigation and chilling with balanced salt solution within the trephine. All eyes received proparacaine 0.5% and tetracaine 0.5% drops intraoperatively. The goal of all surgeries was emmetropia. Following surgery, all patients received a topical antibiotic drop, a steroid drop and preservative-free tears. In the PRK eyes, a bandage contact lens was placed and left on until the cornea reepithelialized. Topical antibiotic and steroids were applied four times a day for post-operative week 1, as well as preservative-free artificial tears. The steroid was tapered to TID in the second week in the PRK eyes, followed by BID in the third week, and once a day thereafter. The PRK eyes also received Acular LS (ketorolac, Allergan, Irvine, CA) which did not exceed 3 times per day for the first 3 days, in addition to acetaminophen/hydrocodone 1-2 tablets, 4-6 times per day for pain control. No topical anesthetic drops were applied. Although the full results of this study are due to be published later this year, visual results for the SBK eyes have shown a quick return to functional vision with 100% of the 50 eyes achieving 20/40 uncorrected visual acuity on the first post-operative day, compared to 42% in the PRK eyes. At one month post-operatively, 88% of the femtosecond eyes achieved 20/20 or better visual acuity, compared to 48% of the PRK eyes. Also significant was the fact that the femtosecond laser assisted eyes had lower levels of HOAs at 1 and 3 months post-operatively (coma and spherical aberration) than the PRK eyes. corneal response factor (CRF) and ocular pulse amplitude. The evaluation showed that PRK had no biomechanical advantage over a flap-based approach; corneal hysteresis decreased after both SBK and PRK, and the CRF results indicated biomechanical weakening seen in both the SBK and PRK eyes. This initial study indicates that the SBK procedure offers refractive surgeons and patients the best of both LASIK and PRK, while avoiding the disadvantages. SBK in the Future Although further clinical studies on the SBK procedure are required, this hybrid technique, which combines LASIK and PRK, cancels out the negatives of both procedures, leaving a single superior method for performing corneal refractive surgery. Combining the use of customized flaps with the SBK procedure, using the femtosecond laser, achieves both efficacy and safety, with the best possible visual results. The results of our study purport that the SBK procedure is superior to PRK in almost every pertinent aspect, particularly in the immediate post-operative period, when considering visual results and patient feedback. Currently we can customize the corneal flap thickness and diameter to cater to individual patients. In the future, surgeons will be able to create ‘smart’ flaps, with the ability change the shape of the flap, taking astigmatism into account, and adjust the flap edge based on the thickness of the epithelium. The SBK procedure may constitute the establishment of a new “K” in refractive surgery, and as studies continue, the procedure may become an essential tool in the evolution of laser refractive surgery. References 1. Comprehensive Report on the Global Refractive Surgery Market. MarketScope 2006; Ballwin, MO. 2. Kurtz RM, Liu X, Elner VM, et al. Photodisruption in the human cornea as a function of laser pulse width. J Refract Surg 1997; 13:653– 658. It took up to 6 months for the PRK eyes to achieve the same level of vision as the SBK eyes at 1 month post-operatively. Although the follow-up results of the two groups were relatively equal by six months post-operatively, it is important to consider that patients make up their minds about how successful or unsuccessful their laser vision procedure was in the first few months, and they will talk to family and friends about their experience in the immediate post-operative period. 3. Kim JY, Kim MJ, Kim TI, et al. A femtosecond laser creates a stronger flap than a mechanical microkeratome. Invest Ophthalmol Vis Sci 2006; 47:599–604. 4. Montes-Mico R, Rodriguez-Galietero A, Alio JL. Femtosecond laser versus mechanical keratome LASIK for myopia. Ophthalmology 2007; 114:62–68. 5. Binder PS. One thousand consecutive IntraLase laser in situ keratomileusis flaps. J Cataract Refract Surg 2006; 32:962–969. Patients expressed their preference for their femtosecond lasertreated eye to their PRK-treated eye, as the femtosecond eye caused less pain and achieved better visual results during the first 3 postoperative months. In fact, patients preferred the vision in their SBK eye over their PRK eye out to three months by a margin of 2 to 1. There was less sensitivity and fluctuation of vision through one month in the SBK group, and the group also had better high and low contrast acuity and retinal image quality, compared to the PRK group. The SBK group achieved less dry eye, double vision and blurry vision, glares/halos, grittiness and difficulty with night driving through three months post-operatively. 6. Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical microkeratomes for laser in situ keratomileusis. J Cataract Refract Surg 2004; 30:804–811. 7. Durrie DS, Kezirian GM. Femotsecond laser vesus mechanicalmicrokeratome flaps in wavefront-guided laser in situ keratomileusis: prospective contralateral eye study. J Cataract Refract Surg 2005; 31:120–126. 8. Tran DB, Sarayba MA, Bor Z, et al. Randomized prospective clinical study comparing induced aberrations with IntraLase and Hansatome flap creation in fellow eyes: potential impact on wavefront-guided laser in situ keratomileusis. J Cataract Refract Surg 2005; 31:97– 105. 9. J. Marshall et al., The effects of varying forms of corneal flap creation on wound healing and biomechanics, unpublished data; J. Marshall The Optical Response Analyzer (Reichert) and the Pascal Dynamic Contour Tonometer (SMT/Ziemer Ophthalmic Group) were used to evaluate biomechanical results, by assessing corneal hysteresis, www.dosonline.org 35 et al., The impact of flap depth on corneal biomechanics and wound healing in laser refractive surgery, unpublished data 13. Dupps WJ Jr, Wilson SE. Biomechanics and wound healing in the cornea. Exp Eye Res. 2006;83:709-20 10. Dupps WJ Jr, Wilson SE. Biomechanics and wound healing in the cornea. Exp Eye Res. 2006;83:709-20. 14. J.L. Alio, Aberrometric outcomes and very high-frequency digital ultrasound evaluation of the flap thickness profile in LASIK surgery using three different methods for lamellar keratotomy, unpublished data 11. Deenadayalu C, Mobasher B, Rajan SD, et al. Refractive change induced by the LASIK flap in a biomechanical finite element model. J Refract Surg 2006;22:286–292. 12. Alastrue V, Calvo B, Pena E, et al. Biomechanical modeling of refractive corneal surgery. J Biomech Eng 2006; 128:150–160. 15. Marshall J. Femtosecond vs. epi-LASIK. Cataract & Refractive Surgery Today Europe 2006; 1:44–49. 16. Flanagan GW, Binder PS. Precision of flap measurements for laser in situ keratomileusis in 4428 eyes. J Refract Surg 2003;19:113-23. First Author Stephen G. Slade MD Monthly Clinical Meetings Calendar 2007-2008 Centre for Sight th 29 July, 2007 (Sunday) 25th November, 2007 (Sunday) Dr. R.P. Centre for Ophthalmic Sciences Mohan Eye Institute th 26 August, 2007 (Sunday) 30th December, 2007 (Sunday) Dr. Shroff Charity Eye Hospital Venu Eye Institute th 30 September, 2007 (Sunday) 20th January, 2008 (Sunday) Guru Nanak Eye Centre Army Hospital (R&R) th 28 October, 2007 (Sunday) 24th February, 2008 (Sunday) Midterm Conference of DOS Safdarjung Hospital th th 17 ,18 November, 2007 (Saturday - Sunday) 36 Sir Ganga Ram Hospital March, 2008 DOS Times - Vol. 13, No.4, October 2007 Retina Central Serous Retinopathy Bhuvan Chanana MD, Raj Vardhan Azad MD, FRCSEd entral serous retinopathy (CSR) or Central serous chorioretinopathy is an idiopathic, self limiting, noninflammatory, serous detachment of the sensory retina resulting from altered barrier and deficient pumping functions at the level of the retinal pigment epithelium (RPE). In some cases serous detachments of the RPE may also be present. C 1 month of presentation as compared with 18% of control subjects.4 Haimovici et al evaluated systemic risk factors for CSR in 312 patients and 312 control subjects. Systemic steroid use and pregnancy were most strongly associated with CSR. Other risk factors included antibiotic use, alcohol use, untreated hypertension, and allergic respiratory disorders.5 CSR is most common in male patients aged 20-55 years. This condition affects men 6-10 times more often than it affects women. CSR is common among Caucasians, Hispanics, and Asians, and rare in African Americans. Patients may present with a later age of onset (>50 y). Spaide et al reviewed 130 consecutive patients with CSCR and found the age range at first diagnosis to be 22.2-82.9 years, with a mean age of 49.8 years.1 Patients diagnosed at 50 years or older are found to have bilateral disease, demonstrate a decreased male predominance (2.6:1), and show more diffuse RPE changes. Furthermore, these patients are more likely to have systemic hypertension or a history of corticosteroid use. Cotticelli et al showed an association between Helicobacter pylori infection and CSR.6 The prevalence of H pylori infection was 78% in patients with CSR compared with a prevalence of 43.5% in the control group. The authors proposed that H pylori infection may represent a risk factor in CSR, though no further studies have substantiated this claim. Pathophysiology Previous hypotheses for the pathophysiology have included abnormal ion transport across the RPE and focal choroidal vasculopathy. ICG angiography has demonstrated both multifocal choroidal hyperpermeability and hypofluorescent areas suggestive of focal choroidal vascular compromise. Some investigators believe that initial choroidal vascular compromise subsequently leads to secondary dysfunction of the overlying RPE. Studies employing multifocal electroretinography have demonstrated bilateral diffuse retinal dysfunction even when CSR was active only in one eye. These studies support the belief of diffuse systemic effect on the choroidal vasculature. Type A personalities, systemic hypertension, stress and obstructive sleep apnea may be associated with CSR. The pathogenesis here is thought to be elevated circulating cortisol and epinephrine, which affects the autoregulation of the choroidal circulation. 2 Furthermore, Tewari et al demonstrated that patients with CSCR showed impaired autonomic response with significantly decreased parasympathetic activity and significantly increased sympathetic activity.3 Systemic associations of CSR include organ transplantation, exogenous steroid use, endogenous hypercortisolism (Cushing syndrome)2, systemic hypertension, systemic lupus erythematosus, pregnancy, gastroesophageal reflux disease, use of sildenafil citrate, and use of psychopharmacologic medications. Corticosteroids have a direct influence on the expression of adrenergic receptor genes and, thus, contribute to the overall effect of catecholamines on the pathogenesis of CSR. Consequently, multiple studies have conclusively implicated the effect of corticosteroids in the development of CSR. Carvalho-Recchia et al showed in a series that 52% of patients with CSR had used exogenous steroids within Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi www.dosonline.org Natural course Most patients with CSR (80-90%) resolve spontaneously within 3 to 4 months, with vision returning to 20/25 or better. Even with return of good central visual acuity, many of these patients still notice dyschromatopsia, loss of contrast sensitivity, metamorphopsia, or, rarely, nyctalopia. • Patients with classic CSR (characterized by focal leaks) have a 40-50% risk of recurrence in the same eye. • Risk of choroidal neovascularization from previous CSR is considered small (<5%) but has an increasing frequency in older patients diagnosed with CSR. • A subset of patients (5-10%) may fail to recover 20/30 or better visual acuity. These patients often have recurrent or chronic serous retinal detachments, resulting in progressive RPE atrophy and permanent visual loss to 20/200 or worse. The final clinical picture represents diffuse retinal pigment epitheliopathy. Figure 1. Fundus photograph showing localized neurosensory detachment in the macula from central serous chorioretinopathy 39 Figure 2. Fluorescein angiography in the above patient. A focal hyperfluorescent leak is present superior to fovea with gradual leakage of fluorescein dye within the neurosensory detachment. Clinical features Patients typically present with acute symptoms of blurred and dim vision, micropsia, or paracentral scotoma. In general, the vision ranges from 20/20 to 20/200, but in most patients vision is better than 20/30. The decreased vision usually is improved by a small hyperopic correction. Other clinical signs include a delayed retinal recovery time following photostress, loss of color saturation, and loss of contrast sensitivity. Slit lamp non-contact biomicroscopy or contact lens biomicroscopy typically shows a round, well-delineated, shallow, serous macular neurosensory detachment, which is often surrounded by a halo light reflex, involving the posterior pole mainly macula (Figure 1). Subretinal fibrin precipitates may be seen as multiple, gray-white, dot like condensations on the posterior surface of the detached retina. Small, round, yellow or gray serous RPE detachments (PEDs) may be present. These serous PEDs are typically less than a quarter of a disc diameter in size, are located in the superior half of the neurosensory detachment. RPE atrophy may be present in one or both eyes as evidence of an active or previous CSR episode. An atypical variant of CSR usually is found in healthy middle-aged men and presents with multiple PEDs and multiple bullous serous neurosensory detachments that demonstrate shifting fluid. These detachments are located in the midperiphery or more posteriorly. This form of CSR is characterized by a more fibrinous subretinal exudate that imparts an opaque appearance to the subretinal fluid. 40 Late sequelae of this fibrinous exudate include subretinal fibrosis, CNV or RPE rips. Another atypical CSR includes inferior, peripheral, atrophic RPE tracts (linear pigment lines) and is associated with a poorer prognosis. Excessive or prolonged subretinal leakage is responsible for this type of CSR. Gravity causes the subretinal fluid to collect inferiorly, forming a “teardrop” or “hourglass” shape. This severe type of CSR is more common in persons of Hispanic or Asian ancestry. Fluorescein Angiography of CSR Three characteristic Fluorescein Angiographic patterns are seen in CSR: • Expansile dot pattern • Smokestack pattern • Diffuse pattern An expansile dot of hyperfluorescence is the most common presentation. A small, focal hyperfluorescent leak from the choroid through the RPE appears in the early phase of the angiogram and increases in size and intensity as the angiogram progresses (Figure 2). In some patients, several leaking expansile dots may be present. Smokestack pattern is uncommon, occurring in approximately 10% of cases. The fluorescein starts with a central DOS Times - Vol. 13, No.4, October 2007 diffuse CSR from occult choroidal neovascularization (CNV) in older individuals and idiopathic polypoidal choroidal vasculopathy. Multiple patches of hyperfluorescence presumably are due to choroidal hyperpermeability, which, in later phases, results in silhouetting or negative staining of larger choroidal vessels. spot of hyperfluorescence that spreads vertically and, finally, laterally, in a configuration evocative of a plume of smoke. This unique pattern is felt to be secondary to convection currents and a pressure gradient between the protein concentration of the subretinal fluid and the fluorescein dye entering the detachment. Rarely a diffuse pattern of fluorescein leakage is present, often without any obvious leakage point. Patients with this condition have large, gravity dependent, serous detachment of the retina and extensive RPE changes. Other Tests • Multifocal electroretinography has been used to identify focal regions of decreased retinal function, even in asymptomatic or clinically inactive eyes. 7 Furthermore, investigators, including Lai et al, are using multifocal electroretinography as a means of assessing the efficacy and safety of new treatment modalities for CSR.8 • Microperimetry (using the Nidek MP-1 microperimeter) has also shown that, despite clinical resolution of CSR, there is lower retinal sensitivity in the macula even once visual acuity returned to 20/20. Fixation studies showed stability of central fixation. Other Imaging Studies • • Optical coherence tomography (OCT) reveals many aspects of the pathophysiology of CSR, ranging from subretinal fluid (Figure 3), pigment epithelial detachments, and retinal atrophy following chronic disease. OCT is especially helpful in identifying subtle, even subclinical, neurosensory macular detachments (Figure 3). ICG angiography has shown hypofluorescent areas early in the angiogram followed by late hyperfluorescence and leakage in choroidal vasculature. Often, multiple areas of leakage are seen on ICG angiography that are not evident clinically or on FA. ICG angiography can be useful to differentiate atypical Medical Care • Psychopharmacologic agents (eg, anxiolytics, antidepressants) were a risk factor for CSR. Corticosteroids may result in exacerbation of serous detachments in CSR. Figure 3. OCT showing fluid in the subretinal space from central serous chorioretinopathy. www.dosonline.org 41 • Acetazolamide has been suggested to hasten the resolution of subretinal fluid. • Tatham and Macfarlane described a case series of patients who were treated with propranolol for CSR.9 They suggested that beta-blockade had a hypothetical mechanism in treating CSR. Further evidence is needed to substantiate this potential treatment. • Nielsen et al proposed the use of mifepristone in the treatment of chronic CSR in a case report.10 • Intravitreal bevacizumab (Avastin) has been used to treat choroidal neovascularization following CSR. Patient Education • If possible, patients should avoid stressful situations. Patient participation in stress-reducing activities (eg, exercise, meditation, yoga) is recommended. • Control of systemic hypertension may reduce the incidence of CSR. Complications • A small minority of patients develops choroidal neovascularization at the site of leakage and laser treatments.11, 12 A retrospective review of cases shows that one half of these patients may have had signs of occult choroidal neovascularization at the time of treatment. In the other patients, the risk of choroidal neovascularization may have been increased by the laser treatment. • Acute bullous retinal detachment may occur in otherwise healthy patients with CSR. This appearance may mimic VogtKoyanagi-Harada disease or rhegmatogenous retinal detachment. • Recurrent attacks leads to RPE atrophy and subsequent retinal atrophy. Surgical Care Current treatment guidelines suggest that patients may be observed for at least 3-4 months in most first episodes of unilateral