EuroTimes March 2022, Volume 27, Issue 2

Research Education Innovation

ESCRS’s vision is to educate and help our peers excel in our field. Together, we are driving the field of ophthalmology forward.

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Contributing Editors

Cheryl Guttman Krader

Howard Larkin

Dermot McGrath

Roibeárd O’hÉineacháin

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Priscilla Lynch

Soosan Jacob

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Published by the European Society of Cataract and Refractive Surgeons, Temple House, Temple Road, Blackrock, Co Dublin, Ireland. No part of this publication may be reproduced without the permission of the executive editor.

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ESCRS PRESIDENT

Making a Difference

– Archbishop Desmond Tutu

MEDICAL EDITORS

Two years ago, in March 2020, it was becoming clear that the world faced a major threat in the form of a potential pandemic wrought by the SARS-CoV-2 virus. In only a few months, the coronavirus spread to every corner of the world. No person or region was unaffected. Medicine is perhaps the most affected of all professions.

Two years later, the virus is still with us, continuing to spread and mutate. But the scientific community has responded with incredible alacrity. Thanks to the world’s research institutions, we now know a lot more about the virus—we have effective vaccines and antiviral treatments. But every time we think it is safe to relax and take off our masks, maybe go out for a meal, another outbreak causes us to reconsider.

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 (USA), 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)

The pandemic has helped us remember how interlinked we are on a global scale.

The ESCRS was able to hold its annual meeting in person in Amsterdam in 2021 during a brief respite, with plenty of caution, lots of testing, masks at the ready. There was a palpable relief among those who attended, seeing friends and colleagues, attending a live conference that reminded us of better times. There was a feeling that we could adapt and function within the constraints of the pandemic. Sadly, the virus came rushing back in the form of the delta and omicron variants, and we once again had to make our February 2022 ESCRS Winter meeting virtual.

Meanwhile, on the clinical front, we are still trying to solve the riddle of presbyopia treatment that restores the full range of vision without inducing unwanted photic effects. We report presentations from recent conferences that look at new IOL options, better outcomes assessment, and post-SMILE enhancements. We also look at some remarkable developments in gene therapy for retinal disease.

The pandemic has helped us remember how interlinked we are on a global scale. We face a huge issue in the form of global climate change. The cover story by Dr Soosan Jacob looks at what role ophthalmology can play towards the goal of a more sustainable approach to more efficient, less wasteful care delivery that will help meet the challenge on the global scale. This timely article considers how the objective of sustainability is best adopted when there is a maintained/improved standard of care, reduced cost, and shared goals of responsible behaviour. She highlights many changes made at the 104 branches of Dr Agarwal’s Eye Hospitals in India that have reduced waste without compromising patient safety or clinical outcomes.

Dr Jacob’s article also highlights the value of telemedicine in ophthalmology. This includes large-scale screening of retinal conditions, remote consultations, the capture and quick transmission of slit-lamp images, and expanding educational opportunities while reducing the need to travel.

Dr Jacob reminds us we can all play a part in helping to make a more equitable world for subsequent generations that is not ravaged by climate change, loss of biodiversity, depleted natural resources, and the resulting challenges from these.

José Güell

Paul Rosen

Thomas Kohnen

Oliver Findl

Do your little bit of good where you are; it’s those little bits of good put together that overwhelm the world.

Fundus image acquisition with macula and disc capture in one image on OCT, for enhanced screening and clinical efficiency

FAF model

Standard model

Retina map

Denoising technique

Widefield image capture in a single shot

High definition OCT image for all scans

Denoising technique with deep learning

Images courtesy of Rodrigo Abreu González, MD, PhD, FEBO, University Hospital of La Candelaria, Spain

Sustainability and Waste Reduction in Ophthalmology

Dr Soosan Jacob MS, FRCS, DNB

As responsible world citizens, we need to look inwards for means to reduce our contribution to climate change and non-sustainable practices. Ophthalmology as a specialty needs to do its part in making a difference.

Lasting prosperity needs sustainability— not just industrialisation and economic development but ecological and environmental health and social equity. By definition, sustainable development means making sure we meet our needs while ensuring future generations are not deprived of the ability to meet theirs. A crucial pillar of sustainability is preserving our environment and decreasing our carbon footprint so Earth and its living systems perpetually thrive and continue as a wonderful home for all our future generations.

Statistics regarding healthcare contribution to greenhouse gases can be alarming, with most of us probably unaware of the magnitude. For example, the National Health Service contributes one-fourth of the carbon footprint of the public sector of the United Kingdom. The healthcare sector of the US contributes one-tenth of its greenhouse gas emissions. These are possibly extrapolatable to most developed countries to a greater or lesser extent.

Sustainability is best adopted when there is a maintained/improved standard of care, reduced cost, and shared goals of responsible behaviour.

Ophthalmic patients often need multiple outpatient visits for chronic disorders, each contributing to carbon emissions. Surgical solutions are often needed, and faster, more ophthalmic surgeries can be performed in a short time, leading to increased waste generation—compounded further by the high use of disposables.

CATARACT SURGERY’S HIGH CARBON FOOTPRINT

Since cataract surgery is one of the most common elective procedures and has a high carbon footprint (one cataract surgery equates driving a car for 500 kilometres), it would be an ideal case study to try and initiate changes in. Small-incision cataract surgery has less carbon footprint than phacoemulsification, however, it is not practical to do this for all cases. Most contribution from cataract surgery is from pharmaceuticals and disposables. A focused approach is needed here.

At the moment, organisational hesitancy impedes the adoption of sustainable practices, mainly because of regulatory and practical obstacles to instituting changes. The US, for instance, doesn’t allow phaco tip reuse. Regulatory obstacles are more common in some parts of the world than others. However, even where changes are happening, they are more voluntary than compulsory. In an ideal scenario, regulatory bodies would make adherence to a decreased carbon footprint compulsory while maintaining the framework of safety. But in reality, the converse seems to be the case. Wider awareness is therefore needed to understand sustainable practices need not mean lower standards. Research should be directed towards setting safe and sustainable protocols. Data regarding waste generation from each procedure should be analysed and attempts made to decrease carbon footprint.

A recent landmark publication from the Aravind Eye Care System (AECS) that included 85,552 patients studied the effect on postoperative endophthalmitis rates after introducing a set of four temporary operating room protocols as part of COVID19 related protocols. These protocols, often mandatory in the West even before COVID-19, included gowning of patients, changing surgical gloves between each case, cleaning OR floors and counters between patients, and having only one patient at a time in the OR for preparation and surgery. No decrease in endophthalmitis rate was found when adopting these measures. And significantly, the rate in more than 3,35,000 cases without these additional measures (0.01%) was less than that reported by the American Academy of Ophthalmology (0.04%), pointing to the futile waste of resources and the increase in carbon footprint introduced by such measures.

Possibly the existence of many other such “standard” protocols needs to be revisited. Another study by AECS found its minimalistic yet proven-safe approach generates 5% of the carbon footprint per phacoemulsification as that of the United Kingdom.

At the Dr Agarwal’s group of Eye Hospitals, we have dedicated sterilisation units at each of the hospital chain’s 104 branches, with the type and capacity varying depending on type of surgeries performed at each branch. Surgical gowns, cloth drapes, etc., are laundered, sterilised, and reused while minimum standards

Sustainability is best adopted when there is a maintained/improved standard of care, reduced cost, and shared goals of responsible behaviour.

are set to ensure safety. Larger reusable cotton draping is topped by a smaller, impermeable single-use drape of cellulose/polyethylene. Unlike the West, most surgeries are carried out without the patient sedated, and local anaesthetic vials are shared. These measures are not unique to us alone. Many other large and small volume centres in the developing and underdeveloped world share these protocols as well as the protocols adopted by AECS. These include autoclaving and reusing drapes and surgeon’s gowns as well as sharing anaesthetic vials, dilating drops, multidose medications, irrigating solutions, intra-ocular drugs, etc. Irrigation/aspiration tubing, phaco tips, vitrectomy sets, etc., are sterilised and reused a certain maximum number of times until efficiency starts to drop.

Sustainability should and indeed is already being widely implemented by our specialty via various other measures too.

