November 2022 | Vol 27 Issue 9
New presbyopia EDOF looking options good, for now s
CATARACT & REFRACTIVE | CORNEA | RETINA | GLAUCOMA PAEDIATRIC OPHTHALMOLOGY
Choose OZURDEX® (dexamethasone intravitreal implant) 0.7mg for suitable naïve DMO patients or those with insufficient response to anti-VEGF.1 With a MOA shown to inhibit multiple inflammatory processes, OZURDEX® may help suitable DMO patients achieve real world visual acuity gains with fewer injections vs anti-VEGF.1-5
IS IT TIME TO TREAD A DIFFERENT PATH?
OZURDEX® is indicated for the treatment of adult patients with visual impairment due to diabetic macular oedema (DMO) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy.1 Real world evidence is collected outside of controlled clinical trials and has inherent limitations including a lesser ability to control for confounding factors. 1. OZURDEX®. Summary of Product Characteristics. Available at: [https://www.medicines.org.uk/emc/product/5654.] (accessed: December 2021). 2. Boyer D et al. Ophthalmology 2014; 121(10):1904-14. 3. Kodjikian A et al. 2018. https://doi.org/10.1155/2018/8289253. 4. EYLEA®. Summary of Product Characteristics. Available at: [https://www.medicines.org.uk/emc/product/2879.] (accessed: December 2021). 5. LUCENTIS®. Summary of Product Characteristics. Available at: [https://www.medicines.org.uk/emc/product/307] (accessed: December 2021). OZURDEX® (Dexamethasone 700 micrograms intravitreal implant in applicator) Abbreviated Prescribing Information. Presentation: Intravitreal implant in applicator. One implant contains 700 micrograms of dexamethasone. Disposable injection device, containing a rod-shaped implant which is not visible. The implant is approximately 0.46 mm in diameter and 6 mm in length. Indications: Treatment of adult patients: with macular oedema following either Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO), inflammation of the posterior segment of the eye presenting as non-infectious uveitis and visual impairment due to diabetic macular oedema (DMO) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy. Dosage and Administration: Please refer to the Summary of Product Characteristics before prescribing for full information. OZURDEX must be administered by a qualified ophthalmologist experienced in intravitreal injections. The recommended dose is one OZURDEX implant to be administered intra-vitreally to the affected eye. Administration to both eyes concurrently is not recommended. Repeat doses should be considered when a patient experiences a response to treatment followed subsequently by a loss in visual acuity and in the physician’s opinion may benefit from retreatment without being exposed to significant risk. Patients who experience and retain improved vision should not be retreated. Patients who experience a deterioration in vision, which is not slowed by OZURDEX, should not be retreated. In RVO and uveitis there is only very limited information on repeat dosing intervals less than 6 months. There is currently no experience of repeat administrations in posterior segment noninfectious uveitis or beyond 2 implants in Retinal Vein Occlusion. In DMO there is no experience of repeat administration beyond 7 implants. Patients should be monitored following the injection to permit early treatment if an infection or increased intraocular pressure occurs. Single-use intravitreal implant in applicator for intravitreal use only. The intravitreal injection procedure should be carried out under controlled aseptic conditions as described in the Summary of Product Characteristics. The patient should be instructed to self-administer broad spectrum antimicrobial drops daily for 3 days before and after each injection. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active or suspected ocular or periocular infection including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. Advanced glaucoma which cannot be adequately controlled by medicinal products alone. Aphakic eyes with ruptured posterior lens capsule. Eyes with Anterior Chamber Intraocular Lens (ACIOL), iris or transscleral fixated intraocular lens and ruptured posterior lens capsule. Warnings/Precautions: Intravitreous injections,
including OZURDEX can be associated with endophthalmitis, intraocular inflammation, increased intraocular pressure and retinal detachment. Proper aseptic injection techniques must always be used. Patients should be monitored following the injection to permit early treatment if an infection or increased intraocular pressure occurs. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients must be instructed to report any symptoms suggestive of endophthalmitis or any of the above mentioned events without delay. All patients with posterior capsule tear, such as those with a posterior lens (e.g. due to cataract surgery), and/or those who have an iris opening to the vitreous cavity (e.g. due to iridectomy) with or without a history of vitrectomy, are at risk of implant migration into the anterior chamber. Implant migration to the anterior chamber may lead to corneal oedema. Persistent severe corneal oedema could progress to the need for corneal transplantation. Other than those patients contraindicated where OZURDEX should not be used, OZURDEX should be used with caution and only following a careful risk benefit assessment. These patients should be closely monitored to allow for early diagnosis and management of device migration. Use of corticosteroids, including OZURDEX, may induce cataracts (including posterior subcapsular cataracts), increased IOP, steroid induced glaucoma and may result in secondary ocular infections. The rise in IOP is normally manageable with IOP lowering medication. Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex and not be used in active ocular herpes simplex. OZURDEX is not recommended in patients with macular oedema secondary to RVO with significant retinal ischemia. OZURDEX should be used with caution in patients taking anti-coagulant or anti-platelet medicinal products. OZURDEX administration to both eyes concurrently is not recommended. Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, consider evaluating for possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Interactions: No interaction studies have been performed. Systemic absorption is minimal and no interactions are anticipated. Pregnancy: There are no adequate data from the use of intravitreally administered dexamethasone in pregnant women. OZURDEX is not recommended during pregnancy unless the potential benefit justifies the potential risk to the foetus. Lactation: Dexamethasone is excreted in breast milk. No effects on the child are anticipated due to the route of administration and the resulting systemic
levels. However OZURDEX is not recommended during breast-feeding unless clearly necessary. Driving/Use of Machines: Patients may experience temporarily reduced vision after receiving OZURDEX by intravitreal injection. They should not drive or use machines until this has resolved. Adverse Effects: In clinical trials the most frequently reported adverse events were increased intraocular pressure (IOP), cataract and conjunctival haemorrhage*. Increased IOP with OZURDEX peaked at day 60 and returned to baseline levels by day 180. The majority of elevations of IOP either did not require treatment or were managed with the temporary use of topical IOP-lowering medicinal products. 1% of patients (4/347 in DMO and 3/421 in RVO) had surgical procedures in the study eye for the treatment of IOP elevation. The following adverse events were reported: Very Common (≥ 1/10): IOP increased, cataract, conjunctival haemorrhage*. Common (≥1/100 to <1/10): headache, ocular hypertension, cataract subcapsular, vitreous haemorrhage*, visual acuity reduced*, visual impairment/disturbance, vitreous detachment*, vitreous floaters*, vitreous opacities*, blepharitis, eye pain*, photopsia*, conjunctival oedema*, conjunctival hyperaemia. Uncommon (≥1/1,000 to <1/100): migraine, necrotizing retinitis, endophthalmitis*, glaucoma, retinal detachment*, retinal tear*, hypotony of the eye*, anterior chamber inflammation*, anterior chamber cells/flares*, abnormal sensation in eye*, eyelids pruritus, scleral hyperaemia*, device dislocation* (migration of implant) with or without corneal oedema , complication of device insertion resulting in ocular tissue injury* (implant misplacement). (*Adverse reactions considered to be related to the intravitreous injection procedure rather than the dexamethasone implant). Please refer to Summary of Product Characteristics for full information on side effects. Basic NHS Price: £870 (ex VAT) per pack containing 1 implant. Marketing Authorisation Number: EU/1/10/638/001. Marketing Authorisation Holder: Allergan Pharmaceuticals Ireland, Castlebar Road, Westport, Co. Mayo, Ireland. Legal Category: POM. Date of Preparation: May 2019.
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ Adverse events should also be reported to Allergan Ltd. UK_Medinfo@allergan.com or 01628 494026. Date of preparation: December 2021 ALL-OZU-210319
Publishers Publishers Vanessa Vanessa McCourt McCourt Operations Operations Director Director ESCRS ESCRS Barbara Calderwood Calderwood Barbara Mark Wheeler Wheeler Mark Executive Executive Editor Editor Stuart Stuart Hales Hales firstname.lastname@example.org email@example.com Editor-in-Chief Editor-in-Chief Sean Sean Henahan Henahan Senior Senior Content Content Editor Editor Kelsey Ingram Ingram Kelsey Design Design Director Director Kelsy Kelsy McCarthy McCarthy Designer Designer Stephanie Donnelly Jennifer Lacey Circulation Circulation Manager Manager Vanessa McCourt McCourt Vanessa Contributing Contributing Editors Editors Cheryl Cheryl Guttman Guttman Krader Krader Howard Larkin Howard Larkin Dermot McGrath McGrath Dermot Roibeárd O’hÉineacháin O’hÉineacháin Roibeárd Contributors Contributors Gearóid Tuohy Leigh Spielberg Soosan GearóidJacob Tuohy Clare Quigley Priscilla Lynch
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Published by the European Society of Cataractbyand Published theRefractive EuropeanSurgeons, Society Temple House, Road, of Cataract andTemple Refractive Surgeons, Blackrock, Co Dublin, Temple House, TempleIreland. Road, No part of thisCo publication may beNo Blackrock, Dublin, Ireland. reproduced without themay permission part of this publication be of the executive editor. reproduced without the permission Letters to the editor and other of the executive editor. unsolicited contributions are Letters to the editor and other assumed intended for thisare unsolicited contributions publication and arefor subject assumed intended this to editorial review acceptance. publication andand are subject to editorial review and acceptance. ESCRS EuroTimes is not responsible for statements made byresponsible any ESCRS EuroTimes is not contributor. These contributions for statements made by any are presentedThese for review and contributor. contributions comment andfor notreview as a statement are presented and on the standard ofas care. Although comment and not a statement all material expected on advertising the standard of care.isAlthough to to ethical medical all conform advertising material is expected standards, does not to conformacceptance to ethical medical imply endorsement by ESCRS standards, acceptance does not EuroTimes. ISSN 1393-8983 imply endorsement by ESCRS EuroTimes. ISSN 1393-8983
COVER STORY: TEXT
NEW PRESBYOPIA OPTIONS
CATARACT & REFRACTIVE 08 Capsular Bag or Sulcus? 10 Unilateral Approach Works Well in France
11 Tackling Carbon Emissions
CORNEA 22 Prudence Urged When
Prescribing Antibiotics for Acute Conjunctivitis
24 Weighing the Options
36 Paediatric Cataract
26 Innovations in
Treatment for Corneal Endothelial Disease
16 Taking Advantage of
18 Digital Revolution
28 Virtual Perimetry
Modern IOL Formulas Transforming the Face of Ophthalmic Practice
20 EUREQUO Registry Provides a Mine of Valuable Data
for DME and DR
OSD in Cataract Patients
Waste Generated by Cataract Surgery Driving Innovation
33 New Therapy for LHON? 34 Better Education Needed
25 Coming to Grips with
14 ESCRS Research Projects
for Novel DME Treatment
in Cataract and Corneal Endothelial Disease
from Cataract Surgery
12 Operating Room
32 Early Trial Data Promising
02 Editorial 38 Leadership Development and Business Innovation
40 Industry News 41 JCRS Highlights
30 Imaging Techniques
Shed Light on Retinal Disease Mechanisms
31 Visual Risks for PDE5I Users As certified by ABC, the EuroTimes average net circulation for the 10 issues distributed between February 2021 and December 2019 48,580. was 47,863
EUROTIMES | NOVEMBER 2022
“Better make the horizon your goal; it will always be ahead of you.” —William Makepeace Thackeray
ooner or later, it happens to all of us. You notice it when reading a menu in a restaurant at night or reading your email in the morning. Your natural accommodative process is not working as well as it used to. You are presbyopic. Along with the more than one billion people on the planet who develop presbyopia, you may experience a decrease in quality of life, have difficulty with near-vision-related tasks, and develop a strong dislike for reading glasses. Indeed, annual global productivity losses associated with uncorrected or undercorrected presbyopia are believed to exceed €25 billion.* This situation has spurred a long-running effort in the ophthalmology research community to develop workable solutions for presbyopic patients. The ideal treatment for presbyopia would be a safe, effective procedure that provides accommodative vision at near, middle, and far distances. For decades, it seems, we have been encouraged to believe such a procedure is just over the horizon. The problem with the distant horizon is it continues to recede as you approach. While the holy grail of a truly accommodating lens has not appeared, current options do illustrate the progress made in providing a good range of vision for presbyopic patients while minimising unwanted visual effects seen in earlier times. Reporting from the ESCRS Annual Congress in Milan, Howard Larkin reviews the state of presbyopia treatment, from treatments currently available to those that may soon become available. Dissatisfaction with photic side effects seen with earlier iterations of multifocal IOLs led to low adoption rates among surgeons and patients. However, the current batch of extended depth of focus (EDOF) IOLs and enhanced monofocal lenses appears to have generated new enthusiasm for lenticular treatment of presbyopia.
Oliver Findl ESCRS PRESIDENT
IOLs offering some degree of accommodation also appear promising. These include the LensGen Juvene® IOL and the AkkoLens Lumina sulcus-fixated accommodating lens, both in advanced clinical trials. Topical treatments for presbyopia are also entering the market. This includes Allergan Vuity®, a pilocarpine solution and the experimental compound UNR844 (lipoic acid/choline ester 1.5% solution, Novartis), which works “While the holy grail of not by affecting pupil size but by increasing a truly accommodating the flexibility of lens has not appeared, the crystalline lens, current options do theoretically restoring some accommodation. illustrate the progress It is currently in phase made in providing a 2b clinical trials as a good range of vision for presbyopia treatment. presbyopic patients while Any cataract procedure depends minimising unwanted on reliable IOL power visual effects.” calculations, and this is particularly true for presbyopic treatments. The ESCRS IOL Calculator, launched at the Milan ESCRS Congress, aggregates several of the latest formulae in one convenient location. Dr Oliver Findl describes the calculator in this issue from the AAO conference in Chicago (page 16). The ESCRS IOL Calculator is available for free at iolcalculator.escrs.org. *Berdahl J et al., Clin Ophthalmol. 2020; 14: 3439–3450.
Thomas Kohnen Chief Medical Editor
INTERNATIONAL EDITORIAL BOARD Noel Alpins (Australia), Bekir Aslan (Turkey), Roberto Bellucci (Italy), Hiroko Bissen-Miyajima (Japan), John Chang (China), Béatrice Cochener-Lamard (France), Oliver Findl (Austria), Nino Hirnschall (Austria), Soosan Jacob (India), Vikentia Katsanevaki (Greece), Daniel Kook (Germany), Boris Malyugin (Russia), Marguerite McDonald (US), Cyres Mehta (India), Sorcha Ní Dhubhghaill (Ireland), Rudy Nuijts (The Netherlands), Leigh Spielberg (The Netherlands), Sathish Srinivasan (UK), Robert Stegmann (South Africa), Ulf Stenevi (Sweden), Marie-José Tassignon (Belgium), Manfred Tetz (Germany), Carlo Enrico Traverso (Italy) EUROTIMES | NOVEMBER 2022
Research | Education | Innovation Access the latest articles, presentations, podcasts, webinars, and videos. Find where and when the latest events, meetings, and conferences are happening.
