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UK EDITION SUMMER 2012 / ISSUE 13 Glistening-free, hydrophobic acrylic IOL JUST SAY ‘NO’ TO GLISTENINGS PAGE 10 Pure Vision 2 for astigmatism 4 with high definition optics CE mark approval for Victus 13 Femtosecond Laser Platform Bausch + Lomb instruments – 16 made in Germany Focus on glaucoma 7 The science of Preservative14 Associated Transient new, modern tool for managing 18Apost-cataract inflammation ® ™ Hyperfluorescence (PATH) GIVE YOUR PATIENTS CONSISTENTLY CRISP, CLEAR VISION THROUGHOUT THE DAY NEW P ureVision®2 contact lenses for Astigmatism with High DefinitionTM Optics A uto Align DesignTM – delivers outstanding stability for consistently crisp, clear vision throughout the day l High Definition™ Optics – for crisp, clear vision especially in low light. The only silicone hydrogel toric lens to control spherical aberration in both the sphere and cylinder meridians of the lens lC omfortMoistTM – improves comfort on insertion and throughout the day l BiotrueTM is the recommended multi-purpose solution, helping keep lenses moist for up to 20 hours1 1 Results of a US in vitro study performed to evaluate the release of wetting agents from various silicone hydrogel lens materials over a period of 20 hours. ©2011 Bausch & Lomb Incorporated. ®/™ denote trademarks of Bausch & Lomb Incorporated. COMING SOON – APRIL 2012 To find out more, speak to your Bausch + Lomb Sales Representative today or call customer services, details listed opposite. 3 DEAR COLLEAGUES Welcome to the Summer edition of Visions magazine. We look forward to meeting many of you at the major congresses in the coming months. Bausch + Lomb is one of the best-known and most respected healthcare brands in the world, offering the widest and finest range of eye health products. Our contact lens and lens care offerings span the entire spectrum of wearing modalities. Our pharmaceutical products treat a wide range of eye conditions including glaucoma, eye allergies, conjunctivitis, dry eye and retinal diseases. We offer branded and generic prescription ophthalmic pharmaceuticals as well as a wide variety of over-the-counter eye health products. We offer a full suite of ophthalmic surgical products, intraocular lenses (IOLs) and delivery systems. Bausch + Lomb’s centres for research, development and manufacturing are located throughout the world and our products are sold in more than 100 countries. We look forward to partnering with you to meet the challenges and celebrate the successes of the year ahead. Jill Collishaw, Editor, Visions Magazine Belgium/Luxembourg Tel: +32 3 280 82 40 Fax: +32 3 280 82 59 Germany/ Switzerland/Austria Tel: +49 30 33093 5431 Fax: +49 30 33093 5470 Portugal Tel: +351 214241425 Fax: +351 214241518 Emerging Markets Tel: +33 4 67 12 30 30 Fax: +33 4 67 12 30 32 Italy Tel: +39 029 148 3851 Tel: +33 4 67 12 30 30 Fax: +33 4 67 12 30 31 Tel: +31 20 6554555 Fax: +31 20 655 4640 Tel: +34 902 381 010 Fax: +34 902 250 310 France Netherlands Spain South Africa Tel: +27 11 372 5600 Nordic Countries Tel: +46 8 616 95 00 Fax: +46 8 669 86 23 United Kingdom Tel: +44 20 8781 0000 Fax: +44 20 8781 0001 www.bausch.com ™ © and ® denotes trademark and registered mark of Bausch & Lomb Incorporated. Copyright 2008 Bausch & Lomb Incorporated. All rights reserved. Design: balldesignconsultancy.com Bausch & Lomb Incorporated Bausch & Lomb House 106 London Road Kingston-upon-Thames Surrey, KT2 6TN, UK Tel: 020 8781 2900 Fax: 020 8781 2901 4 MAGAZINE Throughout the history of contact lens design the challenge of meeting the needs of astigmatic individuals has been significant. It is important to continue to strive to meet those needs when we consider the population that requires this correction. It has been reported that approximately 37% to 45% of adults have 0.75D or more of astigmatism.1‑3 With almost half of the population of contact lens wearers having significant astigmatism2, the contact lens industry as a whole must continue to support the needs of this large group of patients. PUREVISION 2 ® FOR ASTIGMATISM WITH HIGH DEFINITION OPTICS In a survey of 201 astigmatic contact lens wearers, the symptoms most often cited while wearing current toric lenses included regularly or occasionally experiencing blurry/hazy vision, fluctuating vision, and distorted vision.4 Forty seven percent of subjects reported experiencing blurry or hazy vision, 37% reported fluctuating vision, and 32% reporting distorted vision. Additionally, 32% of toric patients reported experiencing glare and halos in low-light conditions. Product benefits of toric lenses (in the categories of vision, comfort, health and convenience) were presented to patients randomly in successive groups of four for ranking. The benefit of highest relative importance for a toric soft contact lens was that it should ‘deliver consistently sharp vision all day’. Attributes and performance of current toric lenses may limit the ability of patients to achieve consistently crisp, clear vision throughout the day. Patients are looking for contact lenses that offer uncompromised vision and stability without compromising comfort. Definition™ Optics. Three lens design attributes have been incorporated to work together and achieve exceptional toric lens performance: High Definition™ Optics, Auto-Align Design™, and ComfortMoist™ Technology. Design Attributes and Clinical Experience A conventional spherical contact lens does not consistently control spherical aberration across the power range. Spherical lens designs inherently demonstrate spherical aberration due to their highly curved spherical surfaces; negative spherical aberration for negative power lenses, and Addressing the needs of astigmatic patients was the primary goal when Bausch + Lomb designed PureVision®2 For Astigmatism with High High DefinitionTM Optics Spherical aberration is the inability of the eye to focus light rays passing simultaneously through the centre and the periphery of the eye. The retinal image appears blurred because the peripheral light rays are focused anterior to the retina (Figure 1). Spherical aberration can be a barrier to highquality vision in low light, resulting in blurred vision, halos and glare. Bausch + Lomb lenses with High Definition™ Optics are designed to reduce the positive spherical aberration that is naturally occurring in the human eye to minimise halos and glare and bring all of the light rays to the same focal point to create clear, crisp vision all day – especially in low light. (Figure 2). Figure 1. A lens with spherical aberration has different focal points for the light rays passing through the center and the periphery of the lens. Figure 2. Bausch + Lomb lenses with High DefinitionTM Optics are designed to reduce the positive spherical aberration that is naturally occurring in the human eye and bring all of the light rays to the same focal point. 5 positive spherical aberration for positive power lenses, in proportion to their back vertex power. Aspheric Bausch + Lomb contact lenses with High DefinitionTM Optics are designed to reduce the inherent spherical aberration of the eye and reduce the spherical aberration induced by the contact lens on-eye. PureVision®2 HD For Astigmatism was designed with High Definition™ Optics to reduce spherical aberration in both the sphere and cylinder meridians, in quarter dioptre steps across the power range, for clear, crisp vision all day – especially in low light. PureVision®2 HD For Astigmatism is the only silicone hydrogel toric soft contact lens that reduces spherical aberration on both the spherical and cylinder meridians of the lens. By controlling spherical aberration in both the sphere and cylinder meridians, PureVision®2 HD For Astigmatism corrects for not only astigmatism and spherical aberration, but also reduces secondary astigmatism. It has been reported that approximately 37% to 45% of adults have 0.75D or more of astigmatism.1–3 When the eyelids close during a complete blink, there is a slight downward displacement of the lens and the lids typically meet at a point 1–2mm from the base of the lens. For a lens to effectively