TECHNOLOGY ADOPTION

Ophthalmology has always been at the forefront of technology, and COVID-19 helped hasten this trend. Many services and meetings can be effectively conducted online. Tele-ophthalmology and camp services introduce great efficiency into primary and secondary care centres, reducing the need for travel by both patients and specialists and making possible decentralisation of specialised opinion and care. Easy capture and quick transmission of slit-lamp images and digital diagnostic outputs by opticians, optometrists, or even trained personnel allow rapid and accurate clinical and surgical decisions and even cross-subspecialty consultations.

Camp/mobile screening services and diagnostic/surgical units can reach large catchment areas and provide specialist care. The Orbis Flying Eye Hospital—with operating and recovery rooms, classrooms, etc., on the plane—is one such example.

Artificial Intelligence and machine learning can detect (with high sensitivity and specificity) certain diseases such as diabetic retinopathy, while predictive modelling can suggest treatment guidelines that can act as a base to make decisions or refer if required.

Tele-education helps facilitate training and mentoring remotely. At the Dr Agarwal’s Eye Hospital, an extensive network of electronic medical records and digital communities makes it possible to give instant opinions, educate, and train while also making follow-up of patients possible from anywhere in the world. Cloudbased EMR helps decrease the need for paper, large physical storage spaces, and related disadvantages. Efficient supply chains and logistics help prevent wastage of material, transport, and manpower and thus decrease carbon footprint.

VOLUNTARY AND CHARITABLE WORK

Preventive eyecare, charity-based screening, and surgical camps are widely adopted practices, especially in parts of the world such as India and Nepal. Screening in large areas such as communities, elderly care homes, and schools is an efficient way to enhance community health while decreasing carbon footprint. Investing in preventive health strategies avoids the high carbon output from treating disease in the future.

Primary, secondary, and tertiary care centres, hub, and spoke models—as well as shared-resource practices—decrease resource requirements, optimise utilization, and make care available while contributing towards local economy and self-sufficiency by bringing balance between urban and rural development.

We need to do still more. Equipment manufacturers should be motivated to make remote access and remote capturing possible. Decreasing equipment size while increasing or maintaining sensitivity, specificity, and operating/software prowess is important. One example is the virtual reality perimetry the AVA™ (Elisar, India), which is as accurate as the Humphrey perimeter but handheld and easily portable.

Efficient water taps, lighting designs, optimal energy utilization techniques, efficient IT systems with decreased environmental footprint, and clean energy sources such as solar or wind energy should be incentivized. Just as carbon taxes and carbon trading schemes encourage energy conservation, it is time that safe and scientific reduction of surgical waste and adoption of other sustainability measures are incentivized and celebrated by all stakeholders.

As parents, we intuitively try and ensure for our children a future with a good home and the right environment. So why then is there hesitancy in adopting sustainable practices? Advocacy is needed by individuals as well as state, national, and international level ophthalmic societies and organisations to remove regulatory and practical obstacles to instituting change. Other involved associations such as national medical and nursing associations and regulatory bodies need to be made aware of the difference in ophthalmic surgeries compared to nonocular specialties.

The industry and manufacturers should be encouraged to make reusable options, and the logic behind many of the “single-use” directives should be re-examined. The “reuse is misuse” philosophy adopted by health systems needs to change. In addition, our practice as a specialty needs to adopt general principles of sustainability that are universally applicable. We owe it to our children to play our part in allowing them to have a world not ravaged by climate change, loss of biodiversity, depleted natural resources, and all the consequences arising from these.

Dr Soosan Jacob is Director and Chief of Dr Agarwal’s Refractive and Cornea Foundation at Dr Agarwal’s Eye Hospital, Chennai, India, and can be reached at dr_soosanj@hotmail.com.

A, B—Used drapes and surgical gowns are laundered, sterilised, and reused again. C, D—In-hospital sterilisation units allow immediate sterilisation and reuse.

Defining the Limits of Excimer Laser Surgery for Hyperopia

Accommodation in younger patients may result in undercorrection.

Dermot McGrath reports

Despite significant improvement in visual outcomes driven by advances in laser technology in recent years, excimer laser-based hyperopia correction remains more difficult than myopia correction, especially for higher corrections, according to Jesper Hjortdal MD, PhD.

“There have been significant improvements in the safety, efficacy, stability, and accuracy of LASIK treatment for hyperopia and hyperopic astigmatism within the past two decades. However, it is clear accommodation in younger patients may result in differences in manifest and cycloplegic refraction resulting in apparent undercorrection,” he reported.

Looking at the evolution of excimer-laser-based correction for hyperopia over the years, Dr Hjortdal said such corrections are typically less forgiving than those for myopia due to the nature of the surgical procedure.

“For hyperopia, the surgeon has to remove more tissue in the periphery and the optical zone will not be as large as for myopic correction. This means that less correction can be obtained. The centration of the laser correction is also very important in hyperopic corrections due to the smaller optical zone,” he said.

Although photorefractive keratectomy (PRK) is a viable option for hyperopic treatments, Dr Hjortdal said LASIK has steadily become the laser treatment of choice over the years.

“LASIK is attractive to patients because there is no pain compared to PRK, and the visual recovery is rapid with good postoperative vision on day one after surgery,” he said.

In terms of which procedure delivers better outcomes in hyperopic patients, Dr Hjortdal said a Cochrane study that addressed the question in 2012 found a lack of randomised controlled trials precluded any firm conclusions, but the nonrandomised trials appeared to agree both treatment approaches offered comparable efficacy.

Some interesting results were also reported in a recent single centre, retrospective, non-comparative study on hyperopic LASIK on 379 eyes treated with LASIK for hyperopia and hyperopic astigmatism.i

“The authors also included a meta-analysis of 28 published studies [dating] back to 1998. Of the small number of patients over +3.0 D treated, there was a clear tendency for undercorrection. And [fewer] patients obtained 20/20 uncorrected distance visual acuity and experienced greater loss of lines of vision. Overall, the results were better for patients treated after 2005, undoubtedly due to improvements in excimer laser technology and larger treatment zones after that period,” he said.

Excimer laser treatment may also be an option for select cases of hyperopia in children, Dr Hjortdal said. He cited the Eustis [et al] study in which simultaneous PRK and strabismus surgery was deemed safe and effective in treating accommodative esotropia.ii Another study by Kulikova [et al] reported FS-LASIK effective in children with hyperopia and anisometropic amblyopia when traditional methods failed.iii

Dr Hjortdal said his personal preference is to recommend correction of hyperopia with excimer laser up to +4.0 D of spherical equivalent refraction.

“Using femtosecond-LASIK is probably preferable to surface ablation techniques and time will show whether SMILE for hyperopia becomes a safe, efficient, and accurate surgical technique,” he concluded.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

i Moshirfar M et al, Ophthalmology and Therapy, vol. 10, 3 (2021): 547–563.

ii Eustis et al, Am J Ophthalmol. 2018 Mar; 187: 125–129.

iii Kulikova et al, J Refract Surg. 2020 Jun 1; 36(6): 366–373.

Jesper Hjortdal MD, PhD, is a consultant and clinical professor of ophthalmology at Aarhus University Hospital in Denmark and medical director of the Danish Cornea Bank. jesper. hjortdal@dadlnet.dk

“LASIK is attractive to patients because there is no pain compared to PRK, and the visual recovery is rapid with good postoperative vision on day one after surgery.”

Combining EDOF and Monofocal IOLs

Implanting EDOF in second eye may improve vision outcomes. Howard Larkin reports

Patients implanted with an extended depth of focus (EDOF) intraocular lens in the second eye after receiving a monofocal IOL in the first may reap similar vision benefits as those implanted with EDOF lenses bilaterally, reported Guy Kleinmann MD.

The usual recommendation is to implant EDOF lenses in both eyes, Dr Kleinmann said. But occasionally, patients already implanted with a monofocal don’t like it, don’t want monovision, and ask for another solution.

THREE GROUPS COMPARED

The retrospective study compared 18 patients implanted with an AcrySof® SN60WF/SA60AT (Alcon) monofocal lens in one eye and a TECNIS Symfony™ (Johnson & Johnson Vision) EDOF lens in the other. Thirty-six patients were implanted bilaterally with the Symfony and 22 implanted bilaterally with the AcrySof lenses. All patients had their vision examined and answered a questionnaire at least three weeks after surgery.