New presbyopia EDOF looking options good, for now s
Howard Larkin reports
EUROTIMES | NOVEMBER 2022
ffecting about 1.5 billion people worldwide, presbyopia is among the most prevalent visual needs. As populations age, those numbers are rising, as is the proportion of people seeking spectacle-free solutions, according to presenters at the 40th Congress of the ESCRS in Milan. Indeed, industry sources said at the inaugural ESCRS iNovation programme that presbyopia-correcting IOLs (PCIOLs) are picking up market share. And while 55% of ESCRS members surveyed for the programme implant PCIOLs—in less than 5% of eligible patients—65% see their usage increasing in the next year. Newer monofocal-plus and extended depth of focus (EDOF) IOLs are driving much of the interest, said Lucio Buratto MD, who chaired a symposium on presbyopia correction at the Congress. These lenses reduce optical disturbances such as glare, halos, and starbursts that many users found intolerable in earlier multifocal lenses—though newer multifocal and hybrid designs also reduce these phenomena. Presbyopia-correcting corneal laser surgery is an option for younger patients, as is a new presbyopia-correcting phakic IOL. Monovision, either alone or in combination with PCIOLs, is another option, as is optimising spherical aberration (SA) in monofocal lenses for individual patient pupil size and corneal SA. But a solution that reliably duplicates the long-lasting accommodative function of the natural crystalline lens remains in the future, said George Beiko MD. In the meantime, available static solutions involve trade-offs. Matching the strengths and weaknesses of each to specific patient needs and preferences is still critical, the presenters emphasised.
PRESBYOPIC LASIK Presbyopia LASIK imparts multifocality to the cornea, said Thomas Kohnen MD, PhD. It can be performed with a peripheral zone for near vision and a central zone for distance, but a centre near add ablates less tissue, making it the preferred method. Ablation profiles can vary to increase the depth of field, which can be used to create blended vision by targeting the distance eye for plano and the non-dominant eye for -1.25 D to -1.5 D. The two extended in-focus zones overlap, potentially improving binocular summation while providing approximately 3.0 D of pseudoaccommodation. However, he noted a trade-off between increased depth of field and reduced quality of vision. In a study Dr Kohnen conducted using the Schwind PresbyMAX system, 15 patients were treated with a micromonovision approach, and 15 with a hybrid approach with less depth of focus in the distance-corrected eye. Overall, there was a slight loss of corrected distance visual acuity, from -0.16 to -0.06 logMAR, and a big gain in uncorrected near vision, from 0.48 to 0.05 logMAR. There were no significant differences in distance and intermediate vision, but the micromonovision group had better near vision at 0.09 versus 0.30 logMAR. Overall, only 10% used spectacles for reading, and 82% would undergo the same procedure again. However, presbyopic LASIK outcomes can be problematic. In a 2017 review, most authors reported a significant risk of loss of two or more lines of distance visual acuity, which can result from dry eye or induction of higher order aberrations.i “Corneal multifocality is a developing area. It can restore near vision, but it comes with risks,” Dr Kohnen said. This is a major reason why Dr Buratto said he no longer does presbyopic LASIK. In addition, it is a temporary solution patients in their 40s may outgrow as presbyopia progresses, and it limits later options for presbyopic IOLs, he noted. The new presbyopiacorrecting Staar Surgical Visian® ICL™, which is reversible, may be an option for younger presbyopic patients.
MULTIFOCAL AND EDOF IOLs Presbyopia-correcting IOLs range from enhanced monofocal to EDOF to multifocal lenses, and these address the problem in a variety of ways involving different trade-offs, said Rudy MMA Nuijts MD, PhD of Maastricht University, the Netherlands.
“...a solution that reliably duplicates the long-lasting accommodative function of the natural crystalline lens remains in the future... In the meantime, available static solutions involve trade-offs.” For example, the Johnson & Johnson Tecnis Eyehance™ is a refractive lens that continuously increases refractive power from the periphery to the centre, delivering distance visual acuity and a dysphotopsia profile similar to monofocal IOLs while improving intermediate vision. In a comparative study against a monofocal lens and the first-generation EDOF Symfony, the Eyehance delivered similar defocus at -1.0 D and similar binocular intermediate vision with the Eyehance with better results for halos and glare, though less near vision. Contrast sensitivity was similar among the three lenses.ii The Bausch & Lomb LuxSmart™ enhanced monofocal IOL uses non-diffractive technology combining two zones of opposite spherical aberration, which more than doubles the subjective depth of field. The BVI/Physiol ISOPure IOL enhanced monofocal uses aspherical anterior and posterior surfaces to increase negative spherical aberration, increasing depth of field and intermediate vision by one line compared with a monfocal lens. The Mini Well® non-diffractive EDOF IOL incorporates three optical zones, including a central distance surrounded by distance with spherical aberration of the opposite sign to extend focus and a peripheral monofocal zone with a total add of +3.0 D. This results in a defocus of 0.8 decimal or better from +1.0 D to -2.0 D with mild glare and halos, Dr Nuijts noted. The Alcon Clareon® Vivity® EDOF IOL uses a smooth wavefront-shaping element that continuously extends depth of focus. A study Dr Nuijts conducted with colleagues found a binocular defocus curve of better than 0.1 logMAR from +0.5 D to -2.0 D with no halos, glare, or starbursts in more than 90% of patients when implanted using a minimonovision approach targeting -0.25 D to -0.5 D in the non-dominant eye. For enhanced monofocal and EDOF lenses, Dr Nuijts looks for patients with a high demand for distance vision, significant activities at intermediate distance, and active and dynamic lifestyles desiring some degree of spectacle independence. Patients who are not candidates for diffractive technology and are risk-averse towards visual disturbances were also candidates. Recent multifocal IOLs include the hybrid Tecnis Synergy™, which combines the good near and distance vision of a bifocal lens with complete vision over a range of distance and intermediate range of the Symfony, Dr Nuijts said. Compared with the PanOptix® trifocal lens, the Synergy delivered similar performance in distance, intermediate, and near visual acuity in one study, while another gave the edge to Synergy at intermediate and near distances.iii–iv In searching for ideal candidates for trifocal PCIOLs, Dr Nuijts looks for a healthy eye with no corneal pathology, no severe corneal irregularities, and no diabetic retinopathy, macular pathology, or glaucoma. For enhanced monofocal or EDOF technology, he said he is more tolerant with inclusion. Trifocals still give the highest chance of spectacle independence for reading, but the trade-off is increased visual disturbances, though these are reduced in newer lenses. Another option currently gaining favour in the United States is the AcuFocus IC-8® small aperture IOL. With the lens implanted in the non-dominant eye, most patients achieved distance, intermediate, and near vision of 20/32 or better, which was maintained for up to 1.5 D astigmatism in one study, Dr Nuijts said.v EUROTIMES | NOVEMBER 2022
ACCOMMODATING IOLs Many accommodating IOLs have fallen by the wayside, either because they offer limited or no accommodation or lost accommodative power due to loss of flexibility in the capsular bag, Dr Beiko noted. Lens epithelial cells appear to play a role in maintaining capsular bag flexibility, and more research will be required to understand it. “Will there be an accommodating lens in the short term? I don’t think there will be,” he said. Nonetheless, accommodating lenses are in development. The LensGen Juvene® has been approved for a pivotal clinical trial in the United States based, in part, on a study suggesting it retains accommodation for 24 months. The AkkoLens Lumina sulcusfixated accommodating lens is also planning market entry in Europe. It may bypass the issues of capsular bag fibrosis, said Jorge Alió MD, PhD. (See page 8 for more.)
PHARMACEUTICAL SOLUTIONS Drugs that constrict the pupil offer another presbyopia solution. These include Allergan Vuity®, a pilocarpine solution. However, the effect is temporary and may not provide spectacle-free reading vision for patients with more advanced hyperopia, though they generally will improve intermediate vision. Side effects such as headache and eye irritation are also possible, and the drugs affect night vision. Several other agents that work by constricting the pupil are in development, as is a drop that softens the crystalline lens, restoring some flexibility to accommodate.
MONOVISION AND SPHERICAL ABERRATION OPTIMISATION For younger presbyopic patients, LASIK monovision is an option, Dr Buratto said. He recommends a trial with contact lenses to assess patient tolerance. Monovision with monofocal lenses also can be effective, and it tends to enhance the nearvision performance of EDOF lenses, several presenters noted. Dr Beiko also recommends customising IOL selection based on individual patients’ pupil size and the degree of corneal SA. On average, unablated corneas have about 0.27 to 0.3 μm of positive SA. Combined with the positive SA of an IOL, this can add up to 0.5 to 0.6 μm of SA, which provides some pseudoaccommodation—though the effect is seen only in patients with larger pupils. “If the pupil is small, I’ll target plano; if the pupil is large, I will target a refraction that balances the corneal SA or maximises the effect in the first eye. Then in the second eye I’ll purposely go for a little bit of myopia,” Dr Beiko said. This typically results in good distance vision and enough intermediate and near vision for daily activities and computer work but not enough for prolonged reading. The process mimics natural pseudoaccommodation, which contributes significantly to near vision, Dr Beiko
EUROTIMES | NOVEMBER 2022
“Many accommodating IOLs have fallen by the wayside, either because they offer limited or no accommodation or lost accommodative power due to loss of flexibility in the capsular bag.”
added. Many IOL manufacturers are working with SA to extend depth of focus in new designs, Dr Buratto noted. Vargas-Fragoso V, Alió J. Eye and Vision. 2017; 4(11). Corbelli E. Journal of Cataract and Refractive Surgery. 2022; 48: 67–74. iii Ferreira TB et al. Journal of Cataract and Refractive Surgery. 2022 Mar; 48(3): 280–287. iv Dick HB et al. Journal of Cataract and Refractive Surgery. 2022 May 12. doi: 10.1097. epub ahead of print. v Dick HB. Journal of Cataract and Refractive Surgery. 2017; 43(7): 956–968. i
Lucio Buratto MD is a LASIK and cataract surgery pioneer and director of Centro Ambrosiano Oftalmico in Milan, Italy. George HH Beiko BM, BCh, FRCS(C) is a lecturer at the University of Toronto and a cataract, refractive, and anterior segment surgeon practicing in St Catharines, Ontario, Canada. Thomas Kohnen MD, PhD, FEBO is professor and chair, Department of Ophthalmology, Goethe University, Frankfurt, Germany. Rudy MMA Nuijts MD, PhD is professor of ophthalmology, vice-chairman, and director of the Cornea Clinic and the Center for Refractive Surgery at the University Eye Clinic Maastricht, Maastricht Medical University, the Netherlands.
POWERFUL. PREDICTABLE. PROVEN
PROVEN PLATFORM iStent inject® is the gold standard in Trabecular Micro-Bypass surgery, continuing the legacy of excellence set throughout 20 years of iStent® devices. It’s backed by the most robust, diverse, and longest-term body of clinical evidence for any MIGS procedure available today, given through clinical rigor and integrity. 8 year study with iStent demonstrated sustained protection against visual field loss, as well as preservation of best corrected visual acuity, cup to disc ratio, and retinal nerve fiber layer thickness9
<0.01 decibel mean change in visual field mean deviation from baseline at 24 months in iStent inject-treated eyes in a pivotal trial1
38 publications demonstrate the power of iStent technologies to protect against visual field loss†
PROTECTS VISUAL FIELDS1,9
PROVEN LOW RATE OF SECONDARY SURGERY INTERVENTIONS4,5,10
4% of 125 patients in real world study of stand alone and combined iStent inject cases required a secondary procedure during 5 years of follow up4
2.6% of 778 patients in a meta-analysis of stand alone iStent inject eyes went on to require secondary incisional surgery during follow up5
Only 1% of 186 eyes in a randomised controlled trial went on to require secondary incisional surgery during 3 years follow up10
LEGACY OF EXCELLENCE 20 Years of Data. 20K+ Eyes Studied. 20+ Countries. Scientific evidence and clinical rigor have been at the heart of Glaukos, with the earliest publication on iStent® dating back to 2002 - years prior to the iStent ® pivotal trial. Today, this same rigor and integrity is applied to our business as we remain focused on generating strong clinical evidence. 1. Samuelson, Thomas W., et al. “Prospective, randomized, controlled pivotal trial of an ab interno implanted trabecular micro-bypass in primary open-angle glaucoma and cataract: two-year results.” Ophthalmology 126.6 (2019): 811-821. 4. Hengerer, Fritz H., Gerd U. Auffarth, and Ina Conrad-Hengerer. “iStent inject Trabecular Micro-Bypass with or Without Cataract Surgery Yields Sustained 5-Year Glaucoma Control.” Advances in Therapy (2022): 1-15. 5. Healey, Paul R., et al. “Standalone iStent trabecular micro-bypass glaucoma surgery: A systematic review and meta-analysis.” Journal of Glaucoma 30.7 (2021): 606-620. 9. Salimi, Ali, Harrison Watt, and Paul Harasymowycz. “Long-term outcomes of two first-generation trabecular micro-bypass stents (iStent) with phacoemulsification in primary open-angle glaucoma: eight-year results.” Eye and Vision 8.1 (2021): 1-12. 10. Samuelson TW, on behalf of the iStent inject Pivotal Trial Study Team. Three-Year Effectiveness and Safety of 2nd-Generation Trabecular Micro-Bypass (iStent inject). Paper at the Annual Meeting of the American Academy of Ophthalmology (AAO). Virtual Meeting: November 13-15, 2020. † Data on file. iStent inject® W IMPORTANT SAFETY INFORMATION INDICATION FOR USE: The iStent inject W, is intended to reduce intraocular pressure safely and effectively in patients diagnosed with primary open-angle glaucoma, pseudo-exfoliative glaucoma or pigmentary glaucoma. The iStent inject W, can deliver two (2) stents on a single pass, through a single incision. The implant is designed to stent open a passage through the trabecular meshwork to allow for an increase in the facility of outflow and a subsequent reduction in intraocular pressure. The device is safe and effective when implanted in combination with cataract surgery in those subjects who require intraocular pressure reduction and/or would benefit from glaucoma medication reduction. The device may also be implanted in patients who continue to have elevated intraocular pressure despite prior treatment with glaucoma medications and conventional glaucoma surgery. CONTRAINDICATIONS: The iStent inject W System is contraindicated under the following circumstances or conditions: • In eyes with primary angle closure glaucoma, or secondary angle-closure glaucoma, including neovascular glaucoma, because the device would not be expected to work in such situations. • In patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS/ PRECAUTIONS: • For prescription use only. • This device has not been studied in patients with uveitic glaucoma. • Do not use the device if the Tyvek® lid has been opened or the packaging appears damaged. In such cases, the sterility of the device may be compromised. • Due to the sharpness of certain injector components (i.e. the insertion sleeve and trocar), care should be exercised to grasp the injector body. Dispose of device in a sharps container. • iStent inject W is MR-Conditional; see MRI Information below. • Physician training is required prior to use of the iStent inject W System. • Do not re-use the stent(s) or injector, as this may result in infection and/or intraocular inflammation, as well as occurrence of potential postoperative adverse events as shown below under “Potential Complications.” • There are no known compatibility issues with the iStent inject W and other intraoperative devices. (e.g., viscoelastics) or glaucoma medications. • Unused product & packaging may be disposed of in accordance with facility procedures. Implanted medical devices and contaminated products must be disposed of as medical waste. • The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. If intraocular pressure is not adequately maintained after surgery, the surgeon should consider an appropriate treatment regimen to reduce intraocular pressure. • Patients should be informed that placement of the stents, without concomitant cataract surgery in phakic patients, can enhance the formation or progression of cataract. ADVERSE EVENTS: Please refer to Directions For Use for additional adverse event information. CAUTION: Please reference the Directions For Use labelling for a complete list of contraindications, warnings and adverse events. © 2022 Glaukos Corporation. Glaukos, iStent inject® and iStent inject® W are registered trademarks of Glaukos Corporation. PM-EU-0163
EUROTIMES | NOVEMBER 2022
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Capsular Bag or Sulcus? Which is better for accommodating IOLs? Fixation site may influence longevity of action, risk of complications. Howard Larkin reports from Milan
ccommodating intraocular lenses (AIOLs) are the ultimate goal for treating presbyopia and cataract. As AIOLs are developed, whether it’s better to fixate them in the capsular bag or the sulcus has emerged as a significant design question. The answer turns on the durability and reliability of any mechanism of action between the two locations and whether one may be more prone to inflammation or other complications than the other. Eric Donnenfeld MD and Jorge L Alió MD, PhD debated the relative merits of each option in the Journal of Cataract and Refractive Surgery symposium at the 40th Congress of the ESCRS in Milan.
