Download Deep Anterior Lamellar Keratoplasty

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
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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.
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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 &
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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.
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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.
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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",
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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.
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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)
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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).
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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
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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
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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
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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.
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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
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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
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110
DOS Times - Vol. 13, No.4, October 2007