leverage these blink dynamics and maintain stable orientation, the toric stabilizing ballast should be designed with this in mind. By positioning the maximum ballast thickness low on the lens, the design can leverage the full motion of the upper lid while gaining support from the lower lid. Understanding eyelid movement during the blink and lens movement associated with eye and eyelid movement helped guide the development of the Auto-Align Design™ feature of PureVision®2 HD For Astigmatism. This feature allows the lens to achieve stability and orientation while providing consistently crisp, clear vision throughout the day. With optimized ballasting, a large lens diameter, and a large optic zone, PureVision®2 HD For Astigmatism minimizes lens mis-rotation to help ensure outstanding stability and vision throughout the day. ComfortMoist™ Technology ComfortMoistTM Technology has two key features: a thin lens design to provide a natural feel throughout the day and a moisture-rich packaging solution to provide excellent comfort upon insertion. PureVision®2 HD For Astigmatism continues to use a thin rounded edge design from PureVision®2 HD sphere, to enable a smooth, gentle transition of the lid from the lens to the conjunctival. The new lens design also features reduced lens markings providing a more continuously smooth surface. Auto-Align Design™ The stability of a toric lens is governed by several forces. Those forces can be divided into static (which include surface tension of the tears, gravity, conformity of the lens, and lid pressure at the top and/or bottom of the lens) and dynamic forces (which include upper and lower eyelid movement and eye movement). To better understand how lenses behave on-eye, several experiments were undertaken to understand one of the main drivers of instability; blinking dynamics. Blinking is essential to maintenance of the ocular surface and occurs at a speed that is almost imperceptible. The main muscle drivers of the blink are the horizontally aligned obicularis oculi and the more vertically aligned, levator palpaebra and Muler’s muscles. To capture the motion of these muscles, a high speed camera, capable of recording 300 frames per second was employed. The results showed that from initiation to completion of the natural blink, only 1 tenth of a second passes. In that time the upper lid has traveled approximately 7.5 mm down and 4.8 mm nasal. Interestingly, the lower lid has limited vertical motion, leaving the upper lid to be almost entirely responsible for rewetting the ocular surface through the blink mechanics. Understanding these dynamics helps design a lens which can work with the dynamic range of the eyelids. compared to PureVision® Toric (Figure 3). This helps create a more comfortable wearing experience, while maintaining the same large optic zone as PureVision® Toric. The large optic zone (8.0mm for a –3.00 –1.25x180 lens) also helps to reduce potential glare in low light conditions. Clinical Findings A B Figure 3. Thickness profiles of PureVision®2 HD For Astigmatism (a) and PureVision® Toric (b), where the red color indicates the thickest portions of the lens and the blue color represents the thinnest portions of the lens. Maintaining the stability of the optic in the eye while providing comfortable, all day wear, is a critical balance manufacturers face. Various innovative techniques have been employed to create a stable contact lens including truncation, dual slab-off, peri ballast and prism ballast, to name a few, and there are multiple designs currently commercialized which are founded on these basic geometries. The new PureVision®2 HD For Astigmatism lens is founded on solid understanding of contact lens stability techniques. Sophisticated lens design software and innovative manufacturing techniques have allowed Bausch + Lomb to develop a lens that uses the best aspects of prism and peri ballasting to create a hybrid ballasting system. The design provides excellent stability for consistent vision, with repeatable orientation even with the blink and eye movement. Manufacturing sophistication has also come of age and is carefully sculpting the contours of these lenses to blend with and work with the eye To improve centration, PureVision®2 HD For Astigmatism was designed with a larger diameter compared to PureVision® Toric. PureVision®2 HD For Astigmatism was designed with a 14.5mm outer diameter and a base curve of 8.9mm. The larger diameter of PureVision®2 HD For Astigmatism offers more area to spread out the ballast design to reduce the maximum thickness In a study evaluating the orientation characteristics and vision performance of PureVision® Toric, an established balafilcon A toric design, and PureVision®2 HD For Astigmatism, with advanced aspheric optics, 20 investigators enrolled subjects into a multi-site cross-over study.5 A total of 292 subjects completed the two week study. Lens orientation measures indicated there was a greater proportion of eyes with < 10° rotation from the 6 o’clock position for PureVision®2 HD For Astigmatism at both the dispensing visit and the two week follow up visit (p<0.05 for both). Over all visits, there was no significant differences between the lenses for movement, however, the PureVision®2 HD For Astigmatism had a greater proportion of “Excellent” ratings for centration (p<0.05). Visual acuity was excellent with the PureVision®2 HD For Astigmatism lens. Subject preference favored PureVision®2 HD For Astigmatism 2:1 over PureVision® Toric for vision characteristics, clear vision throughout the day, stable and consistent vision throughout the day, clear vision in low light, clear night vision, and do not see glare/halos with lenses (p<0.001). Conclusion Vision and optical expertise remain fundamental in the development of new contact lens designs. Patients are looking for contact lenses that offer stable and consistent vision throughout the day without compromising comfort. The lens design of PureVision®2 HD For Astigmatism combines High Definition™ Optics, Auto-Align Design™, and ComfortMoist™ Technology to provide the clear, crisp vision all day without compromising comfort that patients desire. 1.Attebo K, Ivers RQ, Mitchell P. Refractive errors in an older population: the Blue Mountains Eye Study. Ophthalmology. Jun 1999;106(6):1066‑1072. 2.Holden BA. The principles and practice of correcting astigmatism with soft contact lenses. Aust J. Optom. 1975;58:279‑299. 3.Katz J, Tielsch JM, Sommer A. Prevalence and risk factors for refractive errors in an adult inner city population. Invest Ophthalmol Vis Sci. Feb 1997;38(2):334‑340. 4. Consumer Toric Needs Study: US. Millward Brown.December 2010. 5.Reindel WT, Cairns G, Liranso T. Improving vision performance for astigmatic patients through lens design. Optom Vis Sci. 2011;88:E – abstract 115803. 6 MAGAZINE KEEPING SOFT LENSES CONTINUOUSLY MOIST FOR UP TO 20 HOURS SUSAN BURKE, PHD, PRINCIPAL SCIENTIST, BAUSCH & LOMB INCORPORATED Difficulty in wearing soft lenses comfortably throughout the day due to dryness symptoms is common,1, 2 and end of day discomfort is a challenge for many patients. Improving the wettability oflenses throughout the lens wearing experience is a good approach to combat dryness symptoms and improve lens wearing comfort. Surfactant Wetting Wetting agents (surfactants) have long been included in virtually all MPS lens care formulations to support the wettability of soft lenses. The wetting agent surfactants, such as the block co-polymers poloxamine, poloxamer and tetronics, combat dryness symptoms and enhance patient lenswearing experience by being attracted to the hydrophobic areas of the lens surface, helping to spread moisture across the entire surface area of the lens.3 Soft lens-wearing comfort that decreases throughout the day may be related to the loss of the wetting agent, with dryness symptoms becoming an issue by end-of-day. To partly address this issue, a longer retention time of surfactants on the lens surface may bring benefits. To that end, in vitro studies have demonstrated that Biotrue™ multi‑purpose solution helps keep lenses moist for up to 20 hours6 (Figure 1). Hydration