IN THE BAG Arguing for capsular bag fixation, Dr Donnenfeld pointed out the bag is avascular, stable, reproducible, and non-inflammatory. However, he noted the lessons learned from previous failed attempts at in-the-bag AIOLs. The Crystalens® (Bausch + Lomb) relied on capsular bag contraction to move its single optic back and forth on hinged haptics. But fibrosis quickly reduced its ability to contract and potentially move the lens, also leading to decentration and tilt, Dr Donnenfeld said.
Figure 1: Accommodation of sulcus-fixated AIOL compared with young eye and monofocal IOL.
EUROTIMES | NOVEMBER 2022
The Visiogen Synchrony showed that by filling the capsular bag, posterior capsule opacification (PCO) and fibrosis could be greatly reduced. But its dual optic design required moving the lenses to accommodate, which turned out to be more difficult than changing the curvature of a fluid-filled optic, he said. Newer, fluid-filled ACIOL designs prevent capsular bag opacification by limiting contact between the anterior capsule and the anterior optic surface and maintaining an open and expanded capsular bag. These include the Gemini Refractive Capsule (Omega Ophthalmics), PowerVision (Alcon), and Juvene (LensGen) modular lenses. “The capsule remains clear, it remains pliable, and five-year clinical data supports PCO prevention, refractive, and long-term accommodation stability. Capsular fibrosis and opacification are not unavoidable,” Dr Donnenfeld said. He noted the Juvene IOL, which he has helped test, provided binocular visual acuity of better than 20/40 from +2.00 D to -2.50 D—and maintained this range up to two years after surgery, though long-term efficacy is unknown. The capsular bag is also easy to access for surgeons, Dr Donnenfeld added. By contrast, the sulcus is very tight, crowded by the iris, ciliary processes, and choroid. And unlike the capsular bag, these tissues are highly vascular, metabolically active, and subject to inflammatory responses. Known complications of
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Figure 2: Capsular bag-fixated AIOL retains accommodation 25 months after implant.
sulcus fixation include chronic tissue irritation, anterior uveitis, iridocyclitis, and iris chaffing. The sulcus is also rigid with variable anatomy making sizing critical, and visualisation is difficult, Dr Donnenfeld added. “Putting a lens there is like putting it between a rock and a hard place,” he said. “The question is not whether Jorge Alió can implant a haptic in the sulcus without visualisation, but whether the average surgeon can.”
He concluded accommodative IOLs are monofocal lenses that change in power according to distance. This concept completely differs from monofocality, he said, which involves an overlap of images requiring neuroadaptation—something that does not happen in real accommodative lenses. “Once AIOLs are developed adequately, multifocal IOLs will be unable to compete, as happened with pseudophakic glasses and monofocal lenses of the first generation.”
IN THE SULCUS
Alió JL, Ben-Nun J. Journal of Refractive Surgery. 2015; 31: 124–128. Alió JL, Ben-Nun J. Journal of Refractive Surgery. 2005; 31: 1802–1808. iii Alió JL et al. American Journal of Ophthalmology. 2016 Jan 29. doi: 10.1016/j.ajo.2016.01.006. iv Alió JL et al. American Journal of Ophthalmology. 2016 Apr; 164: 37–48.
Arguing for sulcus fixation of AIOLs, Dr Alió noted the capsular bag is the basal membrane of the lens epithelium—and once the lens tissue is removed, it has no anatomical reason to exist, making fibrosis and atrophy inevitable. He has demonstrated this in a primate model, in which a measuring device implanted in the capsular bag to detect the forces of the ciliary body continued to generate contractile force in the sulcus, but not in the capsular bag six months after lens removal. There was also no inflammation due to the sulcus-fixated haptics for five years after implant.i–ii Dr Alió has extensively tested the AkkoLens Lumina, a sulcusfixated AIOL that accommodates by sliding two optics across each other in response to ciliary contraction. It objectively shows accommodation under stimuli of up to -3.00 D. Contract sensitivity is also like a monofocal lens. The Lumina AIOL also showed objective accommodation of about two-thirds the magnitude of a 30-year-old control patient 1 year after surgery.iii Current studies show a stable accommodative outcome out to 3.3 years after surgery, Dr Alió said. Refraction also remained stable across all distances after YAG capsulotomy, and the lens can be implanted even after a posterior capsule break. In addition, the Lumina provided better quality of vision compared to an extended depth of focus IOL. Dr Alió pointed out the Lumina is the only AIOL with highly rated published evidence, demonstrating that a sulcus-fixated AIOL is viable.iv
Eric D Donnenfeld MD is clinical professor of ophthalmology at New York University in New York City, US; trustee of Dartmouth Medical School in Hanover, New Hampshire, US; and in private practice in New York State, US. ericdonnenfeld@ gmail.com Jorge L Alió MD, PhD is professor and the chairman of ophthalmology at Miguel Hernández University of Elche and scientific director at Vissum in Alicante, Spain. firstname.lastname@example.org
EUROTIMES | NOVEMBER 2022
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Unilateral Approach Works Well in France Customised PresbyLASIK results “impressive” in presbyopia study. Dermot McGrath reports from Paris
sing customised unilateral PresbyLASIK can deliver consistent visual outcomes with a high rate of spectacle independence and a low incidence of side effects in presbyopic patients, according to Catherine Albou-Ganem MD. “We have obtained very good results using the excimer laser to modify corneal asphericity exclusively in the non-dominant eye, thereby increasing the depth of field. This modification of the depth of field associated with micromonovision enables us to obtain satisfactory near vision while conserving very good distance vision.” Dr Albou-Ganem presented three-month results using the TECHNOLAS Perfect Vision GmbH TENEO™ 317 software (Bausch + Lomb) to treat the dominant eye with a classic aspheric photoablation (PROSCAN) and SUPRACOR to correct presbyopia in the nondominant eye. “It was our experience using bilateral SUPRACOR treatments that the distance visual acuity was slow to adapt, and this created dissatisfaction for some patients,” she said. Dr Albou-Ganem’s study included 137 eyes of 80 patients with a mean age of 53 years, divided into either emmetropic or hyperopic treatment groups. All emmetropic patients had visual acuity of 10/10 in both eyes and underwent surgery in the non-dominant eye using SUPRACOR strong mode with a micromonovision of -0.75 D. Hyperopic patients were treated in the dominant eye using aspheric PROSCAN ablation and in the non-dominant eye using SUPRACOR strong mode with a micromonovision of -0.5 D.
“The results were impressive, with over 96% of patients achieving uncorrected distance visual acuity of 8/10 or better and a binocular near distance visual acuity of Parinaud 2 or 3.” The mean spherical equivalent preoperatively was 1.52 D (± 1.23 D). In the hyperopic group, the targeted mean ametropia using PROSCAN for the dominant eyes was 1.65 D and 1.43 D for the non-dominant eyes with SUPRACOR. “The results were impressive, with over 96% of patients achieving uncorrected distance visual acuity of 8/10 or better and a binocular near distance visual acuity of Parinaud 2 or 3,” she said. In terms of refractive results, the mean binocular uncorrected distance visual acuity was 9.67/10 (±0.92), and the mean binocular uncorrected near visual acuity was Parinaud 2.26 (±0.51). The postoperative spherical equivalent for the PROSCAN-treated eyes was -0.14 D and -1.57 D for the SUPRACOR-treated eyes. Of all the patients operated on, five required a touch-up intervention at three months to obtain binocular vision of 10/10 Parinaud 2. “The majority of reinterventions in four out of five patients were to improve distance vision. The mean residual SE before reintervention was -0.63 D. This is why I systematically perform a PROSCAN in the dominant eye because I want to attain 10/10 one day after surgery and not have to wait for several weeks of adaptation,” Dr Albou-Ganem said. Summing up, Dr Albou-Ganem said the approach of PROSCAN in the dominant eye and SUPRACOR in the non-dominant eye gives excellent predictable results and high rates of patient satisfaction. “All patients obtained uncorrected visual acuity of 8/10 or better and Parinaud 3 or better. The advantage of this approach is that it avoids the possible transitory reduction of distance vision frequently encountered with a bilateral SUPRACOR procedure,” she concluded. Dr Albou-Ganem presented the study at the French Implant and Refractive Surgery Association (SAFIR) Annual Meeting in Paris. Catherine Albou-Ganem MD is an ophthalmologist at the Clinique de la Vision, Paris, France. email@example.com *Dr Albou-Ganem has financial interest in Bausch + Lomb, BVI, HOYA, and Zeiss.
EUROTIMES | NOVEMBER 2022
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Tackling Carbon Emissions from Cataract Surgery Green campus sequestration shown an effective part of the solution. Cheryl Guttman Krader reports from Milan
novel green campus design at the Sankara Eye Hospital in Coimbatore, India, aims to offset the carbon footprint associated with the huge volume of cataract surgeries the institution performs each year, reported Atul Kamath MD. “Global warming is one of the largest threats of the 21st century, and healthcare facilities are a main contributor to carbon emission that leads to global warming,” Dr Kamath said. “With an average of 32,000 to 33,000 small-incision cataract surgeries (SICS) performed annually at our tertiary eye hospital, the carbon dioxide (CO2) equivalent and carbon footprint are highly significant and will have a tremendous impact on the environment and global warming. “With the humongous green cover of our campus, along with maximum recycling and reusing of the generated waste and minimal usage of disposables, we are able to arrest this burden with ease,” he continued. “Thus, we believe that our tertiary eye care centre has become a model health setup for arresting [the growth of] the carbon footprint and mitigating global warming.” To assess the environmental benefit of the green campus, Dr Kamath and colleagues conducted a retrospective observational study in which they determined the carbon emissions produced by SICS procedures performed between March 2018 and April 2019. Then they compared that figure to the amount of CO2 consumed by the green cover. The computations for determining the number of carbon emissions produced considered all the materials used during a standard SICS procedure, including drapes, syringes, and other plastic derivatives; the estimated lifespan and weight of each tool and surgical instrument; and the waste products consumed by patients during their stay, such as pharmaceuticals, medical equipment, paper, ink, food, and information technology. An online tool calculated the produced CO2 equivalent. The results showed that each case of SICS measured from the time of surgical procedure until patient discharge generated an average of 310 g of waste, resulting in a total CO2 equivalent of 3.2 kg. Considering the 32,073 SICS cases performed during the study period, the total generated CO2 amounted to 113.13 tonnes. The carbon sequestration calculations showed that the carbon fixation of all the trees on the campus totalled 36.3 tonnes of carbon per year, which translated into fixation of 133.22 tonnes of CO2.
LEAFY LAYOUT During his presentation, Dr Kamath illustrated the campus’s green cover with a series of pictures and described its features. Dr Kamath said the part of campus encompassing the medical centre measures five acres. Only one acre covers the hospital itself—the hospital, developed area, and roads. The green campus accounts for the remaining four acres. Within the green campus, there are 55 fully grown trees representing several different varieties—as well as 100 coconut trees in the outermost periphery adjacent to the compound wall and more than 200 ornamental plants. In addition, the institution has implemented the Miyawaki method of plantation to mitigate the campus’s CO2 equivalent. “The cumulative carbon fixation of all the trees per year is 36.3 tonnes of carbon, which in turn indicates a fixation of 133.22 tonnes of CO2. One hundred percent of 113.13 tonnes of CO2 produced by operating 32,073 SICS in our hospital was completely absorbed by the green cover in the campus.” Atul Kamath MD is senior ophthalmology resident, Yenepoya Medical College, Mangalore, India. firstname.lastname@example.org Acknowledgement: Sankara Eye Hospital and team, Coimbatore, Dr Dhananjay Bhosale and Dr Aditi Pai.
“Global warming is one of the largest threats of the 21st century, and healthcare facilities are a main contributor to carbon emission that leads to global warming.” Trees line the entry to the eye hospital in Coimbatore, India.
EUROTIMES | NOVEMBER 2022
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Operating Room Waste Generated by Cataract Surgery
Surveys examine surgeons’ opinions on the problem, its causes, and solutions. Cheryl Guttman Krader reports from Milan
ecent surveys of attitudes towards operating room waste show a clear consensus among ESCRS members and colleagues in North America about their concern for global warming and the amount of trash produced by cataract surgery as excessive. Furthermore, a majority in both surveys is willing to reuse many pharmaceutical and surgical supplies, reported Sjoerd Elferink MD. “In the absence of evidence to the contrary, surgeons should have more discretion over this reuse,” said Dr Elferink. “Following the example of a recently released North American multisociety position statement on reusing multidose topical medications and through collaboration with industry, our profession can take major strides towards reducing surgical waste.” Issued by the American Society of Cataract and Refractive Surgery (ASCRS), American Academy of Ophthalmology, American Glaucoma Society, and Outpatient Ophthalmic Surgery Society, the joint position statement recommends surgical facilities be permitted to use topical drugs in multidose containers on multiple patients until the manufacturer’s labelled date of expiration (if proper guidelines are followed). Dr Elferink summarised the responses to the Operating Room (OR) Waste Survey sent to ESCRS members and, earlier, to cataract
Using a face drape only and not using a patient gown (practice done in Flevoziekenhuis, the Netherlands). This practice is now done in 25% of the eye clinics in the Netherlands.