CSR. Laser treatment induces rapid remission of subretinal fluid and shortens the course of the disease, but it does not appear to improve the final visual prognosis. Laser photocoagulation should be considered under the following circumstances: • Persistence of a serous retinal detachment for more than 3-4 months Prognosis • Recurrence in an eye with visual deficit from previous CSR • • Presence of visual deficits in opposite eye from previous episodes of CSR Typical serous retinal detachments resolve spontaneously in most patients, with most patients (80-90%) returning to 20/25 or better vision. • Bilateral CSR for early rehabilitation • • Occupational or other patient need requiring prompt recovery of vision. Even with return of good central visual acuity, many of these patients still notice dyschromatopsia, loss of contrast sensitivity, metamorphopsia, or nyctalopia. • • Patients with recurrent episodes of serous detachment with a leak located more than 300 µm from the center of the fovea. Patients with classic CSR (characterized by focal leaks) have a 40-50% risk of recurrence in the same eye. • A subset of patients (5-10%) may fail to recover 20/30 or better visual acuity. These patients often have atypical CSR, recurrent or chronic serous retinal detachments, resulting in progressive RPE atrophy and permanent visual loss to 20/200 or worse. The final clinical picture represents diffuse retinal pigment epitheliopathy. • Risk of choroidal neovascularization from previous CSR is considered small (<5%) but has an increasing frequency in older patients diagnosed with CSR. Photodynamic therapy Photodynamic therapy (PDT) has growing support in the literature as a treatment of chronic CSCR and, most recently, acute phases of this condition. PDT is known to have a direct effect on the choroidal circulation but was limited by potential adverse effects, such as macular ischemia. Authors, such as Lai et al, are describing reduced dosing of verteporfin. The rates of adverse events have decreased significantly with these modifications. PDT is believed to hasten both fluid resorption and visual recovery. Lai et al described the use of half dose verteporfin in the treatment of CSR.8 They proposed 3 mg/m2 of verteporfin infused over 8 minutes, followed 2 minutes later with ICG guided PDT. Of the eyes treated, 85% showed complete resolution of the neurosensory retinal detachment and/or pigment epithelial detachment by 1 month after treatment. Further Outpatient Care 42 • Most patients receive follow-up care for 2 months to determine whether the fluid resolves spontaneously. • If laser is performed, follow-up within 3-4 weeks should be done to determine the rare complication of post laser CNV.11 References 1. Spaide RF, Campeas L, Haas A, Yannuzzi LA, Fisher YL, Guyer DR, et al. Central serous chorioretinopathy in younger and older adults. Ophthalmology. Dec 1996;103(12):2070-9. 2. Bouzas EA, Scott MH, Mastorakos G, Chrousos GP, Kaiser-Kupfer MI. Central serous chorioretinopathy in endogenous hypercortisolism. Arch Ophthalmol. Sep 1993;111(9):1229-33. 3. Tewari HK, Gadia R, Kumar D, Venkatesh P, Garg SP. Sympatheticparasympathetic activity and reactivity in central serous chorioretinopathy: a case-control study. Invest Ophthalmol Vis Sci. Aug 2006; 47(8): 3474-8. 4. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, Spaide RF, Freund KB, Rodriguez-Coleman H, et al. Corticosteroids and central serous DOS Times - Vol. 13, No.4, October 2007 chorioretinopathy. Ophthalmology. Oct; 2002; 109(10):1834-7. 5. 6. 7. 8. Haimovici R, Koh S, Gagnon DR, Lehrfeld T, Wellik S. Risk factors for central serous chorioretinopathy: a case-control study. Ophthalmology. Feb 2004; 111(2):244-9. Cotticelli L, Borrelli M, D’Alessio AC, Menzione M, Villani A, Piccolo G, et al. Central serous chorioretinopathy and Helicobacter pylori. Eur J Ophthalmol. Mar-Apr 2006; 16(2):274-8. Marmor MF, Tan F. Central serous chorioretinopathy: bilateral multifocal electroretinographic abnormalities. Arch Ophthalmol. Feb 1999; 117(2):184-8. Lai TY, Chan WM, Li H, Lai RY, Liu DT, Lam DS. Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study. Br J Ophthalmol. Jul 2006; 90(7):869-74. 9. Tatham A, Macfarlane A. The use of propranolol to treat central serous chorioretinopathy: an evaluation by serial OCT. J Ocul Pharmacol Ther. Apr 2006; 22(2):145-9. 10. Nielsen JS, Weinreb RN, Yannuzzi L, Jampol LM. Mifepristone treatment of chronic central serous chorioretinopathy. Retina. Jan 2007; 27(1):119-22. 11. Gomolin JE. Choroidal neovascularization and central serous chorioretinopathy. Can J Ophthalmol. Feb 1989; 24(1):20-3. 12. Matsunaga H, Nangoh K, Uyama M, Nanbu H, Fujiseki Y, Takahashi K. [Occurrence of choroidal neovascularization following photocoagulation treatment for central serous retinopathy]. Nippon Ganka Gakkai Zasshi. Apr 1995; 99(4):460-8. Author Raj Vardhan Azad MD, FRCSEd www.dosonline.org 43 Santosh G. Honavar MD, FACS R etinoblastoma is the most common intraocular malignancy in children, with a reported incidence ranging from 1 in 15,000 to 1 in 18,000 live births.1 It is bilateral in about 25 to 35% of cases.2 The average age at diagnosis is 18 months, with unilateral cases being diagnosed at around 24 months and bilateral cases before 12 months.2 Early tumor recognition aided by indirect ophthalmoscopy and refined enucleation technique contributed to an improved survival from 5% in 1896 to 81% in 1967.1-4 Advances in external beam radiotherapy in the 1970s and further progress in planning and delivery in the next two decades provided an excellent alternative to enucleation and resulted in substantial eye salvage. 2 Focal measures such as cryotherapy, photocoagulation and plaque brachytherapy allowed targeted treatment of smaller tumors optimizing vision salvage.2 Parallel advancements in ophthalmic diagnostics such as ultrasonography, computed tomography, and magnetic resonance imaging contributed to improved diagnostic accuracy and early detection of extraocular retinoblastoma. The recent advances such as identification of genetic mutations5, 6 replacement of external beam radiotherapy by chemoreduction as the primary management modality, use of chemoreduction to minimize the size of regression scar with consequent optimization of visual potential, 7-11 identification of histopathologic high-risk factors following enucleation 12 and provision of adjuvant therapy to reduce the incidence of systemic metastasis, 13 protocol-based management of retinoblastoma with accidental perforation or intraocular surgery 14-16 and aggressive multimodal therapy in the management of orbital retinoblastoma 17,18 have contributed to better survival, improved eye salvage and potential for optimal visual recovery. Ocular Tumours Current Concepts in Retinoblastoma Genetic counseling is an important aspect in the management of retinoblastoma. In patients with a positive family history, 40% of the siblings would be at risk of developing retinoblastoma and 40% of the offspring of the affected patient may develop retinoblastoma. In patients with no family history of retinoblastoma, if the affected child has unilateral retinoblastoma, 1% of the siblings are at risk and 8% of the offspring may develop retinoblastoma. In cases of bilateral retinoblastoma with no positive family history, 6% of the siblings and 40% of the offspring have a chance of developing retinoblastoma. 2 Clinical Manifestations of Retinoblastoma Leucocoria is the most common presenting feature of retinoblastoma, followed by strabismus, painful blind eye and loss of vision. Table 1 lists the common presenting signs and symptoms of retinoblastoma. 21 The clinical presentation of retinoblastoma depends on the stage of the disease.10 Early lesions are likely to be missed, unless an indirect ophthalmoscopy is performed. The tumor appears as a translucent or white fluffy retinal mass (Figure 1). The child may present with strabismus if the tumor involves the macula or with reduced visual acuity. Genetics of Retinoblastoma Out of the newly diagnosed cases of retinoblastoma only 6% are familial while 94% are sporadic.2,19 Bilateral retinoblastomas involve germinal mutations in all cases. Approximately 15% of unilateral sporadic retinoblastoma is caused by germinal mutations affecting only one eye while the 85% are sporadic.2 In 1971, Knudson proposed the two hit hypothesis.20 He stated that for retinoblastoma to develop, two chromosomal mutations are needed. In hereditary retinoblastoma, the initial hit is a germinal mutation, which is inherited and is found in all the cells. The second hit develops in the somatic retinal cells leading to the development of retinoblastoma. Therefore, hereditary cases are predisposed to the development of nonocular tumors such as osteosarcoma. In unilateral sporadic retinoblastoma, both the hits occur during the development of the retina and are somatic mutations. Therefore there is no risk of second nonocular tumors. Figure 1. Early manifestation of retinoblastoma with a localized tumor at the posterior pole Moderately advanced lesions usually present with leucocoria due to the reflection of light by the white mass in the fundus (Figure 2). As the tumor grows further, three patterns are usually seen: 10 • Ocular Oncology Service, LV Prasad Eye Institute, LV Prasad Marg, Banjara Hills, Hyderabad www.dosonline.org Endophytic, in which the tumor grows into the vitreous cavity (Figure 3). A yellow white mass progressively fills the entire vitreous cavity and vitreous seeds occur. The retinal vessels are not seen on the tumor surface. 45 Figure 2. Lecocoria is the most common clinical presentation of retinoblastoma Figure 3. Endophytic tumor with vitreous seeds Figure 5. Diffuse infiltrative retinoblastoma with placoid retinal thickening seen on gross examination of the enucleated eye in a 7-year-old child. Figure 4. Exophytic retinal tumor with exudative retinal detachment Table 1. Common presenting features of retinoblastoma Figure 6. Retinoblastoma with orbital extension in a 3-year-old child. 46 • Exophytic, in which the tumor grows towards the subretinal space (Figure 4). Retinal detachment usually occurs and retinal vessels are seen over the tumor. • Diffuse infiltrating tumor, in which the tumor diffusely involves the retina causing just a placoid thickness of the retina and not 1. Leucocoria 56% 2. Strabismus 20% 3. Red painful eye 7% 4. Poor vision 5% 5. Asymptomatic 3% 6. Orbital Cellulitis 3% 7. Unilateral Mydriasis 2% 8. Heterochromia Iridis 1% 9. Hyphema 1% a mass. This is generally seen in older children and usually there is a delay in the diagnosis (Figure 5). Advanced tumors manifest with proptosis secondary to optic nerve extension or orbital extension (Figure 6) and systemic metastasis.10 Retinoblastoma can spread through the optic nerve with relative DOS Times - Vol. 13, No.4, October 2007 Figure 7. A 5-year-old child with retinoblastoma with anterior segment seeding manifesting with tumor hypopyon Figure 9. Spontaneous vitreous hemorrhage as the presenting feature of retinoblastoma in a 4-year-old child Figure 8. A 4-year-old with spontaneous hyphema in the left eye. Ultrasonography confirmed the diagnosis of retinoblastoma. Figure 10. An 18-month-old child with bilateral retinoblastoma. The right eye has secondary glaucoma and enlarged cornea while the left eye is phthisical. ease especially once the lamina cribrosa is breached. Orbital extension may present with proptosis and is most likely to occur at the site of the scleral emissary veins. Systemic metastasis occurs to the brain, skull, distant bones and the lymph nodes. Some of the atypical manifestations of retinoblastoma include pseudohypopyon (Figure 7), spontaneous hyphema (Figure 8), vitreous hemorrhage (Figure 9), phthisis bulbi (Figure 10) and preseptal or orbital cellulites (Figure 11). 10 Diagnosis of Retinoblastoma A thorough clinical evaluation with careful attention to details, aided by ultrasonography B-scan helps in the diagnosis. 10 Computed tomography and magnetic resonance imaging are generally reserved for cases with atypical manifestations and diagnostic dilemma and where extraocular or intracranial tumor extension is suspected.10 A child with suspected retinoblastoma necessarily needs complete ophthalmic evaluation including a dilated fundus examination under anaesthesia.10 The intraocular pressure is measured and the anterior segment is examined for neovascularization, pseudohypopyon, hyphema, and signs of inflammation.10 Bilateral fundus examination with 360 degree scleral depression is mandatory. Direct visualization of the tumor by an indirect www.dosonline.org Figure 11. A 3-year-old child with retinoblastoma presenting with orbital cellulites ophthalmoscope is diagnostic of retinoblastoma in over 90% of cases. 21 RetCam is a wide-angle fundus camera, useful in accurately documenting retinoblastoma and monitoring response to therapy (Figure 12). Ultrasonography B-scan shows a rounded or irregular intraocular mass with high internal reflectivity representing typical intralesional 47 Figure 12. RetCam, a wide-angle digital fundus camera and image archival system helps in documentation and assessment of tumor regression on follow-up calcification (Figure 13).10 Computed tomography delineates extraocular extension and can detect an associated pinealoblastoma (Figure 14).10 Magnetic resonance imaging is specifically indicated if optic nerve invasion or intracranial extension is suspected.10 On fluorescein angiography, smaller retinoblastoma shows minimally dilated feeding vessels in the arterial phase, blotchy hyperfluorescence in the venous phase and late staining (Figure 15).10 Management of Retinoblastoma The management of retinoblastoma needs a multidisciplinary team approach including an ocular oncologist, pediatric oncologist, radiation oncologist, radiation physicist, and an ophthalmic oncopathologist. The management strategy depends on the stage of the disease – intraocular retinoblastoma, retinoblastoma with high-risk characteristics, orbital retinoblastoma and metastatic retinoblastoma. Management of retinoblastoma is highly individualized and is based on several considerations - age at presentation, laterality, tumor location, tumor staging, visual prognosis, systemic condition, family and societal perception, and, to a certain extent, the overall Figure 14. Computed tomography scan shows pinealoblastoma 48 Figure 13. Ultrasonography B-scan showing multifocal retinal tumors prognosis and cost-effectiveness of treatment in a given economic situation. Intraocular Retinoblastoma A majority of children with retinoblastoma manifest at the stage when the tumor is confined to the eye. About 90-95% of children in developed countries present with intraocular retinoblastoma while 60-70% present at this stage in the developing world.10 Diagnosis of retinoblastoma at this state and appropriate management are crucial in life, eye and possible vision salvage. Classification of Intraocular Retinoblastoma The Reese Ellsworth classification was introduced to prognosticate patients treated with methods other than enucleation.22 This classification was devised prior to the widespread use of indirect ophthalmoscopy and focal measures of management of retinoblastoma. Although the Essen classification addressed some of the shortcomings of Reese Ellsworth classification, it is considered too complex. Further, none of the older systems of classification had been designed to prognosticate chemoreduction, the current favored method of retinoblastoma management. The new International Classification of Intraocular Retinoblastoma is a Figure 15. Fundus fluorescein angiography in retinoblastoma in the early phase shows blotchy hyperfluorescence DOS Times - Vol. 13, No.4, October 2007 Table 2. International Classification of Intraocular Retinoblastoma Cryotherapy administered 2-3 hours prior to chemotherapy can increase the delivery of chemotherapeutic agents across the blood retinal barrier and thus has synergistic effect.10 Group A. Small tumors (< 3 mm) outside macula Laser photocoagulation Group B. Bigger tumors (> 3 mm) or any tumor in macula or any tumor with subretinal fluid Laser photcoagulation is used for small posterior tumors 4 mm in basal diameter and 2 mm in thickness.2,10 The treatment is directed to delimit the tumor and coagulate the blood supply to the tumor by surrounding it with two rows of overlapping laser burns. Complications include transient serous retinal detachment, retinal vascular occlusion, retinal hole, retinal traction, and preretinal fibrosis. It is less often employed now with the advent of thermotherapy. In fact, laser photocoagulation is contraindicated while the patient is on active chemoreduction protocol. 