Another component of wetting of the lens surface is the availability of hydration. Hyaluronan (HA) is a natural lubricant of the eye that attracts up to 1000 times its weight in water and helps draw moisture to the lens surface.5 Biotrue™, inspired by the biology Figure 1: Hours of continuous wetting agent release from silicone hydrogel lenses.4* Biotrue™ helps keep lenses continuously moist for up to 20 hours7 of your eyes, is the only multi-purpose solution in the U.S. that contains HA. The long-lasting availability of HA on hydrogel and silicone hydrogel lenses with Biotrue has been demonstrated by another in vitro study showing that HA is present for up to 20 hours6 (Figure 2). Patient Comfort Experiences Patients have noticed the difference made by Biotrue in making wearing contact lenses easier on their eyes. In a large, multi-centre clinical trial, 84% of patients indicated that Biotrue provided them with continuous comfort.7 In other surveys of Biotrue users: • 8 1% of Biotrue users agree that it makes wearing lenses so comfortable that they sometimes forget they are wearing contact lenses8, • 9 3% of patients who self-selected as having soft lens wear-related dryness symptoms rated overall comfort with Biotrue as good to excellent9; 83% agreed Biotrue makes every day easier on the eyes9, • 9 0% of over 380 users of Biotrue rated overall comfort good to excellent.9 The conditioning system of Biotrue™ provides the benefit of both the surfactant wetting ability and the outstanding water attracting (humectant) properties of HA with silicone hydrogel and hydrogel lenses. You can be confident that your soft lens patients will experience exceptional comfort when using bioinspired Biotrue, since the unique combination of continuous wetting agent release and the long-term presence of HA helps to keep lenses continuously moist for up to 20 hours.4,6 Figure 2: HA remains on lenses for up to 20 hours.6 100 RevitaLens OcuTec† 4 OPTI-FREE RepleniSH 4 OPTI-FREE PureMoist*** % hyaluronan remaining on lenses 4 Clear Care** 6 Biotrue 20 0 5 10 15 Silicone hydrogel lenses Hydrogel lenses 80 60 40 20 0 Initial 20 5 hours 10 hours 15 hours 20 hours Time (Hours) * ** *** † Balafilcon A, senofilcon A, and lotrafilcon B. Outside of the USA, Clear Care is marketed as AOSept Plus. Outside of the USA, OPTI-FREE PureMoist is marketed as OPTI-FREE EverMoist. Outside of the USA, RevitaLens OcuTect is marketed as Complete RevitaLans. References 1. Needs, Symptoms, Incidence, Global Eye Health Trends (NSIGHT) Study. Market Probe Europe. December 2009. 2. The 2009 Study of the Consumer Contact Lens Market. Multi-Sponsor Surveys. September 2009. 3. Surfactants and interfacial phenomena, Rosen, MJ John Wiley & Sons, Inc.: 1978. 4. Scheuer CA, Doly K, Liranso T, Burke SE Wetting agent retention and release from hydrogel and silicone hydrogel contact lenses. Invest Ophthalmol Vis Sci 2011 ;52: ARVO E-Abstract 6487. 5. Rah MJ. A review of hyaluronan and its ophthalmic applications. Optometry. 2011 Jan;82(1):3843. 6. Scheuer CA, Fridman KM, Bamiak VL, Burke SE, Venkatesh S Retention of condioning agent hyaluronan on hydrogel contact lenses. Contact Lens & Anterior Eye 2010, 33(1S), 2–6. 7. Results from a clinical trial in which a total of 291 subjects were enrolled across 15 investigative sites, wearing a range of marketed soft contact lenses and using various soft contact lens care products. Subjects were dispensed Biotrue and participated in CAWI (Computer Aided Web Interviewing) between day 7 and day 11 of the clinical trial. Subject responses were measured using a six-point Likert Scale in which 1 = strongly disagree and 6 = strongly agree. Results represent reported percentage agreement. 8. Consumer Preference Study (Dec 2010) conducted by Bruno and Ridgeway among 201 consumers who have tried Biotrue. 9. Results from a survey questionnaire in which 389 users (and 20 eye care practitioners) of various multi-purpose contact lens solutions, including OPTI-FREE, Clear Care, and ReNu products, used Biotrue multi-purpose solution for two weeks and reported their experiences. Among 237 patients self identified as having dry eye symptoms. Among the group were 237 patients self identified as having dry eye symptoms. Subject responses were measured using Likert Scales. 7 FOCUS ON GLAUCOMA BY SASKIA AGUADO Glaucoma is a group of diseases of varied aetiology that damage the optic nerve, and can result in loss of vision. Often asymptomatic, glaucoma can remain undiagnosed with slowly progressive loss of peripheral vision. The target cells in glaucoma are the retinal ganglion cells and their axons which constitute the optic nerve. According to the World Health Organization (WHO), glaucoma is the leading cause of preventable irreversible blindness worldwide. Roughly 70 million of the world’s population are affected by glaucoma, and epidemiological studies suggest that up to 50 percent of cases may go undiagnosed. Population studies indicate that around 10 per cent of patients diagnosed with glaucoma will go blind bilaterally and 20 percent will go blind unilaterally after 20 years. There are a variety of glaucomas, most of which may remain asymptomatic until the late stages. The most common form of glaucoma is primary open angle glaucoma. Early detection is the key to limiting damage from this insidious, painless cause of vision loss. While there are a number of risk factors for vision loss from glaucoma, the primary one is elevated eye pressure also known as intraocular pressure (IOP). In healthy adults IOP ranges from about 10 to 20 mm Hg (16 mm Hg ± 2.5). Elevated IOP occurs when aqueous humour (clear fluid inside the eye) that is necessary for intraocular nutrition, fails to drain properly through the anterior chamber 8 MAGAZINE use for the longest time and appears to be better tolerated with a lower rate of adverse effects when compared with the other hypotensive drugs as well as other agents in the same class such as bimatoprost. angle (where de cornea and iris meet) leaving the eye. When this situation is sustained, it may cause a cascade of events that leads to damage to the optic nerve. There are cases, however, where elevated IOP is tolerated and no damage occurs. This condition is referred to as ocular hypertension. With Normal or Low Tension Glaucoma, the converse may be true and a “normal” IOP may result in damage to the optic nerve. Latanoprost Efficacy The average IOP drop from baseline in patients on latanoprost 0.005% therapy ranges from 28–31% (meta-analysis of randomized clinical trials) at trough and peak moments. Other risk factors for glaucoma, apart from elevated IOP, include age, race, genetic factors, chronic corticosteroid use, and eye conditions such as ocular trauma or inflammation. African Americans have been shown to be at risk at an earlier age than Caucasians, for example. Individuals with a family history are at increased risk, especially when they are over 60 years of age or have a sibling diagnosed with glaucoma. Other factors that may represent risks are medical or physical conditions, including diabetes mellitus or vascular conditions such as migraine or vasospastic dysregulation. Maximal IOP reduction is observed for 12 hours after drug administration, and the IOP remains below the pre-treatment level for at least 24 hours. Side-effects Prostaglandin analogs have a few common side effects, including stinging and burning when put in the eye, darkening of the eye due to an increase of pigmentation in the iris, and lengthening and curling of the eyelashes. The drug generally produces no adverse pulmonary or cardiovascular sideeffects and has not been shown to affect ocular hemodynamics. Currently, all treatments for glaucoma are aimed at reducing IOP. The results of several large studies indicate that reducing IOP in patients with ocular hypertension and glaucoma significantly reduced the risk of glaucomatous changes to the optic nerve or changes in the visual field. The goal in glaucoma management is to achieve and maintain an intraocular pressure within the target range considered to be “safe” for each patient individually. The management of