EUROTIMES | NOVEMBER 2022
“In addition, more than 90% of surgeons in both groups believe the amount of waste produced during cataract surgery is excessive, and nearly all respondents agree about the need to seek ways to reduce surgical waste.” surgeons belonging to various professional societies in North America. The online survey—designed by the US Ophthalmic Instrument Cleaning and Sterilization Task Force—consisted of 23 multiple choice questions, prefaced with information about the carbon footprint of cataract surgery in the United Kingdom versus the Aravind Eye Care System in India. A total of 458 ESCRS members completed the online survey, of whom 77% practiced in Europe. The North American survey group comprised 1,241 respondents. In both groups, nearly 40% of respondents were “high volume” surgeons performing more than 500 procedures per year, but the proportion practicing in a hospital was twice as high in the ESCRS cohort than the North American group (68% versus 33%). The responses from both survey groups showed overwhelming concern about global warming, with 99% of ESCRS respondents and 91% of North American respondents expressing concern. In addition, more than 90% of surgeons in both groups believe the amount of waste produced during cataract surgery is excessive, and nearly all respondents agree about the need to seek ways to reduce surgical waste. The proportion of surgeons wanting medical societies to advocate for reducing the environmental impact of ophthalmic surgery was higher in the ESCRS group than in the North American cohort (94% versus 87%). Responses to questions about drivers of waste generation showed the two survey groups agreed on some factors. Perceived safety benefits of disposable items were identified by about three-fourths of both the ESCRS and North American surgeons, and slightly higher percentages of respondents in both groups felt manufacturers pushing the market towards more profitable single-use products had a role. The North Americans were more likely than the ESCRS members to believe hospital and facility policies were creating more OR waste because of the necessity to use disposable items (74% versus 58%). Nearly all respondents in both groups (≥92%) agreed that manufacturers should offer more reusable instruments and supplies. Responses to questions about current sustainable practice patterns showed some differences between surgeons on the two continents but were similar in indicating willingness to consider various measures. Multidose containers of various drug types (mydriatics, antibiotics,
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“Sequential bilateral surgery has positive consequences for decreasing transport and carbon dioxide emissions from travel.” surgery. “Sequential bilateral surgery has positive consequences for decreasing transport and carbon dioxide emissions from travel, but it is not being done a lot now,” Dr Elferink said. Dr Elferink also encouraged his colleagues to visit the website EyeSustain (eyesustain.org). Sponsored by the ESCRS and the ASCRS, EyeSustain was created with the mission of making healthcare delivery and services in ophthalmology more sustainable environmentally and economically. Sjoerd Elferink MD is an ophthalmologist at Flevoziekenhuis, Almere, the Netherlands. email@example.com
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NSAIDs, anaesthetics, and IOP-lowering medications) were used by 32% to 43% of the ESCRS surgeons and at slightly higher rates among the North Americans. Both groups showed willingness to consider using more multidose products. There was a greater difference between the two survey cohorts in current use of multidose intraocular pharmaceuticals (antibiotics, lidocaine, alpha agonist/mydriatics, capsular dyes) with the ESCRS members more likely to use these products (up to 48%). On the other hand, willingness to consider multidose intraocular pharmaceuticals was much higher among the North Americans (up to 80%). Almost half of the respondents in both groups reuse appropriately cleaned and sterilised supply items (phaco and irrigation/aspiration tips). Reusing other supply items such as tubing, metal blades, and nonmetal surgical devices (e.g., pupil expansion rings, iris, and capsule retractors) was limited among surgeons in both survey groups, as was the use of an open BSS bottle for more than one patient. However, the survey participants indicated a high willingness to consider these practices and other measures for minimising surgical waste—i.e., eliminating full body drapes and hospital gowns for patients and using the same surgical mask and surgical gown all day. In addition, almost half of the surgeons in both cohorts showed willingness to consider immediate sequential bilateral cataract
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EUROTIMES | NOVEMBER 2022
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ESCRS Research Projects Driving Innovation E
ducation and research have always been at the heart of the ESCRS’s mission to serve its members and advance patient care in the field of cataract and refractive surgery. It’s a commitment that takes concrete form in a number of ESCRS research awards regularly open for competition, which offer substantial funding for the best research projects as decided by an expert evaluation panel. Two principal types of research funding are currently available from the ESCRS: the Clinical Research Awards and the Pioneer Awards. To these, the ESCRS has recently added the Systematic Review Awards and the Digital Research Awards as two new categories.
The Pioneer Awards target funding any new initiative, which may include: a novel research idea for development of clinical trial studies, a non-interventional or observational study, a natural history/ epidemiological study, a comprehensive series of retrospective casecontrol studies, and a patient or disease registry. The Awards are open to ESCRS members who have been a member for at least the last three consecutive years and who hold a full-time clinical/research post at an EU-based clinical or academic centre. The amount for funding awarded to a successful applicant is between €5,000 and €50,000 (maximum) for a project with a duration no longer than two years.
CLINICAL RESEARCH AWARDS
The Clinical Research Awards aim to support and encourage independent clinical research in cataract and refractive surgery. The amount of funding awarded to a successful applicant is up to €750,000, which is open to clinicians and researchers with a current ESCRS membership who have been a member for at least the last three consecutive years. Applicants must hold a full-time clinical/research post at an EU-based clinical or academic centre. Ideas and initiatives such as clinical research into the use of specific medical treatments and surgeries, clinical research on the pharmacoeconomic analysis of particular treatments, or research into the optimal management of national and global healthcare systems in ophthalmology may be eligible for consideration in the Awards.
PIONEER AWARDS Open to young ophthalmologists aged 40 or younger, the Pioneer Awards support and encourage independent clinical research in cataract and refractive surgery. Applicants are invited to introduce and develop a body of clinical research work addressing a challenging “problem” to devise a practical “solution” for the benefit of patients.
“Education and research have always been at the heart of the ESCRS’s mission to serve its members and advance patient care in the field of cataract and refractive surgery.”
SYSTEMATIC REVIEW AWARDS The 2022 ESCRS Systematic Review Awards (“SRA”) is a new initiative sponsored by the Society to produce a high-quality body of research intent on preparing, collating, analysing, synthesising, and reporting medical research. The initiative will provide a new scholarly output in cataract and refractive surgery or medicine focused on the methodology created by the Cochrane Library. The competition is open to all ophthalmologists (MD, and/or PhD, or experienced ophthalmic nurses) holding a fulltime clinical/research post at an EU-based clinical or academic centre. ESCRS is offering up to five SRAs in 2022–23, with funding up to €10,000 for each applicant.
DIGITAL RESEARCH AWARDS This latest ESCRS initiative is designed to support and encourage research leading to digital transformation in cataract, refractive, and corneal surgery. The competition is open to all clinicians and researchers. Support of up to €500,000 is available over a maximum of three years for a project with suitable infrastructure and experience leading to the collection of high-quality healthcare data in routine clinical practice and/or the development of open access data sets for clinical research either from prospective data collection or the transfer of existing anonymized data sets to the public domain. Projects may be small or large, with clear goals and a well-designed plan for project execution. Researchers should be able to frame at least one important clinical research question that appropriate analysis of collected data will ultimately help answer.
EUROTIMES | NOVEMBER 2022
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ESCRS LAUNCHES THE
DIGITAL RESEARCH AWARDS 2022! The 2022 ESCRS Digital Research Awards are an initiative sponsored by the Society to support and encourage research leading to digital transformation in the fields of cataract, refractive, and corneal surgery. The competition is open to ALL clinicians and researchers with the selected project(s) eligible to receive funding of up to €500,000 over a maximum of three years.
NOVEMBER 14, 2022
Deadline for receipt of preliminary applications
NOVEMBER 28, 2022
Invitation to shortlisted applicants to submit full proposals
JANUARY 30, 2023
Receipt of full proposals from shortlisted candidates
FEBRUARY 27, 2023
Notification of successful candidates
For more information:
escrs.org/education/grants-awards/digital-research-awards/ EUROTIMES | NOVEMBER 2022
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Taking Advantage of Modern IOL Formulas Free ESCRS online tool aggregates formulae to streamline power calculation. Cheryl Guttman Krader reports from Chicago
he ESCRS IOL Calculator is a new online tool that allows cataract surgeons to access results from multiple modern IOL formulas with the ease of inputting the necessary data one time into a single entry form. Introduced early in September 2022 at the 40th Congress of the ESCRS in Milan, Italy, this “internet way” of performing IOL calculations is available at iolcalculator.escrs.org. It currently includes seven formulas for standard non-toric IOL power calculations. Two more formulas will join, said Oliver Findl MD, and new calculators for toric IOLs and use in eyes with a history of corneal refractive surgery are under development. Dr Findl described the calculator during the ESCRS Symposium session of the AAO 2022 Refractive Subspecialty Day meeting. He prefaced his talk by telling attendees it would contain information they could use immediately on their return home. “Power calculation is key for good outcomes—particularly for the presbyopia-correcting IOLs—and we know that ray tracing, newer vergence formulas, and especially artificial intelligence-based formulas have been enhancing refractive outcomes. However, a lot of these formulas are not available on biometry devices. To use them and compare their results, surgeons must go online to access each formula and enter the data, which can become tedious and possibly cause errors.” Dr Findl said the idea for the ESCRS IOL Calculator was proposed to the ESCRS leadership by Dante Louis Buonsanti MD, a young Argentinian ophthalmologist. Leadership then organised an ESCRS IOL Calculator Team, which developed the online tool in just a few months. Using web scraping technology, the calculator sends entered data to the respective website for each formula. The returned results display on
The new ESCRS tool allows members to compare data across seven formulae to obtain more precise results.
EUROTIMES | NOVEMBER 2022
the ESCRS IOL Calculator website as a single page, making comparison easy. Surgeons can also choose to print a hard copy of the data. No inputted data are stored or collected. To use the calculator, surgeons enter their name, patient identifying information, and the target refraction. They choose an index of refraction from a list of five, along with the desired IOL and its manufacturer. The online form has fields for entering biometry data for the left and right eyes, including axial length, K1, K2, anterior chamber depth, lens thickness, central corneal thickness, and corneal diameter (white-to-white). Values used for A-constants continuously update through a link with the IOLCon database. Dr Findl noted in an example that there can be a disparity in the IOL power recommended by the different formulas. “Surgeons may still need to make a decision about which power to choose,” Dr Findl said. The formulas included in the ESCRS online calculator are the Barrett Universal II, a modern theoretical optics formula; Cooke K6, a modern thin lens formula; EVO, a thick lens formula based on the theory of emmetropisation; Hill-RBF, an artificial intelligence formula using pattern recognition; Hoffer® QST, an evolution of the Hoffer Q formula improved by artificial intelligence; Kane formula, a formula combining artificial intelligence with theoretical optics; and PEARL-DGS, a formula based on thick lens equations and machine learning models. Oliver Findl MD, MBA is the President of the ESCRS and founder and chair, Vienna Institute for Research in Ocular Surgery, Vienna, Austria. firstname.lastname@example.org
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Our IOL Calculator is now live on the ESCRS website! This first-of-its-kind web application for IOL power calculations uses multiple modern formulas simultaneously, and suggests lens constants for a wide range of IOL models.
Find out more at iolcalculator.escrs.org/ EUROTIMES | NOVEMBER 2022
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Digital Revolution Transforming the Face of Ophthalmic Practice
ESCRS Ridley Medal Lecture demystifies AI for ophthalmology community. Dermot McGrath reports from Milan
he ophthalmic profession should broadly embrace the new wave of digital tools steadily making their way into clinical practice and which have the potential to greatly assist physicians in day-to-day patient care, said Béatrice CochenerLamard MD, PhD. In a wide-ranging lecture titled “How the digital world is entering our practice”, Prof Cochener-Lamard focused on the diverse ways digital technologies such as telemedicine, machine learning, and deep learning with artificial intelligence (AI) are profoundly changing the healthcare landscape for the benefit of physicians and their patients.
“One of the key challenges to overcome is that of human acceptance...because the critical point is AI has to be designed to serve medicine and not to supplant the doctor.” Prof Cochener-Lamard began her talk with a reference to Harold Ridley, the great IOL innovator, who she said would probably have understood more than most the rich possibilities of embracing new technological tools such as AI and machine learning. She noted that AI has been frequently misunderstood and misrepresented as a potential threat to the physician’s role in general and the ophthalmologist in particular. “One of the key challenges to overcome is that of human acceptance. That means we need to communicate better on the subject of AI, educate doctors, stop demonizing AI, share and secure data of quality, invest health authorities, and let the doctors decide what to ask of AI, because the critical point is AI has to be designed to serve medicine and not to supplant the doctor,” she said.
TELEMEDICINE ON THE RISE
Prof Cochener-Lamard noted digital tools have already made a major impact in transforming healthcare in the wake of the COVID-19 pandemic. She cited the massive upsurge in telemedicine applications that developed in France and elsewhere as a response to the need to see patients without exposing them to the risk of infection. “We saw a real explosion of interest in telemedicine in France— which went from 1% of teleconsultations before the COVID-19 crisis to over 20% in April 2020, even if ophthalmology is not easily suitable to remote exam,” she said. As well as remote consultations and delegating tasks between the various players in the visual sector, mobile consultation cabin use can also play an important role in helping screen and monitor the ocular health of populations in remote and rural areas.
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She noted that web-based applications are also useful for research purposes. For instance, the University of Brest is currently piloting a smartphone-accessible application to evaluate ocular surface disease in patients with primary Sjögren’s syndrome in the framework of the NECESSITY European research project. “It allows us to monitor the symptoms of the patient and their eyedrop use on a daily basis and to contact them directly as required,” she said. Once validated, the app will be adapted to other national health regulations and translated into six languages for use in the NECESSITY trial to define new clinical endpoints in primary Sjögren’s syndrome, Prof Cochener-Lamard added.
CATARACT & REFRACTIVE
AI OUTPACING LEGAL FRAMEWORK
In terms of AI applications, Prof Cochener-Lamard said the technology is currently advancing faster than public health measures and legal approvals. “We are facing key limitations in terms of bioethics, data protection, and the distrust of the medical community, which is afraid of doctor substitution and the transfer of competencies to other actors such as optometrists, opticians, or nurses,” she said. She explained AI is particularly visible in three key domains in ophthalmology: registries and big data, imaging, and robotization. She detailed how each of these areas are transformed by AI but also highlighted some of the remaining challenges.
EMBRACING PROMS AND PATIENT DATA COLLECTION
Incorporating patient-reported outcome measures (PROMs) into registry data represents an important step forward in developing evidence-based guidelines for cataract and refractive surgery across Europe, she said, citing the PromCat France national cataract registry—which recently became part of the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO). “Incorporating PROMs in our data is definitely the way to go in improving the management of our patients and improving our surgery,” she said. As well as its increasing role in IOL power calculation and cataract workflow systems, Prof Cochener-Lamard said AI has radically transformed the automated recognition of ophthalmic imaging. Deep learning (DL)—a subset under the broad term AI—enables rapid detection and screening in several areas, such as diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, glaucoma, dry eye, and cataract.