10 Group C. Localized seeds (subretinal or vitreous) Group D. Diffuse seeds (subretinal or vitreous) Group E. Tumor touching the lens, Neovascular glaucoma, Tumor anterior to anterior vitreous face involving ciliary body or anterior segment, Diffuse infiltrating retinoblastoma, Opaque media from hemorrhage, Tumor necrosis with aseptic orbital cellulitis, and Phthisis bulbi logical flow of sequential tumor grading that linearly correlates with the outcome of newer therapeutic modalities (Table 2).23, 24 This classification is currently being validated.25 Management of Intraocular Retinoblastoma The primary goal of management of intraocular retinoblastoma is to save life. Salvage of the organ (eye) and function (vision) are the secondary and tertiary goals respectively. There are several methods to manage intraocular retinoblastoma - focal (cryotherapy, laser photocoagulation, transpupillary thermotherapy, transcleral thermotherapy, plaque brachytherapy), local (external beam radiotherapy, enucleation), and systemic (chemotherapy). While primary focal measures are mainly reserved for small tumors, local and systemic modalities are used to treat advanced retinoblastoma. Cryotherapy Cryotherapy is performed for small equatorial and peripheral retinal tumors measuring up to 4 mm in basal diameter and 2 mm in thickness.2, 10 Triple freeze thaw cryotherapy is applied at 4-6 week intervals until complete tumor regression. Cryotherapy produces a scar much larger than the tumor (Figure 16). Complications of cryotherapy include transient serous retinal detachment, retinal tear and rhegmatogenous retinal detachment. Thermotherapy In thermotherapy, focused heat generated by infrared radiation is applied to tissues at subphotocoagulation levels to induce tumor necrosis.26 The goal is to achieve a slow and sustained temperature range of 40 to 60 degree C within the tumor, thus sparing damage to the retinal vessels (Figure 17). Transpupillary thermotherapy using infrared radiation from a semiconductor diode laser delivered with a 1300-micron large spot indirect ophthalmoscope delivery system has become a standard practice. It can also be applied transpupillary through an operating microscope or by the transscleral route with a diopexy probe. The tumor is heated until it turns a subtle gray. Thermotherapy provides satisfactory control for small tumors - 4 mm in basal diameter and 2 mm in thickness. Complete tumor regression can be achieved in over 85% of tumors using 3-4 sessions of thermotherapy.26 The common complications are focal iris atrophy, focal paraxial lens opacity, retinal traction and serous retinal detachment. The major application of thermotherapy is as an adjunct to chemoreduction. The application of heat amplifies the cytotoxic effect of platinum analogues. This synergistic combination with chemoreduction protocol is termed chemothermotherapy. Plaque Brachytherapy Plaque brachytherapy involves placement of a radioactive implant on the sclera corresponding to the base of the tumor to transsclerally irradiate the tumor.27 Commonly used radioactive materials include Ruthenium 106 (Figure 18) and Iodine 125. The Figure 16. A peripheral retinal tumor that underwent Cryotherapy (left). The tumor has completely regressed but the scar is much larger than the tumor itself (right) www.dosonline.org 49 Figure 17. Three focal tumors treated with transpupillary thermotherapy: Note flat scars with patent blood vessels coursing through the scars. Transpupillary thermotherapy classically spares the blood vessels from occlusion and produces a compact scar. Figure 18. Ruthenium 106 plaque. Table 3. Special considerations for enucleation in retinoblastoma a. Minimal manipulation b. Avoid perforation of the eye c. Harvest long (> 15 mm) optic nerve stump d. Inspect the enucleated eye for macroscopic extraocular extension and optic nerve involvement e. Harvest fresh tissue for genetic studies f. Avoid biointegrated implant if postoperative radiotherapy is necessary advantages of plaque brachytherapy are focal delivery of radiation with minimal damage to the surrounding normal structures, minimal periorbital tissue damage, absence of cosmetic abnormality because of retarded bone growth in the field of irradiation as occurs with external beam radiotherapy, reduced risk of second malignant neoplasm and shorter duration of treatment. Plaque brachytherapy is indicated in tumors less than 16 mm in basal diameter and less than 8 mm thickness. It could be the primary or secondary modality of management. Primary plaque brachytherapy is currently performed only in situations where chemotherapy is contraindicated. It is most useful as secondary treatment in eyes that fail to respond to chemoreduction and external beam radiotherapy or for tumor recurrences. Plaque brachytherapy requires precise tumor localization and measurement of its basal dimensions. The tumor thickness is measured by ultrasonography. The data is used for dosimetry on a three-dimensional computerized tumor modeling system. The plaque design is chosen depending on the basal tumor dimensions, its location, and configuration. The dose to the tumor apex ranges 50 Figure 19. Osteosarcoma of the frontal bone in a 20-year-old patient with bilateral retinoblastoma who had undergone external beam radiotherapy at 1-year age. from 4000-5000 cGy. The plaque is sutured to the sclera after confirming tumor centration and is left in situ for the duration of exposure, generally ranging from 36 to 72 hours. The results of plaque brachytherapy are gratifying with about 90% tumor control. The common complications are radiation papillopathy and radiation retinopathy. External Beam Radiotherapy External beam radiotherapy was the preferred form of management of moderately advanced retinoblastoma in late 1900s.28, 29 However with the advent of newer chemotherapy protocols, external beam radiotherapy is being used less often. Presently it is indicated in eyes where primary chemotherapy and local therapy has failed, or rarely when chemotherapy is contraindicated. 10 The major problems with external beam radiotherapy are the stunting of the orbital growth, dry eye, cataract, radiation DOS Times - Vol. 13, No.4, October 2007 Figure 20. Enucleated eyeball showing 18 mm optic nerve stump. Note the proximal portion of the optic nerve is thickened indicating tumor infiltration. Figure 21. Enucleated eyeball showing extrascleral tumor extension. retinopathy and optic neuropathy. External beam radiotherapy can induce second malignant neoplasm especially in patients with the hereditary form of retinoblastoma (Figure 19). There is a high 30% chance of developing another malignancy by the age of 30 years in such patients if they are given external beam radiotherapy compared to a less than 6% chance in those who do not receive external beam radiotherapy.30 The risk of second malignant neoplasm is greater in children under 12 months of age.30 Enucleation Enucleation is a common method of managing advanced retinoblastoma. Just about 3 decades ago, a majority of patients with unilateral retinoblastoma and the worse eye in bilateral retinoblastoma underwent primary enucleation. A substantial reduction in the frequency of enucleation has occurred in the late last century.31 Concurrently, there has been an increase in the use of alternative eye- and vision-conserving methods of treatment.9,32 Primary enucleation continues to be the treatment of choice for advanced intraocular retinoblastoma with neovascularization of iris, secondary glaucoma, anterior chamber tumor invasion, tumors occupying >75% of the vitreous volume, necrotic tumors with secondary orbital inflammation, and tumors associated with hyphema or vitreous hemorrhage where the tumor characteristics can not be visualized, especially when only one eye is involved.10 Figure 22.Retinoblastoma in the right eye following enucleation with orbital implant by the myoconjunctival technique (left). Excellent cosmesis follwing fitting of a custom ocular prosthesis (right). Minimum-manipulation surgical technique should be necessarily practiced.11 It is important not to accidentally perforate the eye. The sclera is thin at the site of muscle insertions and the rectus muscles have to be hooked delicately. It is important to obtain a long optic nerve stump, ideally more than 15 mm, but never less than 10 mm (Figure 20).11 Certain steps can be taken to obtain about 15 mm long optic nerve stump in all cases of advanced retinoblastoma.11 Gentle traction can be applied by the traction sutures applied to recti muscle stumps prior to transecting the optic nerve. As an alternative to the traction sutures, medial or lateral rectus muscle stumps may be kept long and traction exerted with an artery clamp. A 15-degree curved and blunt-tipped Figure 23. Macular retinoblastoma in a 6-month-old child (left), completely regressed with 6 cycles of chemoreduction alone (right). www.dosonline.org 51 Table 4. Chemoreduction regimen and doses for intraocular retinoblastoma Day 1: Vincristine + Etoposide + Carboplatin Day 2: Etoposide Standard dose: (3 weekly, 6 cycles): Vincristine 1.5 mg/m2 (0.05 mg/kg for children < 36 months of age and maximum dose < 2mg), Etoposide 150 mg/m2 (5 mg/ kg for children < 36 months of age), Carboplatin 560 mg/m2 (18.6 mg/kg for children < 36 months of age) High-dose (3 weekly, 6-12 cycles): Vincristine 0.025 mg/Kg, Etoposide 12 mg/Kg, Carboplatin 28 mg/Kg tenotomy scissors is introduced from the lateral aspect (or a straight scissors from the medial aspect) and the optic nerve is palpated with the closed tip of the scissors while maintaining gentle traction on the eyeball. The scissors is moved posteriorly to touch the orbital apex while “strumming” the optic nerve. The scissors is lifted by 3 or 4 millimeters off the orbital apex (to preserve the contents of the superior orbital fissure), the blades of the scissors are opened to engage the optic nerve, and the nerve is transected with one bold cut. This maneuver generally provides at least 15 mm long optic nerve stump.11 Enucleation spoon and heavy enucleation scissors limit space for maneuverability and may result in a shorter optic nerve stump. In addition, one should be careful not to accidentally perforate the eye during enucleation. The enucleated eyeball is inspected for optic nerve (Figure 20) or extraocular extension (Figure 21) of tumor. Eyes manifesting tumor necrosis with aseptic orbital cellulitis pose specific problem. These patients should be imaged to rule out extraocular extension. Enucleation is best performed when the inflammation is resolved. 11 A brief course of preoperative oral and topical steroids help control inflammation. Patients with retinoblastoma presenting as phthisis bulbi need imaging to exclude extraocular and optic nerve extension. 11 Phthisis generally results following spontaneous tumor necrosis and an episode of aseptic intraocular and orbital inflammation. Enucleation in these cases is often complicated by excessive peribulbar fibrosis and intraoperative bleeding. 11 Placement of an orbital implant following enucleation for retinoblastoma is the current standard of care. The orbital implant promotes orbital growth, provides better cosmesis and enhances prosthesis motility. The implants could be non-integrated (polymethyl methacrylate or silicon) or bio-integrated (hydroxyapatite or porous polyethylene). Placement of a biointegrated implant is generally avoided if post-operative adjuvant radiotherapy is considered necessary. 11 Although most implants structurally tolerate radiotherapy well, implant vascularization may be compromised by radiotherapy thus increasing the risk of implant exposure. Use of myoconjunctival technique and custom ocular prosthesis have optimized prosthesis motility and static cosmesis (Figure 22). Chemotherapy Chemoreduction, defined as the process of reduction in the tumor volume with chemotherapy, has become an integral part of the current management of retinoblastoma.32 Chemotherapy alone is however not curative and must be associated with intensive local therapy. Chemoreduction coupled with focal therapy can minimize the need for enucleation or external beam radiotherapy without significant systemic toxicity. Chemoreduction in combination with focal therapy is now extensively used in the primary management of retinoblastoma. 33-36 There are different protocols in chemotherapy. The commonly used drugs are vincristine, etoposide and carboplatin, for 6 cycles. 7-10 (Table 4) Standard dose chemoreduction is provided in Reese Ellsworth groups I-IV. 10 In high dose chemoreduction, the dose of etoposide and carboplatin is increased. This is indicated in Reese Ellsworth group V tumors. 10 With chemoreduction and sequential local therapy, it is now possible to salvage many an eye and maximize residual vision. Chemoreduction is most successful for tumors without associated subretinal fluid or vitreous seeding.7,8 Risk factors for tumor, subretinal seed and vitreous seed recurrence, and failure of chemoreduction leading to external beam radiotherapy and/or enucleation have been identified.7, 8 Chemoreduction offers satisfactory tumor control for Reese Ellsworth groups I-IV eyes, with treatment failure necessitating additional external beam radiotherapy in only 10% and enucleation in 15% at 5-year followup. Patients with Reese Ellsworth group V eyes require external beam radiotherapy in 47% and enucleation in 53% at 5 years.7, 8 Figure 24. Multifocal retinoblastoma (left) following chemoreduction and transpupillary thermotherapy (right). Note flat scars that are much smaller than the original tumor. 52 DOS Times - Vol. 13, No.4, October 2007 Figure 25. A juxtapapillary retinal tumor in a 9-month-old child (left) partially regressed with 3 cycles of chemoreduction (middle) and completely regressed with 6 cycles of chemoreduction and transpupillary thermotherapy (right). Note the completely exposed fovea following treatment, thus maximizing visual potential. Chemoreduction is an option for selected eyes with unilateral retinoblastoma.9 Figure 23 shows a tumor involving the macula at presentation. With chemoreduction and transpupillary thermotherapy, there was complete tumor regression. Figure 24, 25 and 26 show that the resulting scar with chemoreduction was much smaller than the original tumor with the foveola fully exposed, thus maximizing visual potential. It is important to be aware of the adverse effects and interactions of chemotherapeutic agents, which include myelosuppression, febrile episodes, neurotoxicity and non-specific gastrointestinal toxicity. Chemotherapy should be given only under the supervision of an experienced pediatric oncologist. Periocular chemotherapy Carboplatin delivered deep posterior subtenons has been demonstrated to be efficacious in the management of Reese Ellsworth Group VB retinoblastoma with vitreous seeds because it can penetrate the sclera and achieve effective concentrations in the vitreous cavity. This modality is currently under trial. Our Table 5. Histopathologic high-risk factors predictive of metastasis • Anterior chamber seeding • Iris infiltration • Ciliary body infiltration • Massive choroidal infiltration • Invasion of the optic nerve lamina cribrosa • Retrolaminar optic nerve invasion • Invasion of optic nerve transection • Scleral infiltration • Extrascleral extension www.dosonline.org Figure 26. Multifocal retinoblastoma (top) regressed following chemoreduction and transpupillary thermotherapy (bottom). early results have shown that periocular chemotherapy achieves 70% eye salvage in patients with Reese Ellsworth group VB retinoblastoma (Figure 27).37 Follow-up Schedule The usual protocol is to schedule the first examination 3–6 weeks after the initial therapy. In cases where chemoreduction therapy has been administered, the examination should be done every 3 weeks with each cycle of chemotherapy. Patients under focal therapy are evaluated and treated every 4-8 weeks until complete tumor regression. Following tumor regression, subsequent examination should be 3 monthly for the first year, 6 monthly for three years or until the child attains 6 years of age, and yearly thereafter. High Risk Retinoblastoma Systemic metastasis is the main cause for mortality in patients with retinoblastoma. Although the life prognosis of patients with retinoblastoma has dramatically improved in the last three decades, with a reported survival of more than 90% in developed countries,38 mortality is still as high as 50% in the developing nations.39,40 Reduction in the rate of systemic metastasis by identification of high-risk factors and appropriate adjuvant therapy may help improve survival. 53 Retinoblastoma with massive vitreous seeds (Figure 27a, left). Following 3 cycles of high-dose chemoreduction. Figure 28. Histopathology of retinoblastoma showing anterior chamber seeding, iris infiltration, trabecular meshwork infiltration and ciliary body invasion. (Figure 27a, right). The tumor is partially regressed but the vitreous seeds persist. With periocular carboplatin injection in addition to high dose chemoreduction, the vitreous seeds show complete regression. Figure 29. Histopathology of retinoblastoma showing massive choroidal infiltration, scleral infiltration and extrascleral extension. Figure 30. Histopathology of retinoblastoma showing infiltration of the optic nerve beyond the lamina cribrosa. High–Risk Factors None of the clinical high-risk factors seem to strongly correlate with mortality. Recent studies have evaluated the role of histopathologic high-risk factors identified following enucleation. The identification of frequency and significance of high-risk histopathologic factors (Figures 28-31) that can reliably predict metastasis is vital for patient selection for adjuvant therapy. Several studies have addressed this issue.39, 41-49 It is now generally agreed 54 Figure 31. Histopathology of retinoblastoma showing optic nerve infiltration to the level of transection. DOS Times - Vol. 13, No.4, October 2007 Figure 32. Primary orbital retinoblastoma manifesting with proptosis (left). Computed tomography scan shows massive orbital tumor (right). Figure 33. Secondary orbital retinoblastoma following enucleation, manifesting with extrusion of the prosthetic eye (left). CT can shows an orbital tumor (right). that massive choroidal infiltration, retrolaminar optic nerve invasion, invasion of the optic nerve to transection, scleral infiltration, and extrascleral extension are the risk factors that are predictive of metastasis (Table 5).39, 41-49 The reported occurrence of anterior chamber seeding (7%),45 massive choroidal infiltration (12-23%),43-49 invasion of optic nerve lamina cribrosa (6-7%),43-49 retrolaminar optic nerve invasion (612%),43-49 invasion of optic nerve transection (1-25%),43-49 scleral infiltration (1-8%),43-49 and extrascleral extension (2-13%),43-49 widely vary even in developed countries. Vemuganti and associates have reported that 21% of the 76 eyes enucleated for advanced retinoblastoma in India had anterior chamber seeding, 54% had massive choroidal infiltration, 46% had optic nerve invasion at or beyond the lamina cribrosa and 7% had scleral infiltration or extrascleral extension. 