ocular hypertension and glaucoma involves frequent monitoring and adjusting therapy over the patient’s lifetime to ensure the IOP remains at acceptable levels in an effort to limit optic nerve damage. There is no cure for glaucoma but it can be managed in two ways: medication and surgery. Both treatments manage the disease by lowering the intraocular pressure. Medical therapy is the most common method used for the reduction of the IOP associated with ocular hypertension and open-angle glaucoma. Several classes of drugs (prostaglandin analogs, beta-adrenergic antagonists, carbonic anhydrase inhibitors, adrenergic agonists and cholinergic agonists) may be used to reduce the IOP. Medications are often compared based upon several features: efficacy, safety, tolerability, cost and patient acceptance. In an ideal situation, the clinician would like to select an agent that shows excellent efficacy and persistency, as well as being safe and well-tolerated. Patient Compliance and Persistence Credit: José María Martínez de la Casa prostaglandin analogues were all evaluated with limited success. In general, side-effects were significant and efficacy was low. A breakthrough came with the development of the prostaglandin analogue PhXA34. This compound was produced by modification of the PGF-2 alpha molecule. A phenyl group was added at position 17 and the double bond at C 13-14 reduced. These changes affected potency as well as reducing side-effects. This molecule went on to become latanoprost (Xalatan). Since the release of Xalatan, three additional analogues have been approved: bimatoprost, travoprost and tafluprost. PG analogues are effective in IOP reduction and have a convenient once-daily dosing schedule. Among the PG analogues latanoprost has been in Although the preferred practice pattern of the American Academy of Ophthalmology lists medical therapy, laser trabeculoplasty, and surgical treatment as reasonable options for the initial treatment of glaucoma, most patients initially receive topical ocular hypotensive agents. If topical treatment lowers IOP adequately, the patient remains on therapy indefinitely with regular follow up to monitor the health of the optic nerve. Although recent studies clearly have documented that the lowering of IOP decreases the risk of visual field loss and slows progression from ocular hypertension to glaucoma, lack of compliance with topical hypotensives is major challenge in glaucoma management. The ease of use accompanying the once daily dosing regimen for prostaglandins, lack of systemic side-effects and high efficacy are all factors that help improve compliance. Rahman et al. reported the persistence of glaucoma medical therapy in a database of 1006 patients with ocular hypertension, normal tension glaucoma and primary open-angle glaucoma attending the Glaucoma Clinic at Glasgow Royal Infirmary, Glasgow, UK, and determined that the introduction of the first prostaglandin analogue, latanoprost, dramatically improved treatment persistence for glaucoma patients. PROSTAGLANDIN ANALOGS Prostaglandin analogs, such as latanoprost 0.005%, are the most effective drugs at lowering IOP and can be considered as first line medical therapy unless other considerations such as cost, side effects or intolerance preclude this. The first clinical study of the use of prostaglandins to reduce IOP was performed by Camras using the compound prostaglandin PGF-2 alpha. It produced a limited reduction in IOP with significant side-effects that included conjunctival hyperemia, foreign body sensation and headache. Other • Q uigley HA. Number of people with glaucoma worldwide. BrJ Ophthalmol 1996; 80: 389–393) • van der Valk R, et al. Intraocular pressure – lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials. Ophthalmology. 2005;112:1177–1185. • Camras CB, Bito LZ. Reduction of intraocular pressure in normal and glaucomatous primate (Aotus trivirgatus) eyes by topically applied prostaglandin F2 alpha.Curr Eye Res. 1981;1:205–209 • Johan Wilhelm Stjernschantz. From PGF2a-Isopropyl Ester to Latanoprost: A Review of the Development of Xalatan. The Proctor Lecture. IOVS, May 2001, Vol. 42, No. 6 • The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000; 130: 429–40 • Denis P, Baudouin C, Bron A, et al. First-line latanoprost therapy in ocular hypertension or open-angle glaucoma patients: a 3-month efficacy analysis stratified by initial intraocular pressure. BMC Ophthalmol 2010; 10: 4. • Nordstrom BL, et al. Persistence and Adherence With Topical Glaucoma Therapy. Am J Ophthalmol 2005;140:598–606. • Rahman MQ, Abeysinghe SS, Kelly S, et al. Persistence of glaucoma medical therapy in the Glasgow Glaucoma Database. Br J Ophthalmol 2011 (epub ahead of print). • Reardon G, Schwartz GF, Mozaffari E. Patient persistency with pharmacotherapy in the management of glaucoma. Eur J Ophthalmol 2003; 13(Suppl 4): S44–52. 22 24-hour coverage for chronic dry eye n For chronic tear dysfunction n Long-lasting relief with no blurring effect1 Artelac® Rebalance and Artelac® Nighttime Gel Specifically formulated to keep eyes hydrated and comfortable — day and night Reference: 1. Data on file (Vitadrop [K5] [ophthalmic solution] scientific profile), Bausch & Lomb Incorporated Artelac Nighttime Gel ® n Unique three-layer action provides hydration and seals in moisture n Mixes quickly with natural tears See better. Live better. Learn more at: www.artelac.co.uk Contact your local wholesaler to order Artelac products today! UK/ART/12/002 February 2012 225006_Artelac_Ad.indd 1 24/04/2012 10:15 10 MAGAZINE ENVISTA JUST SAY ‘NO’ TO GLISTENINGS 11 As the first hydrophobic acrylic IOL from Bausch + Lomb, the enVista lens represents a significant step forward in IOL technology. Setting the enVista apart from currently available IOLs is the unique combination of aspheric, aberration-free Advanced Optics technology, designed to deliver enhanced contrast sensitivity and better quality of vision, with a clinically proven glistening-free material. In addition, the enVista lens design is intended to minimise posterior capsular opacification (PCO), a common long-term problem with IOLs that can cause a patient’s vision to become clouded postsurgery. These features, combined into one platform with the enVista lens, provide surgeons with the opportunity to optimise short-term and long-term outcomes for their patients.1-3 LENS MATERIAL Glistening-Free Glistenings are fluid-filled microvacuoles that can form within an IOL, and are common in most hydrophobic acrylic IOLs, especially AcrySof4. They cause a portion of the light coming into the eye to be scattered in all directions, and have been shown to have a negative impact on visual acuity.4 In a recent survey by IPSOS Health, glistening-free was ranked as one of the top features that differentiates enVista from other IOLs by surgeons currently using other hydrophobic IOLs.5 enVista is made from a unique glistening-free material. Pre-hydration to equilibrium in 0.9% saline, eliminates the propensity for water absorption, so it will neither gain nor lose aqueous when implanted in the capsular bag.6-8 The lens is then packaged in a physiological saline solution to maintain its hydration and to inhibit formation of glistenings.6–8 Not only are glistenings prevented, but the material’s stability is believed to be enhanced by hydrating the lens to equilibrium.6–8 “We are proud to innovate the hydrophobic lens category with an IOL that provides a high quality of vision and addresses the common issue of glistenings. It was important that we deliver an advanced hydrophobic lens that surgeons and patients can count on now and over the long-term, and data shows that we have achieved that with the enVista lens.”Spokesperson, Bausch + Lomb Surgical Hydrophobic The enVista polymer is formed from a combination of hydroxyethyl methacrylate (HEMA) and a polyethylene glycol phenylether acrylate styrene copolymer. The cross linking of these two polymers with a 3rd ethylene glycol dimethacrylate form the lens material for enVista, which is not only biocompatible but also has a high refractive index (1.54). The enVista material is hydrophobic