Mean uncorrected distance visual acuity outcomes were similar between the eyes implanted with an EDOF and a monofocal, at about 20/21, and those with the EDOF lens bilaterally, at about 20/22 (p=0.043). The bilateral monofocal group achieved about 20/25, which was significantly worse than the mixed implant group (p=0.002).

Both the mixed implant and the bilateral EDOF groups had a mean intermediate uncorrected vision of about 20/25. Intermediate vision results were not reported for the bilateral monofocal group. Mean uncorrected near vision was 20/25, 20/32, and 20/40 in the three groups respectively, with no significant difference in spherical equivalent among them.

More than 84% of patients in all groups rated their distance vision “good” or “excellent,” with 61.5%, 72%, and half of patients in the three groups (EDOF and monofocal, bilateral EDOF, and bilateral monofocal, respectively) saying the same of intermediate vision, results that were not statistically significant, Dr Kleinmann reported. However, both groups receiving EDOF lenses reported significantly better near vision than the bilateral monofocal group.

Glare and halo reports were low in all groups. Overall spectacle independence for any distance was 61% for the mixed lens group, 78% for the bilateral EDOF group, and 50% for the bilateral monofocal group. These differences were not statistically significant.

“Patients implanted with a monofocal IOL in previous cataract surgery who are interested in improving their visual outcomes and do not like monovision can be considered for implantation of an EDOF IOL in the second surgery,” Dr Kleinmann concluded.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

Prof Guy Kleinmann MD is chairman of the Ophthalmology Department at the Edith Wolfson Medical Centre, Holon, Israel. guykl.email@gmail.com

EUREQUO and Beyond

Registry provides real-world, evidence-based knowledge to cataract and refractive surgeons.

Roibeárd O’hÉineacháin reports

The European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) continues to evolve in the scope of its research and the number of its participants collecting and collating data on cataract and refractive surgery, according to Professor Mats Lundström MD, PhD.

Prof Lundström noted that EUREQUO started in 2008 as a three-year project, co-funded by the EU and ESCRS, with 11 national societies and EyeNet Sweden as associated partners. Since October 2011, the project has been funded entirely by the ESCRS. As of January 31, 2020, it has included data from 3,296,147 cataract and 150,191 refractive cases, and currently, 25 countries are participating.

“The purpose of the EUREQUO project was to improve treatment and standards of care for cataract and refractive surgery, make a significant impact on the exchange of best practices [concerning] patient safety, and develop evidence-based guidelines for cataract and refractive surgeries across Europe. Today it is also a reference database for ESCRS members,” Prof Lundström said.

He noted the many reasons for participating: As a service, it provides ESCRS members a means of benchmarking, outcome comparisons, and stimulation for improving cataract and refractive surgery. In addition, participation contributes new knowledge in the field as well as provides an opportunity for research and education.

Between 2008 and 2013, EUREQUO extended its data to include information from countries outside of Europe and added new parameters to be investigated and patient-reported outcomes. The registry’s steering committee designed and validated new questionnaires and changed its data collection system to make it more flexible.

CLINICAL RESEARCH

Using its huge database, EUREQUO has published several studies regarding practice styles and outcomes in cataract and refractive surgery. They include evidence-based guidelines for cataract surgery published in 2012, a 2013 study on visual outcomes of cataract surgery, a 2015 study on the changing pattern of cataract surgery indications (which also included data from the Malaysian database), and a 2016 case-control study comparing femtosecond laser-assisted cataract surgery with standard phacoemulsification cataract surgery.

EUREQUO has also published a number of studies analysing surgical complications and outcomes in complex cases. They include a 2018 study on risk factors for refractive error after cataract surgery, a 2015 study on cataract surgery outcomes in eyes that have undergone previous corneal refractive surgery, a 2020 study on risk factors for dropped nuclei in cataract surgery, and a 2020 study on cataract surgery in eyes that have undergone previous vitrectomy.

EUREQUO is now in the process of making its system more efficient and user-friendly. One approach under consideration is a data warehouse with automated data entry. There remain several technical, ethical, and legal issues to be resolved to meet that goal. One idea under consideration is travelling algorithms, where countries collect data in a similarly structured way and use an algorithm to calculate and analyse it. The final data then enters the international database.

Prof Lundström acknowledged all participating surgeons, clinics, and patients, as well as all steering group members past and present—most especially the late Peter Barry, “who saw the light”.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

Mats Lundström MD, PhD is the clinical director of EUREQUO and Professor of Ophthalmology at Lund University, Sweden. mats.lundstrom@med.lu.se

“The purpose of the EUREQUO project was to improve treatment and standards of care for cataract and refractive surgery, make a significant impact on the exchange of best practices [concerning] patient safety, and develop evidence-based guidelines for cataract and refractive surgeries across Europe.”

Retreatment after SMILE

What are the benefits and techniques for performing thin-flap LASIK? Cheryl Guttman Krader reports

Photorefractive keratectomy was the initially recommended method for retreatment after SMILE. Alternatively, refractive surgeons can choose from two other approved “on-label” procedures that involve converting the SMILE cap into a LASIK flap either by the CIRCLE technique or with a side cut only.

For Dan Z Reinstein MD, MA (Cantab), FRCSC, FRCOphth, DABO, FEBO, however, an off-label thin-flap LASIK technique is the preferred approach.

“LASIK is a great procedure that gives patients the fastest visual recovery in a way that, for [their] experience, is also the least invasive. It has the best accuracy and, compared to the CIRCLE or sidecut only procedure, thin-flap LASIK preserves a greater amount of uncut stroma,” he said.

PLANNING FLAP THICKNESS

OCT Epithelial Map showing the maximum epithelial thickness value within the central cornea, from which it can be determined the new interface programmed at 100 µm will be well over four standard deviations (4 x 4.4 µm=18 µm) from the epithelium above and well over four standard deviations from the stromal cap interface below.

Dr Reinstein said he generally performs SMILE with a minimum of a 135 μm cap because this has the benefit of maximising corneal nerve preservation and biomechanical residual strength.i Additionally, using a 135 μm cap almost always allows for a thinflap LASIK enhancement with a 100 μm flap. Surgeons in the US who must do SMILE with a 120 μm cap can create a 90 μm flap when doing a LASIK retreatment, he suggested.

The flap thicknesses he recommended for these two scenarios mathematically derive from calculations that consider the standard deviation of the VisuMax femtosecond laser and the creation of a flap that will not cross superficially into the epithelium or deeper into the SMILE interface. As an added precaution, Dr Reinstein routinely evaluates epithelial and cap thicknesses on a three-dimensional pachymetry map obtained using the very highfrequency digital ultrasound Insight® 100 (ArcScan Inc) or an anterior segment optical coherence tomography such as the MS-39 (CSO Italia) to assess the three-dimensional biometry, and hence safety of performing a thin-flap LASIK enhancement.

LESSONS FROM THE LEARNING CURVE

The safety and success of performing a thin-flap LASIK enhancement over SMILE also involve the use of a specific flap lift technique and appropriate LASIK nomogram.

“We now teach the specifics of LASIK over SMILE in our Forefront Refractive Surgery Courseii and have delineated the method in our textbookiii so others may learn from all of the difficulties we encountered during the development of this protocol,” Dr Reinstein said.

The flap lift technique Dr Reinstein developed at the London Vision Clinic was refined over time to minimise the risk of tearing the SMILE incision or entering the SMILE interface, creating multiple planes. Described as a bimanual inferior pseudo-hinge fulcrum technique, a review of outcomes for a total of 135 LASIK retreatment cases performed using different flap lift techniques established its safety.iv The analysis, updated

to include all treatments to date, showed no complications occurred in the last 237 retreatments, which represented all cases performed using the optimised approach.