12 It is apparent that the incidence of histopathologic risk factors is strikingly high in developing countries compared to the published data from developed countries. Adjuvant Therapy Studies on the efficacy of adjuvant therapy to minimize the risk of metastasis initiated in the 1970s were marked by variable results and provided no firm recommendation.18 A recent study with a long-term follow-up provides useful information.13, 50 It included a www.dosonline.org subset of patients with unilateral sporadic retinoblastoma who underwent primary enucleation. The study used specific predetermined histopathologic characteristics for patient selection. A minimum follow-up of 1 year was allowed to include metastatic events that generally occur at a mean of 9 months following enucleation.13, 50 The incidence of metastasis was 4% in those who received adjuvant therapy compared to 24% in those who did not. The study found that administration of adjuvant therapy significantly reduced the risk of metastasis in patients with highrisk histopathologic characteristics. Our current practice is to administer 6 cycles of a combination of carboplatin, etoposide and vincristine (identical to the protocol used for chemoreduction of intraocular retinoblastoma) in patients with histopathologic high-risk characteristics. All patients with extension of retinoblastoma up to the level of optic nerve transection, scleral infiltration, and extrascleral extension receive high dose chemotherapy for 12 cycles and fractionated 4500 to 5000 cGy orbital external beam radiotherapy. Orbital Retinoblastoma Orbital retinoblastoma is rare in developed countries. Ellsworth observed a steady decline in the incidence of orbital retinoblastoma in his large series of 1160 patients collected over 50 years.51Orbital 55 Figure 34. A child with retinoblastoma misdiagnosed as traumatic hyphema in the left eye and treated with hyphema drainage without a baseline ultrasonograpy evaluation presents after 1 year with extraocular extension (left) and regional lymph node metastasis (right). retinoblastoma is relatively more common in the developing countries. In a recent large multi-center study from Mexico, 18% of 500 patients presented with an orbital retinoblastoma.52 A Taiwanese group reported that 36% (42 of 116) of their patients manifested with orbital retinoblastoma.53 The incidence is higher (40%, 19 of 43) in Nepal, with proptosis being the most common clinical manifestation of retinoblastoma.54 Clinical Manifestations There are several clinical presentations of orbital retinoblastoma. a. Primary Orbital Retinoblastoma Primary orbital retinoblastoma refers to clinical or radiologically detected orbital extension of an intraocular retinoblastoma at the initial clinical presentation, with or without proptosis or a fungating mass (Figure 32). Silent proptosis without significant orbital and periocular inflammation in a patient with manifest intraocular tumor is the characteristic presentation. Proptosis with inflammation generally indicates reactive sterile orbital cellulitis secondary to intraocular tumor necrosis. b. Secondary Orbital Retinoblastoma Orbital recurrence following uncomplicated enucleation for intraocular retinoblastoma is named secondary orbital retinoblastoma (Figure 33). Unexplained displacement, bulge or extrusion of a previously well-fitting conformer or a prosthesis is an ominous finding suggestive of orbital recurrence. c. Accidental Orbital Retinoblastoma Inadvertent perforation, fine-needle aspiration biopsy or intraocular surgery in an eye with unsuspected intraocular retinoblastoma should be considered as accidental orbital retinoblastoma and managed as such (Figure 34). d. Overt Orbital Retinoblastoma Previously unrecognized extrascleral or optic nerve extension discovered during enucleation qualifies as overt orbital retinoblastoma. Pale pink to cherry red episcleral nodule, generally in juxtapapillary location or at the site of vortex veins, may be visualized during enucleation. An enlarged and inelastic optic nerve 56 with or without nodular optic nerve sheath are clinical indicators of optic nerve extension of retinoblastoma that should be recognized during enucleation. e. Microscopic Orbital Retinoblastoma In several instances, orbital extension of retinoblastoma may not be clinically evident and may only be microscopic. Detection of full-thickness scleral infiltration, extrascleral extension and invasion of the optic nerve on histopathologic evaluation of an eye enucleated for intraocular retinoblastoma are unequivocal features of orbital retinoblastoma. Tumor cells in choroidal and scleral emissaria and optic nerve sheath indicate possible orbital extension mandating further serial sections and detailed histopathologic analysis. Diagnostic Evaluation A thorough clinical evaluation paying attention to the subtle signs of orbital retinoblastoma is necessary. Magnetic resonance imaging preferably, or computed tomography scan of the orbit and brain in axial and coronal orientation with 2-mm slice thickness helps confirm the presence of orbital retinoblastoma and determine its extent. Systemic evaluation, including a detailed physical examination, palpation of the regional lymph nodes and fine needle aspiration biopsy if involved, imaging of the orbit and brain, chest x-ray, ultrasonography of the abdomen, bone marrow biopsy and cerebrospinal fluid cytology are necessary to stage the disease. Technetium-99 bone scan and positron-emission tomography coupled with computed tomography may be useful modalities of the early detection of subclinical systemic metastases. Orbital biopsy is rarely required, and should be considered specifically when a child presents with an orbital mass following enucleation or evisceration where the primary histopathology is unavailable. Management of Orbital Retinoblastoma Primary orbital retinoblastoma has been managed in the past with orbital exenteration, chemotherapy or external beam radiotherapy in isolation or in sequential combination with variable results.55-60 It is well known that local treatments have a limited effect on the course of this advanced disease. Orbital exenteration alone is unlikely to achieve complete surgical clearance and preclude DOS Times - Vol. 13, No.4, October 2007 to triple-freeze-thaw cryotherapy and enucleation should be performed at the earliest possible convenience. Histopathologic evaluation of such eyes may include specific analysis of the sites of sclerotomy ports or the cataract wound for tumor cells. If an extraocular extension is macroscopically visualized during enucleation, special precaution is taken to excise it completely along with the eyeball, preferably along with the layer of Tenon’s capsule intact in the involved area. 11 All patients with accidental, overt or microscopic orbital retinoblastoma undergo baseline systemic evaluation to rule out metastasis. Orbital external beam radiotherapy (fractionated 4550 Gy) and 12 cycles of high dose chemotherapy is recommended.16 Metastatic Retinoblastoma Figure 35. A child with primary orbital retinoblastoma (top left), showing massive orbital tumor on computed tomography scan (top right). Following 12 cycles of high-dose chemotherapy, extended enucleation and orbital external beam radiotherapy (bottom left). The child is alive and well and wears a custom ocular prosthesis 3 years following completion of treatment (bottom right). secondary relapses; external beam radiotherapy does not generally prevent systemic metastasis; and chemotherapy alone may not eradicate residual orbital disease. 55-60 Therefore, a combination therapy is considered to be more effective. We have developed a treatment protocol comprising of initial three drug (Vincristine, Etoposide, Carboplatin) high dose chemotherapy (3-6 cycles) followed by surgery (enucleation, extended enucleation or orbital exenteration as appropriate), orbital radiotherapy, and additional 12 cycle standard dose chemotherapy.17 In 6 carefully selected cases without intracranial extension and systemic metastasis, there was dramatic resolution of orbital involvement. All the involved eyes became phthisical after 3 cycles of high dose chemotherapy. No clinically apparent orbital tumor was found during enucleation. All patients completed the treatment protocol of orbital external beam radiotherapy, and additional 12 cycle standard chemotherapy. All the patients were free of local recurrence or systemic metastasis at a mean follow-up of 36 months (range 12102 months) and achieved acceptable cosmetic outcome (Figure 35). 17 Our treatment protocol outlined for primary orbital retinoblastoma is currently under evaluation for secondary orbital retinoblastoma and early results have been very encouraging. Surgical intervention in such cases may be limited to excision of the residual orbital mass or an orbital exenteration depending on the extent of the residual tumor after the initial 3-6 cycles of highdose chemotherapy. All eyes that have undergone an intraocular surgery for unsuspected retinoblastoma should be promptly enucleated. 16 Conjunctiva overlying the ports with about 4 mm clear margins should be included en-bloc with enucleation. Random orbital biopsy may be also obtained, but there is no data to support its utility. If immediate enucleation is not logistically possible, then the vitrectomy ports or the surgical incision should be subjected www.dosonline.org Metastatic disease at the time of retinoblastoma diagnosis is very rare. Therefore, staging procedures such as bone scans, lumbar puncture, and bone marrow aspirations at the initial presentation are generally not recommended. The common sites for local spread and metastasis include orbital and regional lymph node extension, central nervous system metastasis, and systemic metastasis to bone and bone marrow. Metastasis in retinoblastoma usually occurs within one year of diagnosis of the retinoblastoma. If there is no metastatic disease within 5 years of retinoblastoma diagnosis, the child is usually considered cured. Metastatic retinoblastoma is reported to develop in fewer than 10% of patients in advanced countries. However, it is a major contributor to retinoblastoma related mortality in developing nations. Until recently, the prognosis with metastatic retinoblastoma was poor. Conventional dose chemotherapy using vincristine, doxorubicin, cyclophosphamide, cisplatin, and etoposide combined with radiation therapy has yielded only a few survivors. Dismal results with conventional therapy has prompted the use of high dose chemotherapy with hematopoietic stem cell rescue. Twenty-five patients with extra ocular disease or invasion of the cut end of optic nerve received high-dose chemotherapy including carboplatin, etoposide, and cyclophosphamide followed by autologous hematopoietic stem cell rescue. The three year disease-free survival was 67%. 60,61 All except one patient with central nervous system disease died. The main side effects were hematological, mucositis, diarrhoea, ototoxicity, and cardiac toxicity. Overall the response rate suggested that the treatment regimen was promising in patients with bone or bone marrow involvement, but not in patients with central nervous system disease. Children’s Oncology Group will be conducting a trial for the treatment of metastasis retinoblastoma. In this trial, the patients will be stratified into 3 groups: orbital/nodal disease, central nervous system disease, and systemic disease. Each patient will undergo induction therapy with cisplatin, cyclophosphamide, vincristine, and etoposide. Those with systemic metastasis or central nervous system disease will then receive high dose therapy with etoposide, carboplatin and thiotepa. The chemotherapy protocol will be changed as preliminary data with other agents becomes available. Conclusion There has been a dramatic change in the overall management of retinoblastoma in the last decade. Specific genetic protocols have 57 been able to make prenatal diagnosis of retinoblastoma. Early diagnosis and advancements in focal therapy have resulted in improved eye and vision salvage. Chemoreduction has become the standard of care for the management of moderately advanced intraocular retinoblastoma. Periocular chemotherapy is now an additional useful tool in salvaging eyes with vitreous seeds. Enucleation continues to be the preferred primary treatment approach in unilateral advanced retinoblastoma. Post-enucelation protocol, including identification of histopathologic high-risk characteristics and provision of adjuvant therapy has resulted in substantial reduction in the incidence of systemic metastasis. The vexing orbital retinoblastoma now seems to have a cure finally with the aggressive multimodal approach. Future holds promise for further advancement in focal therapy and targeted drug delivery. 14. Honavar SG, Rajeev B. Needle Tract Tumor Cell Seeding Following Fine Needle Aspiration Biopsy for Retinoblastoma. Investigative Ophthalmology and Visual Science 1998; 39: S 658. Reference 19. Murphree AL, Benedict WF: Retinoblastoma: Clues to human oncogenesis. Science 1984: 223:1028-1033. 1. 2. Bishop JO, Madsen EC: Retinoblastoma. Review of current status. Surv Ophthalmol 19: 342-366, 1975. Shields JA, Shields CL. Intraocular tumors – A text and Atlas. Philadelphia, PA, USA, WB Saunders Company, 1992. 3. Albert DM: Historic review of retinoblastoma. Ophthalmology 94; 654-662, 1987. 4. Jackson E: Report of the committee to investigate and revise the classification of certain retinal conditions. Trans Am Ophthalmol Soc 24:38-39, 1926 5. Ata-ur-Rasheed M, Vemuganti G, Honavar S, Ahmed N, Hasnain S, Kannabiran C. Mutational analysis of the RB1 gene in Indian patients with retinoblastoma. Ophthalmic Genet. 2002;23:121-8. 6. Kiran VS, Kannabiran C, Chakravarthi K, Vemuganti GK, Honavar SG. Mutational screening of the RB1 gene in Indian patients with retinoblastoma reveals eight novel and several recurrent mutations. Hum Mutat. 2003;22:339. 7. Shields CL, Honavar SG, Shields JA, Demirci H, Meadows AT, Naduvilath TJ. Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma. Arch Ophthalmol. 2002;120:460-4. 8. Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Singh A, Friedman DL, Naduvilath TJ. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol. 2002;133:657-64. 16. Shields CL, Honavar S, Shields JA, Demirci H, Meadows AT. Vitrectomy in eyes with unsuspected retinoblastoma. Ophthalmology. 2000;107:2250-5. 17. Honavar SG, Reddy VAP, Murthy R, Naik M, Vemuganti GK. Management of orbital retinoblastoma. XI International Congress of Ocular Oncology. Hyderabad, India, 2004. pp. 51. 18. Stallard HB: The conservative treatment of retinoblastoma. Trans Am Opththalmol Soc UK 1962; 82:473-534. 20. Knudson AG: Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci, USA 1971:68: 820-823. 21. Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd NW 3rd. Presenting signs of retinoblastoma. J Pediatr. 1998; 132:505-8. 22. Ellsworth RM. The practical management of retinoblastoma. Trans Am Ophthalmol Soc 1969: 67: 462-534. 23. Linn Murphree A. Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North Am. 2005;18:41-53. 24. Shields CL, Shields JA. Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol.2006;17:228-34. 25. Shields CL, Mashayekhi A, Demirci H, Meadows AT, Shields JA. Practical approach to management of retinoblastoma. Arch Ophthalmol. 2004;122:729-35. 26. Shields CL, Santos MC, Diniz W et al. Thermotherapy for retinoblastoma. Arch Ophthalmol 1999; 117: 885-893. 27. Shields CL, Shields JA, Cater J et al. Plaque radiotherapy for retinoblastoma, long term tumor control and treatment complications in 208 tumors. Ophthalmology 2001;108: 2116-2121. 28. Ellsworth RM. Retinoblastoma. Modern problems in ophthalmology. 1977; 96:1826-1830. Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Naduvilath TJ. Chemoreduction for unilateral retinoblastoma. Arch Ophthalmol. 2002;120:1653-8. 29. Hungerford JL, Toma NMG, Plowman PN, Kingston JE. External beam radiotherapy for retinoblastoma: I, whole eye technique. Br J Ophthalmol. 1995; 79: 112-117. 10. Murthy R, Honavar SG, Naik MN, Reddy VA. Retinoblastoma. In: Dutta LC, ed. Modern Ophthalmology . New Delhi, India, Jaypee Brothers; 2004:849-859. 30. Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma; a possible age effect on radiation-related risk. Ophthalmology. 1998; 105: 573-580. 11. Honavar SG, Singh AD. 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Changing trends in the management of retinoblastoma: 1951-1965 vs 19661980. J Pediatr Ophthalmol Strabismus 1994; 31:32-7. 39. Singh AD, Shields CL, Shields JA. Prognostic factors in retinoblastoma. J Pediatr Ophthalmol Strab 2000; 37:134-41. 40. Ajaiyeoba IA, Akang EE, Campbell OB, Olurin IO, Aghadiuno PU. Retinoblastomas in Ibadan: treatment and prognosis. West African Journal of Medicine 1993; 12:223-7. 41. Kingston JE, Hungerford JL, Plowman PN. Chemotherapy in metastatic retinoblastoma. Ophthalmic Paediatr Genet 1987; 8:6972. 42. White L. Chemotherapy for retinoblastoma: where do we go from here? Ophthalmic Pediatr and Genet 1991; 12:115-30. 43. Kopelman JE, McLean IW, Rosenberg SH. Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation. Ophthalmology 1987; 94:371-7. 48. Chantada GL, de Silva MTG, Fandino A, et a. Retinoblastoma with low risk for extraocular relapse. Ophthalmic Genet 1999; 20:13340. 49. Khelfaoui F, Validire P, Auperin A, Quintana E, Michon J, Pacquement H, et al. Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution. Cancer 1996; 77:1206-13. 50. Honavar SG, Singh AD, Shields CL, Demirci H, Smith AF, Shields JA. Post-enucleation prophylactic chemotherapy in high- risk retinoblastoma. Arch Ophthalmol 2002; 120:923-31. 51. Ellsworth RM. Orbital retinoblastoma. Trans Am Ophthalmol Soc 1974;72:79-88. 52. Leal-Leal C, Flores-Rojo M, Medina-Sanson A, et al. A multicentre report from the Mexican Retinoblastoma Group. Br J Ophthalmol 2004;88:1074-1077. 53. Kao LY, Su WW, Lin YW. Retinoblastoma in Taiwan: survival and clinical characteristics 1978-2000. Jpn J Ophthalmol 2002;46:577580. 54. Badhu B, Sah SP, Thakur SK, et al. Clinical presentation of retinoblastoma in Eastern Nepal. Clin Experiment Ophthalmol 2005;33:386-389. 55. Pratt CB, Crom DB, Howarth C. The use of chemotherapy in extraocular retinoblastoma. Med and Pediatr Oncol 1985;13:330333. 56. Kiratli H, Bilgic S, Ozerdem U. Management of massive orbital involvement of intraocular retinoblastoma. Ophthalmology 1998;105:322-326. 57. Goble RR, McKenzie J, Kingston JE, et al. Orbital recurrence of retinoblastoma successfully treated by combined therapy. Br J Ophthalmol 1990;74:97-98. 44. Magramm I, Abramson DH, Ellsworth RM. Optic nerve involvement in retinoblastoma. Ophthalmology 1989; 96:217-22. 58. Doz F, Khelfaoui F, Mosseri V, et al. The role of chemotherapy in orbital involvement of retinoblastoma. The experience of a single institution with 33 patients. Cancer 1994;74:722-732. 45. Messmer EP, Heinrich T, Hopping W, de Sutter E, Havers W, Sauerwein W. Risk factors for metastases in patients with retinoblastoma. Ophthalmology 1991; 98:136-41. 59. Antoneli CB, Steinhorst F, de Cassia Braga Ribeiro K, et al. Extraocular retinoblastoma: a 13-year experience. Cancer 2003;98:1292-1298. 46. Shields CL, Shields JA, Baez KA, et a. Choroidal invasion of retinoblastoma: Metastatic potential and clinical risk factors. Br J Ophthalmol 1993; 77:544-8. 60. Dunkel IJ, Aledo A, Kernan NA, Kushner B, Bayer L, Gollamudi SV, et al. Successful treatment of metastatic retinoblastoma. Cancer 2000; 89:2117-21. 47. Shields CL, Shields JA, Baez K, Cater JR, De Potter P. Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors. Cancer 1994; 73:692-8. 61. Rodriguez-Galindo C, Wilson MW, Haik BG, Lipson MJ, Cain A, Merchant TE, et al. Treatment of metastatic retinoblastoma. Ophthalmology 2003; 110:1237-40. Author Santosh G. Honavar MD, FACS www.dosonline.org 59 Rohit Saxena MD, Munish Dhawan MD O ptic disc and the retina are the only portions of the central nervous system that can be viewed during a clinical examination. Swelling of the disc is the only visible acute response of the optic disc to most pathological processes that can damage it. The main causes of disc edema are increase in the intracranial tension, inflammation and ischemia. There are 2 subtypes of AION. The first one is the arteritic variety, associated with giant cell arteritis (GCA). The second one is the more common nonarteritic variety, presumably solely due to atherosclerosis and occlusive small vessel disease. Patients with optic disc edema may present in a variety of ways ranging from being asymptomatic (papilledema) to severe visual loss (papillitis) depending upon the etiology of the nerve swelling. • Unilateral, painless, moderate to severe loss of vision. • Field defect is most commonly an inferior altitudinal defect. • Visual acuity ranges from 20/200 to no light perception. Pathophysiology • Age group affected is from middle-aged to elderly. Disc edema occurs due to stasis of the axoplasmic flow, or slowed cellular conduction along the nerve. There is an obstruction to flow at the level of the lamina cribrosa resulting in accumulation of the intracellular fluids and metabolic by-products which collect at the level of the optic nerve head. Mechanical compression, infiltration, infection, inflammatory disease, demyelinating disease, or compromised vascular perfusion to the nerve may all lead to disc edema. • NAION is usually associated with systemic vascular disease [hypertension (35-50% cases), diabetes (10-25%), atherosclerosis, blood coagulopathies, nocturnal hypotension) or collagen vascular disease]. • Arteritic AION is associated with GCA, in which the patient may have associated signs of anorexia, weight loss, decreased appetite, jaw claudication, scalp tenderness and malaise. Neurophthalmology Analyzing Disc Edema Clinical Features Causes of Unilateral optic disc edema Hyperemic disc edema • Papillitis • Asymmetric papilledema (Figure 1) • Compressive optic neuropathy • Pseudopapilledema • Others (uvietis, hypotony etc.) Pale disc edema • Anterior Ischemic Optic Neuropathy (AION) Causes of Bilateral optic disc edema • Papilledema (Figure 2) • Hypertensive retinopathy ( Figure 3) • Atypical optic neuritis • Pseudopapilledema • Compressive optic neuropathies • Others (uveitis, infiltrative etc.) Anterior Ischemic Optic Neuropathy Anterior ischemic optic neuropathy (AION) is a general term referring to all causes resulting in temporary or permanent obstruction to the vascular flow. It presents with segmental or diffuse pale disc edema. Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi www.dosonline.org Figure 1. Asymmetric papilledema. 65 Workup disc edema Figure 2. Papilledema. • Embolic disease • Migraine Clinical setting in which ischemic optic neuropathy is seen are • Sudden and severe hypotension • Giant cell arteritis • Cardiac insufficiency • Collagen vascular diseases • • Syphilis Patients on systemic therapy with certain drugs e.g. amiodarone • Herpes zoster Pathophysiology • Arteriosclerosis • Diabetes mellitus • Hypertension AION occours due to acute infarction of the short posterior ciliary arteries supplying the anterior part of the optic nerve. In the nonarteritic form, these vessels are compromised by vascular disease and arteriolosclerosis. In the case of arteritic AION, these vessels, • 66 Fundus picture shows focal or diffuse pale disc edema with flame shaped hemorrhages near the disc margins. (Figure 4) DOS Times - Vol. 13, No.4, October 2007 as well as the ophthalmic and central retinal arteries, are compromised by an idiopathic infiltration of the vessels walls by inflammatory macrophages, lymphocytes, and multinucleate giant cells. As most arteries are affected in GCA, there usually is a constellation of systemic symptoms. Due to the widespread involvement in GCA, there is a very high chance for involvement of the fellow eye within days, therefore requiring immediate intervention, if suspected. Management • Complete ocular and systemic history • Erythrocyte sedimentation rate (ESR). Elevated in arteritic AION, normal in NAION • • For NAION, underlying predisposing factor (diabetes, hypertension, hyperlipidemia, smoking) should be investigated for and treated, if present to prevent bilateral involvement which can occur in about 33% cases. Optic Neuritis (Figure 5) Optic neuritis (ON) is defined as acute inflammation of the optic nerve. When the inflammation involves the disc, it is termed as papillitis. When it involves the posterior part of the optic nerve, the fundus appears normal and it is termed as retrobulbar neuritis. Etiologies The most common etiology is demyelination, which can occur with or without evidence of multiple sclerosis (MS). Others include: C - Reactive Protein (CRP) Elevated in arteritic AION, normal in NAION • Infection (syphilis, mumps, measles). Infiltrative/ inflammatory disease (sarcoidosis, lupus). • Temporal artery biopsy - To rule out GCA • • In Arteritic AION, 1-2g I.V. methylprednisolone should be given for two to three days, followed by oral steroids for two to four years to prevent progression of visual loss to the other eye. Optic Neuritis and Multiple Sclerosis ON is the initial presenting feature in 20 to 25 percent of MS patients and occurs in about 50% of cases of MS. About 35% to 75% of patients who present with ON go on to develop clinical Figure 3. HT retinopathy. All B/L disc edema are not papilledema; BP was 220/110 at presentation. Figure 4. U/L pale disc edema. www.dosonline.org 67 MS. Although long term studies from the Asian population are not available, the risk of progression to clinical MS appears to be low. The risk of developing MS increases steadily during the first 10 years after the initial presentation of ON. • Pulfrich's stereo phenomenon (beer barrel appearance of the environment) • Systemic signs and symptoms may include headache, nausea Clinical features Management The clinical presentation of demyelinating optic neuropathy varies. The currently accepted management is with intravenous methylprednisolone sodium succinate 250 mg every 6 hours or 1 gram every day for three days followed by oral prednisone (1 mg/ kg per day) for 11 days as per the Optic Neuritis Treatment Trial (ONTT). At our centre we routinely give intravenous dexamethasone 200 mg every day for three days followed by oral taper. • Sudden onset, moderate-severe loss of vision, which can be progressive for about 10-14 days which then stabilizes and begins to improve. • Periocular eye eyeache, increasing on eye movements. • Dyschromatopsia. • Decreased brightness sense. • Relative afferent pupillary defect in the involved eye. • Visual field defects (could be of variable severity and type though frequently central / cecocentral). • Disc swelling with or without vitreous cells. • Uhtoff 's sign (decreased vision with or without limb weakness following increasing body temperatures i.e., a hot bath or exercise) • Romberg's sign (patient falls when they close their eyes), The aim of this treatment is for the purpose of accelerating visual recovery only and it does not affect visual outcome after one year. The ONTT also determined that the use of oral prednisone in routinely prescribed doses (1 mg/kg per day) alone for 14 days is contraindicated, and was associated with increased risk of reccurrence. Patients receiving this therapy had a higher rate of new attacks of ON in both the initially affected and fellow eye, than did the group receiving intravenous steroids and placebo. Treatment with intravenous methylprednisolone followed by oral corticosteroid regimen also reduces the two-year risk of development of clinical MS, particularly in patients with demyelinating lesions on MRI of the brain at the time of episode Figure 5. Unilateral papillitis: hyperemic disc edema. 68 DOS Times - Vol. 13, No.4, October 2007 Workup of of ON. Though serious side effects of dexamethasone or methylprednisolone therapy are infrequent, monitoring during I/V administration is necessary. Prior to giving steroids, a chest X-ray and proper clinical examination to rule out tuberculosis or any other focus of infection is necessary. weeks. The term should not be used to describe optic disc swelling with underlying infectious, infiltrative, or inflammatory etiologies. • Increase in cerebrospinal fluid (CSF) pressure Papilledema (Figure 6) • Increase in peri-neural pressure (transmitted) around the optic nerve sheath • Impediment of axoplasmic transport at the level of the lamina cribrosa • Intra-axonal edema in the area of the optic disc Papilledema is an optic disc swelling that is secondary to elevated intracranial pressure. In contrast to other causes of optic disc swelling, vision usually is well preserved with acute papilledema. Papilledema almost always presents as a bilateral phenomenon though may be asymmetrical and may develop over hours to www.dosonline.org Pathophysiology 69 Figure 6. Severe papilledema. • Swelling of the optic nerve head Papilledema occurs only if there is continuation of the subarachnoid space of the brain with the spaces around the optic nerve sheath. Papilledema does not occur in eyes with pre-existing optic atrophy. Clinical features Narrow and sheathed vessels. • Peri-papillary pigmentary changes / choroidal folds. Causes • Any tumors or space-occupying lesions of the CNS. • Idiopathic intracranial hypertension (IIH). • Decreased CSF resorption (eg, venous sinus thrombosis, inflammatory processes, meningitis, subarachnoid hemorrhage). • H/o nausea, vomiting, headache, nerve palsies etc. • Usually bilateral. • No significant visual function loss in the early stages. • Transient obscuration of vision. • Increased CSF production (tumors). • Enlarged blind spots and peripheral field constriction. • Obstruction of the ventricular system. • Diplopia due to VI nerve underaction. • Cerebral edema/encephalitis. • Craniosynostosis. Early 70 • • Hyperaemia, indistinct margins (lower pole first). • Blurring of peri-papillary retinal nerve fiber layer. • Splinter haemorrhages in the peri-papillary region. • Absence of SVP ( absent in 20% of normals). Diagnostic techniques • Hemogram. • Chest X ray. Established • MRI . • Obvious swelling, numerous haemorrhages. • CT Scan (non contrast and contrast enhanced). • Engorged veins, obscuration of surface vessels. • Lumbar puncture. • Paton's lines, cotton wool spots, macular fan or star. Management Chronic Treatment of the underlying cause. • Haemorrhages and exudates resolve. Management of Idiopathic intracranial hypertension (IIH): • Disc has rounded appearance, milky gray colour. The treatment of IIH is initially medical. • Obliteration of cup, NFL defects (slit like). • The cornerstone of medical treatment is weight loss. Atrophic • Diuretics (Lasix, furosemide). • • Diamox (acetazolamide) is the most commonly used medication. Pale disc. DOS Times - Vol. 13, No.4, October 2007 Not associated with any retinal haemorrhages, exudates, cotton wool spots. No peri-papillary nerve fiber layer edema, so the surface arteries close to the disc are clearly visible On FFA: may see autofluorescence at disc. No disc leak. USG may show high spikes at disc even with low gain settings due to presence of drusen. Compressive optic neuropathies (Figure 8) Figure 7. FA of case of pseudopapilledema Note tortuous vessels, no disc leak. Lesions in the orbit, optic canal and rarely intracranial lesions may cause compressive swelling of the optic nerve head. Most cases have significant and progressive visual loss, however some cases may present only as disc swelling (orbital hemangiomas near disc and nerve sheath meningiomas) Clinical Features • Transient monocular visual loss, in a particular gaze (direct pressure of optic nerve or interruption of blood supply). • Enlargement of blind spot on field analysis. • RAPD and color vision abnormalities. • Chronic compression leads to a triad of visual loss, swelling evolving into atrophy and optociliary shunt (shunting the blood from retina to choroid) • Rarely optic disc swelling may occur in intracranial lesions eg. Sphenoid wing meningioma. • Features of orbital disease: proptosis, limitation of ocular movements, orbital congestion. Diagnosis Ultrasound of the orbit. Radio imaging (CT or MRI). Figure 8. Thyriod exophthalmos: At risk compressive optic neuropathy Surgical treatment The surgical treatments currently used are optic nerve sheath fenestration and lumbar shunting procedures. These procedures are used when patients do not respond adequately to medical therapy. Optic nerve sheath fenestration is done first by an incision into the orbit. The eyeball is moved to the side and the optic nerve sheath is exposed. Slits or a large hole are then placed in the optic nerve sheath to drain out fluid, thereby taking pressure off the optic nerve and halting pressure induced optic atrophy. Pseudopapilledema (Figure 7) • Provide more information than USG • CT useful for imaging of bones and metallic foreign body (MRI contraindicated). • MRI more useful in cases of inflammatory lesion and lesions of optic pathway. • Fat subtraction technique and gadoliniuim - DTPA contrast aid in demarcation of optic nerve sheath meningioma. Essential to rule out thyroid ophthalmopathy and pseudotumor. Although disc edema may be due to a large number of causes, a proper history, detailed systemic and ophthalmic examination and a systemic approach can lead to the correct diagnosis in a large number of cases, and avoid unnecessary and expensive investigations in most. Ophthalmoscopic features Usually associated with hyperopia. Small disc, with absent physiological cup. Abnormal branching and tortuosity of retinal vessels. No dilated capillaries on surface of the disc. Increased number of central retinal vessels arising from optic disc First Author Rohit Saxena MD Scalloped margins/ irregular disc surface or visible optic disc drusen. www.dosonline.org 71 Madhu Karna MS Case 1 Answers This 8 day old female baby had firm, non-tender bilateral bluish swellings at birth accompanied by discharge. What is your diagnosis? Case 1 Case 2 This 20 day old female baby had soft, non-tender bilateral pulsatile swellings at birth. What is your diagnosis? Photo Essay Congenital Midline Facial Swellings This is bilateral congenital dacryocele/ amniontocele/ dacryocystocele. If not infected, it is treated with warm compresses, massage and topical antibiotics. If infected it is treated with IV antibiotics in addition. If unresolved within 2 weeks of medical management, it is probed and irrigated. a b Figure 1. Congenital Dacryocele c Figure 2a,b,c. Meningocoele Case 2 (a,b,c) This is bilateral encephalocele characterized by soft pulsatile swelling above the medial canthal tendon. It is confirmed by MR imaging and requires neurosurgical intervention. Rarely it is associated with Morning Glory syndrome or dysplastic disc. Figure 2. Meningocoele Pediatric Ophthalmologist, Centre for Sight, Safdarjung Enclave, New Delhi. www.dosonline.org Author Madhu Karna MS 73 Noopur Gupta MS, DNB NASA Approves Advanced Lasik for Use on Astronauts AMO’s Advanced CustomVue(TM) LASIK with the IntraLase® Method Proves Ready for the Rigors of Space TravelAdvanced Medical Optics, Inc. (AMO) (NYSE: EYE), a global leader in ophthalmic surgical devices and eye care products, announced on Sept. 21in California that the National Aeronautics and Space Agency (NASA) has approved the company’s LASIK technologies for use on U.S. astronauts. The NASA decision was made following review of extensive military clinical data using AMO’s Advanced CustomVue(TM) LASIK with the IntraLase® Method, which showed the combination of technologies provides superior safety and vision.Approved for use on consumers almost a decade ago, more than 11 million LASIK procedures have been performed todate, making it the most-common elective surgical procedure in the U.S. But it wasn’t until LASIK developed into an all-laser procedure that NASA approved it for use on pilots, mission and payload specialists who face extreme, physically demanding conditions in space. The all-laser LASIK technologies, which utilize wavefront guided and femtosecond lasers, have also been cleared for U.S. military personnel, including most recently Air Force pilots.NASA followed the Naval Aviation clinical studies closely with a particular interest in both safety and quality of vision under extreme conditions. Wavefront guided and femtosecond lasers were proven to provide excellent safety with consistent visual results of 20/20 or better. LASIK was able to withstand even the most extreme rigors of warfare and flight. All surgical procedures have risks, but with this exceptional track record, the average consumer has nothing to fear from. Bausch & Lomb Launches the Stellaris™ Vision Enhancement System in Europe at ESCRS 2007 The Stellaris system is the cornerstone of Bausch & Lomb’s microincision cataract surgery (MICS™) platform, to which ophthalmologists around the world are transitioning. Delivering safety, efficiency and ease-of-use, the system is ideal for all techniques, particularly 1.8 mm biaxial (B-MICS) and 1.8 mm coaxial (C-MICS) procedures. The Stellaris EQ™ fluidics management technology allows surgeons to choose either a flow-vacuum module (AFM) or an advanced vacuum module (AVM). Using the flow based module, surgeons can switch between flow and vacuum modes for optimal surgical flexibility and efficiency. The inherent safety of the Stellaris system stems from the novel EQ technology, which balances aspiration dynamics in flow and vacuum modes for exceptional chamber stability. A new ergonomically-designed, six-crystal phaco handpiece, Bluetooth wireless-enabled dual-linear foot pedal, and high-definition touch-screen display have been designed to address the demanding needs of today’s surgical environments. Industry News Industry News The Stellaris system offers greater performance, control and versatility than its predecessors, with optimized cutting to deal with even the hardest nuclei. The improved fluidics are increasingly important for chamber stability in both biaxial and micro-coaxial phaco. Surgical control is improved in the wide range of lens opacities,” commented H. Burkhard Dick, M.D., UniversitätsAugenklinik, Center for Vision Science, Ruhr University. In addition to the Stellaris system, Bausch & Lomb showcased new advancements in refractive surgery during ESCRS 2007, including:• Zyoptix® ACE™ Advanced Control Eyetracking technology. Zyoptix ACE is designed to further improve the accuracy and predictability of refractive surgery outcomes by dynamically compensating for intraoperative cyclotorsion (eye rotation). Seeing Machines Receives FDA Clearance for Truefield Analyzer Seeing Machines (AIM: SEE), a leading developer of advanced computer based imaging software systems, received marketing clearance from the United States Food and Drug Administration (FDA) for its revolutionary new medical device, the TrueField(R) Analyzer (TFA). The TFA helps doctors measure defects in a patient’s visual field, a crucial step in the detection and management of diseases of the vision system, including glaucoma. The TFA offers many outstanding new benefits to both the patient and the doctor. The systems work in real-time, enabling the behaviour of subjects to be tracked in real-time Most importantly the device is both objective and it is quick and easy for the patient and operator. Unlike traditional standard automated perimetry (SAP) devices, the TFA measures both eyes concurrently, and does the entire test of both eyes in approximately 5 minutes (including rest breaks within the test). The objectivity of the TFA test offers doctors the possibility of significant improvements over the test-retest variability issues that impact SAP. For patients it means an end to the button pressing associated with SAP - the only task required of the patient in the TFA test is simply to look at the display. The TrueField Analyzer(R) offers a new objective method to help doctors diagnose and manage a range of eye diseases including glaucoma, age related macular degeneration and diabetic retinopathy. It has the potential to become a new standard in the measurement of visual field defects and thus in the diagnosis and management of glaucoma. Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi www.dosonline.org 75 Abstracts Association between cultures of contact lens and corneal scraping in contact lens related microbial keratitis Das S, Sheorey H, Taylor HR, Vajpayee RB. Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia. OBJECTIVE To study the association between cultures of contact lens and corneal scraping in contact lens-related microbial keratitis. METHODS A retrospective analysis of the culture results of corneal scrapings and contact lenses of patients with contact lens-related microbial keratitis who were initially seen at Royal Victorian Eye and Ear Hospital, Melbourne, Australia, between January 1, 2001, and December 31, 2004, was conducted. RESULTS: Fifty eye specimens of 49 patients were included in the study. Corneal scrapings and contact lenses were culture positive in 17 eyes (34%) and in 35 eyes (70%), respectively. In 13 eyes, corneal scrapings and contact lenses yielded identical organisms. Serratia marcescens was the most common organism isolated from the corneal scrapings and from the contact lenses. CONCLUSION Contact lens culture may sometimes give a clue to the organism involved in cases of microbial keratitis in which the corneal scraping is culture negative and may help in choosing the appropriate antimicrobial therapy. Application of Shape-based Analysis Methods to OCT Retinal Nerve Fiber Layer Data in Glaucoma Gunvant, Pinakin BS Optom, PhD, FAAO, Zheng, Yufeng PhD, Essock, Edward A. PhD, Parikh, Rajul S. MS, Prabakaran, Selvaraj BS Optom, Babu, Jonnadula Ganesh BS Optom, Shekar, Garudadri Chandra MD, Thomas, Ravi MD Journal of Glaucoma. 16(6):543-548, September 2007. PURPOSE To evaluate the performance of shape-based analysis [wavelet-Fourier analysis (WFA) and fast Fourier analysis (FFA)] applied to retinal nerve fiber layer (RNFL) thickness values obtained from the optical coherence tomograph (OCT) to discriminate healthy and glaucomatous eyes. To compare the performance of the shape-based metrics to that of the standard OCT output measures (Inferior Average and Average Thickness). METHODS RNFL values were obtained from 152 eyes of 152 individuals (83 healthy and 69 “mild”-stage perimetric glaucoma). WFA and FFA were performed on the RNFL values and linear discriminant functions for both were obtained using Fisher linear discriminant analysis. Performance was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (ROC area). RESULTS The ROC area of the shape-based methods [0.94 (WFA) and 0.88 (FFA)] was greater than that of OCT metrics [0.81 (Inferior Average) and 0.74 (Average Thickness)]. Specifically, WFAs performance was significantly better than both the FFA (P=0.009) and the Inferior Average (P=0.001). Inferior average performed significantly better than Average Thickness (P=0.006). CONCLUSIONS The ability to differentiate glaucomatous from healthy eyes using stratus OCT measurements is improved by using these analysis methods that emphasize the shape of the RNFL thickness pattern. www.dosonline.org 77 Low-Dose Mitomycin C as a Prophylaxis for Corneal Haze in Myopic Surface Ablation Ivey Thorntona, b, Ashok Puric, Meng Xud and Ronald R. Kruegera a Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky c Rajasthan Laser Eye Center, Jaipur, India d Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio (M.X.) b PURPOSE To evaluate the efficacy of low-dose (0.002%) mitomycin C (MMC) vs no prophylactic MMC (control) in reducing corneal haze after surface laser ablation. DESIGN Two-year retrospective follow-up study performed in Jaipur, India. METHODS Ninety-two eyes with no MMC application and 83 eyes with 0.002% MMC application during laser epithelial keratomileusis (LASEK) were analyzed in a retrospective chart review with one month, two months, three months, six months, one year, and two years of postoperative follow-up. Postoperative haze, visual acuity, and efficacy ratio (EFFR) then were analyzed statistically. RESULTS The no-dose MMC and low-dose MMC groups were statistically similar except for a thinner corneal pachymetry (P < .001), higher spherical equivalent error (P = .006), and smaller ablation zone (P = .009) in eyes not treated with MMC when subjected to univariate analysis. Multivariate analysis was used to overcome the preoperative statistical differences among the two groups. Eyes treated with low-dose MMC (0.002%) demonstrated statistically less haze at all postoperative time points and in each myopic subgroup (P < .001). The postoperative uncorrected visual acuity (UCVA) and EFFR, however, showed no difference between the groups, except for better EFFR with MMC at one month (P < .001) and two months (P = .034). CONCLUSIONS Low-dose MMC (0.002%) in eyes after LASEK results in less corneal haze than in eyes not receiving this agent. Concerns regarding the potential toxicity of MMC make a 10-fold less concentration more desirable in refractive surgery. Further comparative study of low- vs higher-dose MMC is recommended to characterize its clinical benefit fully. 78 DOS Times - Vol. 13, No.4, October 2007 Sandeep Buttan MS, Suma Ganesh MS, Manish Sharma MS, Archana Gupta DNB O phthalmoplegia or anomalies of ocular movements may present in a variety of settings and may have coexisting complex neurological features that often have no obvious relation. To form a clinical diagnosis from these quanta’s of information is like putting together the pieces of a jigsaw puzzle. A keen sense of suspicion and a thorough neurological workup, keeping in mind both the common and the not so common differentials are essential to reach the right diagnosis. Case History A 39-year-old non-Diabetic, normotensive male presented to us with sudden onset diplopia since one day. The diplopia was horizontal and constant and not associated with ocular or facial pain. He also complained of paraesthesiae in his hands and mild weakness of lower limbs off and on for past 3-4 days. There was no history of any headache, dysarthria, dysphagia, hearing disturbances, bowel / bladder involvement, fever or upper respiratory infection in the recent past. On ophthalmic examination there was esotropia of left eye with limitation of abduction. There was horizontal uncrossed diplopia with maximum separation of images in levoversion. Hess charting also revealed left lateral rectus underaction and right medial rectus overaction. (Figure 1) The pupils were symmetrical and well reacting with no RAPD. Posterior segment examination was unremarkable. MRI brain showed no abnormalities. Three days later the patient developed ptosis of both eyelids, more so in the left eye. There was gross limitation of all ocular movements. The pupils were symmetrical and briskly reactive. (Figure 2,3) The patient was referred to a neuro- physician for detailed neurological evaluation. The deep tendon reflexes were diminished with normal motor power in all limbs. A provisional diagnosis of Myasthenia Gravis was made and the patient was put on Tab. Pyridostigmine 60 mg QID for 5 days but no clinical or subjective improvement was noticed. Three weeks after the IV IG therapy, the patient had recovered some vertical movements and was prescribed horizontal prisms for diplopia. At last follow up (5 months) the patient has full recovery of ocular movements with no diplopia (Figure 4). Clinical Meeting: Case 1 Ophthalmoplegia: Looking Beyond the Obvious Discussion The patient is a young male who presents with acute progressive bilateral ophthalmoplegia unassociated with head or eye pain. Examination reveals bilaterally symmetric limitation of both horizontal and vertical eye movements. Additional features include bilateral ptosis, facial paresis and diminished deep tendon reflexes. The first question to address is whether this constellation of findings could be the result of a single lesion. In evaluating any patient with acquired ophthalmoparesis, one must consider three main etiologies: myopathic, neuromuscular, and neurologic. In this patient, the presence of hyporeflexia (a lower motor neuron sign), with normal strength eliminate most of the myopathic and a neuromuscular etiology. The evaluation should therefore focus on a neurologic cause. (Table 1) Supranuclear gaze palsy A structural lesion extensive enough to impair both horizontal and vertical gaze would of necessity cause a variety of other neurologic deficits. Even multifocal brainstem disease, such as brainstem encephalitis, would likely cause additional motor and sensory deficits as well as more severe changes in sensorium. It is hard to imagine a single intraxial lesion that could produce a bilateral generalized ophthalmoplegia, and hyporeflexia. Such a lesion would have to extend from the mesencephalon to the pons and involve the corticospinal and cerebellar tracts as well and would leave the patient much more neurologically impaired than he is. One week later, the patient developed facial weakness on the left side with deviation of the angle of mouth. The patient was admitted for investigations. The routine hematological and blood biochemistry tests were within normal limits. Nerve conduction velocity test was suggestive of facial demyelination and repetitive nerve stimulation was negative. MRI thorax and Acetyl cholinesterase antibodies were also negative. CSF analysis showed elevated proteins (65.6 mg/dl) with near normal WBCs (7 / mm3) A clinical diagnosis of Miller Fisher syndrome was made and the patient was put on intravenous immunoglobulin (IV IG) therapy for five days. Figure 1: Hess Charting (Day 1) Smaller OS chart, OS under action of LR, OD medial rectus overaction Dr. Shroff's Charity Eye Hospital, 5027 Kedarnath Road, Daryaganj, New Delhi www.dosonline.org 81 Table 1: (Acute ophthalmoplegia) Causes of Acute Bilateral Ophthalmoplegia Figure 2. (Day 3), Bilateral Ptosis, Gross limitation of eye movements • Myasthenia gravis • Pituitary apoplexy • Demyelinating disease • Miller Fisher syndrome • Brainstem ischemia or hemorrhage • Botulism • Diphtheria • Whipple's disease • Wernicke's encephalopathy Myasthenia Gravis Multiple cranial nerve palsy The next cause to consider is multiple cranial nerve palsies. A process involving cranial nerves III, IV, and VI bilaterally would cause horizontal and vertical ophthalmoplegia that could involve lids and pupils. Several pathologic processes may sometimes involve both cavernous sinuses and, thus, could produce such a clinical picture. Examples include intracavernous carotid aneurysms, dural-cavernous fistulas, cavernous sinus thrombosis, and large skull-base tumors. A negative Neuroimaging and presence of lower motor neuron signs make these highly unlikely. A more likely cause of acute weakness with this pattern is disease of the neuromuscular junction. Myasthenia could certainly present with acute onset of painless, bilateral, symmetric ophthalmoplegia with ptosis, and it would fit some of the clinical features of this case. Myasthenia gravis should always be considered in a patient with an external ophthalmoplegia; however, as noted above, the presence of hyporeflexia and absence of fatigability in this patient makes a diagnosis of myasthenia gravis untenable. Various neurophysiological tests like repetitive nerve stimulation test and singlefibre electromyography (SFEMG) are also helpful for confirmation of the diagnosis. Figure 3. (Day 3), Gross limitation of all extra ocular movements 82 DOS Times - Vol. 13, No.4, October 2007 Figure 4. (5 months), Total recovery of extra ocular movements Botulism Miller Fisher syndrome Another condition that affects the neuromuscular junction, causing similar manifestations is botulism. Symptoms of food-borne botulism usually begin 12 to 36 hours after ingestion of contaminated food and include weakness, lassitude, and decreased lacrimation and salivation. Miller Fisher syndrome (MFS) is one of a spectrum of acute demyelinating inflammatory polyneuropathies, which include Guillain – Barré syndrome, acute ophthalmoplegia and Bickerstaff ’s encephalitis. Originally described by Miller Fisher (1956), MFS is a triad of ataxia, areflexia, and ophthalmoplegia. Toxins elaborated by the organism Clostridium botulinum impair neuromuscular transmission by interfering with the release of acetylcholine at the presynaptic side of the neuromuscular junction. The neuro-ophthalmologic findings typically include ophthalmoplegia and ptosis. The male/female ratio is 2:1, with a mean age of 43.6 years at the onset of the disease. A viral infection which is seen preceding the neurological symptoms in 71.8% of the cases ,2, 3 was not present in our case. This patient did not have any gastroenteritis, there is also no evidence of generalized proximal motor weakness, and his pupils are not dilated and non-reactive, findings that typically occur with botulism. Although ophthalmoplegia is prominent, bulbar and extremity weakness are also characteristic and their absence speaks against botulism as the cause. Diplopia is the presenting feature in 38.6% cases, with the remainder presenting with only ataxia (20.6%) or with both symptoms simultaneously.1, 2 The disease progresses over five to ten days, sometimes up to three weeks. External ophthalmoplegia begins relatively symmetrically and most patients progress to have complete immobilization of the globes. Wernicke’s encephalopathy Additional features consistent with a peripheral neuropathy including paraesthesiae (50%), oropharyngeal weakness (26%), or bi-facial weakness (32%). Bladder dysfunction (16%) or more widespread dysautonomia is occasionally seen.2, 3 In 1881, Carl Wernicke described a syndrome primarily found in alcoholics characterized by nystagmus usually preceding complete or incomplete ophthalmoplegia, gait ataxia, and mental confusion that may develop acutely or subacutely. Many of these patients are hyporeflexic. Although most patients with the so-called Wernicke syndrome have significant mental confusion, confabulation, or amnesia, in which case the condition is called the Wernicke-Korsakoff syndrome. Although Wernicke syndrome is typically associated with a nutritional deficiency of thiamine and usually found in alcoholics, it can also occur in patients on fad diets or under other circumstances. Wernicke syndrome is a medical emergency with 17% mortality if left untreated and, once suspected, requires the immediate administration of thiamine. Recovery of neurologic deficits can be dramatic, often with improvement of the ocular motor abnormalities within hours following the administration of thiamine. As there is no evidence that this patient has a history of alcohol abuse or was on a fad or starvation diet, this diagnosis was excluded. www.dosonline.org The diagnosis of MFS is still descriptive, depending on the presentation of the triad of MFS. Although, almost half of the cases are not the pure syndrome, it is important to emphasize that the diagnosis of MFS should be considered in any patient who develops an acute ophthalmoparesis with or without either ataxia or hyporeflexia, or even acute onset of either ataxia or areflexia without ophthalmoplegia.3 Cranial nerves other than the oculomotor nerve may be involved in more than half of the cases (56 .9%), most commonly the facial nerve (45.7%) followed by IX and X (39.9%), and XII (13%). 4 CSF examination may show an elevated protein value with a normal cell count. A tetrasyaloganglioside (GQ1b) antibody in patient serum may give clues in the diagnosis of MFS variants .Due to the linkage between this antibody and MFS, especially ophthalmoplegia; it may prove a highly sensitive and specific clinical 83 marker for the diagnosis of typical and atypical MFS. It would also differentiate MFS ophthalmoplegia from ophthalmoplegia of other causes. GQ1b antibody is supportive but not essential for the clinical diagnosis of MFS.3, 5 Because of the relative scarcity of MFS, it is usually incorporated with GBS in the evaluation of therapy. The treatment options are steroids, plasma exchange (PE) and intravenous immunoglobulin (IVIG). 3 diagnosis of MFS, and therefore the diagnosis needs to be established with the combination of serologic studies, CSF, and electrophysiology. The authors present this case to highlight the existence of this acute neurological illness with a relatively benign course if recognized and managed appropriately. References 1. Prognosis is good with recovery after a mean of 10 weeks, 2, 3 although as in the present case the total recovery may be delayed up to several months. Prisms may be prescribed in the meantime for the diplopia. Most patients show a complete remission without any residual symptoms. 2. In summary, the importance of recognizing the significance of the triad of acute ophthalmoparesis, ataxia, and hyporeflexia, especially following either a gastroenteritis or upper respiratory infection, greatly limits the differential diagnosis. As discussed above, ophthalmoparesis without ataxia or areflexia does not eliminate a 4. 3. 5. Berlit P, Rakicky J.The Miller Fisher syndrome. Review of the literature. J Clin Neuroophthalmol 1992; 12:57-63 Mori M, Kuwabara S, Fukutake T, Yuki N, Hattori T. Clinical features and prognosis of Miller Fisher syndrome. Neurology. 