“We are facing key limitations in terms of bioethics, data protection, and the distrust of the medical community, which is afraid of doctor substitution and the transfer of competencies to other actors.” While the pace of innovation shows no sign of slackening, a number of hurdles need to be surmounted to take full advantage of the advanced technologies now available to ophthalmologists. “There are some limits that we need to work around. We need to ensure the collection of good quality data that is systematic and accessible. We need to count on the support of national health authorities and academic societies because we need to develop health data hubs and obtain access to electronic medical records worldwide. We also need to define an economic model for AI and guarantee the integrity and cybersecurity of our medical data, as well as ensure access to bioethics for doctors and patients,” she said. Béatrice Cochener-Lamard MD, PhD is Professor and Head of the Ophthalmology Department in Brest University Hospital, France, member of the LATIM (Inserm 1101 – Laboratory of research in analysis and treatment of medical imaging), and Dean of faculty of Medicine and Medical Sciences at the UBO University. email@example.com
EUROTIMES | NOVEMBER 2022
CATARACT & REFRACTIVE
EUREQUO Registry Provides a Mine of Valuable Data W
ith more than 3.6 million cataract cases and over 150,000 refractive surgeries now recorded since its launch in 2008, the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) continues to yield extremely valuable data on surgical practices and outcomes. Funded by the ESCRS, with initial support from the EU, EUREQUO is one of the largest international IT projects in ophthalmology, connecting surgeons all over the world and building a network to facilitate the exchange of expertise. All ESCRS members can access the registry free of charge. By collecting data, surgeons can monitor their results over time and anonymously compare with other colleagues, clinics, and countries. Cataract, refractive, and patient-reported outcomes are all available in one web-based platform. “EUREQUO provides a means to audit surgical results and encourages surgeons to make adjustments to their techniques and improve their outcomes,” said Mats Lundström MD, PhD, the original driving force behind EUREQUO and now a member of the EUREQUO Steering Committee. For its part, the ESCRS believes that a continuing audit of surgical outcomes is necessary to ensure the best care for patients—by making comprehensive data available for visual outcome comparisons. The number of cataract extractions reported to the database in 2021 was 219,672, with a mean patient age of 74 years and 57% women. In 7.9% of the cases, the preoperative corrected distance visual acuity
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(CDVA) was 0.1 or below, and in 49.1%, the CDVA was 0.5 or better. In 25.3%, there was a co-existing eye disease in the surgery eye. The registry also contains data about surgical difficulties, type of operation, IOL optic biomaterial, and surgical complications. For 74,781 cases, follow-up data were also reported. A refractive surgery was reported for 1,801 eyes. Dr Lundström said the EUREQUO Steering Committee is constantly updating the platform with new parameters to reflect the development of new surgical techniques and trends in the field. The committee is also committed to analysing the aggregate data of the database and developing new scientific papers. It has already released 16 publications to date, and more are in the pipeline. Such a big registry is very suitable for studies of rare events in terms of complications or preoperative conditions, Dr Lundström noted. To this end, the registry has generated studies on cataract surgery outcomes in eyes with previous corneal refractive surgery, risk factors for dropped nucleus and posterior capsule rupture, and cataract surgery in eyes with previous vitrectomy. Looking to the future, EUREQUO plans to continue expanding into new regions and adding more surgical data. Earlier this year, the registry started to include data on refractive surgery in the Netherlands as well as cataract data from France. Further information on EUREQUO is available at https://www.escrs.org/about-escrs/registries/eurequo/
To be the leading community and trusted source for science, education, and professional development in the fields of cataract and refractive surgery. Learn more at ESCRS.org EUROTIMES | NOVEMBER 2022
Prudence Urged When Prescribing Antibiotics for Acute Conjunctivitis Misuse can lead to serious visual and financial ramifications. Cheryl Guttman Krader reports from Milan
ntibiotic misuse for acute conjunctivitis is a common and serious issue, as it contributes to the growing global problem of antimicrobial resistance, said Mina Abdelmseih MD, MS, FEBO. “I want to emphasise this problem because we are seeing an increasing number of challenging cases of ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant S aureus. Sadly, some of these patients ended up blind because we could not use anything to treat them,” Dr Abdelmseih told EuroTimes. “New scientific guidelines should be developed to help doctors and patients avoid misuse of antibiotics. In addition to new generations of antibiotics, proper use of antibiotics could be a lifesaving factor, and it will also help to decrease billions in unnecessary costs.”
CONSIDER THE DIAGNOSIS Acute conjunctivitis is a common condition with multiple aetiologies, and most cases are not related to bacterial infection, said Dr Abdelmseih. “Only 135 in 10,000 cases of acute conjunctivitis are bacterial disease. About 80% of cases of acute conjunctivitis are viral, and allergy is also a more common cause of acute conjunctivitis than bacterial infection,” he said. Other entities to consider in the differential diagnosis include blepharitis, dry eye syndrome, subconjunctival haemorrhage, acute glaucoma, episcleritis, scleritis, and now, SARS-CoV-2 infection.
Misuse of antibiotics chart.
Types of conjunctivitis : A- Viral Conjunctivitis: •viruses occur in 80% of all patients of acute conjunctivitis. Most cases are wrongly diagnosed as bacterial conjunctivitis.
B-Allergic conjunctivitis •There is no role of antibiotics in allergic conjunctivitis.
c- Bacterial Conjunctivitis: •the occurrence of bacterial conjunctivitis was approximated to be 135 in 10,000.
D- Chemical burns E- Ophthalmia Neonatorum F- Zika Virus G- SARS-CoV-2 (Coronavirus):
Differential diagnosis : ´A-blepharitis ´B-subconjunctival hemorrhage ´C-dry eye syndrome ´D-acute glaucoma ´E-keratitis ´F-iritis ´G-scleritis ´H-episcleritis
•Conjunctivitis is reported, and it is associated with fever and respiratory symptoms such as sneezing, cough and shortness of breath besides a history of international travel.
Types of conjunctivitis and differential diagnosis.
UNNECESSARY USE Even if the conjunctivitis is bacterial, antibiotic treatment is usually unnecessary because most cases of bacterial conjunctivitis are mild, self-limiting, and do not lead to serious complications. Although antibiotic treatment may shorten symptom duration and hasten microbiological eradication, results from placebo-controlled studies show the benefit is modest. A review of the available literature revealed antibiotic treatment for acute bacterial conjunctivitis had an advantage for improving clinical outcomes only between days two and five. Within the placebo-treated groups, about 65% of patients achieved complete resolution of bacterial conjunctivitis within five days and the percentage rose to 90% by two weeks. EUROTIMES | NOVEMBER 2022
“When antibiotics are used to treat bacterial conjunctivitis, clinicians should be aware that misuse with improper dosing, repeated use, and extended use also promote antimicrobial resistance.”
“Misuse of antibiotics has also led to increased ocular surface colonisation with coagulasenegative Staphylococcus...and there are increasing reports of vancomycin-resistant S aureus isolating from ocular infections.” “There is not a big difference in outcomes between the placebo and active treatment groups. Furthermore, no serious side effects have been reported in the active or placebo groups, indicating that sight-threatening complications are infrequent in cases of acute bacterial conjunctivitis. So, there is no need to use antibiotics for most patients,” Dr Abdelmseih told EuroTimes. When antibiotics are used to treat bacterial conjunctivitis, clinicians should be aware that misuse with improper dosing, repeated use, and extended use also promote antimicrobial resistance.
DOCUMENTING RESISTANCE Reports in the published literature document the existence of antimicrobial resistance to commonly used topical antibiotics among clinical isolates from patients with bacterial conjunctivitis. Researchers report resistance to gentamicin, tobramycin, and polymyxin B among Streptococcus pneumoniae strains isolated from children with acute conjunctivitis as well as high levels of resistance to azithromycin among clinical isolates of Haemophilus influenzae, S pneumonmiae, S aureus, and Staphylococcus epidermidis. In addition, an increase in bacterial conjunctivitis caused by MRSA has been noted, Dr Abdelmseih said. “Misuse of antibiotics has also led to increased ocular surface colonisation with coagulase-negative Staphylococcus. These organisms express methicillin and multidrug-resistant isolates, and there are increasing reports of vancomycin-resistant S aureus isolating from ocular infections,” he said. Mina Abdelmseih MD, MS Ophthalmology, FEBO works in the department of ophthalmology, Augen AMVZ, Germany. firstname.lastname@example.org
EUROTIMES | NOVEMBER 2022
Weighing the Options in Cataract and Corneal Endothelial Disease Increased demand for triple-DMEK necessitates new surgeon strategy. Dermot McGrath reports from Milan
everal viable options exist for the surgical treatment of patients with concomitant cataract and corneal endothelial disease, but no “one size fits all” approach exists to consistently deliver optimal outcomes for these complex cases, according to Björn Bachmann MD, PhD, FEBO, FEBO-CR. Dr Bachmann noted the increasing demand in recent years for so-called triple Descemet membrane endothelial keratoplasty (DMEK) surgery, which combines phacoemulsification, IOL implantation, and DMEK in one procedure. “There is a significant and growing population of patients with cataract and corneal endothelial diseases, and we need to have a strategy to be able to deal with them in the future,” he said, adding that the key question is whether combined (triple-DMEK) or sequential cataract surgery and endothelial keratoplasty is the best approach for these patients.
PROS AND CONS
“All surgical approaches have their advantages and disadvantages,” he said. “The advantages of triple-DMEK are that phacoemulsification and lens implantation does not affect the graft while the downside is inaccurate IOL calculation and variable pupil size during DMEK with this approach.”
Before deciding the optimal approach, it is important to establish both cataract surgery and endothelial keratoplasty are indeed required. The LOCS III classification for cataract is not always well correlated with visual impairment, and phakic patients after DMEK need cataract surgery within two years in 40% of cases, Dr Bachmann said. Likewise for endothelial keratoplasty surgery, the Krachmer system or more advanced grading systems are not always well correlated with visual impairment. And, there are limited predictive parameters for endothelial decompensation by cataract surgery. There are two options for sequential surgery, said Dr Bachmann: cataract surgery and then DMEK surgery, or DMEK surgery followed by cataract surgery. “The advantage of the first approach is that DMEK may be avoided if the patient is satisfied and comfortable after cataract surgery alone. The disadvantage is the possibility of further endothelial decompensation and corneal opacification while waiting for DMEK. And there is also the risk of a hyperopic shift if the patient does proceed to have DMEK surgery.” If inversed, with DMEK performed first, he said the main advantage is improved predictability of IOL calculation, while the downside is the cataract surgery will decrease the endothelial cell density of the DMEK graft. “DMEK first is a suitable approach for younger patients with corneal oedema, corneal opacification, and a clear lens. It is also appropriate for patients with massive corneal opacification as the improved visualisation after corneal clearing increases safety during cataract surgery,” he said. Based on the available evidence and his own clinical experience, Dr Bachmann said triple-DMEK is a viable option in patients with pronounced corneal oedema and cataract with both causing significantly reduced visual acuity. “These patients will benefit in quality-of-life gain through rapid success with combined surgery, although it is important to take into account the presumed postoperative posterior to anterior corneal curvature radii ratio to ensure optimal outcomes,” he said. Patients with mild corneal oedema and mild cataract might be bothered by postoperative refractive error, he said. “Consider DMEK first in extremely demanding patients and again take into account the true posterior to anterior corneal curvature radii ratio for the IOL calculation.” For patients without corneal oedema and with cataract, Dr Bachmann advised cataract surgery first to see whether the problem sufficiently resolved and transplant surgery might be avoided. Björn Bachmann MD, PhD, FEBO, FEBOS-CR is a Consultant Ophthalmologist at the Department of Ophthalmology, University of Cologne, Germany. email@example.com
Before DMEK in patients with marked FECD, elevation maps show depression of the posterior surface. After DMEK, the posterior surface curvature may transform into excess elevation leading to an altered postoperative posterior to anterior corneal curvature radii ratio (as demonstrated by Diener et al. Graefes Arch Clin Exp Ophthalmol 2020).
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Coming to Grips with OSD in Cataract Patients Helping patients own their condition minimises dissatisfaction. Dermot McGrath reports from Milan
cular surface disease (OSD) is a major cause of suboptimal cataract surgery outcomes, but having a clear strategy and ensuring careful preoperative screening to detect potential issues can help to avoid many of the pitfalls associated with OSD in cataract patients, according to Allan R Slomovic MD. “OSD is very prevalent in the cataract patient population,” Prof Slomovic said. “Remember, these are elderly patients [who] are often on numerous medications—especially anti-glaucoma medications—which can affect the ocular surface. Moreover, OSD can significantly affect keratometry and biometry, leading to refractive postoperative surprises and patient dissatisfaction following Assessing and treating severely dry eyes like this one before cataract surgery, said Dr Slomovic, is vital for maximising refractive outcomes. cataract surgery.” The best approach, he said, is to perform “DED can cause corneal staining and abnormalities in a staged procedure, taking care first of keratometry, topography, and biometry,” he said. “Dry eye the ocular surface disease and waiting six to eight weeks before treatment leads to changes in IOL power calculations and repeating biometry and topography prior to cataract removal. postoperative refractive outcomes. Therefore, assessing and Prof Slomovic focused on three principal ocular surface treating patients for dry eyes prior to cataract surgery is important problems: pterygium, epithelial basement membrane dystrophy in maximising refractive outcomes.” (EBMD), and dry eye disease (DED). Prof Slomovic stressed that the ophthalmologist’s role is to To effectively deal with a patient presenting with both pterygium optimise the ocular surface before and after surgery and set and cataract, it is critical to understand the effects pterygium has realistic expectations by explaining to the patient how they have on corneal topography. “It causes flattening of the cornea in the two separate conditions needing treatment. area of the pterygium [and] results in irregular with-the-rule “If you tell the patient about their ocular surface disease before astigmatism and an increase in higher-order aberrations,” he said. the surgery, they own it,” he said. “However, if they only become Prof Slomovic advised first removing the pterygium with a aware of it after the cataract surgery, they will presume the surgeon conjunctival autograft, then waiting six to eight weeks to obtain caused the problem.” stable keratometry and topography. Once achieved, the surgeon Particular vigilance is needed in the use of non-steroidal antican proceed with biometry and phacoemulsification to remove inflammatory drugs (NSAIDs) in the presence of DED, as it can the cataract. lead to corneal melts and perforation, Prof Slomovic warned. “We looked at patients treated this way in a previous study, and “We now have seven studies in the scientific literature reporting it showed pterygium surgery successfully reduces the topographic the association of NSAIDs and corneal melts in the setting of and refractive astigmatism, thereby making biometry more cataract surgery,” he said. accurate,” he said. “The best-corrected visual acuity also improved,
and pterygium excision reduced higher-order aberrations caused by the pterygium.” Anterior basement membrane dystrophy is the most common corneal dystrophy and is especially significant if the changes manifest in the visual axis, Prof Slomovic explained. He presented the case of a 75-year-old male with declining visual acuity referred for consideration of cataract surgery. The patient had two central Salzmann nodules and irregular astigmatism. Six weeks after superficial keratectomy to remove the nodules, the best-corrected visual acuity recovered to 20/25, avoiding cataract surgery. For cases of DED, Prof Slomovic emphasised the importance of addressing the problem preoperatively.