in nature, and its contact angle is greater than that of the AcrySof material, meaning its surface is even more hydrophobic than AcrySof 6. Highly Durable The enVista material offers a more durable optical surface for resistance to abrasion and wear during insertion which helps keep enVista free of permanent surface marks. The enVista material also has minimised silicone oil adhesion of less than 5% — a major advantage for vitreoretinal surgeons. Silicone oil adhesion can be as high as 35% in other commercially available hydrophobic IOLs.9 LENS DESIGN Designed to Minimise PCO Low incidence of PCO is a critical requirement for IOL selection and one of the main reasons for choosing an IOL.5 enVista is designed to minimise PCO by reducing the radius of curvature between the lens edge and the optical surface of the lens, providing for a very sharp square edge. It is important to note that not all lenses are produced in this way and this is one of the most important factors in preventing PCO.10 Differences in the posterior optic edge profile may explain why some IOLs have higher PCO rates and why some IOLs appear to perform better. enVista has a radius of curvature of 8µm giving it a high quality square edge, this is comparable to other hydrophobic acrylic IOLs with good PCO performance. 10 The enVista lens has a full 360° sharp square posterior edge, step-vaulted haptics which are designed to vault the optic posteriorly, to ensure direct contact with the capsular bag and prevent LEC migration. The fenestration holes at the base of the haptics are designed to evenly transmit forces to the optic, promoting even pressure on the 360° square barrier edge. “The enVista hydrophobic lens has been clinically demonstrated to be free of glistenings, a key attribute to help improve visual acuity,” said Professor David Spalton, FRCS, FRCP, FRCOphth, St. Thomas Hospital, London. “Its 360° square-edge barrier also provides an effecti e optic-haptic junction, which is associated with a low incidence of PCO.” Advanced Optics Standard spherical intraocular lenses have inherent positive spherical aberration, in which the refracting power of the lens increases from center to edge. This results in degradation in retinal image quality, causing a loss in contrast sensitivity. Pseudophakic eyes with standard IOLs have more positive spherical aberration than phakic eyes of the same age. In the younger population, the negative spherical aberration of the crystalline lens partially compensates for the positive spherical aberration of the cornea. However, with age, this partial compensation is gradually lost, leading to an increase in positive spherical aberration11–14. Implanting a spherical IOL adds to the already positive spherical aberration of the cornea and can impair the visual outcome with a loss of contrast sensitivity in low light conditions. Aspheric lenses with negative spherical aberration are designed to compensate for the average amount of positive spherical aberration in the cornea. Intuitively this strategy makes sense, but HYDROPHOBICITY In chemistry, hydrophobicity (from the combining form of water in Attic Greek hydro and for fear phobos) is the physical property of a molecule (known as a hydrophobe) that is repelled from a mass of water. Hydrophobic molecules tend to be non-polar and thus prefer other neutral molecules and non-polar solvents. Hydrophobic molecules in water often cluster together, forming micelles. Water on hydrophobic surfaces will exhibit a high contact angle. 12 MAGAZINE can cause problems as every patient has a unique optical system. Aspheric lenses with negative spherical aberration can potentially cause visual impairment, if ocular misalignment occurs, leading to higher order aberrations, such as coma.15 These lenses have also been designed for an average of corneal profiles, and may not be appropriate for patients, whose corneas deviate from the average cornea. Bausch + Lomb’s Advanced Optics technology, which exists on the entire lens portfolio, has aspheric anterior and posterior surfaces that do not induce positive or negative spherical aberration. The lenses are neutral to the cornea, making them suitable for all patients regardless of corneal shape. Based on published studies, this leaves the eye with its natural degree of corneal positive spherical aberration, with improved contrast sensitivity, but still providing patients with a good depth of field.16 “This lens has other optical advantages. Its optic is aberration-free which means it does not increase the optical aberrations of the cornea which is especially useful in eyes already operated for refractive corneal surgery.” Roberto Bellucci, Director Ophthalmic Unit, Hospital of Verona, Italy Predictable Refractive Outcomes A lens is said to be decentred if it is not aligned with the visual axis. Independent studies have shown that 33% of all IOLs decentre by approximately 0.5mm from the pupil. True decentration of an IOL is probably even greater than reported, as the visual axis doesn’t pass through the centre of the pupil.17 enVista has a uniform power from the centreto-edge, which means that it is not impacted by decentration. Lenses which do not have a uniform power may provide poorer outcomes if they are subject to decentration or tilt. LENS DELIVERY Single use inserter There has been a clear trend in recent years towards the increasing adoption of single-use instruments. 72% of surgeons now use single use instruments, which is an increase from 55% in 2008.18 This lens has other optical advantages. Its optic is aberration-free which means it does not increase the optical aberrations of the cornea which is especially useful in eyes already operated for refractive corneal surgery. ROBERTO BELLUCCI “The advantages of having single-use inserter are probably threefold. Firstly, if you have an injector of this type it means that you don’t have to worry about the possibility of infection related to a multi-use injector. Secondly, the injector will always be the same and therefore injection will be completely repeatable, and thirdly because you don’t have to sterilise a multi-use injector, there could be significant ost savings.” Mr Richard Packard, Prince Charles Eye Unit, King Edward VII Hospital Windsor. 2.2mm Implantation 2.2mm has become the industry standard for hydrophobic IOL incision size with many cataract surgeons working or wanting to work at 2.2mm The flexibility of the enVista material enables you to insert it easily through a 2.2mm incision with more controlled unfolding than current hydrophobic acrylic IOLs, facilitating precise lens placement and removal of the viscoelastic at the end of the procedure. Amvisc Plus by Bausch + Lomb is a viscoelastic that performs effectively throughout the entire procedure. It has the perfect balance in one syringe with unique lasting chamber retention and efficient removal. Amvisc Plus is efficient in small incision surgery due to its dynamic viscosity and excellent transparency. Bausch + Lomb also offers a wide range of single use instruments for MICS surgery. Capsule Guard I/A has a unique design for advanced capsule cleaning. These single use, silicone-tipped, irrigation/aspiration hand pieces protect the capsule during the entire procedure. Smooth ports designed to reduce the risk of capsular rupture and the adhesive properties of the silicone tip allow for effective and efficient cortical removal. CONCLUSION The enVista hydrophobic acrylic intraocular lens is a significant addition to the surgeon’s current armamentarium. The enVista lens features a highly durable, clinically proven glistening-free material with a lens design developed to minimise posterior capsular opacification. The unique material combined with the aspheric, aberrationfree Advanced Optics technology, provides surgeons with a new lens platform for optimal patient outcomes. References 1.Pepose JS, Qazi MA, Edwards KH, Sanderson JP, Sarver EJ. Comparison of contrast sensitivity, depth of field and ocular wavefront aberrations in eyes with an IOL with zero versus positive spherical aberration. Graefes Arch Clin Exp Ophthalmol. 2009;247(7):965–973. 