Dr Reinstein said analyses of the refractive outcomes of the LASIK enhancements showed good accuracy for correcting astigmatism and hyperopia.v However, the analyses did note a tendency for overcorrection in cases of myopic enhancements. He explained that, in retrospect, this could have been expected, as he performed these myopic enhancements using the same nomogram as for consecutive myopic LASIK enhancement. The epithelial profile changes after myopic SMILE being different from those of LASIK require a different nomogram. The analysis found no nomogram adjustment was needed for enhancements after SMILE using the TSA or Triple-A ablation profiles on the MEL 90— although the data entry did need to be increased for enhancements after LASIK.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

i Reinstein DZ, Archer TJ, Randleman JB. “Mathematical model to compare the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction”. Journal of Refractive Surgery. 2013 Jul; 29(7): 454–460. doi: 10.3928/1081597X-20130617-03. Erratum in: Journal of Refractive Surgery. 2017 Nov 1; 33(11): 788. PMID: 23820227.

ii www.londonvisionclinic.com/courses

iii The Surgeon’s Guide to SMILE. Reinstein DZ, Archer TJ, Carp GI. ISBN 10: 1630912654. Slack Inc. 2018.

iv Journal of Cataract & Refractive Surgery. 2018; 44(11): 1355–1362.

v Reinstein DZ, Carp GI, Archer TJ, Vida RS. “Outcomes of Retreatment by LASIK after SMILE”. Journal of Refractive Surgery. 2018 Sept 1; 34(9): 578–588. doi: 10.3928/1081597X-20180717-02. PMID: 30199561.

Dan Z Reinstein MD, MA (Cantab), FRCSC, FRCOphth, DABO, FEBO is the medical director of the London Vision Clinic, London, UK. dzr@londonvisionclinic.com

Update on Premium IOL Evaluation

Premium IOLs require premium assessment of postoperative optical quality. Roibeárd O’hÉineacháin reports

Amyriad of new presbyopic IOLs with a range of optical qualities designed to provide the optimum compromise between depth of focus and quality of vision are now becoming available. Assessing and comparing outcomes with the lenses requires a careful examination of the image quality they produce in the eye and the patient’s postoperative visual experience, emphasises Prof Béatrice Cochener-Lamard MD, PhD.

“Quality of vision is a primary requirement for all of these socalled premium IOLs. With aspheric IOLs, you want to improve mesopic vision; with multifocality, you want to know to what extent you are affecting contrast sensitivity; with extended depth of focus (EDOF) lenses, we are all looking for social vision. But we understand today that it is still compromise we need to discuss with the patient,” she said.

With multifocal and EDOF IOLs, physicians must assess monocular and binocular UCVA and BCVA visual acuity at different distances—including the intermediate ranges of 60-80-70 cm and distances of four metres for distance acuity and 35 cm for near visual acuity. Quality of vision assessment should include subjective evaluation and objective measurement because this involves a range of vision and not a specific distance.

The subjective assessment should start with a questionnaire relating to patients’ vision-related quality of life, such as how often they require spectacles, whether they would redo the surgery, and whether they recommend it to friends. Other questions include the frequency and severity of visual complaints such as dysphotopsias, halos, and diplopia. Note should also be taken of patients’ spontaneous complaints, which are different from the reported functional symptoms.

OBJECTIVE MEASUREMENT OF OPTICAL QUALITY

Objective measurements include corneal topography, which may reveal corneal irregularities or tear film, and the corneal asphericity correlated to spherical aberrations. In terms of aberrometry, the most reliable machine currently is the iTrace (Tracey Technologies), which provides measurements of the lower order aberrations connected to the refraction in addition to the higher order aberrations—including spherical aberration tilt and trefoil.

There are also halometry devices available that provide a more reliable measurement of the impact of halos on visual comfort by simulating the lighting conditions that typically give rise to the phenomenon.

“Halos can be reported in more than 40% of patients with multifocal IOLs, but among them, only 10% are really severe and spontaneously reported. EDOF IOLs also induce halos in around 20% of patients, so there is no way to get perfect quality of vision with presbyopic IOLs,” Prof Cochener-Lamard noted.

Devices are also available to measure the quality of light diffusion: the C-Quant (OCULUS), which provides an objective measurement of light scattering, and the OQAS system (Visiometrics), which provides a good assessment of opacities or disturbance of light transmission inside the eye. In addition, they allow for a static or dynamic pupillometry performance,

which is important in the case of multifocal IOLs because they are pupil-size dependent. EDOF lenses, on the other hand, are not dependent on pupil size when their concept is based on asphericity modulation.

Prof Cochener-Lamard noted that classical machines from Vector Vision provide useful measurements of contrast mesopic and photopic conditions with or without glare. There are also new ophthalmic assessment platforms such as the EyeVis Pod CSV 1000 (Vector Vision) that allow the objective measurement of quality of vision and provide contrast sensitivity and defocus curve in a more dynamic and user-friendly way.

“The beauty of these new platforms is the very automatic way you can get the defocus curve from -4.0 to +2.0 D. We are all looking for a continuity of this kind of dome-shaped curve as opposed to the two peaks we associate with a bifocal lens,” she said.

Last but not least, Prof Cochener-Lamard emphasised the importance of the ocular surface and the tear film because of the impact they can have on both preoperative and postoperative measurement. There is also an increase in tear evaporation with the aging process with MGD present about 50% at the time of cataract. The refractive power of the tear film is demonstrated by the fact the difference in refraction between two blinks will increase and induce visual fluctuation in case of OSD.

However, expensive equipment is not necessary or mandatory to check for signs of ocular surface disease. Just one drop of fluorescein and careful examination of the eyelids to check for meibomian gland dysfunction is adequate and brings so much information, she advised.

“The outcome evaluation of advanced IOL implantation goes far beyond visual acuity. Achieving 20/20 is not enough. Visual quality is even more crucial than it is with corneal refractive surgery—presbyopic surgery is much more demanding. There are tools we can use to quantify the quality of vision required nowadays to evaluate outcomes in refractive IOLs to demonstrate the additional value of new optics and compare one concept to another,” Prof Cochener-Lamard concluded.

Professor and Head of the Department of Ophthalmology at the University Hospital of Brest, France. beatrice.cochener@univ-brest.fr

Béatrice Cochener-Lamard MD, PhD,

This presentation occurred at the 39th Congress of the ESCRS in Amsterdam.

is

“Quality of vision is a primary requirement for all of these socalled premium IOLs.”

Reducing the Risk of Refractive Surprise in Hyperopic Patients

Prevention is better than cure when it comes to reducing the risk of a refractive surprise after IOL implantation in hyperopic patients, according to Nino Hirnschall MD, PhD, FEBO.

“The reality is that short eyes requiring a higher IOL power are at high risk of a refractive surprise. We need to explain this to the patient before surgery, and especially when we are implanting a multifocal or toric lens, as they will not be happy afterwards if the refractive target is not met,” he advised.

Although data from the EUREQUO database in 2019 of 171,930 cataract extractions showed an average spherical equivalent error of -0.04 D with 74% of patients within 0.5 D of target refraction, Dr Hirnschall said such refractive accuracy does not typically extend to short eyes (axial length less than 22 mm).

“If we look at the study from Aristodemou [et al]i , it turns out that of the subset of patients with an axial length of 20 mm to 22 mm, not even half were within 0.5 D of target refraction. For very short eyes, less than 20 mm, maybe 30% are within 0.50 D. So, we are not very good in these cases, and there is clearly scope for improvement,” he said.

and anterior chamber depth. The second big problem is that with short eyes, we are using a higher-powered IOL, and this has a greater impact,” he said.

In terms of the best IOL power calculation formulae to use, Dr Hirnschall said that while popular formulae such as Hoffer Q, Barrett Universal, and Hill-RBF Calculator are acceptable for normal eyes, other formulae showed a better prediction for short eyes.

While there are multiple potential sources of error in IOL power calculations, Dr Hirnschall cited a study by Norrby et alii that showed preoperative estimation of postoperative intraocular lens (IOL) position, postoperative refraction determination, and preoperative axial length (AL) measurement are the largest contributors of error (35%, 27%, and 17%, respectively) with a mean absolute error (MAE) of 0.6 D for an eye of average dimensions.

“Although axial eye length measurements are quite good nowadays, we need to keep in mind that an error in axial length measurement of 1.0 mm in normal eyes means a refractive surprise of 2.5 D, whereas a short eye more than 1.0 mm equates to a 4.0 D to 6.0 D refractive error,” he said.

A key part of the problem lies in the false assumption that the anterior chamber depth in short eyes is usually flat, Dr Hirnschall explained.

“Studies by Rafik [et al] and Erb-Eigner [et al] have shown short eyes can in some cases have a regular anterior chamber depth. This does not fit our IOL power calculations because all the formulae used include some ratio between axial eye length

“Studies have shown modern formulae such as Castrop-Rauxel, Kane, OKULIX (ray tracing), and EVO 2.0 perform better in short eyes,” he said.