Allan R Slomovic MD is professor of ophthalmology at the University of Toronto, Canada. allan. firstname.lastname@example.org
EUROTIMES | NOVEMBER 2022
Innovations in Treatment for Corneal Endothelial Disease Techniques using rho-kinase inhibitors explored as alternatives to keratoplasty. Cheryl Guttman Krader reports from Milan
ultiple surgical techniques exist for treating corneal endothelial disease—but innovative researchers are pursuing the possibility topical pharmacotherapy with a rho-kinase inhibitor (RKI) might be an effective non-invasive option for certain forms of corneal endothelial disease, according to Shigeru Kinoshita MD, PhD. “Recent studies have shown that RKIs have potentially beneficial effects on corneal endothelial cells. Currently, several RKIs are available worldwide. They include the antiglaucoma agents ripasudil HCl hydrate ophthalmic solution 0.4%, netarsudil ophthalmic solution 0.02%, as well as the investigational compound Y-27632,” he said. Dr Kinoshita reviewed the preclinical evidence underlying interest in RKI therapy for corneal endothelial disease and findings from limited clinical experience investigating it as a topical treatment. He also briefly reviewed the inclusion of Y-27632 in a protocol for human corneal endothelial cell injection therapy for corneal endothelial failure. In this minimally invasive regenerative treatment approach, the RKI is used both for cell cultivation and administered with the cell suspension into the anterior chamber. In fact, the cell injection therapy with RKI shows very dramatic, promising clinical results as a surgical treatment for corneal endothelial failure.
EARLY EVIDENCE Dr Kinoshita credited work published by Japanese investigators Dr Yoshiki Sasai Figure 2 and colleagues in 2007 as the impetus for pursuing RKI treatment for corneal endothelial disease. In their in vitro study, the researchers showed that Y-27632 promoted attachment of human embryonic stem cells on extracellular matrix. “Therefore, we thought, ‘Why not use an RKI to promote the initial attachment of the human corneal endothelial cell in culture?’,” he explained. In a study investigating the effect of Y-27632 on cultivating monkey corneal endothelial cells, Dr Kinoshita and colleagues were surprised to find benefits for promoting cell adhesion, increasing cell proliferation, and inhibiting apoptosis. Subsequent in vivo studies conducted first in rabbits and then in monkeys showed the potential for topical Y-27623 10 mM to treat corneal EUROTIMES | NOVEMBER 2022
endothelial dysfunction. In these experiments, researchers created a partial corneal endothelial defect using the transcorneal freezing technique, then treated eyes with Y-27623 or control (PBS) six times daily for two days. Results showed Y-27623 increased cell proliferation and accelerated wound healing.
CLINICAL APPLICATION The first clinical use of RKI treatment for corneal endothelial disease involved a patient with Fuchs’ endothelial corneal dystrophy (FECD). After damaged endothelial cells were removed by transcorneal freezing, the eye was treated with Y-27623 10 mM six times daily for one week.
CORNEA “At one week, the cornea was already transparent, and at one month, visual acuity improved to 20/20, central corneal thickness decreased to the normal range, and the patient was very happy,” Dr Kinoshita said. However, additional experience in a limited number of eyes showed the treatment combining partial endothelial removal followed by topical Y-27623 was effective for rescuing endothelial dysfunction in eyes with central corneal oedema related to early FECD, but not in cases of diffuse oedema associated with laser iridotomy-induced bullous keratopathy or pseudoexfoliation syndrome keratopathy. Reports from Kathryn Colby MD and Gregory Moloney MD showed the potential benefit of using topical ripasudil as a rescue strategy for eyes that failed to clear after undergoing Descemet-stripping only (DSO) for FECD. “Now the multicentre K-321-201 study has been performed in the United States, and in the near future, we will see whether K-321 (a novel formulation of riparsudil) is safe and effective for promoting healing after DSO for FECD,” Dr Kinoshita said. Dr Kinoshita presented another clinical case involving an eye in which two-thirds of Descemet membrane was accidentally peeled off during cataract surgery. Because the healthy endothelial cells remained, he considered treating the eye with Y-27632 using a concentration of 1 mM. After just 11 weeks, the patient’s vision improved from count fingers to 20/25, the cornea became transparent, and CCT decreased from 964 μm to 582 μm. (Figure 1) “The results are extraordinary. I have never seen such an effect using another kind of medical treatment,” Dr Kinoshita emphasised. He said the limited experience suggests RKI treatment could enhance wound healing after DSO for FECD or in eyes with endothelial injury following cataract surgery where healthy endothelium remains. However, he noted there is no evidence whatsoever it could improve the corneal endothelial cell layer in eyes with early-to-moderate stage FECD presenting with corneal guttae and low corneal endothelial cell density without any disruption to the corneal endothelial cell layer. (Figure 2)
MECHANISTIC INSIGHTS Studies by Dr Kinoshita and colleagues indicate that RKI topical instillation quickly induces morphological changes in healthy human corneal endothelial cells. However, the effect is only transient with the morphology returning to normal by six hours. A recent paper by Dr Schlötzer-Schrehardt (et al.) at Erlangen University, Germany, sheds light on the potential mechanism by which RKI treatment modulates corneal endothelial cell function in eyes with FECD. Using tissue from post-DMEK specimens, the researchers found that incubation with ripasudil induced endothelial cell proliferation and migration, downregulated endothelial-tomesenchymal transition, and upregulated the expression of genes related to endothelial pump function. Shigeru Kinoshita MD, PhD, Professor and Chair, Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. email@example.com CONFLICTS OF INTEREST: Dr Kinoshita receives research support and consultant fees from Senju Pharmaceutical Co., Ltd.; consultant fees from Kowa Co., Ltd.; research support and patent from CorneaGen; patent and shareholder from Aurion Biotechnologies; and consultant fees from Aerie Pharmaceuticals.
EUROTIMES | NOVEMBER 2022
Virtual Perimetry Reaches More
New virtual reality perimetry system an alternative to Humphrey field analysis. Roibeárd O’hÉineacháin reports
lauCUTU, a new perimetry system that uses a virtual reality (VR) headset and machine and deep learning algorithms, could provide results clinically comparable to those of a Humphrey field analyser (HFA) at a fraction of the cost, according to Visanee Tantisevi MD. “This novel perimetry system will be beneficial to both the healthcare system and the patients by serving as an applicable and affordable screening tool for glaucoma to prevent delayed diagnosis and treatment,” she said. The GlauCUTU system’s VR headset initially presents the patient with the stimulus at its lowest intensity—which gradually increases in intensity until the patient perceives it and presses the clicker. Novel machine and deep learning-derived automated transformation algorithms then convert GlauCUTU sensitivity in seconds into HFA sensitivity in decibel units. On behalf of her associates, Dr Tantisevi explained their study evaluated the GlauCUTU perimetry system and the new transformation algorithms in 62 eyes of 31 participants. They included 16 eyes of eight glaucoma patients and a control group of 46 eyes of 23 participants without glaucoma. Among the glaucomatous eyes, the defects were early in seven, moderate in three, and severe in six. All participants underwent perimetry using the 24-2 test pattern with both the standard HFA and the GlauCUTU system. The statistical analysis revealed no significant differences between the visual field index (VFI) of HFA and the VFI of GlauCUTU transformations based on machine learning or deep learning for the entire data set in all stages of glaucoma. The machine learning algorithm of GlauCUTU had the lowest root
“This novel perimetry system will be beneficial to both the healthcare system and the patients by serving as an applicable and affordable screening tool for glaucoma to prevent delayed diagnosis and treatment.” mean square error (RMSE) and the lowest mean absolute error (MAE). GlauCUTU trained with synthetic data has the highest MAE, which may be due to test-retest variability. Dr Tantisevi noted the GlauCUTU platform has advantages over HFA in terms of comfort, portability, and expense. For example, unlike the HFA, GlauCUTU’s head-mounted VR device does not require the patient to maintain a fixed head position. In addition, the average test duration with the GlauCUTU system is less than five minutes compared to 10 minutes with the HFA. That, in turn, helps decrease test-induced eye fatigue leading to more reliable results. The size and portability of the system mean it is easy to transport to rural, under-resourced areas. Moreover, the GlauCUTU system costs around US$1,000, compared to US$40,000 for the HFA device.
Image Courtesy of P. Kunumpol et al.: GlauCUTU: TUP VR Perimetry, IEEE Access, April, 2022: DOI 10.1109/ACCESS.2022.3163845 Figure 1: GlauCUTU perimetry setup composed of the portable GlauCUTU VR module, a display screen, keyboard, and mouse set.
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Image Courtesy of P. Kunumpol et al.: GlauCUTU: TUP VR Perimetry, IEEE Access, April, 2022: DOI 10.1109/ACCESS.2022.3163845 Figure 2: Grayscale mapping of non-glaucoma subjects evaluated using a) time until perceived, b) GlauCUTU-original, c) GlauCUTU-ML, d) GlauCUTU-DL, and e) HFA. Average time until perceived from shortest to longest is shown in the lightest to darkest tone, respectively. Average sensitivities from lowest to highest are represented by darkest to lightest tone, respectively, in columns b, c, d, and e. Column b is reported in GlauCUTU sensitivity (dB), while columns c, d, and e are reported in HFA sensitivity (dB).
“As accessibility to HFA in low-resource countries is limited, a novel VR technology that is portable and inexpensive has the potential to improve glaucoma care in countries such as Thailand,” she said. Dr Tantisevi added that several studies revealed deep learning has exciting potential in detecting glaucoma. For example, by using archetypal analysis—an unsupervised deep learning approach—it is possible to quantitively and objectively classify regional patterns of visual field loss. The “archetypes” of the analysis are the extremes of measurement. Research shows eyes with high weighting coefficients for archetypes consistent with advanced glaucoma are also more likely to have high cup-to-disc ratios. Conversely, deep learning models using enface retinal nerve fibre layer (RNFL) imaging strongly correlate with standard automated perimetry (SAP) quantitative measurements.
“Deep learning could pave the way for future glaucoma screening, particularly in addressing the undetected cases in our communities,” she added. Dr Tantisevi presented the study during the World Ophthalmology Congress Virtual 2022. GlauCUTU originated from a collaboration between the Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University and the Faculty of Engineering, Thammasat University, Bangkok, Thailand. isanee Tantisevi MD is an Associate Professor V of Ophthalmology, Head of the Center of Excellence in Glaucoma, and based at the Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. firstname.lastname@example.org
EUROTIMES | NOVEMBER 2022
Imaging Techniques Shed Light on Retinal Disease Mechanisms OCTA imaging supports histopathological observations. Dermot McGrath reports from Hamburg
he rich potential of multimodal imaging to shed light on poorly understood anatomical features and disease mechanisms in age-related macular degeneration (AMD) and other retinal diseases was the main focus of the keynote Ophthalmologica Lecture by Enrico Borrelli MD, FEBO at the 22nd EURETINA Congress. Titled “Pushing Retinal Imaging Forward: Innovations and their Clinical Meaning”, Dr Borrelli’s lecture explained how recent advances in retinal imaging have significantly improved the capability to assess retinal disorders in vivo with details resembling histology. Using structural optical coherence tomography (OCT), Dr Borrelli and co-workers investigated the reflectivity of the ellipsoid zone (EZ), which is a surrogate of photoreceptor health. “We demonstrated that the EZ reflectivity is reduced in intermediate AMD eyes, which confirms a damage of photoreceptors since the earliest stages of the disease. More importantly, we found a strong relationship between inner retinal thickness and EZ reflectivity in intermediate AMD eyes, while [we saw] no relationship between these two parameters in healthy eyes. Our results suggest that in AMD, there appears to be some pathological dependence between these two neuroretinal structures, at least on OCT,” he said. Dr Borrelli used structural OCT to investigate whether the transition from intermediate to exudative neovascular AMD has any impact on the inner retina. “Our analysis revealed the development of exudative neovascularization is associated with significant neuronal loss that may be detected once the exudation is resolved. Notably,
“We found a strong relationship between inner retinal thickness and EZ reflectivity in intermediate AMD eyes.” OCT analysis demonstrates a significant relationship between morphological alterations (presence of intraretinal fluid and damage of the outer retinal layers) and the amount of inner retinal thinning,” he said. Dr Borrelli also used optical coherence tomography angiography (OCTA) to demonstrate that the choriocapillaris is impaired (hypoperfused) in intermediate AMD eyes. “We provided imaging evidence to support the histopathologic observation that drusen co-localise to regions of choriocapillaris impairment,” he said. The second part of Dr Borrelli’s presentation focused on imaging biomarkers that may be employed to guide follow-up and treatment of patients with retinal disorders. Dr Borrelli discussed the results of a three-year longitudinal study which showed the presence of intraretinal hyperreflective foci and/or inner choroidal attenuation on structural OCT images is associated with a greater risk for progression to macular complications in patients with chronic central serous chorioretinopathy (CSC). “Our analysis revealed that presence of inner choroidal attenuation, outer nuclear layer (ONL) thinning, and domeshaped pigment epithelium detachment (PED) were risk factors for atrophy within three years, while the presence of intraretinal hyperreflective foci and/or inner choroidal attenuation was associated with a greater risk for progression to choroidal neovascularization (CNV),” he said. Imaging biomarkers may also prove useful in detecting recurrences in myopic CNV that can significantly impact longterm visual outcomes. “Overall, we reported OCT risk factors for developing exudative recurrences within 36 months of follow-up,” he said. Dr Borrelli also cited specific biomarkers he has identified, which are associated with a worse long-term visual outcome in diabetic macular oedema (DME) patients. “An early identification of these OCT findings may adapt therapy in DME patients, and our findings may be employed to guide the optimal anatomic target in patients with this disorder,” he said. Enrico Borrelli MD, FEBO is a retina specialist at San Raffaele Hospital in Milan, Italy. email@example.com
EUROTIMES | NOVEMBER 2022
Visual Risks for PDE5I Users Erectile dysfunction medications increase the risk of retinal and optic nerve pathology. Roibeárd O’hÉineacháin reports
he results of a large observational study indicate that men who regularly use phosphodiesterase 5 inhibitors (PDE5Is) have a nearly two-fold risk of having ocular adverse events such as ischemic optic neuropathy (ION), serous retinal detachment (SRD), or retinal vein occlusion (RVO) as those who do not use the medications. “To our knowledge, this is the largest epidemiologic cohort study to examine the association between these three important ocular outcomes and the use of PDE5Is, one of the most prescribed classes of medications,” the study authors said. “We found a combined increase in the risk of SRD, RVO, and ION associated with the use of PDE5Is in older men. For each individual outcome, use of PDE5Is was independently associated with an increase in risk.” They note the results of their study confirm the findings from previous reports showing an increased risk of ION associated with PDE5I use but also, for the first time, quantifies the risk of SRD and RVO associated with use of these drugs. Based on their findings, the study authors recommend physicians advise regular PDE51 users of the potential of the ocular adverse events and patients alert their physicians of any visual deficits. Speaking with EuroTimes, the study’s lead author, Mahyar Etminan PharmD, MSc, an Associate Professor of Ophthalmology at the University of British Columbia said ophthalmologists may have role to play in that regard. “I am not an ophthalmologist, so I do not like to make specific recommendations. I can say that based on our research, men who have had a previous history of the three conditions should talk with their ophthalmologist before starting or continuing these medications, as these patients might be at a higher risk of developing these conditions,” he noted.