2001 Apr 24; 56(8): 1104-6. LI Haifeng. Miller Fisher syndrome: toward a more comprehensive understanding. Chinese Medical Journal, 2001, Vol. 114 No. 3 : 235-239 Michael S. Vaphiades, DO, The Double Vision Decision Surv Ophthalmol 48 (1) January–February 2003 M Odaka, N Yuki, K Hirata Anti-GQ1b IgG antibody syndrome: clinical and immunological range J Neurol Neurosurg Psychiatry 2001; 70:50-55 (January) First Author Sandeep Bhuttan MS 84 DOS Times - Vol. 13, No.4, October 2007 Suneeta Dubey MS, M.Agarwal MS, Monica Gandhi MS, Gaurav Sood MS, A.Pandey MS, Julie Pegu MS N eovascular glaucoma (NVG) is defined as rubeosis irides with secondary angle closure glaucoma1 and is characterized by widespread retinal ischemia most commonly associated with anterior segment neovascularization and subsequent raised intraocular pressure (IOP). The increased IOP is often difficult to control and frequently results in loss of vision.2 Prompt diagnosis and treatment of the underlying etiology is essential. There are two key aspects to the management of NVG: namely, treatment of the underlying disease process responsible for rubeosis and treatment of the increased IOP. The standard treatment for NVG includes retinal photocoagulation and cyclodestructive or drainage procedures. Studies have shown that iris neovascularization (INV) is highly correlated with retinal ischemia which stimulates the production of vascular endothelial growth factor (VEGF), a key molecule in ocular neovascularization.3 Direct targeting of VEGF might be another possible therapeutic strategy to treat neovascularization Clinical Meeting: Case 2 Bevacizumab (Avastin) in the Management of Neovascular Glaucoma visual acuity was perception of light with accurate projection in her right eye and 6/36 in her left eye. Florid neovascularization of iris (INV) extended from pupillary margin to angle in her right eye with 270 degrees of synechial angle closure (Figure 1,2a, 2b). The pupil was central, round and fixed with ectropion uveae involving more than 270 degrees (Weiss and Gold classification grade-4).4 Dense cataract obscured visualization of the vitreous, optic nerve, and retina. Fluorescein angiography of the iris (IFA) revealed marked leakage from rubeotic vessels (Figure 3). There was no iris neovascularization in the patient’s left eye, the ocular media were clear and there was evidence of prior panretinal photocoagulation. The patient’s IOPs were 48 mm Hg in the right eye and 12 mm Hg Case Report A 60 year old female presented to us in October 2006 with a tenmonth history of gradual decrease of vision, which was more in her right eye . She had a 30- year history of diabetes with coexisting hypertension. The patient had undergone panretinal photocoagulation bilaterally in 2003 for proliferative diabetic retinopathy. She had also undergone vitrectomy in her right eye in 2004 and cataract surgery in her left eye in 2005. The patient’s Figure 2a. Extensive PAS of the angle 270 Degrees Figure 1. Extensive NVI – Grade IV (Weiss & Gold Classification) Dr. Shroff's Charity Eye Hospital, 5027 Kedarnath Road, Daryaganj, New Delhi www.dosonline.org Figure 2b. Neovascularization of inferior angle 87 Figure 3. Extensive Leakage from INV on iris fluorescein angiography Figure 5. Post Phaco trabeculectomy phacotrabeculectomy with MMC (0.4 mg for 2 minutes) ( Figure5). Additional laser photocoagulation was performed two weeks after the surgery for the anterior non ablated retina. At the most recent follow-up (16 weeks after the injection), best corrected visual acuity was 6/24, the IOP was 16.0 mm Hg with no clinically evident rubeosis. Discussion Figure 4. Regression of INV post avastin injection on Iris fluorescein angiography in the left eye. An ultrasound B-scan performed on her right eye demonstrated that the retina was attached, and there were multiple dot opacities in vitreous suggestive of vitreous hemorrhage. The patient was immediately started on medical management. Topical steroids, cycloplegics and anti-glaucoma drugs in the form of tab acetazolamide 250 mg (QID), timolol 0.5% (BID) and brimonidine 0.2% eye drops (BID) were started. The patient was offered an off-label intravitreal and intracameral injection of Bevacizumab (Avastin; Genentech, San Francisco, California). After discussion of the risks and benefits of the treatment, the patient signed consent for the off-label use of injection. The Injection was given in a dose of 1.25 mg in 0.05 ml intravitreally and 0.25 mg in 0.02 ml Intracamerally. It was given under topical anesthesia under aseptic conditions. The injection was well tolerated without observed side effects. At a follow-up examination 5 days later, the visual acuity of her right eye was perception of light with accurate projection of rays with an IOP of 20.0 mm Hg on maximal tolerable medical therapy for glaucoma. Slit-lamp examination revealed dramatic regression of the previously visible rubeotic vessels, and IFA showed substantial reduction in iris neovascularization with minimal leakage (Figure 4). Three weeks after the bevacizumab injection, the patient underwent an uncomplicated 88 The visual prognosis and control of neovascular glaucoma still remains a challenge despite many advances. Although PRP is considered the standard treatment of retinal ischaemia, the best alternative method is still undetermined. Consideration of visual potential is also important. If there is no useful vision, the goal of therapy becomes patient comfort and the management protocol may differ. In conditions precluding PRP due to media opacities, other modalities should be considered including pan-retinal cryotherapy, and trans-scleral diode laser retinopexy.2 If NVG follows its natural course to the angle closure glaucoma stage, medical therapy usually becomes ineffective and surgical intervention is required. It is a general belief that standard filtering procedures in eyes with NVG are rarely successful primarily because of the high risk of intraoperative bleeding and post operative progression of the neovascular membrane. Therefore there is a need to achieve complete regression of neovascularization in order to have a better outcome of the surgical procedure. Advances in the understanding of the angiogenic process have led to the development of compounds that are approved for the treatment of neovascularization. Bevacizumab is a humanized recombinant antibody that binds all isoforms of VEGF-A and its off label use has been reported by a few authors to be of benefit in regression of iris and retinal neovascularization. Cases of intraocular inflammation after intravitreal bevacizumab were low, suggesting that intravitreal bevacizumab seems safe over the short term. It’s role has also been evaluated in patients with NVG. In a case series of six patients of CRVO with NVG reported by Iliev et al 5, Intravitreal Bevacizumab (IVB) resulted in a marked regression of anterior segment neovascularization and relief of symptoms within 48 hours with no side effects. Similarly, Avery 6 has reported a single case of regression of retinal and iris neovascularization, due to PDR, one week after IVB without any observed side effects. DOS Times - Vol. 13, No.4, October 2007 Paula et al 7 also have a single case report with positive results of IVB. Davidorf et al 8 have described a one-eyed patient with PDR and NVG who showed rapid improvement of rubeosis irides from a single bevacizumab injection. This patient subsequently underwent a remarkably routine trabeculectomy three weeks after the IVB without any hemorrhage leading the authors to conclude that anti – VEGF therapy may have application in the preoperative preparation of trabeculectomy for NVG. In a series of three patients with NVG reported by Mason et al, 9 IVB resulted in total regression of INV with control of IOP surgically in one case and medically in two cases. The tube drainage surgery done in one case was without bleeding complications resulting in less operative time and quicker recovery for the patient. References 1. Chen KH, Wu CC, Roy S, Lee SM, Liu JH. Increased interleukin-6 in aqueous humor of neovascular glaucoma. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2627-32. 2. Sivak-Callcott JA, O’Day DM, Gass JD, Tsai JC. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma.Ophthalmology. 2001 Oct;108(10):1767-76 3. Oshima Y, Sakaguchi H, Gomi F, Tano Y. Regression of iris neovascularization after intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy.Am J Ophthalmol. 2006 Jul;142(1):155-8. 4. Weiss DI, Gold D. Neofibrovascularization of iris and anterior chamber angle: a clinical classification. Ann Ophthalmol. 1978 Apr;10(4):488-91. 5. Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf S, Sarra GM. Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am J Ophthalmol. 2006 Dec;142(6):1054-6. 6. Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):352-4. 7. Silva Paula J, Jorge R, Alves Costa R, Rodrigues Mde L, Scott IU.Shortterm results of intravitreal bevacizumab (Avastin) on anterior segment neovascularization in neovascular glaucoma. Acta Ophthalmol Scand. 2006 Aug;84(4):556-7. 8. Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina. 2006 Mar;26(3):354-6. 9. Mason JO 3rd, Albert MA Jr, Mays A, Vail R. Regression of neovascular iris vessels by intravitreal injection of bevacizumab. Retina. 2006 Sep; 26(7):839-41. Although the optimal approach for management of NVG can only be determined through future research, IVB might be able to open a therapeutic window for PRP and also surgical intervention for IOP control can be performed in a quieter eye with less operative time, decreased risk of hemorrhage and quicker recovery. PRP takes time to achieve regression of INV and alone it does not achieve complete success in halting INV in every patient. Literature suggests that IVB is well tolerated and might be an emergent treatment of choice for INV that is poorly responsive to conventionally approved treatments. Also, IVB may be an advantageous treatment option rather than PRP, especially in eyes with fundus- obscuring cataract or vitreous hemorrhage. In conclusion, injection Bevacizumab shows promise as an adjunct in the treatment of refractory NVG. How long this regression will persist is unknown, but even a transient effect could be of benefit as a surgical adjuvant in the preoperative preparation of filtering surgery for NVG. However, randomized case control studies are necessary to evaluate the long term effectiveness and safety of IVB for wide spread use in the management of NVG. First Author Suneeta Dubey MS www.dosonline.org 89 Gaurav Sood MS, Suneeta Dubey MS, Monica Gandhi MS, Julie Pegu MS P rimary open angle glaucoma is a chronic, progressive optic neuropathy characterized by morphological changes at the optic nerve head and retinal nerve fibre layer in the absence of other ocular disease or congenital anomalies(with or without raised IOP) Strategies for judging progression on perimeter (White on White Perimetry) • Clinical judgment- overview • Defect classification system by various landmark studiesAGIS, CIGTS, EMGT • Box plot • Event analysis- GPA • Trend analysis-Progressor Why We Want To Know Progression? The important tool for treatment in primary open-angle glaucoma (POAG) is a documented progression of glaucomatous optic neuropathy (GON). Retinal ganglion cell loss is a continuous physiological process. But in glaucoma, this loss is exaggerated. So knowing progression at the earliest can help to modify treatment strategies and the new target intraocular pressure (IOP) can be set. The ganglion cell loss can be monitored structurally as well as functionally. Structural changes can be assessed by optic nerve head evaluation using stereophotography or newer machines like HRT, GDx, OCT whereas functional changes can be judged by perimetry. Clinical Meeting: Clinical Talk Determining Progression of Glaucoma on Perimetry Overview Overview presents all the single field analysis examinations of up to 16 tests on a single page for comparison. But, the most important thing to know is that it does not give any additional information over the single field analysis printout. Overview printout showing stable fields over 3 years Fluctuation Perimetry in Progression Although structural damage can usually be detected in simple glaucoma before functional damage, evaluation of a longitudinal series of visual fields remains one of the most frequently used methods to detect early evidence of glaucoma and to observe patients. The perimetry methods are used to chart the course of disease in patients with glaucoma, wherein progressive visual field loss is taken to reflect the worsening of the disease and is therefore usually regarded as a strong indication that the treatment regimen should be intensified (therapeutic impact). If an abnormality is found, it needs to be confirmed on repeated visual field examination. But worsening of fields is not always progression. There exists Test-Retest Variability in Perimetry called Figure 1. Ganglion cell loss in a normal individual and in a patient with Glaucoma Dr. Shroff's Charity Eye Hospital, 5027 Kedarnath Road, Daryaganj, New Delhi www.dosonline.org Figure 2. Overview printout showing stable fields over 3 years 91 Figure 3. Short term fluctuation measurement at 10 points in Humphrey machine Figure 4. Box plot fluctuation. Also abnormal and peripheral points fluctuate more. Always remember to follow patient by same strategy (SITA Standard or Full threshold) Fluctuation can be of two types Short term fluctuation This is intra -test variability.Visual field variability increases in and around a scotoma. Short-term fluctuation (STF) represents the average of the local scatter over the entire visual field.Values greater than > +2.00 db are usually abnormal. Short term fluctuation measurement at 10 points in Humphrey machine Long term fluctuation It is a reversible, physiological variation of visual field thresholds over two or more examinations, which is exclusive of reproducible deterioration, improvement or artifacts. Figure 5. Findings of Box Plot Suggested criteria for visual field defect progression For a new defect in a previous normal area (Hodapp et al, clinical decision in glaucoma 1993, Eugs 2003) 92 First step is to establish a baseline visual field for further follow up tests A cluster of three or more non edge points, each of which declines? 5db compared to baseline on two consecutive fields or • What will not form baseline? A single non edge point that declines ? 10 db compared to baseline on two consecutive fields • Learning curve Deepening of a preexisting defect • High false positive • High false negative A cluster of three non-edge points, each of which declines >10 db compared to baseline on two consecutive fields. • Rim artifacts How is technology helping us? • Small pupil Box plot • Clover leaf deformity • Scotomas d/t congenital anomalies • Wrong prescription The box plot is a modified histogram of the threshold values. It is based on total deviation numerical plot. The box represents the range of deviation for the middle 70% of points (sd).Upper tail represents the range of the 15% best points. Lower tail represents the range of the 15% worst points. DOS Times - Vol. 13, No.4, October 2007 Figure 8. Legend for Progressor Figure 6. GPA single-page summary printout What are important deductions from Box Plot? Same shape as normal but graph at a lower point = depression in height. Bottom of box same positioned, elongating tail = localized loss/ scotomas deepening. Two-tests are averaged to establish a baseline, and up to 14 followup tests may be compared to averaged thresholds of 2 baseline exams GPA single-page summary printout GPA Symbols Event analysis (GPA) • Event analysis uses the first few visual fields in a series as a baseline, then compares subsequent visual fields to that baseline to determine whether change has occurred. A single solid dot indicates a point not changing by a significant amount. • A small open triangle identifies degree of deterioration that is significant at the 5%level (p<0.05). • A half filled triangle indicates deterioration at that point in 2 consecutive tests. • A solid triangle indicates deterioration at that point in 3 consecutive tests. • An X signifies that the point is out of range for analysis. Event analysis is implemented in the glaucoma progression analysis (GPA) software for the humphrey field analyzer. It is based upon significance limits for test-retest variability on pattern deviation. It helps accurately identify clinically significant progression of visual field loss in glaucoma patients. It is compatible with • Sita standard • Sita fast • Full-threshold tests (only for baseline) GPA Alert Possible progression: same 3 or more points show deterioration in at least 2 consecutive tests. Requisites for GPA Minimum of three tests required: two baseline and 1 follow-up exam Likely progression: same 3 or more points show deterioration in at least 3 consecutive tests. Figure 7. Image of Grey Scale printout on Progressor www.dosonline.org 93 Trend analysis Trend analysis measures the rate of change of the visual field and the statistical significance of that rate. Measurement may be made for each test point (pointwise linear regression [PLR]) or on a cluster basis. Trend analysis is implemented in the Progressor software (Moorfields eye hospital/ medisoft ltd.). Defect Classification System developed by different landmark studies are complex and not very practical to use. To conclude,Visual fields is still considered to be the gold standard in the diagnosis and management of glaucoma. It is a cost effective and easily available means to judge progression and it's parameters can be helpful to modify therapy in glaucoma. References Progressor is a trend analysis for identifying progression in serial visual software package which analyses visual field progression using point wise linear regression of sensitivity on time. 1. Properties of Perimetric Threshold Estimates from Full Threshold, SITA Standard, and SITA Fast Strategies Paul H. Artes et al IOVS. 2002;43:2654-2659. Image of Grey Scale printout on Progressor 2. The image indicates the significance of change for each point tested in the visual fields. Each bar represents a Humphrey field analyser test. The length of the bars indicate the amount of change in visual field sensitivities. Lee AC, Sample PA, Blumenthal EZ, Berry C, Zangwill L, Weinreb RN. Infrequent confirmation of visual field progression. Ophthalmology. 2002;109(6):1059-65. 3. Fitzke et al, analysis of vf progression in glaucoma Br. J. Ophthalmology 1996 80; 40-48. 4. Wilkins MR, Fitzke FW, Khaw PT. Pointwise linear progression criteria and the detection of visual field change in a glaucoma trial. Eye. 2006; 20(1):98-106 Anderson's perimetry. The legend provides the color key for the significance of change, where a positive slope indicates improvement, a negative slope deterioration and grey indicates no change. First Author Gaurav Sood 94 DOS Times - Vol. 13, No.4, October 2007 Anagram Time Columns DOS Quiz Each of the following words is a jumbled ophthalmic or related term. There is, however, an extra letter in every set of letters. These extra letters will also form a eight letter ophthalmic word when unjumbled. So get cracking. 