Other tips to improve outcome accuracy include optimising IOL constants with online tools such as Ocusoftiii and IOL Coniv and learning from the first eye surgery to correct for the second eye, Dr Hirnschall concluded.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

i Journal of Cataract & Refractive Surgery, 2011; 37: 63–71.

ii Journal of Cataract & Refractive Surgery, 2008 Mar; 34(3): 368–76.

iii ocusoft.de/ulib

iv https://iolcon.org

Dr Hirnschall is an ophthalmologist at the Kepler University Clinic in Linz, Austria. nino.hirnschall@gmail.com

Dermot McGrath reports

“The reality is that short eyes requiring a higher IOL power are at high risk of a refractive surprise.”

Extending IOL Options for Monofocality

An array of new enhanced monofocal intraocular lenses (IOLs) and monofocal extended depth of focus (monoEDOF) IOLs are becoming available. The new options appear to provide patients with the same distance visual acuity as standard monofocal IOLs but with better intermediate visual acuity and without the photic phenomena of EDOF and multifocal IOLs.

“Enhanced IOLs are a very fluid field of lenses, using different strategies, different technologies, different materials, and different designs. This is leading to a sort of Tower of Babel effect in which everyone speaks his own language and there is confusion when comparing IOLs and results,” notes Rita Mencucci MD.

The new IOLs include the TECNIS® Eyhance ICB00 (Johnson & Johnson), the xact™ Mono-EDoF™ IOL (Santen), the ISOPURE® (PhysIOL/BVI), and the RayOne® EMV (Rayner). The Eyhance IOL’s optics are based on a purely refractive technology with a modified anterior aspheric optic with a continuous power profile that increases from the periphery to the centre of the lens. The xact has four diffractive rings on the anterior surface that direct the light mainly towards far and intermediate focus. The ISOPURE’s optic design is based on unique polynomial technology developed to improve intermediate vision without inducing photic phenomena. The RayOne EMV increases depth of focus by inducing a small amount of extra positive spherical aberration, Dr Mencucci explained.

She noted at the six-month follow-up, there were no significant differences between the two groups in terms of uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), and distance-corrected near visual acuity (DCNVA). Furthermore, the Eyhance IOL provided significantly better results at a defocus of -1.0 D and -1.5 D. No patients reported the use of spectacles to correct distance visual acuity in either group, but only 20% in the Eyhance group needed intermediate correction in their everyday life compared to 90% in the TECNIS group.

There were no significant differences between the two groups in terms of contrast sensitivity at any spatial frequency as measured with the Optec® 6500 Vision Tester or optical quality as measured with the OQAS system.

Similar results have been reported with the Eyhance IOL at other centres and with the xact and ISOPURE IOLs in visual acuity, contrast sensitivity, and photic phenomena.

“And although enhanced monofocal IOLs are not suitable for patients seeking spectacle independence for near vision, they can offer improved functional performance in daily life and may therefore represent a premium option for monofocality,” Dr Mencucci said.

Studies published to date indicate the new lenses deliver on their promise. As an illustration, she reviewed the results of a study she and her associates conducted comparing visual outcomes, spectacle independence, and quality of vision achieved in 40 patients, split into two groups of 20. Half of the patients underwent bilateral implantation of the new TECNIS Eyhance IOL, and the other 20 patients underwent standard aspheric TECNIS ZCB00 IOL implantation.

Enhanced monofocal IOLs provide improved vision for day-to-day activities compared to standard monofocal IOLs. Roibeárd O’hÉineacháin reports

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

Rita Mencucci MD is a Professor of Ophthalmology at the University of Florence, Italy. rita.mencucci@unifi.it

“Enhanced IOLs are a very fluid field of lenses, using different strategies, different technologies, different materials, and different designs.”

Fuchs’ Dystrophy and Cataract

Treating endothelial disease and cataract: Phaco, graft, or triple procedure? Roibeárd O’hÉineacháin reports

Patients with Fuchs’ endothelial corneal dystrophy (FECD) and cataract can present a dilemma when deciding whether to perform cataract surgery alone, a triple procedure, or sequential endothelial grafting and cataract surgery, Prof Jod S Mehta PhD, FRCOphth, told the conference.

“If an FECD patient has cataract but few guttata and a good endothelial cell count, cataract surgery alone is indicated. If a patient has cataract and a lot of corneal oedema, a triple procedure is likely indicated, but between these two extremes, there is a large grey zone, and the treatment choice will depend on a detailed assessment of patient phenotype,” Prof Mehta said.

He noted mild FECD corneal guttae cause forward light to scatter, and the area of guttae correlates with visual acuity, contrast sensitivity, and intraocular straylight. He added anterior corneal changes associated with backscatter can occur in the initial stages of corneal guttae development and may precede clinically detectable oedema. In some cases, subclinical oedema may warrant endothelial keratoplasty even with the presence of fewer than five guttae and a pachymetry below 630 µm.

CATARACT SURGERY ALONE

Performing cataract surgery alone improves vision in patients with early and subclinical FECD, but the visual outcomes are not as good as in patients without the corneal condition. Data from Swedish National Cataract Surgery Register showed that cataract surgery improved corrected distance visual acuity, whether or not patients had guttata. The presence of corneal guttata was significantly associated with a poorer visual acuity and worse self-assessed visual function.

In addition, cataract surgery can aggravate FECD. In the Swedish registry study, those with corneal guttata had a greater reduction in daylight and nightlight contrast sensitivity after cataract surgery compared to those without guttata, particularly in the first three postoperative weeks, but persisting for at least three months.

Furthermore, the relative risk for corneal transplant after surgery is nearly 70-fold higher in patients with guttata than patients without guttata. Besides which, the risk for transplant after cataract surgery increases three-fold when there is dense cataract posterior capsule rupture, whether a patient has guttata or not.

“This suggests that in the presence of guttata, we should perform cataract surgery earlier—otherwise, the risk of needing a transplant increases dramatically,” Prof Mehta said.

He added that among eyes with cataract and guttata but without morning blur and a central corneal thickness less than 630 µm, around 80% will achieve a good visual outcome from cataract surgery without endothelial keratoplasty and around 20% will eventually require an endothelial graft. Anterior layer corneal backscatter and relative increase in central corneal thickness following phacoemulsification are indicators of the need for endothelial graft later.

THE TRIPLE OPTION

Performing a triple procedure with Descemet-stripping Automated Endothelial Keratoplasty (DSAEK) or Descemet Membrane Endothelial Keratoplasty (DMEK) has poorer refractive predictability than cataract surgery alone, as the graft procedure changes the optical properties of the cornea.

He noted DSAEK induces a moderate mean hyperopic shift of around 1.0 D. But there can be a wide variability related to graft profile, the meniscal edge profile, and the difference in thickness between the periphery and the centre of the graft. DSAEK grafts made with a femtosecond laser tend to be more planar with a better centre-to-periphery thickness profile.

DMEK induces a smaller hyperopic shift of approximately 0.5 D, even though grafts are thin and planar. That is because following the graft procedure, the central oedema thins more than the peripheral oedema, and the central posterior corneal curvature steepens. In addition, the transient rise in intraocular pressure resulting from the inflation of air or gas during graft attachment may have a hyperopia-inducing effect.

Some have hypothesised that guttae alone distort the cornea’s refraction and may affect axial measurements used in IOL formulae. Moreover, small areas of epithelial oedema or preoedema can affect keratometry. As a result, triple procedures with DMEK are still not as predictable as cataract surgery alone, with around -47% within -0.5 D of target refraction and 60% within 1.0 D.

DMEK THEN CATARACT

In some patients with cataract, it may be more advisable to perform DMEK first and then perform the cataract procedure based on the postoperative refraction. This could include cases with localised bullae, which can complicate biometry, or younger patients (those below the age of 50 with minimal cataract).