ELEVATED RISK The new study’s cohort included 213,033 men in the PharMetrics Plus insurance database (IQVIA) who were new users of PDE5Is and had received a prescription for the medications every three months in the year prior to entering the study. The case-control analysis included 278 cases of SRD, 628 of RV0, 240 of ION, and 4,584 corresponding controls. The mean age in both groups was 64.6 years. Patients with SRD, RVO, and ION were more likely than those in the control group to have hypertension, diabetes, cardiovascular disease, or sleep apnoea. After adjusting for potential confounding factors such as hypertension, coronary artery disease, smoking, and diabetes as well as sleep apnoea for the ION outcome, the researchers found the incidence rate ratio (IRR) for all three outcomes combined was 1.85, with an incidence of 15.5 cases per 10,000 person-years. As individual outcomes, the adjusted incident ratios were 2.58 for SRD, 1.44 for RVO, and 2.02 for ION, with incidences of 3.8, 3.2, and 8.5 cases per 10,000 person-years, respectively. The study’s findings also indicate more frequent usage increases the risk of adverse events. Dose-response analysis showed those taking five or more prescriptions had an overall incident rate ratio of 2.90, compared to an overall IRR of 1.90 among those taking fewer than five prescriptions.
“This is the largest epidemiologic cohort study to examine the association between these three important ocular outcomes and the use of PDE5Is, one of the most prescribed classes of medications.” The authors note that previous data suggesting an association between the agents has been mostly anecdotal, although a small epidemiological study found an increased risk among PDE5Is and ION. Currently, all PDE5Is include US FDA warnings of the risk of ION, while RVO is listed as a possible adverse event for sildenafil, tadalafil, and vardenafil, but not avanafil. None of the medications carry warnings regarding an increased risk for SRD. The pathogenesis of PDE5I-induced SRD, RVO, and ION remains poorly researched, they add. Theories include a reduced perfusion induced by the medications, which, in turn, makes the circulating blood more prone to coagulation. In addition, PDE5Is as a night-time dosage may further accentuate normal physiologic nocturnal hypotension, which may lead to ischemia.
RETINAL TOXICITY Meanwhile, previous studies share potential visual side effects— such as light sensitivity, a blue haze, or blurry vision—reported in 3% to 11% of patients, depending on the dosage and desired visual outcome. Researchers in these studies have attributed the effects to cross-reactivity with PDE6 in retinal photoreceptors. With very high doses, the effects can be more severe. For example, a case report from 2018 describes a patient who developed colour blindness after receiving a 100 mg dosage of tadalafil, compared to the standard dose of 10–20 mg, to enhance his neurovascular bundle during a radical prostatectomy. Fortunately, the patient later recovered his normal colour vision upon ceasing the medication. The patient’s urologist had advised the tadalafil because it is less cross-reactive with PDE6. “Tadalafil was therefore used in an attempt to regain urologic function without visual impairment. Nonetheless, it produced the same adverse effect once the dosage was increased for greater urologic efficacy,” the report’s authors noted. The research appeared in JAMA Ophthalmology, 2022; 140(5): 480–484). Mahyar Etminan PharmD, MSc, is based at Collaboration for Epidemiology of Ocular Diseases (CEPOD), Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of Vancouver, British Columbia, Canada. firstname.lastname@example.org
EUROTIMES | NOVEMBER 2022
Early Trial Data Promising for Novel DME Treatment Dermot McGrath reports from Hamburg
nterim data from trials of a new drug for patients with advanced diabetic macular oedema (DME) shows the treatment was well tolerated, led to improvements in visual acuity, and preserved retinal structure. Arshad M Khanani MD, MA, FASRS presented 12- and 18-week data from the BEHOLD trial, a phase 2 study of UBX1325 (UNITY Biotechnology), a novel senolytic agent for patients with advanced DME. “The early results showed that the treatment was well tolerated with no serious adverse events and no intraocular inflammation. Patients showed improvement in best-corrected visual acuity (BCVA) through 18 weeks, and the gains were robust across a range of disease severity. The retinal structure was maintained in treated patients compared to sham-treated patients,” Dr Khanani said. UBX1325 proposes a new mechanism of action in age-related ocular diseases by targeting Bcl-xL, a protein senescent cells rely on for survival. “Senescent cells accumulate in areas of disease activity in both DME and wet AMD. They release mediators like growth factors, pro-fibrotic factors, as well as inflammatory factors that drive pathology. UBX1325 targets Bcl-xL to selectively drive apoptosis in senescent cells, restore vascular health, and improve vision,” he said.
“UBX1325 could potentially provide an important benefit as a standalone treatment.” The BEHOLD study is a phase 2a ongoing proof-of-concept study in previously treated patients with DME. Key inclusion criteria included patients with BCVA between 20 to 73 ETDRS letters and central subfield thickness (CST) of 300 microns or greater. “These were previously treated patients and were required to have at least two injections in the preceding six months, with the last injection three to six weeks prior to randomisation. The mean number of injections in this patient population was four before entering this trial,” Dr Khanani said. At baseline, patients received UBX1325 or sham and were then monitored for disease activity at every increment. For all analyses, the primary data sets included 65 patients through 12 weeks and 54 patients through 18 weeks. The study conducted BCVA and CST analyses by mixed model repeated measures (MMRM). “We know this methodology effectively addresses the postrescue data, so the analysis presented reflects the treatment effect and is not confounded by anti-VEGF rescue injections,” Dr Khanani said. EUROTIMES | NOVEMBER 2022
UBX1325 was shown as well tolerated with a favourable safety profile after a single intravitreal injection. “Most of the ocular adverse events were associated with the injection procedure. We did not see any cases of intraocular inflammation, endophthalmitis, retinal artery occlusion, or retinal vasculitis,” he said. In terms of efficacy, patients treated with a single injection of UBX1325 gained 6.1 ETDRS letters at 18 weeks compared to 1.1 letters for sham. The CST data was also encouraging—patients treated with UBX1325 maintained CST values compared to patients receiving sham, where CST gradually worsened over time. Summing up, Dr Khanani said UBX1325 could potentially provide an important benefit as a standalone treatment, in combination regimen, or for use in patients who have a suboptimal response to current standard of care treatments for DME. The trial is ongoing, and UBX1325 is also under evaluation in patients with neovascular AMD in the phase 2 ENVISION study. Dr Khanani presented the results at the 22nd EURETINA Congress in Hamburg, Germany. Arshad M Khanani MD, MA, FASRS is the Director of Clinical Research, Sierra Eye Associates, and Clinical Associate Professor at the University of Nevada, Reno, School of Medicine, US. email@example.com Dr Khanani is a consultant for UNITY Biotechnology and receives research funding from UNITY Biotechnology.
New Therapy for LHON? Encourging results for new gene therapy. Dermot McGrath reports from Hamburg
he first clinical trial results of a new gene therapy for Leber hereditary optic neuropathy (LHON) have shown promising safety and efficacy data with clinically meaningful and sustained visual acuity improvement without toxicity after 12 months of follow-up. Presenting the initial results of post-intravitreal administration of NFS-02 (Wuhan Neurophth Biological Technology) as a LHON treatment, Qiutang Li PhD said the therapy was well tolerated by patients, with no serious adverse events observed thus far. Significant best-corrected visual acuity gains were observed in 6 out of 10 patients at 12 months in the treated eye. “These initial results are very promising, as there is currently no effective treatment for LHON,” Dr Li said. LHON is an inherited mitochondrial disorder characterised by sudden and progressive bilateral vision loss—usually in young males aged 14 to 21, due to the degeneration of retinal ganglion cells. A G3460A point mutation in the ND1 mitochondrial gene causes approximately 13% to 25% of LHON cases, Dr Li explained. NFS-02 uses a recombinant adeno-associated virus vector (rAAV2) via intravitreal injection to deliver healthy ND1 genes to the optic ganglion cells. “The idea is to repair the mitochondrial biological respiratory chain and restore vitality and visual function,” she said. The study included 10 LHON patients aged between 5 and 65 years carrying the ND-1-G3460A mutation who received a single
“This first clinical study of NFS-02 validates the potential of gene replacement therapy as a promising treatment for LHON.”
unilateral intravitreal injection of NFS-02 at two different genome dosages. Group one received 1.5 x 108 vector genome (vg) and group two received 1.5 x 109 vg in 0.05 mL/eye. Researchers compared the incidence of adverse events or serious adverse events—including liver and kidney function in plasma, best-corrected visual acuity (BCVA), optical coherence tomography (OCT), computerised visual field, and retinal nerve fibre layer (RNFL)—before and after treatment at 1-, 3-, 6-, and 12-month intervals. In terms of safety, none of the patients reported drug-related serious adverse events. Treatment-emergent adverse events (TEAE) included seven cases of postoperative conjunctival hyperaemia and two cases of mildly elevated IOP. “The conjunctival hyperaemia resolved spontaneously after one week, and the elevated IOP returned to normal after discontinuation of topical tobramycin-dexamethasone,” Dr Li said. The BCVA showed a clinically meaningful improvement from baseline. A gain of at least -0.3 logMAR (+15 ETDRS letters) was reported in 66.7% of treated eyes in group one and 50% of treated eyes in group two. The higher dose group also showed a statistically significant improvement in visual field index and mean deviation measures at 12 months. Summing up, Dr Li said this first clinical study of NFS-02 validates the potential of gene replacement therapy as a promising treatment for LHON, but further study is needed to confirm the results and better understand the dose-related effect of the treatment. Dr Li presented the results at the 22nd EURETINA Congress in Hamburg, Germany. Qiutang Li PhD is Chief Scientific Officer for Neurophth Therapeutics Ltd, China. firstname.lastname@example.org
iLEARN iLEARN ESCRS is an learning platform, ESCRSiLearn iLearn isiLearn anonline online learning platform, ESCRS is an online learning platform, free members. freefor forESCRS ESCRS members. free for ESCRS members. Visit to over 30 Visitelearning.escrs.org elearning.escrs.org toaccess accessto over 30 over 30 Visit elearning.escrs.org access hours interactive, assessed and hoursof ofhours interactive, assessedassessed andaccredited accredited of interactive, and accredited elearning content, including surgical elearning content,content, including surgicalvideos, videos, videos, elearning including surgical diagrams, animations, quizzes forums. diagrams, animations, quizzesand and forums. diagrams, animations, quizzes and forums.
EUROTIMES | NOVEMBER 2022
Better Education Needed for DME and DR Survey shows patients are not alone in requesting educational material. Cheryl Guttman Krader reports
here is a clear need for improved Global survey enrolment – interim data cut educational materials and jargon-free explanations from practitioners to help patients with diabetic macular oedema (DME) and diabetic retinopathy (DR) better understand the disease and treatment options, according to the results of a global survey presented by Anat Loewenstein MD, PhD. “Clearly, we need to do better, as 55% of patients said they did not know how Of the ~80 clinics in 24 countries enrolled to date, 37 clinics in 16 countries were included many treatments they would have in the in this interim analysis next 12 months, and 50% stated they did not know how long the treatment would last. Over 65% of patients said they found it extremely important to have better material available to understand their DME,” Professor Loewenstein said. The survey’s goal is to better understand Map showing countries included in the interim analysis of the global survey data. DME and DR management from the non-adherent patients: adherent patients were more comfortable perspectives of patients, physicians, and asking their doctor about DME and diabetes and were also more clinic staff. It’s part of the larger, Bayer-sponsored, Barometer likely to seek help in managing their disease. programme—an international coalition of experts in retinal Interestingly, only 26% of providers and 20% of clinic staff disease coming together to enhance care and treatment outcomes considered themselves trained to an expert level in how to avoid by considering the needs and perspectives of patients, caregivers, jargon when communicating with patients, and 29% of providers and healthcare professionals. and 37% of clinic staff indicated they would like more training to “This survey is, to our knowledge, the largest initiative of its address this deficit. kind, providing detailed and systematic data on the challenges and Responses to questions on anti-VEGF treatments and opportunities for managing DME and DR,” she said. contraindications of anti-diabetic medications also highlighted A total of 80 clinics in 24 countries were enrolled at the time the need for greater training. of the presentation, with 37 clinics in 16 countries included “Only 40% of providers considered themselves trained to in the interim analysis Prof Loewenstein presented. The data an expert level on the use of anti-VEGF treatment, and only included 1,073 patients with DME (932 adherent and 100 non15% considered themselves trained to an expert level on the adherent to treatment), 640 patients with DR, 275 providers, and contraindications of anti-diabetic medications, which was a bit surprising to us,” Prof Loewenstein said. Measures to help improve the overall situation could include tailored, easy-to-use educational materials or short information sessions with providers, staff, and patients to improve access to information, education, and guidance, she said. The survey, Prof Loewenstein concluded, finished October 2022, and results of the full analysis as well as country analyses will be presented at future meetings. “The final analysis of this global survey will hopefully generate a wealth of detailed and systematic 558 clinic staff. information to facilitate the enhancement of care and Key findings thus far show 41% of patients with DR said they improve treatment outcomes for our patients,” she said. had not received any information about what to expect with Germany
Enrolled is defined as clinics that have agreed to participate but may not yet be in a contracted status; the final number of clinics may vary at the end of research.
“Clearly, we need to do better [...] Over 65% of patients said they found it extremely important to have better material available.”
treatment over time, while 53% of providers said their clinics did not have sufficient educational material for patients about their condition or what to expect over time. “There is a clear opportunity here to improve educational material about DME and DR since both patients and providers agree that it is extremely important to have better material available to them. This is an important and relatively easy point to improve,” Prof Loewenstein said. The survey showed some clear differences between adherent and
EUROTIMES | NOVEMBER 2022
Prof Loewenstein presented the interim results of the survey at the 22nd EURETINA Congress in Hamburg, Germany. Anat Loewenstein MD, PhD is Chair of the Department of Ophthalmology, Tel Aviv Sourasky Medical Center (TASMC), and Professor of Ophthalmology and Vice Dean, Tel Aviv University, Israel. email@example.com Prof Loewenstein is a consultant to Allergan, Bayer, Beyeonics, Foresight Labs, Notal Vision, Novartis, and Roche.
ESCRS Educational Forum is supported by multiple Industry partners to provide independent didactic education on selected therapeutic areas. The platform combines presentations from ESCRS Winter and Annual Congresses, selected EuroTimes articles, videos and webinars to provide an in depth overview on current clinical outlooks.
Education Forum escrs.org/education/forum/ EUROTIMES | NOVEMBER 2022
Paediatric Cataract Surgery Update Complex cases challenge surgeons. Clare Quigley MD reports from Milan
ttendees at the paediatric cataract session of the World Society of Paediatric Ophthalmology and Strabismus meeting held in conjunction with the annual ESCRS Congress heard a series of presentations on particularly challenging cases. Roberto Caputo MD opened with a discussion of the complex problem of paediatric cataract in uveitis. His approach to cataract in these cases is tailored to each patient. “I ask myself three questions: first of all, who is the patient I am going to treat?” Dr Caputo said. “When can I do the surgery? And how can I do this surgery?” He highlighted that cataract in Juvenile Idiopathic Arthritis (JIA) is particularly challenging, with a high risk of complications.