1. MIGOALO ___ ___ ___ ___ ___ ___ ____ 2. SPOOKIA ___ ___ ___ ___ ___ ___ ____ 3. MEANOMALY ___ ___ ___ ___ ___ ___ ___ ___ ____ 4. GREATMOTA ___ ___ ___ ___ ___ ___ ___ ___ ____ 5. KEANULIME ___ ___ ___ ___ ___ ___ ___ ___ ____ 6. OEPRIMALMOLD ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ____ 7. RAAMBETIONSTOOL ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ____ 8. BARAOMOOCHSYMCARD ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ____ Saurabh Sawhney DO, DNB Ashima Aggarwal MS, DNB Insight Eye Clinic, New Delhi Answers on page number 103 Dr. Shroff’s Charity Eye Hospital Presents an “Update on Retinopathy of Pre-maturity (ROP)” At Gulmohar Hall, India Habitat Center, 13th January’ 2008, 9am-5pm. Faculty Ø Dr. Lingam Gopal – Sankara Nethralaya, Chennai. Ø Dr. R.V. Azad – R.P. Center, AIIMS, Delhi. Ø Dr. Subhadra Jalali – LVPEI, Hyderabad Ø Dr. Mahesh P Shanmugam – Retina Clinic, Bangalore Ø Dr. Mangat Dogra – PGI, Chandigarh Ø Dr. Arvind Taneja & Dr.Manish Malik – Max Hospital, Delhi. Ø Dr. Anand Subramanyam – Wockhardt Hospital, Mumbai Dr. Manisha Agarwal Organizing Secretary Dr. Nishant Taneja Co-organizing Secretary For Registration Contact: Mr. A. K. Singh Dr. Shroff’s Charity Eye Hospital 5027, Kedar Nath Road, Daryaganj Delhi-110002 Email: [email protected] Ph: 9811009434, 011-41564319 www.dosonline.org 99 Journal of Current Glaucoma Practice with DVD Publisher : Jaypee Brothers Medical Publishers (P) Ltd. Chief Editors: Dr Tanuj Dada (Glaucoma Service, RP Centre for Ophthalmic Sciences, AIIMS, New Delhi) Prof. Kuldev Singh (Director Glaucoma Service - Stanford University, USA) Prof. Roger Hitchings (Moorefield Eye Hospital - London, UK) Delhi), Sushmita Kaushik (PGIMER, Chandigarh), P Sathyan (Aravind eye hospital, Madurai) This is the world's first international review journal incorporating a video DVD. The journal publishes invited review articles from top glaucoma experts worldwide and also includes diagnostic and surgical videos in the DVD. The journal covers each subspeciality of glaucoma including : basic and clinical research, epidemiology, biostatistics, genetics, pathophysiology, laboratory methods, clinical examination, perimetry, new structural and functional tests, anterior segment imaging, ocular blood flow, pediatric glaucoma, angle closure glaucoma, open angle glaucoma, secondary glaucoma, medical management, laser therapy, glaucoma and combined cataract glaucoma -surgical techniques, neuroprotection, health economics, quality of life and visual rehabilitation. The journal has a unique video section in the DVD which show-cases basic and advanced glaucoma surgical techniques, management of complications, includes diagnostic techniques and video assisted instruction courses and lectures. Senior Editorial Advisors : Anders Heijl (Sweden),Erik Greve (Netherland), George Spaeth (USA), Graham Trope (Canada), Ivan Goldberg (Australia), Michael Belkin (Israel), Paul Kaufman (USA), Paul Palmberg (USA), Ravi Thomas (India), Robert Weinreb (USA), Sohan Singh Hayreh (USA), Yoshiaka Kitzawa (Japan) Associate Editors: Dr Ronnie George (Sankara Netralaya, Chennai), Dr Jovina See (National University Hospital, Singapore), Rajul Parikh (LV Prasad Eye Institute, Hyderabad) and Robert Campbell (University of Toronto, Canada) Managing Editor: Dr Ritu Gadia (RP Centre, AIIMS, New The first issue covers epidemiology of angle closure glaucoma (David Friedman), the glaucoma vaccine (Michal Schwartz), importance of disc size (Robert Ritch), anterior segment imaging (Jovina See), Ab interno Trabeculotomy (Don Minckler) and many others. The DVD includes nonpenetrating surgery (Andre Mermoud), surgical caveats for implanting Ahmed glaucoma Valve (Lama-Al-Aswad), repair of cyclodialysis cleft (Peter Shah), managing an overhanging bleb (Arun Narayanaswamy) etc etc. This new journal serves as a unique teaching resource for all ophthalmologists and especially for trainee surgeons and glaucomatologists. The combination of practical knowledge provided by the experts combined with video assisted teaching offers an excellent learning experience for the reader. It helps the reader by updating knowledge on current practice and recent advances in the field of glaucoma, and at the same time provides an opportunity to learn new surgical skills and improve existing surgical standards. For details contact: [email protected] [email protected] www.jaypeebrothers.com www.dosonline.org 101 Forthcoming Events : National November 2007 3-4 DHANBAD, JHARKHAND 22nd Easter India Zonal Ophthalmic Congress (EIZOC) & 5th Jharkhand Ophthalmological Society (JOS) Conference “EYEFEST-007” Contact Person & Address Dr. B.N. Gupta, Organising Secretary Navjyoti Netralaya & Research, Joraphatak Road, Dhanbad, JHARKHAND Ph.: 0326-2306030 (R), 2305055 (C) (M): 09431121030, 09431726030, 09334018182 E-mail: [email protected] December 2007 7-9 KOLKATA, WEST BENGAL 17th Annual Conference of Glaucoma Society of India Contact Person & Address Dr. Chandrima Paul B.B. Eye Foundation 2/5, Sarat Bose Road, Sukhsagar 1st & 2nd Floors, Kolkata-700020 Ph: 033-24746608, 24748816 Email: [email protected] 14-16 HYDERABAD, ANDHRA PRADESH Annual Meeting of the Oculoplastic Association of India Contact Person & Address: Dr. Milind Naik, Dr. Santosh G Honavar LV Prasad Eye Institute LV Prasad Marg, Banjara Hills, Hyderabad 500034 Website: http://www.opai.in, E-mail: [email protected], 17-18 NEW DELHI Midterm Conference of Delhi Ophthalmological Soceity Contact Person & Address Dr. Namrata Sharma Room No. 474, 4th Floor, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi – 110029 Ph.: 011-65705229, Fax: 26588919 E-mail: [email protected], Website: www.dosonline.org 23-25 KERALA 34th Annual Conference of Kerala Society of Ophthalmic Surgeons Contact Person & Address Dr. Anup Chirayath Ahalia Foundation Eye Hospital Near Kanalpirivu, Walayar, Palakkad, Kerala Ph: 04923-235999, Tele-Fax: 235900, Cell: 9447774439 Email: [email protected] 30 Nov., 1-2 Dec. BAREILLY, U.P. Annual Conference of U.P. State Ophthalmological Society Contact Person & Address Dr. Kapil Agarwal B-39/B, Rajendra Nagar Bareilly-243122 (U.P.) Ph: 2442592, 2455353 December 2007 1-2 HYDERABAD, ANDHRA PRADESH International Pediatric Ophthalmology Symposium Contact Person & Address: Dr. K. Ramesh Pediatric Ophthalmology, Strabismus & Neuro-Ophthalmology L.V. Prasad Eye Institute L.V. Prasad Marg, Banjara Hills Hyderabad - 500 034 A.P. INDIA Tel : +91-40-30612 644/ 345, Fax : +91-40-2354 827 Email : [email protected], Web : www.lvpei.org 102 22nd NEW DELHI Clinical Meeting of Madan Mohan Cornea Society on “Surgical Management of Corneal Disorders” Contact Person & Address: Dr. Rishi Mohan, Joint Secretary 29, Link Road, Room No. 106, Lajpat Nagar-III, New Delhi - 110 924 Ph.: 29847800/7900, Fax: 29847600, Email:[email protected] 23-24 NEW DELHI Workshop "Knowbology- know your machine" Contact Person & Address: Prof. Kirti Singh, Organizing Secretary Mob. 09968225285 or E-mail: [email protected]. January 2008 13th NOIDA, U.P. 3rd Annual Conference of Noida Ophthalmological Society Contact Person & Address: Dr. Mohita Sharma Tripati Eye Centre C-8, Sector-19, Noida-201301 (U.P.) Ph.: 0120-4266642, 2444349 (M): 9810045425 E-mail: [email protected] Website: www.nos2004.org DOS Times - Vol. 13, No.4, October 2007 Forthcoming Events : International October, 2007 13-17 VIENNA, AUSTRIA May, 2008 21-24 JAPAN 20th ECNP Congress VIENNA, AUSTRIA Tel: +31 20 504 0200 / Fax: +31 20 504 0225 Email: [email protected] 18th International Visual Field & Imaging Symposium (IPS2008) Nara, Japan Contact: Chota Matsumoto Phone: 81-72-366-0221 ext 3335 Fax: 81-72-368-2559 E-Mail: [email protected] 24-27 TAMPA, FLORIDA American Academy of Optometry Meeting Tampa Florida http://www.aaopt.org/meetings 28-31 BELGIUM XI International Orthoptic Congress 2008 ANTWERP, BELGIUM Contact: Daisy Godts Tel: +32 3 8214845 / Fax: +32 3 8251926 Email: [email protected] Web: www.ioacongress2008.org November, 2007 10-13 NEW ORLEANS, UNITED STATES American Academy of Ophthalmology 2007 Annual Meeting New Orleans , Province: LA (United States) Contact: American Academy of Ophthalmology, P.O. Box 7424 San Francisco, CA 94120-7424 Phone: 415-561-8500, Fax: 415-561-8533 E-Mail: [email protected] June, 2008 19-22 WURZBURG, GERMANY 21st Annual Congress of the German Retina Society/ 8th Symposium of Intl Society of Ocular Trauma, Main Topic: Ocular Trauma Wurzburg, Germany http://www.retinologie.de December, 2007 1-5 CALIFORNIA 25th Annual Meeting of the American Society of Retina Specialists Palm Springs area, city of Indian Wells, California. Tel: (914) 722-0664, Fax: (914) 722-0465 [email protected] July, 2008 7-10 MONTREAL, CANADA 9th International Conference on Low Vision Rehabilitation - Vision 2008 Montreal, Province: QC (Canada) Contact: Beatrice Laham Phone: 514-906-1979, Fax: 514-395-1801 E-Mail: [email protected] March, 2008 28 Mar. - 2 Apr. HUNGARY 7th International Symposium on Ocular Pharmacology and Therapeutics Budapest, Hungary Contact: Robert Nesbitt Phone: 44-229-080-488 Fax: 44-227-322-850 E-Mail: [email protected] September, 2008 5-6 NEW DELHI, INDIA Biennial Meeting SAARC Academy of Ophthalmology India Habitat Centre, New Delhi Contact: Dr. Namrata Sharma Phone: 011-26589810 E-Mail: [email protected] April, 2008 12-16 CHICAGO ASCRS/ASOA Symposium and Congress CHICAGO, IL, USA Contact: ASCRS Tel: +1 703 591 2220 Fax: +1 703 591 0614 Web: www.ascrs.org Answer Quiz No. 4 Extra Word: ONCOLOGY 6. LEUKEMIA 5. 2. GLIOMA 1. DERMOLIPOMA KAPOSI 7. 3. RETINOBLASTOMA MELANOMA 8. 4. RHABDOMYOSARCOMA TERATOMA www.dosonline.org 103 Delhi Ophthalmological Society (LIFE MEMBERSHIP FORM) Name (In Block Letters) ___________________________________________________________________________ S/D/W/o _____________________________________________________________ Date of Birth _____________ Qualifications __________________________________________________________ Registration No. __________ Sub Speciality (if any) ____________________________________________________________________________ ADDRESS Clinic/Hospital/Practice _______________________________________________________________________ ________________________________________________________________ Phone __________________ Residence _________________________________________________________________________________ ________________________________________________________________ Phone __________________ Correspondence ____________________________________________________________________________ ________________________________________________________________ Phone __________________ Email ___________________________________________________________ Fax No. _________________ Proposed by Dr. _____________________________________ Membership No. ________ Signature ___________________ Seconded by Dr. _____________________________________ Membership No. ________ Signature ___________________ [Must submit a photocopy of the MBBS/MD/DO & State Medical Council / MCI Certificate for our records.] I agree to become a life member of the Delhi Ophthalmological Society and shall abide by the Rules and Regulations of the Society. (Please Note : Life membership fee Rs. 3100/- payable by DD for outstation members. Local Cheques acceptable, payable to Delhi Ophthalmological Society) Please find enclosed Rs.___________in words ____________________________________________________ by Cash Cheque/DD No.____________________ Dated_____________ Drawn on______________________________________ Three specimen signatures for I.D. Card. Signature of Applicant with Date FOR OFFICIAL USE ONLY Dr._______________________________________________________________has been admitted as Life Member of the Delhi Ophthalmological Society by the General Body in their meeting held on________________________________ His/her membership No. is _______________. Fee received by Cash/Cheque/DD No._______________ dated_________ drawn on __________________________________________________________________. (Secretary DOS) www.dosonline.org 105 INSTRUCTIONS 1. The Society reserve all rights to accepts or reject the application. 2. No reasons shall be given for any application rejected by the Society. 3. No application for membership will be accepted unless it is complete in all respects and accompanied by a Demand Draft of Rs. 3100/- in favour of “Delhi Ophthalmological Society” payable at New Delhi. 4. Every new member is entitled to received Society’s Bulletin (DOS Times) and Annual proceedings of the Society free. 5. Every new member will initially be admitted provisionally and shall be deemed to have become a full member only after formal ratification by the General Body and issue of Ratification order by the Society. Only then he or she will be eligible to vote, or apply for any Fellowship/Award, propose or contest for any election of the Society. 6. Application for the membership along with the Bank Draft for the membership fee should be addressed to Dr. Namrata Sharma, Secretary, Delhi Ophthalmological Society, R.No. 474, 4th Floor, Dr. R.P. Centre for Ophthalmic Sciences, AIIMS, Ansari Nagar, New Delhi - 110 029. 7. Licence Size Coloured Photograph is to be pasted on the form in the space provided and two Stamp/ Licence Size Coloured photographs are required to be sent along with this form for issue of Laminated Photo Identity Card (to be issued only after the Membership ratification). Situation Vacant Muzaffarpur Eye Hospital, the only eye hospital of Bihar with 151 indoor beds and all modern and sophisticated equipments, treating over 1,60,000 outdoor eye patients and performing over 18,000 surgeries annually, needs suitable candidates for the following posts. 1. Chief Medical Officer : 1 Post (Ms/DNB with minimum 10 years experience) 2. Ophthalmologist : 1 Post (Retina & Vitreous Specialist) 3. Ophthalmologist : 3 Post (MS/DNB) 4. Hospital Administrator : 1 post (Degree Hospital Management) The posts are non-practicing and they carry competitive salaries, furnished/semi furnished accommodation and other incentives. Interested candidates should send their resume to:The Secretary, Muzaffarpur Eye Hospital Juran Chapra, Road No. 2, Muzaffarpur - 842001 E-mail to:- [email protected] Mob. No.: 09334910514 106 DOS Times - Vol. 13, No.4, October 2007 DOS Credit Rating System (DCRS) DOS has always been in the forefront of efforts to ensure that its members remain abreast with the latest developments in Ophthalmology. Among the important objectives formulated by the founders of our constitution was the cultivation and promotion of the Science of Ophthalmology in Delhi. The rapid strides in skills and knowledge have created a need for an extremely intensive Continuing Medical Education programme. In a bid to strengthen our efforts in this direction DOS had DOS Credit Rating System (DCRS), the details of which are given below. Our Primary objective is to promote value-based knowledge and skills in Ophthalmology for our members and give recognition and credit for efforts made by individual members to achieve standards of academic excellence in Ophthalmic Practice. DOS CREDIT RATING SYSTEM (DCRS) DCRS Max. 1) Attending Monthly Clinical Meeting* † (For full attendence) 10 90 2) Making Case Presentation at Monthly Meeting** 10 10 3) Delivering a Clinical Talk at Monthly Meeting** 10 10 4) Free Paper Presentation at Annual Conference (To Presenter)** 10 20 5) Speaker/Instructor** in : Monthly Symposium 10 10 : Mid Term Symposium 15 10 : Annual Conference 15 30 6) Registered Delegate at Mid Term DOS Conference 10 10 7) Registered Delegate at Annual DOS Conference 10 10 8) Full Article publication in Delhi Journal of Ophthalmology/DOS Times 15 45 9) Letter to editor in DOS Times 5 10 10) Letter to editor in DJO 5 10 11) > 3 Bonus points for Monthy Clinical Meeting: 10 bonus points — — 12) > 5 Bonus points for Monthy Clinical Meeting: 30 bonus points — — 13) All Monthly Clinical Meeting: 50 Bonus Points — — If any of the presentations is given an Award – Additional 20 bonus Credits. attendance at its meeting is higher (i.e. more than the average attendance of the eight monthly meetings). Member who have earned 100 Credits, are entitled * Based on Signature in DCAC ** Subject to Submission of Full Text to Secretary, DOS † Credits will be reduced in case attendance is only for part of the meeting. a) Certificate of Academic Excellence in Ophthalmic b) Eligible for DOS Travel fellowship for attending conference. If any member earns 200 Credits, he/she shall, in addition to above, be awarded Certificate of Distinguished ResourceTeacher of the Society. Institutional assessment for best performance will be based on the total score of members who attend divided by number of members who attended. Institutional assessment regarding decision to retain the institute for the next year will be based on total score. Please note that the Institutions’ grading increases if the www.dosonline.org DCRS !! Attention !! * * * * Members are requited to sign on monthly meeting attendance register and put their membership number. The DCRS paper will be issued only after the valid signature of the member in the attendance register. Please submit your DCRS papers to the designated DOS Staff only. The collected DCRS papers will be countersigned by President and Secretary and sealed immediately after the meeting is over. 107 Proceeding Protocol for Monthly Clinical Meetings 1. The Host (usually the ophthalmic chief of the Hosting Institution) will welcome the DOS and request the President and Secretary of the DOS to come to the Dais and start the Meeting. 2. The President and the Secretary will take up their seats on the side of the Dais, which is opposite to the Lectern. (They would continue to be in the same position through out the Meeting, including the Mini Symposium.) The Chairman of the Symposium will be invited to a Third seat next to the President on the same table, after the ‘Clinical Talk’. The Speakers, who if they form a Panel would be seated on the same side as the Lectern. 3. The President will declare the Meeting open. 4. The President and the Secretary will then conduct the meeting. 5. The case presentations (2 in no.) will form the first part of the clinical meeting. Each presenter will be allotted 10 min. time for his/her presentation. This will be followed by discussion with the audience on both the cases (Total time allotted is 15 min.). The case presentation will be followed by a Clinical Talk of 15 min. duration. This will be followed by discussion with the audience on the topic for 10 min. 6. After the first part of the meeting is over, the President will introduce the subject of the Mini Symposium (which will be of 1 hour duration) and invite the Chairperson of the Symposium to the Dais to conduct the Symposium. All the speakers may be invited to assume their seats on the Dais at this time or one by one after they have presented their Talks (at the discretion of the chair person of the symposium). 7. After the Symposium is over, the President will thank the Speakers and the Chair person and request Secretary to make any Announcements, including the Prizes etc. 8. By the time, the Clinical Meeting is to be declared closed by the President, the Host or his representative would be at the Lectern to (take the floor immediately after the Meeting is closed) thank people, firms who had helped him in hosting the Meeting and invite the Members of the DOS for Refreshments. 9. Venue : The monthly clinical meeting will definitely be held in the premises of the allotted institution. 10. Day : The meeting shall be held on the last Saturday / Sunday of the month, whichever the institution deems feasible. 11. Presenter : The presenting faculty / resident / fellows should be from the same institute for clinical case presentations and the clinical talk. 12. One person will be allowed only one-presentation for the award-wining session in the same academic year. 13. Exchange of dates : In case two institutions want to exchange the date of the meeting, it can be done with mutual agreement by the heads of the department and with information to the secretary’s office, well in advance. 14. Mini Symposium : It shall be organized by the institution but other DOS members can be invited to participate, if required. There should not be more than 3 speakers in the mini symposium. 15. To qualify for the retention in the monthly meeting calendar, a minimum attendance of 70 members is required (inclusive of the members of the host institute). 16. For the Best Clinical Meeting award i.e. Bodhraj Sabharwal Trophy, the overall assessment of the meeting will be made purely on the overall marks by outside delegates and for Dr. Minoo Shroff Trophy the award will be given to the most popular meeting (based on total attendance including outside and inside delegates as per the attendance register). 17. The attendance will be marked in the register which will be at a separate counter and will be managed by the DOS Staff. At the close of the clinical meeting, the attendance register will be signed by the Secretary and the President on the same day. 18. Meetings in the month of May and June may be opened from the next year (2008) if there are applications for the same. 19. No alcoholic drinks will be served during or after the meeting; only refreshments / snacks/ lunch will be served. 108 DOS Times - Vol. 13, No.4, October 2007 Tearsheet www.dosonline.org 109 110 DOS Times - Vol. 13, No.4, October 2007