2.Johansson B, Sundelin S, Wikberg-Matsson A, Unsbo P, Behndig A. Visual and optical performance of the Akreos® Adapt Advanced Optics and Tecnis Z9000 intraocular lenses: Swedish multicenter study. J Cataract Refract Surg. 2007;33(9): 1565–1572. 3.Nishi O, Nishi K, Osakabe Y. Effect of intraocular lenses on preventing posterior capsule opacification: design versus material. J Cataract Refract Surg. 2004;30(10): 2170–2176 4.Christiansen G, et al. Glistenings in the AcrySof intraocular lens: pilot study. J Cataract Refract Surg. 2001;27:728–33 5.Bausch + Lomb commissioned IPSOS Health to research 182 randomly selected surgeons – all hydrophobic users. Research carried out October – December 2010 in Spain (n=58), Germany (n=66) & UK (n=58). 27 surgeons participated in focus groups or depth interviews. 155 surgeons completed a 30 minuite online survey that was designed and managed by IPSOS health. 6.Mentak P, Elachchabi A, Goldberg E. Hydrophobic character and aqueous wetability of hydrophobic IOLs. Paper presented at the XXVI Congress of the European Society of Cataract and Refractive Surgery; September 13-17, 2008; Berlin, Germany. 7.Mentak P, Elachchabi A, Martin P, Goldberg E, Mentak A. Nanoindentation studies on hydrophobic acrylic IOLs to evaluate surface mechanical properties. Paper presented at the XXV Congress of the European Society of Cataract and Refractive Surgery; September 8-9, 2007; Stockholm, Sweden. 8.Data on File, Bausch and Lomb. Final Clinical Study Report: A prospective multicenter clinical study to evaluate the safety and effectiveness of a Bausch + Lomb one-piece hydrophobic intraocular lens in subjects undergoing cataract extraction. 9.Mentak, K – A new family of high refractive index polymers for IOL and refractive implant applications. Data on file Bausch + Lomb 10.Spalton D, Dhital A, Boyce J. n Evaluation of a new hydrophobic acrylic IOL. Poster presented at the XXVIII Congress of the European Society of Cataract and Refractive Surgery, 2011 Vienna 11.Behndig A, Lundström L, Unsbo P. Aspheric Intraocular Lenses: Mastering the techniques of advanced phaco surgery, Eds. Garg, A; Fine, H; Chang, D, et al., Jaypee Brothers Medical Publishers, Ltd. 2008, ISBN 97881-8448-203-4. 12.Alió JL, Schimchak P, Negri HP, MontesMico, R. Crystalline lens dysfunction through aging. Ophthalmology 2005; 112: 2022-9. 13.Artal P, Benito A, Tabernero J. The human eye is an example of robust optical design. J Vis 2006; 6: 1–7. 14.Guirao A, Gonzalez C, Redondo M, Geraghty E, Norrby S, Artal P. Average oprical performance of the human eye as a function of age in normal phakic population. Invest Ophthalmol Vis Sci 1999; 40: 203–13. 15.Altmann GE, Nichamin LD, Lane SS, Pepose JS. Optical performance of 3 intraocular lens designs in the presence of decentration. J Cataract Refract Surg 2005; 31:574–585 16.Nio Y-K, Jansonius NM, Geraghty E, et al. Effect of intraocular lens implantation on visual acuity, contrast sensitivity, and depth of field. J Cataract Refract Surg. 203;29(11):2073–81 17.Koch D, Wang L. Effect of decentration of wavefront-guided IOLs on the higher order aberrations of the eye, presented at the XXII Congress of the European Congress of Cataract and Refractive Surgeons, September 2004 18.Bausch + Lomb commissioned Milward Brown Health to research 500 cataract surgeons across 5 markets – Spain, UK, France, Germany and Italy. Research carried out in March – April 2011. Surgeons completed a 25 minute online survey – managed and analysed by Milward Brown. 13 BAUSCH + LOMB AND TECHNOLAS™ PERFECT VISION ANNOUNCE CE MARK APPROVAL FOR ™ VICTUS FEMTOSECOND LASER PLATFORM First Single-Platform Femtosecond Laser Now Commercially Available in European Union In December 2011, Bausch + Lomb, the global leader in eye health, and Technolas™ Perfect Vision GmbH (TPV), a leading ophthalmology laser company, announced the commercial availability of the VICTUS™ Femtosecond Laser Platform in the European Union (EU). After securing CE mark approval, the VICTUS platform is approved for LASIK flap, astigmatic keratotomy, INTRACOR, capsulotomy and lens fragmentation. “This is a significant miles one for Bausch + Lomb that will deliver breakthrough capabilities to our eye care professionals and the patients they serve,” said Brent Saunders, Chief Executive Officer of Bausch + Lomb. The VICTUS platform is uniquely designed to support cataract, refractive and therapeutic procedures all on a single platform. The femtosecond laser technology enables greater precision in both cataract and refractive procedures compared to manual techniques, giving ophthalmologists more control and potentially enhancing the patient experience. “This CE mark approval represents a major step for femtosecond laser technology by elevating the role that laser technology can play in refractive and cataract procedures,” said a Spokesperson from Bausch + Lomb. “I am excited that we will begin shipping product by the end of the year.” As previously announced, Bausch + Lomb and TPV will promote the VICTUS platform globally, leveraging their combined cataract and refractive expertise and commercial capabilities. The two organizations are also working with regulatory authorities around the world to secure additional marketing approvals for the platform. “Our focus has been to empower ophthalmic surgeons with the latest advances in laser technology in order to potentially provide patients with better outcomes and quality of life,” said Kristian Hohla, PhD, chief executive officer of Technolas Perfect Vision. “We are very pleased that, together with Bausch + Lomb, we have demonstrated the viability of the VICTUS platform for enhanced cataract surgery.” The VICTUS platform as well as early clinical data was presented at the 2011 European Society of Cataract and Refractive Surgeons (ESCRS) Congress in Vienna, the American Academy of Ophthalmology (AAO) Annual Meeting in Orlando and at the Asia-Pacific Association of Cataract and Refractive Surgeons (APACRS) in Seoul earlier this year. Plans to submit the data for publication in peer-reviewed journals are underway. About Femtosecond Lasers Femtosecond lasers emit optical pulses of extremely short duration in the domain of femtoseconds, as short as one-quadrillionth of a second. With these ultra-short pulses, tissue can be cut more precisely and with practically no heat development. “This is a significant milestone for Bausch + Lomb that will deliver breakthrough capabilities to our eye care professionals and the patients they serve” 14 MAGAZINE THE SCIENCE OF PRESERVATIVEASSOCIATED TRANSIENT HYPERFLUORESCENCE (PATH) To discuss the science of fluorescein, corneal staining, and preservative-associated transient hyperfluorescence (PATH), some of the preeminent research experts in the study of fluorescence spectroscopy and corneal staining from around the world (Drs. Paul Karpecki, Frank Bright, Nathan Efron, and Philip Morgan) gathered to share their new research and personal opinions on these topics. The following is a summary of the key messages from this meeting. 