Dr Hildebrand went on to discuss different approaches to reduce visual axis opacification in children, highlighting the utility of the bag-in-the-lens (BIL), invented by Prof Marie-José Tassignon. For surgeons without access to BIL, optic capture of a sulcus IOL optic through the anterior and the posterior capsule is a potential method to reduce risk of opacification of the visual axis.
“Can we really wait three months without relapses to do surgery?”
Hannah Scanga, genetic counsellor in UPMC Pittsburgh, Pennsylvania, US.
“Can we really wait three months without relapses to do surgery?” The three-month wait is a widespread approach to judging the safe time to wait until cataract surgery in a patient with uveitis, but Dr Caputo questioned whether this is always the best approach, especially in a child with a dense cataract. Marta Morales MD, a paediatric ophthalmologist in Barcelona, Spain, also discussed timing decisions—though in infant cataract surgery. “It is not recommended to implant an IOL before seven months of age,” she said. “This is [particularly] due to the risk of visual axis opacification and subsequent requirement for surgery.” “If we have a dense congenital cataract, we should operate as soon as possible, but it is better not to operate before four weeks of age,” Dr Morales said. “During this age, the anterior segment is still developing.” Performing surgery at this neonatal development stage can increase the risk of glaucoma. Hannah Scanga, genetic counsellor in UPMC Pittsburgh, Pennsylvania, US, talked about genetics of paediatric cataract. “Your highest diagnostic rate will be found with bilateral cataracts,” Ms Scanga said. Determining a genetic cause starts with history and exam, so she suggested examining the parents as well. Important findings in parents can help narrow down the search for a causal mutation—for example, in mothers who are carriers of Lowe syndrome, spoke-like lens changes may be observed. “Genetic causes continue to be identified,” Ms Scanga said. “Customisation is helpful.” She recommended a multigene panel as an effective investigative tool. Göran Darius Hildebrand MD, Oxford, UK, reiterated paediatric cataract surgery is a vital treatment and that problems arise in postponing surgery. “Delayed surgery leads to permanent brain damage in the form of amblyopia, strabismus, and nystagmus.” Dr Hildebrand said the best formulae available for use in children are SRKT and Holladay 1, as evidenced by a recent metaanalysis.i But even the best available formulae do not yield results comparable to the accuracy of biometry in adults. “The [rate of] absolute prediction error outside two dioptres reaches 50%.” This error rate is due to numerous factors specific to children, including technical issues obtaining biometry and variable childhood emmetropization. EUROTIMES | NOVEMBER 2022
Zhong et al. Journal of Refractive Surgery. 2021.
Roberto Caputo MD is Director, Department of Ophthalmology, A Meyer Children’s Hospital, Florence, Italy. firstname.lastname@example.org Marta Morales Ballús MD, SJD Barcelona Children’s Hospital, Barcelona, Spain.
G Darius Hildebrand FRCS, FRCOphth, FEBO is Head of Paediatric Ophthalmology and Strabismus, Oxford Eye Hospital, UK. email@example.com
G L A N C E
We are a society of surgeons who specialise in improving vision and restoring clarity. Since 1991, ESCRS have promoted the education and research of implant and refractive surgery. With over 7,500 member from 130 countries worldwide, ESCRS are a vital global platform for the field of ophthalmology.
LEADERSHIP DEVELOPMENT AND BUSINESS INNOVATION
Lessons in Doing Better for Patients Dr Clare Quigley reviews the ESCRS Leadership Development and Business Innovation Masterclass held during the annual ESCRS Congress in Milan “
hat if loving your patients was the key?” Mr Shareef Mahdavi asked. “Think about your current ophthalmology practice. What if it could be better than you imagined?” Mr Mahdavi’s questions invited the audience—which was, for the most part, ophthalmologists—to reconsider their core motivations and fine-tune their thinking on what they do for patients, with the aim of doing better. “Distance yourself from the general mediocrity of healthcare,” Mr Mahdavi advised the full room of attentive listeners at the daylong course in Milan. “Make one change, then focus on value drivers,” Mr Mahdavi said. “The first step is to love your patients.” Mr Mahdavi’s LinkedIn profile identifies him as an “Expert on Perfecting the Patient Experience”. He heads the consulting firm SM2 Strategic, which advises medical and technology firms, as well as physicians, on adopting new procedures among physicians and consumers. Mr Mahdavi outlined how some doctors go astray of this first step as they build their practice and attempt to grow, using the “Three Little Pigs” fable to illustrate. The first little pig, or little ophthalmologist, built his clinic out of technology; this fragile straw structure swiftly blew down. The second little pig, who built his clinic out of reputation, also found his service floundered, and the sticks fell down. But the third little pig built his clinic on the patient experience, and this solid brick structure stood firm, weathering any wolf’s attempt to bring it down. “How do we stand out?” Mr Mahdavi asked. Ophthalmologists compete for patients’ time, attention, and money. But within healthcare, the patient experience is not on par with other industries, like hospitality, that have moved forward. “Customer experience in healthcare is about ten years behind other industries,” Mr Mahdavi said. Ophthalmologists should look at what they do—and their job responsibilities—through the lens of patient experience to see where they need to make changes. What about marketing? “The truth is, the experience is the marketing,” Mr Mahdavi said. Advertising restrictions apply to healthcare services and vary in different jurisdictions. But providing an excellent patient experience is the best marketing strategy. More questions led to the core of Mr Mahdavi’s message about practice management. What do ophthalmologists do? They provide a service. How do ophthalmologists do their job? They give a patient experience. Why do ophthalmologists do their job? To transform their patients’ lives. The patient is at the centre. “Your role is to be the guide,” he told the ophthalmologists in the room. “The patient is to be the hero.” For patients, their experience is much easier to differentiate than outcomes. At a baseline, patients already expect expertise. Mr Mahdavi ran his masterclass with panel discussions, where panellists discussed and debated different facets of practice management—including the range of patients. And while cataract patients differ from refractive patients, the panel stressed the importance of treating them with the same care. “We give them more than they expect,” Sheraz Daya said of his cataract patients. “We give them all that we give to a refractive surgery patient.” Acknowledging it is not easy for ophthalmologists to make some changes they desire in their workplace, Mr Mahdavi said EUROTIMES | NOVEMBER 2022
a good place to find opportunities is looking at how the patient ventures through the service they provide. “Rekindle the human connection that is so important to healthcare,” he advised. “A patient doesn’t come to you caring about your solution, they come to you caring deeply about their problem.” One key problem that repeatedly comes up is waiting time. It is among the hardest to improve. “The process of healthcare is not the process of car manufacturing,” Sheraz Daya commented. And while ophthalmologists shouldn’t place patients on a timer, waiting should nevertheless be minimised. Changes, Mr Mahdavi said, can start right away. Take the term waiting room, for example, which he dislikes. Better to rename it “reception,” where the patient can relax. Pay attention to what goes on in this area. Don’t play the news on the TV. “Have the nature channel playing or a nice nature documentary,” he advised. News too often features disasters and negative commentary about the world, which can increase anxiety for those watching. Every interaction with the clinic is an opportunity for the patient to weigh judgement towards or against the physician. Each touchpoint can go either way. Doctors need to keep in mind that their interaction with the patient is one of a series for that patient, Mahdavi said. Pitfalls include asking the patient information the doctor already has and having excess waiting time designed to fit the doctor’s schedule. The masterclass was entertaining as well as enlightening, as the informal panel discussion sparked questions from the audience.
“Rekindle the human connection that is so important to healthcare... A patient doesn’t come to you caring about your solution, they come to you caring deeply about their problem.” Topics ranged from ideal lighting in the clinic to smell to where is the best place to recruit staff. The panel discussed different approaches for pricing and whether to publish surgical fees online. One audience member asked about buying online reviews. “You can buy reviews,” panellist Julien Buratto said. “Most of them will have strange names—you’ll know it’s fake instantly.” The take-home: hold off for genuine reviews. Shareef Mahdavi has published Beyond Bedside Manner, a book all about perfecting the patient experience. It is available on amazon.com for anyone interested in finding out more.
27 th ESCRS WINTER MEETING
PORTUGAL 10 –12 MARCH 2023 TIVOLI MARINA, VILAMOURA ALGARVE
Inaugural Sustainable Exhibitor Award
Johnson & Johnson Vision was awarded the inaugural ESCRS Sustainable Exhibitor Award at the annual ESCRS Congress in Milan. The award recognises the company’s “outstanding efforts in innovative booth design and communication leading up to and during the conference.” Johnson & Johnson Vision produced a series of videos providing an overview of its sustainability efforts and progress to date. Half of its booth in the exhibit hall was made from recycled or recyclable sources, and the company plans to use 90% of the booth again. The company also purchased offset to account for 100% of predicted CO2 emissions from the energy used at booth and team travel. “This was a great surprise. The team is passionate about sustainability in Europe. This was the culmination of two years of work reviewing how we construct our booth as well as looking at how we manufacture our products, what we can do better, what can we do to protect the Earth,” said Erin McEachren, Regional Vice President, Europe, Middle East & Africa, Johnson & Johnson Surgical Vision. www.jnjvisionpro.com
Haag-Streit announces the winners of slit lamp imaging competition
Haag-Streit announced the winners of the “Haag-Streit Slit Lamp Imaging Competition”. First place has been awarded to Utpal Sarkar from Disha Eye Hospitals Barrackpore in Kolkata, India. His winning image, taken with a Haag-Streit BX 900 slit lamp imaging system, shows a case of spherophakia. Second place has been awarded to Rob Hancock from Wirral University Teaching Hospitals in Wirral, United Kingdom. His image, also taken on a Haag-Streit BX 900 slit lamp, displays a patient with Ocular Albinism and has been captured with iris transillumination technique. Third place has been awarded to Kathleen Warren from Duke Eye Center, Durham, North Carolina, United States. Her winning image displays a case of epithelial ingrowth, taken with a Haag-Streit BX 900 slit lamp. The winning images can be seen at www.haag-streit.com.
EUROTIMES | NOVEMBER 2022
ROLF SCHWIND STEPS DOWN Rolf Schwind, long-time CEO of SCHWIND eye-tech-solutions GmbH, has withdrawn from active leadership of the company and joined the Advisory Board. In that capacity, he will continue to actively contribute to the growth of SCHWIND with his more than 40 years of extensive experience in the ophthalmology industry. During his tenure, the company shipped its first eye laser (1992), developed the AMARIS refractive laser platform, and, most recently, expanded the product portfolio into an entire refractive suite with the latest laser model, the SCHWIND ATOS femtosecond laser. The previous COO, Domenic von Planta, has taken on the responsibilities of CEO. www.eye-tech-solutions.com
ALCON TO ACQUIRE AERIE PHARMACEUTICALS Alcon announced it would acquire US ophthalmic drug company Aerie Pharmaceuticals in a merger. Aerie Pharmaceuticals is best known for Rocklatan® (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% and Rhopressa® (netarsudil ophthalmic solution) 0.02% eyedrops used primarily for glaucoma treatment. The company also has a pipeline of interesting drugs, including AR-15512, a Phase 3 product candidate for dry eye disease. Alcon also recently expanded its eyedrop portfolio to include exclusive US commercialisation rights to Simbrinza® from Novartis, and Eysuvis® and Inveltys® from Kala Pharmaceuticals. www.alcon.com
THOMAS KOHNEN European Editor of JCRS
OS 4TM THE NEXT GENERATION
JCRS HIGHLIGHTS NEW GLISTENING-FREE HYDROPHOBIC IOL PERFORMS WELL The new CT LUCIA 611P IOL monofocal single-piece hydrophobic acrylic intraocular lens (IOL) achieved excellent refractive predictability, stability, and visual performance in a multicentre US clinical trial. In the study, 339 eyes of 339 patients underwent implantation of the new IOL. Among 310 eyes with 12 months follow-up, 85.8% (266/310) were within 0.5 D of emmetropia, and implanted (300/310) were within 1.0 D at their last visit. Manifest refraction spherical equivalent remained stable throughout follow-up with a mean value of 0.03 D at 12 months. Furthermore, the mean 12-month uncorrected distance visual acuity was 0.09 logMAR and the mean corrected distance visual acuity was 0.02 logMAR. Regarding posterior capsule opacification, only 3.5% (11/310) underwent Nd:YAG capsulotomy within the first year. Moreover, none of the IOLs developed glistenings. In adverse events, there were two cases of IOL tilt, neither of which caused visual symptoms, and two cases of IOL decentration, one of which required IOL removal. S C Schallhorn et al, “Outcomes of a multicenter US clinical trial of a new monofocal single-piece hydrophobic acrylic IOL”, 48(10): 1126–1133.
The new OS 4 marks the beginning of the next generation of retina, glaucoma and cataract surgery. The all-in-one platform has received numerous exciting features that provide even more comfort, precision and safety.
SHAPE-CHANGING PRESBYOPIC IOL SAFE AND EFFECTIVE A new shape-changing presbyopic IOL appears to provide clear functional vision performance across a range of distances with an acceptable safety profile, according to the results of a prospective multicentre noncomparative clinical trial. The new lens, called the Juvene IOL (JIOL, LensGen, Inc.), is composed of a circumferential blue haptic and carries a clear central optic and a fluid lens with a flexible anterior surface filled with proprietary silicone oil. The lens is designed to transfer natural capsular bag forces to the haptic, causing compression of the fluid lens. Among 58 eyes that completed the 12-month visit, the mean monocular logMAR-corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity were 0.01, 0.08, and 0.24, respectively. The most frequent adverse events were prolonged inflammation in six eyes and cystoid macular oedema in four eyes. All resolved without sequelae by the 12-month visit. S Garg, “Twelvemonth clinical outcomes after implantation of a new, modular, anterior shape-changing fluid optic intraocular lens”, 48(10): 1134–1140.
Light: 45% more power*, maximum visibility Pedal: Multifunctional with over 100 setting options Phaco: Speedier readiness, greater controllability User comfort: Even more userfriendly and communicative
POOR EVIDENCE FOR OCULAR INJECTIONS FOR POST-CATARACT OEDEMA
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Not available for sales in the US *Oertli data on file
Ocular injections to treat post-cataract macular oedema have shown promise in many published studies—but a new systematic review shows all those studies suffer from moderate to high degrees of bias. The review authors analysed 18 studies involving intravitreal steroid injections, intravitreal vascular endothelial growth factor inhibitor injections, intravitreal tumour necrosis factor-alpha inhibitor injections, posterior sub-Tenon steroid injections, or intravitreal steroid implants. They found that using the Cochrane Collaboration risk of bias tools, 15 studies (83%) had high risk for bias, and the remaining three a moderate risk for bias. The most common sources of bias were lack of reproducibility of methods, unmasked assessments, lack of statistical testing, selective reporting of results, and missing outcomes data. G Ahmadyar, “Ocular injectable treatment options for postcataract macular edema: systematic review”, 48(10): 1197–1202.
Laser integration: More safety, fully automated user protection filter
EYE SURGERY. SWISS MADE.
JCRS is the official journal of ESCRS and ASCRS
EUROTIMES | NOVEMBER 2022