Oedema in the paracentral cornea can lead to apparent central cornea flattening preoperatively. So when the oedema clears after endothelial keratoplasty, the cornea steepens, causing a myopic shift. In some cases of FECD, corneal tomography has shown that after DMEK, there will be “hot spots” on the posterior corneal surface in the area where the oedema was. That can be an indication of subclinical keratoconus or stromal loss.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

Prof Jod S Mehta BSc (Hons), MBBS, PhD, FRCOphth, FRCS(Ed), FAMS is Distinguished Professor of Clinical Innovation, Head of the Corneal and External Eye Disease Service, and Senior Consultant Refractive Service, Singapore National Eye Centre. Jodmehta@gmail.com

New CXL Technique

New transepithelium CXL technique shows efficacy similar to Epi-off Dresden protocol CXL. Roibeárd O’hÉineacháin reports

Anew transepithelial corneal cross-linking (CXL) technique called Boost Epi-on CXL that involves supplemental oxygen appears to provide the same depth and volume of treatment as standard epi-off crosslinking, according to a study by Clinical Associate Professor Lim Li MBBS, M Med (Ophth), FRCS(Ed), FAMS.

“The corneal stromal demarcation line depth achieved with this technique is comparable to standard Dresden protocol epithelialoff corneal cross-linking and had a similar safety profile. It also has the added advantage of faster recovery and improved patient comfort compared to conventional cross-linking,” Prof Lim said.

The retrospective study included 25 eyes of 25 progressive keratoconus patients who underwent transepithelial CXL with supplemental oxygen between December 2019 and January 2021. The patients had a mean age of 28.3 years, a mean preoperative K1 of 45.9 D, a mean K2 of 50.2 D, and a mean Kmax of 57.5 D.

Anterior segment optical coherence tomography (AS-OCT) showed the mean post-treatment corneal stromal demarcation line was 367.3 µm ± 20.1 µm. The volume of treated cornea including and excluding the central corneal epithelial thickness was 73.3% and 70.4%, respectively. There was no reduction in endothelial cell count (ECC) post-procedure. Adverse events included mild corneal haze in eight eyes (32.0%) and one case of peripheral stromal infiltrate that resolved with topical broad-spectrum antimicrobial treatment.

COMPARABLE TO STANDARD EPI-OFF CXL

Studies with epi-off CXL show that it is a safe and effective procedure for keratoconus since it halts keratoconus progression and improves topographic and visual parameters. However, it can cause considerable postoperative pain. Epitheliumon procedures provide improved patient comfort and faster recovery and may reduce the risk of infection. But they also have a shallower treatment effect, result in less corneal flattening, and are less effective in preventing progression.

“The barrier function of the corneal epithelium may limit the availability of all three key components of crosslinking: Riboflavin, UVA, Oxygen,” Prof Lim said.

The Boost Epi-on procedure addresses all three of those drawbacks. First, it uses a higher, 0.25% concentration of riboflavin together with benzalkonium chloride to increase penetration through the epithelium. Second, it uses a higher intensity of UVA, irradiating the central 9.0 mm of the cornea 30 mW/cm² of UVA light, pulsed at one-second intervals for 11 minutes and six seconds, giving total energy of 10 J/ cm². Third, during the corneal irradiation, patients wear special goggles infused with oxygen at a concentration of 90%.

Following the procedure, patients received a bandage contact lens; a one-month regimen of topical moxifloxacin, preservative-free artificial tear eyedrops, and Loteprednol etabonate eyedrops; and a one-week regimen of oral etoricoxib.

She noted in the present study, the depth of the corneal demarcation line was roughly equivalent to that achieved with standard Dresden Protocol Epi-on CXL and about two to three times that achieved with standard transepithelial CXL.

“Further prospective studies are required to refine treatment parameters and validate the safety and efficacy of the procedure,” Prof Lim concluded.

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

Prof Lim Li is a Senior Consultant of the Corneal & External Eye Disease Department at the Singapore National Eye Centre (SNEC). lim.li@singhealth.com.sg

“The barrier function of the corneal epithelium may limit the availability of all three key components of cross-linking: Riboflavin, UVA, Oxygen.”

Advanced Cell Therapy in Keratoconus

Pilot study shows encouraging results with corneal

Roibeárd O’hÉineacháin reports

Intrastromal implantation of donor corneal lamina lenticules decellularised or recellularised with autologous adipose-derived adult stem cells (ADASCs) can bring about significant long-term clinical improvement in almost all keratoconus disease parameters, according to a pilot study presented by Mona El Zarif OD, MSc, PhD, and colleagues.

“This pilot investigation opens a new area for the management of keratoconus and may offer a less aggressive treatment than the classical corneal transplant and may therefore also reduce the demand for donor corneas, as several laminas can be used from the same donor cornea,” Dr El Zarif said.

In the phase 1 study—principally led by Jorge L Alió MD, PhD, FEBOphth—Dr El Zarif and her associates randomised 14 advanced keratoconus patients into three treatment groups. The first group underwent injection with ADASCs obtained from elective liposuction into a femtosecond laser-created intrastromal pocket. The second group underwent intrastromal implantation of a 120 µm thick decellularised human donor lenticule, and the third group underwent implantation of a donor lenticule recellularised with ADASCs.

Dr El Zarif noted that at one and three years, uncorrected distance visual acuity improved significantly by one to two logMAR lines in all groups, with no statistically significant difference between them. No patient lost visual acuity. All three groups also showed corrected distance visual acuity improvement, although significantly greater improvements appeared in the ADASC group than in the lamina groups.

In addition, optical coherence tomography (OCT) noted a statistically significant increase in central corneal thickness and volume at the one- and three-year follow-ups in the lamina groups compared to the ADASC group. However, there was no significant difference between the two lamina groups in increased corneal thickness. Scheimpflug corneal topography showed improvement

in sagittal curvature, a statistically significant enhancement, and pachymetry improvement in the lamina groups.

Confocal microscopy showed a gradual and significant increase in the cellularity in patients’ anterior and posterior stroma. It also showed significant increase in the mid-corneal stroma in all three groups one year after the surgery compared with the preoperative values. Still, the cell density at the anterior and posterior surfaces and within the lamina was statistically significantly higher in patients that received recellularised laminas than those implanted with decellularised laminas.

Furthermore, in the ADASC-alone group, the stem cells changed progressively to a normal keratocyte-like appearance during the six months post-surgery, becoming more luminous, refringent, and voluminous. In patients with decellularised lenticules, the lamina remained acellular in the first postoperative month but became recellularised with native keratocytes after three months. In the eyes with recellularised lenticules, there was greater number of keratocytes than in the decellularised lenticules at six and twelve months.

Dr Alió and Dr El Zarif added no complications such as haze or infection occurred during the three-year follow-up. Furthermore, all patients recovered full corneal transparency within the first postoperative day, and the increase in corneal cell density was not significantly correlated with the presence of fibrotic tissue.

regenerative treatment in keratoconus.

Dr El Zarif and Dr Alió presented this research at the 39th Congress of the ESCRS in Amsterdam.

Mona El Zarif OD, MSc, PhD, Division of Ophthalmology, Universidad Miguel Hernández, Alicante, Spain monazarifaj@hotmail.com

Single, Double, or Triple? Surgery for Patients with Fuchs’ Dystrophy and Cataract

Cheryl Guttman Krader reports

Should a patient with cataract and Fuchs’ endothelial corneal dystrophy undergo cataract surgery alone or with endothelial keratoplasty (EK)? In the absence of data to support evidence-based practice, patients should be fully informed of the pros and cons of both approaches and the decision should be tailored to meet patient expectations, advised Mor Dickman MD, PhD.

“Significant costs can be avoided, and scarce donor corneas spared if the patient’s vision can improve with cataract surgery alone, but endothelial cell loss after cataract surgery complicates the decision to perform only cataract surgery,” Dr Dickman said.

Staged or simultaneous corneal transplantation exposes patients to risks of graft dislocation, graft failure, and indefinite immune suppression. However, the threshold for a triple procedure is lowered by choosing Descemet Membrane Endothelial Keratoplasty (DMEK), which has a better risk-benefit ratio than Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) or penetrating keratoplasty, he noted.

ASSESSING THE SITUATION

Determining whether Fuchs’ or cataract is the primary cause for the patient’s visual complaints is hampered by the fact that the two conditions have overlapping symptoms. There are also limitations for considering Fuchs’ severity based on morphological staging criteria, central corneal thickness (CCT), or endothelial cell density.