15 Figure 2 (below and right): Fluorescein (negative charge) and MPS preservatives (positive charge) are attracted to one another. The level of attraction depends on the MSP preservative. Figure 1 (left): Adsorbed MPS preservative are released by the lens into the tear film upon application onto the eye. The release rate is dependent on the preservative and lens material combination. Released preservatives are dissipated by normal tear flow. FLUORESCEIN First synthesized in 1871, fluorescein is a molecule not found in nature. Many factors can impact the fluorescent intensity and diagnostic utility of fluorescein. First, the charge of fluorescein is directly related to the pH of the environment and its fluorescence is highly pH dependent (fluorescence intensity increases as pH rises until a pH of 8 is reached). Also, at high concentrations (>0.001%) it is self-quenching (energy emitted by fluorescein molecules is absorbed by nearby fluorescein molecules rather than being emitted as light), so diminished fluorescence occurs with increasing concentration above this threshold. Preservative Uptake and Release All multi-purpose solutions (MPS) contain one or more preservative agents such as polyhexamethylene biguanide (PHMB), polyquaternium-1 (PQ-1), myristamidopropyl dimethylamine (MAPD; also known as Aldox), and alexidine. The total amount of preservative contained in MPS formulations is very small, ranging from 1 to 15 parts per million. Although MPS preservatives are taken up by soft contact lenses while soaking, the amount adsorbed may be too low to quantify. A number of factors can influence the uptake of preservative into a soft contact lens including: the soft contact lens material, type(s) of preservative contained in the MPS, and overall MPS formulation including components such as buffers, wetting agents, or other molecules that carry an electrostatic charge. The amount and rate of uptake for each preservative can vary between hydrogel and silicone hydrogel lenses, as well as among the different silicone hydrogel lens materials. When placed on the eye, the soft contact lens begins to release the adsorbed preservative into the tear film. The rate at which this occurs is dependent on the preservative and type of contact lens material. The preservative is ultimately dissipated through the normal turnover of tear film (Figure 1). Fluorescein and Preservative Interactions Corneal Staining vs. MPS-Associated Hyperfluorescence The MPS preservatives released from soft contact lenses interact with fluorescein dye when it is applied to the eye. Fluorescein is negatively charged and MPS preservatives are positively charged, attracting them to one another (Figure 2). The level of attraction depends on the MPS preservative. Dr. Bright’s studies have found that the attraction between fluorescein and the preservative polyhexamethylene biguanide (PHMB) is up to fifty times greater than the attraction between fluorescein and the preservative polyquaternium-1 (PQ-1). The substantially higher affinity of fluorescein for PHMB may account for the higher levels of hyperfluorescence at a 2-hour time point with PHMB-based solutions versus MPS with other preservatives at all time points. Although a number of eye care professionals (ECPs) have labeled this phenomenon as “corneal staining”, many characteristics of PATH point to it being a distinct entity from corneal staining. One such difference is the etiology of PATH versus corneal staining. While the etiology of PATH is due to the benign preservative interaction with fluorescein, pathological corneal staining is due to damage to the epithelium. Additionally, PATH is generally asymptomatic, has a superficial punctate pattern, and is transient, lasting only several hours following lens insertion, and is not associated with future complications (Figure 3). These characteristics, especially together, are not observed in cases of corneal staining during pathological situations. Figure 3: The binding of PHMB and fluorescein results in a benign, transient hyperfluorescence. The most intense hyperfluorescence it produced during the time of peak PHMB release. PHMB Concentration (μg/μL) Understanding Fluorescein PRESERVATIVE 0.014 0.012 0.010 0.008 0.006 0.004 0.002 0 0 2 4 6 8 10 12 14 Time (hours) CONCLUSION While a significant effort has been made to connect PATH with adverse outcomes over the past decade, to date, no negative sequelae have been shown to be associated with PATH. A large body of literature shows the hyperfluorescence at the time of peak PATH is not pathological corneal staining, a measure of biocompatibility, a cause of infiltrative keratitis or infection, an indicator of cellular damage, or associated with future adverse events. It is essential that clinicians understand what they are observing in patients and why. It is only then the best clinical decisions for patient’s health and satisfaction can be made. 16 BAUSCH + LOMB INSTRUMENTS MADE IN GERMANY BY HORST VOLLMERHAUSEN, PLANT MANAGER MAGAZINE Surgical handheld instruments are key tools for every surgeon when performing surgery. The functionality and quality of an instrument are key elements for achieving the best outcomes in eye surgery. How an instrument fits into a surgeon’s hand and how easily it can be handled are aspects that have direct impact on performance. Cleaning and re‑sterilisation are important features for nurses and administration people. Bausch + Lomb instruments crafted in Heidelberg Manufacturing are designed and produced to optimally meet customers’ expectations. Close to 100 people in Heidelberg Manufacturing have longstanding experience in developing and producing high quality stainless steel reusable instruments and single-use surgical instruments. Heidelberg experience dates back to as early as 1947 when Leonhard Klein started his own company in Heidelberg. Leonhard Klein’s business was continued by Storz Ophthalmics which, today, is the basis and an important part of Bausch + Lomb’s Surgical business. Specific designs for reusable instruments and their size allow them to be crafted by experts only. Our experts – called “Chirurgiemechaniker” – are going through a thourough and very well established training programme of approx. 3 ½ years before they have obtained the necessary skills and qualification to become “Chirurgiemechaniker”. It takes even longer to become a master craftsman in the field of “Chirurgiemechanik”. Such intense education and training combined with longstanding experience are the keys to achieving an excellent level of quality and functionality in instruments which are very well accepted by surgeons. 17 During the past years, upcoming surgical trends – such as smaller incisions (MICS < 2mm incision), increased hygiene guidelines for surgical rooms, expectations for simplifying surgical procedures – have led to the development and production of single-use instruments. Bausch + Lomb Heidelberg subsequently expanded their product portfolio, and now offer a wide range of single-use instruments for cataract and vitreoretinal surgery, which are “Made in Germany”. The overall process from design and development – performed in cooperation with key surgeons and highly experienced craftsmen – to production in our Heidelberg plant are the guarantee for offering and supplying high-end products to our customers. A breakthrough design for irrigation and aspiration handpieces was the development of the Capsule Guard® I/A line with a soft tip made out of silicone. No metal touches the membrane or comes into contact with ocular tissue. This handpiece design offers excellent handling properties for use inside the eye and a fully sealed wound. A manufacturing tour for nurses and surgeons is part of our wetlab trainings which take place all year round. Unique design for advanced capsule cleaning These single use silicone I/A handpieces protect the capsule during the entire procedure. Smooth ports are designed to reduce the risk of capsule rupture and the adhesive properties of the silicone tip allow for effective and efficient cortical removal. Available for 1.8mm MICS and standard incisions. SINGLE USE CATALOGUE PER PROCEDURE KITS INSTRUMENTATION CORNEAL TRANSPLANT CATARACT PROCEDURES VITREORETINAL PROCE DURES INTRAOCULAR LENSE S VISCOELASTICS ACCESSORIES Safety. Consistency. Convenience. www.storzeye.eu © Bausch & Lomb Incorporated. ™/® denote trademark of Bausch & Lomb Incorporated. www.storzeye.eu 18 MAGAZINE A NEW, MODERN TOOL FOR MANAGING POST-CATARACT INFLAMMATION BY MOHAMMAD AL-ADDAI Recent advances in cataract surgery techniques, smaller incisions and foldable intraocular lens design have led to improved outcomes and decreased the resulting trauma. Nevertheless, ocular inflammation may develop and can cause patient discomfort, delay postoperative recovery, and may lead to additional complications. [Wittpenn 2008, Silverstein 2011] It is believed that the stress of ocular surgery initiates a cascade of inflammatory events that can lead to a breakdown of the blood-retinal barrier and the accumulation of intra-retinal fluid. Signs and symptoms of macular thickening typically develop four to six weeks postoperatively, resulting in temporary or, in some cases, permanent loss of best-corrected visual acuity (BCVA).