However, a revised Fuchs’ severity classification proposed in 2018 by Sun et al can be helpful in guiding surgical decisions for eyes that do not have clinically evident oedema. The topographic classification considers irregularity of the isopatches, displacement of the thinnest point of the cornea, and posterior surface depression towards the anterior chamber. The risk of Fuchs’ progression and need for intervention, including after uncomplicated cataract surgery, increases according to the number of parameters present, Dr Dickman explained.

He also noted surgeons should not underestimate the effect of corneal guttata on straylight because it can result in disturbing symptoms despite good subjective high contrast visual acuity.

“We found that DMEK improves straylight and vision-related quality of life to age-normal levels,” Dr Dickman said.

CATARACT SURGERY TECHNIQUE

Evidence supports using the soft-shell technique to protect the endothelium when performing cataract surgery in eyes with Fuchs’. According to the findings of a randomised controlled study conducted by Dr Dickman and colleagues, torsional phacoemulsification reduces surgical time and ultrasound energy when compared to longitudinal phacoemulsification. There are no benefits with torsional phacoemulsification, however, for reducing the risk of corneal decompensation.

Only preoperative CCT predicted the need for DSAEK postoperatively. For each 10-micron increase in CCT above 620 microns, the probability of corneal decompensation increased with an odds ratio of 1.7, he reported.

Results from two seminal randomised clinical trials show no endothelial safety benefit from choosing femtosecond laserassisted cataract surgery over conventional phacoemulsification.

ADDRESSING BOTH CONDITIONS

If the surgeon decides to perform both cataract surgery and DMEK, there are pros and cons to consider for a sequential approach—starting with the cataract procedure and for simultaneous surgery. A sequential approach has the advantage of a more stable iris lens diaphragm. With a triple procedure, patients benefit from having both procedures done in a single session.

EK is associated with short-term risks of graft detachment and primary graft failure. In the long term, graft rejection is less frequent when choosing DMEK. Using topical steroids for immune suppression after EK results in ocular hypertension in one-fourth of patients. Because the endothelial cell count deteriorates over time, a repeat transplant may be needed, especially if the patient was young at the time of the primary surgery.

When choosing a triple procedure, surgeons should make a smaller capsulorhexis to prevent IOL prolapse. Meticulous viscoelastic removal is essential to prevent graft detachment.

Whether the two surgeries are staged or done in the same session, there should be consideration for the risk of a hyperopic shift when choosing an IOL, Dr Dickman stressed.

Data from pseudophakic patients in a randomised controlled trial conducted by Dr Dickman and colleagues show the shift is about 0.25 to 0.5 D with DMEK and about 0.5 to 0.75 D with ultra-thin DSAEK. These numbers correspond to a 0.35 D hyperopic shift found in a recent real-world registry study of DMEK in the Netherlands, Dr Dickman said. Looking at the Q value can also be helpful for avoiding a refractive surprise.

“Oedematous corneas are oblate, have a positive Q value, and are at increased risk for a profound hyperopic shift after surgery,” Dr Dickman explained.

When combining cataract surgery and DMEK, results from several studies did not show differences in refractive outcomes comparing triple and sequential procedures. One retrospective study suggested the triple procedure carries a higher risk of early graft detachment, but the data are controversial. The authors of another study concluded that pseudophakia, not cataract surgery, increases the risk of graft detachment. The same authors also reported that using 20% SF6 gas instead of air tamponade decreased the risk of detachment.

“We also reported in a recently published study that a triple procedure was not a risk factor for rebubbling and primary graft failure,” Dr Dickman reported.

This presentation was made at the 12th EuCornea Congress.

Mor M Dickman MD, PhD, is Professor of Ophthalmology, Maastricht University Medical Centre, the Netherlands. mor.dickman@mumc.nl

Choosing cataract surgery over a triple procedure depends on shared decision making.

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Gene Therapy for AMD and Diabetic Retinopathy

Encouraging results from ongoing studies exploring subretinal and suprachoroidal administration.

Cheryl Guttman Krader reports

Ongoing clinical trials with RGX-314 gene therapy (REGENXBIO) show promise in the treatment of several retinal diseases, reported Robert Avery MD at the Retina Day session.

The investigational agent uses a novel adeno-associated viral vector to deliver a gene for an anti-VEGF monoclonal antibody fragment similar to ranibizumab.

He described the ongoing studies—including ATMOSPHERE, the phase 3 trial comparing subretinal RGX-314 against monthly ranibizumab for neovascular AMD (nAMD) treatment. Studies investigating suprachoroidal RGX-314 for treating nAMD (AAVIATE) and diabetic retinopathy (DR, ALTITUDE) are also enrolling patients, and a second phase 3 trial of subretinal RGX314 for nAMD is expected to start later in 2021.

SUBRETINAL DELIVERY

The clinical development of RGX-314 is supported by the results of a completed two-year, phase 1/2a dose-escalation study of subretinal RGX-314 for nAMD. It enrolled 42 patients across five dose cohorts (3x109 to 2.5x1011 GC/eye). Eligible patients had responded to previous anti-VEGF therapy and received a single injection of RGX-314.

Study researchers observed dose-dependent increases in intraocular RGX-314 protein levels in aqueous samples as well as a dose-dependent treatment benefit based on measures of BCVA and central retinal thickness. A significant reduction in the antiVEGF treatment burden allowed for durable disease control achievement, Dr Avery said.

Subretinal RGX-314 was well-tolerated. Retinal pigmentary changes (69%) were the most common ocular adverse event, and most pigment changes were in the far periphery. Most other side effects were considered related to the surgery. There were no reports of drug-related ocular inflammation.

SUPRACHOROIDAL STUDIES

The phase 2 study of suprachoroidal RGX-314 for nAMD is evaluating three doses of the gene therapy in five cohorts of patients previously treated with anti-VEGF therapy. Safety data from six months of follow-up for 15 patients treated with RGX-314 in the first two dose cohorts show some cases of mild intraocular inflammation and episcleritis that resolved in days to weeks with topical steroid treatment. Efficacy evaluations showed stable visual acuity and stable, even slightly improved, retinal thickness.

“The effects of RGX-314 on treatment burden were significant. Patients in the first two cohorts had a greater than 70% reduction from their previous treatment burden, and 30% to 40% of patients did not require additional treatment for their nAMD,” Dr Avery said.

In the study of suprachoroidal RGX-314 for DR, patients with a Diabetic Retinopathy Severity Scale score of 47 to 61 were randomised to an observational control arm or RGX-314. Dr Avery noted an imbalance in baseline characteristics of patients in cohort one with all five patients in the control arm having moderately severe NPDR while 8 (53.4%) of 15 RGX-314 patients had PDR. Again, suprachoroidal RGX-314 was well-tolerated. A single patient developed mild episcleritis. There were no cases of intraocular inflammation.

Vision remained stable. In addition, 33% of patients in the RGX-314 arm versus none of the controls achieved a two-step improvement in the Diabetic Retinopathy Severity Scale score.

“The 33% rate compares nicely with the results from the PANORAMA study with aflibercept and the RISE and RIDE studies with ranibizumab. Looking only at patients in the RGX314 study who had NPDR at enrolment, 43% had a two-step improvement after three months, which is a very good response,” Dr Avery said.

This presentation was made at the AAO 2021 Congress in New Orleans, Louisiana, USA.

Robert Avery MD is CEO of California Retina Consultants, Santa Barbara, USA. He has been the principal investigator for 12 national clinical trials. bobave@gmail.com

Nonviral Gene Therapy

Plasmids are showing promising results in preclinical studies as an alternative to adeno-associated virus vectors (AAVs) in treating hereditary retinal diseases, says Professor Mariya Moosajee BSc, MBBS, PhD, FRCOphth.

Prof Moosajee noted AAV vectors have good transduction efficiency and are generally well tolerated. However, AAV vectors have some limitations. For example, they are restricted to transfection of genes of a certain size, no more than 4.7 kB. In addition, in 10–20% of cases, they will cause inflammatory reactions, which can result in sight loss.

Moreover, gene therapy with AAV vectors has had variable results. While LUXTURNA® (voretigene neparvovec-rzyl) has been extremely successful in treating Leber congenital amaurosis, the gene therapy trials for choroideremia with an AAV viral vector have failed.