[Wittpenn 2008] Overview of post-operative ocular inflammation Inflammation is the manifestation of cellular and vascular response of the host tissue to injury. Injury to the tissue may be inflicted by physical or chemical agents, pathogens, ischemia, and excessive (hypersensitivity) or inappropriate (autoimmunity) operation of immune mechanisms. Inflammation facilitates the immune response and the subsequent removal of antigenic material and damaged tissue.[Ahuja 2008] Surgical trauma triggers the arachidonic acid cascade, which in turn, generates prostaglandins (PG) by activation of Cyclo-oxygenase (COX) enzymes. Clinical symptoms of PG production include hyperemia, miosis, impaired vision, pain, and diminished visual acuity secondary to cystoid macular edema (CME).[Cho 2009] Two main isoforms of COX, COX-1 and COX2, have been identified. COX-1, a constitutive enzyme, synthesizes PGs that regulate physiologic processes. COX-2 is expressed in response to a noxious stimulus, the induction of which leads to the production of PGs that cause inflammation and 19 Clinical Data NH2 OH Br O Figure 1 Chemical structure of Bromfenac [Cho 2009] pain. It has been demonstrated in rats that COX-2 is the primary mediator for ocular inflammation. Therefore, inhibition of COX-2 is thought to be the most important therapeutic mechanism of ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). [Cho 2009, Kim 2010] Corticosteroids interfere with the activity of phospholipase A2, and in contrast, NSAIDs non‑specifically and irreversibly inhibit the synthesis of PGs by interfering with the activity of COX-1 and COX-2. [Cho 2009] Corticosteroids are frequently used in the management of ocular inflammation, but their antiinflammatory benefits have to be considered in the context of the risk for serious adverse effects like: elevation of intraocular pressure, progression of cataracts, increased risk of infection and worsening of stromal melting. [Ahuja 2008, Cho 2009] Ophthalmic NSAIDs have become a cornerstone for the management of ocular pain and inflammation. Their established safety record, and well characterized anti-inflammatory and analgesic properties have also made NSAIDs an important tool to optimize surgical outcomes.[Donnenfeld 2006] Introducing Yellox (Bromfenac sodium sesquihydrate): A new, modern tool for managing post-cataract inflammation Bromfenac ophthalmic solution 0.1% was first approved in May 2000 as Bronuck® (Senju Pharmaceutical Company, Ltd., Osaka, Japan). [Bronuck package insert, 2003] A similar formulation was approved in the United States by the Food and Drug Administration (FDA) in March 2005 as Xibrom (bromfenac ophthalmic solution 0.09%), and in March 2011, it was approved by the FDA as Bromday for Once Daily (QD) dosing.[Xibrom, Bromday Prescribing Information] Yellox (Bromfenac ophthalmic solution 0.09%) received a pan-European Marketing Authorisation in June 2011, and is indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction. The recommended dosage of Yellox is one drop in the affected eye(s) twice daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period. [Yellox SmPC] Mechanism of action Bromfenac is an NSAID that has anti-inflammatory activity which is thought to be due to its ability to block prostaglandin synthesis by inhibiting primarily COX-2. COX-1 is only inhibited to a small extent. [Yellox SmPC 2011] The efficacy of Yellox in treating post-operative inflammation after cataract surgery, without pre-treatment or concomitant steroids, has been evaluated in the USA in two phase III, doublemasked, placebo-controlled clinical trials. Subjects enrolled had undergone unilateral cataract extraction and posterior chamber intraocular lens implantation and had moderate to severe ocular inflammation (Summed Ocular Inflammation Score [SOIS] ≥3), as assessed 16–32 hours after the procedure. The patients were randomly assigned to Yellox twice daily (n=356), or placebo (n=171) for 14 days (from day 1 to day 15). The main outcome measure was cleared ocular inflammation (SOIS=0) after 14 days of treatment. [Donnenfeld 2006, Donnenfeld 2007] A pooled intent-to-treat (ITT) analysis of these two studies was conducted, including a total of 527 patients. It revealed that significantly more Yellox-treated (64% [228/356]) than placebo patients (43.3% [74/171]; p<0.0001) achieved an SOIS 100 p=0.0012, §p<0.0001 vs placebo # 59.3% § 80 § § 60 40 8.4% § 26.9% 20 1.2% 0 A supplemental analysis of the data while patients were on their assigned treatment only, excluding the effects on any rescue medication, was conducted (last observation carried forward [LOCF] in those patients requiring a change in regimen). This analysis indicated that 59.3% of Yellox-treated patients had an SOIS of 0 versus 26.9% of those receiving placebo (p<0.0001). Clinical effectiveness persisted for up to 4 weeks after 14 days’ treatment, with >80% patients having inflammation controlled. Furthermore, significantly more Yellox patients had marked improvement in ocular inflammation (SOIS≤1) at day 15 compared with placebo (85.1% vs 52.6%; p<0.0001). [Donnenfeld 2006, Donnenfeld 2007] Worldwide, Bromfenac has been used for more than 10 years with more than 20 million patients treated. [CHMP Assessment report] The pooled safety data from the two US Phase III trials show that overall, bromfenac ophthalmic solution was well tolerated, with only 3.4% of patients experiencing one or more adverse events. In two large US phase III clinical trials, there were fewer adverse events in the Yellox group than the placebo group and no serious adverse events (including ocular) considered related to Yellox. [Donnenfeld 2006, CHMP Assessment report] # D3 score of 0 on day 15. It should be noted that the ITT analysis included all patients in their assigned group, regardless of whether they actually received the assigned treatment. Also, the data include the effects of any alternative anti-inflammatory regimens administered after the start of the trial (given, for instance, because of adverse effects or lack of efficacy). [Donnenfeld 2006, Donnenfeld 2007] Safety More Yellox patients achieved ocular inflammation control within 2 weeks: LOCF analysis Patients with SOIS = 0 (%) O D8 D15 D22 D29 Adapted from Donnenfeld et al 2007. Shown are the data from the LOCF analysis (in which the patients were assessed while on their assignment treatment). SOIS is calculated by summing the anterior chamber cell score and flare score (each of these scores being on a scale from 0 to 4). Figure 2 Results of two US Phase III trials, Last Observation Carried Forward (LCOF) analysis No systemic adverse drug reactions have been associated with bromfenac ophthalmic solution across the entire body of clinical and surveillance data. In addition, liver function test values following ophthalmic bromfenac administration found no risk of hepatic toxicity. [Donnenfeld 2006, Donnenfeld 2007] Ocular adverse events occuring in >2% Yellox treated patients in US phase III trials Adverse event Treatment groups Yellox (n=356) Placebo (n=171) Iritis 7.0% 18.1% Abnormal sensation in eye 6.5% 8.2% Eye pain 4.2% 11.7% Eye pruritus 3.9% 2.9% Posterior capsular opacification 3.9% 4.1% Eye irritation (burning/stinging) 2.5% 4.7% Eye redness 2.2% 7.6% Conjunctival hyperaemia 2.2% 11.1% Photophobia 2.0% 11.1% Macular oedema 1.4% 4.7% Figure 3 Pooled safety data from US Phase III trials [Adapted from Donnenfeld 2006, Donnenfeld 2007] Bromday® (previously Xibrom®), prescribing information Wittpenn JR et al. Am J Ophthalmol. 2008;146(4):554–60 Silverstein SM et al. Current Medical Research & Opinion Vol. 27, No. 9, 2011, 1693–1703 Ahuja M et al. AAPS J. 2008 Jun;10(2):229–41. Epub 2008 Apr 25 Cho H et al. Clin Ophthalmol. 2009; 3:199–210 Kim SJ et al. Surv Ophthalmol. 2010;55(2):108–33 Bronuck Package Insert 2003 Donnenfeld ED et al. Ophthalmology 2007;114(9):1653–62 Donnenfeld ED, Donnenfeld A. Int Ophthalmol Clin. 2006; 46(4):21–40 Yellox SmPC Committee for Medicinal Products for Human Use (CHMP) Assessment Report, 17 March 2011 UK/YEL/12/002, April 2012. Prescribing information can be found on page 20.