She pointed out DNA plasmids have the advantage of having unlimited cloning capacity and freedom from toxic viral components. Researchers have manufactured the plasmids with scaffold/matrix attachment regions (S/MARs). An S/MAR is a 300 to 3000 AT-rich base pair nucleotide motif found naturally in the nuclear matrix of cells. S/MARs help with the binding formation of chromatin structure for DNA transcription and replication. When placed into the DNA plasmids, they confer episomal maintenance, prevent epigenetic silencing, and provide mitotic stability.

CHOROIDEREMIA

Prof Moosajee’s team is developing S/MAR plasmid gene therapies for choroideremia and Usher syndrome with many encouraging preclinical findings. She noted choroideremia (CHM) is an X-linked chorioretinal dystrophy with a prevalence of 1 in 50,000–100,000. The condition is caused by a mutation in the CHM gene that has a molecular weight of 1.9 kB and encodes for the REP1 protein.

She and her associates have successfully cloned an S/MAR vector for the CHM gene. In laboratory experiments, fibroblasts from choroideremia patients transfected with the S/MAR vector have

shown persistent expression of the transfected gene. In a zebrafish animal model for choroideremia, embryo transfection resulted in human gene expression in the photoreceptors of the adult fish.

Future work on gene therapy for choroideremia will involve testing S/MAR vectors in retinal pigment epithelium (RPE) cells derived from choroideremia patient induced pluripotent stem cells and evaluation of functional vision in a mouse model of the disease.

USHER SYNDROME

Prof Moosajee noted Usher syndrome has a prevalence of 4–17 in 100,000 and causes hearing and sight loss with variable vestibular dysfunction. A mutation in the large USH2A gene (19 kB cDNA), which codes the Usherin protein, causes the most common form (type 2).

Prof Moosajee and her team have successfully cloned the entire USH2A gene into an S/MAR vector. In laboratory experiments, there was a persistent expression of USH2A in transfected human fibroblasts and transfected zebrafish embryos. The team is now undertaking studies using intravitreal and subretinal injections in animal experiments.

“Nonviral gene therapy holds a great deal of promise, but future work now needs to be focused on improving the transfection efficiency in the retina in a safe and efficient manner. It may involve chemical or physical approaches, such as the use of nanoparticles or electroporation,” she concluded.

The study was presented at the Retina 2021 Meeting in Dublin, Ireland.

Prof Mariya Moosajee BSc, MBBS, PhD, FRCOphth is a Professor of Molecular Ophthalmology at the UCL and the Francis Crick Institute and a Consultant Ophthalmologist in Genetic Eye Disease Moorfields Eye Hospital and Great Ormond Street Hospital for Children, London, UK. m.moosajee@ucl.ac.uk

Plasmid vectors show potential in future of gene therapy for inherited retinal diseases. Roibeárd O’hÉineacháin reports

Image 1. Section through a wildtype zebrafish retina transfected with S/ MAR DNA plasmid vector at the single cell stage, showing widespread transgene GFP expression (red) and DAPI (blue) staining at five days post fertilisation.

Image 2. Wildtype mice received a single subretinal injection of S/ MAR DNA plasmid vector and showed luciferase reporter transgene expression at 12 months post-injection.

Gene Therapy for LHON

Gene therapy with the AAV2 viral vector LUMEVOQ® (GS010, GenSight Biologics) shows encouraging results in patients with Leber’s hereditary optic neuropathy (LHON), according to Patrick Yu-Wai-Man MD, PhD.

He noted that in two phase III studies—the RESCUE and REVERSE trials—vision improved in 78% of LHON patients who underwent the gene therapy to replace the defective mitochondrial gene. Patients tolerated the treatment well and, overall, vision improved by about five lines on the visual chart at two years after receiving the injection. In addition, the patients’ vision has so far continued to improve at up to 52 months of follow-up.

“Gene therapy is a very promising and attractive treatment strategy for LHON. Research is still ongoing, but vision can improve if you correct the underlying genetic defect,” he said.

FROM GENE DISCOVERY TO THERAPY

Professor Yu-Wai-Man explained LHON is an inherited mitochondrial disease that causes dysfunction of the retinal ganglion cells and degeneration of the optic nerve. First described in 1871 by the German ophthalmologist Theodore Leber, this genetic disorder tends to affect young men in their 20s and 30s, and its defining clinical feature is rapid and severe loss of central vision in both eyes. Visual recovery is poor, and most patients fulfil the criteria for blind registration.

In 1988, researchers identified a mutation at position 11778 of the mitochondrial genetic code, which affects the MT-ND4 gene, as the most common cause of LHON. The 11778 ND4 mutation accounts for 60–70% of LHON cases and two other genetic defects at positions 3460 and 14484 account for 10–15% of cases.

Introducing genes into mitochondria is technically challenging because mitochondria have both an inner and outer membrane, which are relatively difficult to penetrate Prof Yu-Wai-Man said. He said using an inactivated adeno-associated viral vector (AAV2) to deliver the replacement gene (MT-ND4) into the nuclear genome helps get around this problem. The gene product has a special “mitochondrial targeting sequence” that acts like a homing device directing the protein to the right location in the cell and facilitating its import into the mitochondria.

VISUAL IMPROVEMENT

The RESCUE study included 39 LHON patients who had been affected for up to six months, whereas the REVERSE study included 34 patients who had been affected for six to 12 months. All patients were 15 years or older and were confirmed carriers of the 11778 MT-ND4 mutation. In both trials, patients received an intravitreal injection of the viral vector (rAAV2/2-ND4) in one eye and a sham injection in the fellow eye.

In the RESCUE study, vision continued to worsen in the first 48 weeks following injection, by which time the eyes lost a mean of around 20 letters, equivalent to about four lines on the visual chart. However, vision began to improve afterwards, and by two years, an average improvement of 26 and 28 letters from the nadir was observed in the RESCUE and REVERSE studies, respectively. The visual recovery seen in these two trials was more than expected based on the natural course of the disease in patients with LHON carrying the 11778 MT-ND4 mutation.

Unexpectedly, the non-injected (sham) eyes showed a parallel visual improvement in both studies. In a subsequent nonhuman primate study, researchers detected viral vector DNA in the fellow non-injected eye when an intravitreal injection of AAV2/2-

ND4 was given to one eye only, providing a possible explanation for the bilateral visual improvement seen in treated patients. The researchers are planning long-term follow-up studies of the patients in the RESCUE and REVERSE trials. In the meantime, preliminary results from the REFLECT study indicate LHON patients carrying the 11778 mutation seemed to achieve a slightly better visual outcome when both eyes were treated with AAV2/2-ND4 rather than just one eye. Future studies will address the question of the ideal timing of the treatment and whether treatment is beneficial in patients with chronic LHON who have been affected for more than one year.

This study was presented at the Fighting Blindness Retina 2021 Meeting in Dublin, Ireland.

Professor Patrick Yu-Wai-Man MD, PhD, FRCPath, FRCOphth is an NIHR Advanced Fellow and an Honorary Consultant Neuro-ophthalmologist based at Moorfields Eye Hospital, London, UK; Addenbrooke’s Hospital, Cambridge, UK; and the University of Cambridge, UK. py237@cam.ac.uk

Mitochondrial gene replacement therapy restores vision in Leber’s hereditary optic neuropathy patients.

Roibeárd O’hÉineacháin reports

Mode of action of LUMEVOQ® (GS010, GenSight Biologics).

2022

Applications are open for the Peter Barry Fellowship 2022. This Fellowship commemorates the immense contribution made by the late Peter Barry to ophthalmology and to the ESCRS.

The Fellowship of €60,000 is to allow a trainee to work abroad at a centre of excellence for clinical experience or research in the field of cataract and refractive surgery, anywhere in the world, for 1 year.

Applicants must be a European trainee ophthalmologist, 40 years of age or under on the closing date for applications and have been an ESCRS trainee member for 3 years by the time of starting the Fellowship.

The Fellowship will be awarded at the ESCRS Annual Congress in 2022, to start in 2023.

To apply, please submit the following:

A detailed up-to-date CV

A letter of intent of 1-2 pages, outlining which centre you wish to attend and why

A letter of recommendation from your current Head of Department

A letter from your potential host institution, indicating that they will accept you if successful

Closing date for applications is 2 May 2022

Applications and queries should be sent to escrs@mci-group.com

Subconjunctival MIGS vs Trabeculectomy

Subconjunctival minimally invasive glaucoma surgery (MIGS) procedures aim to provide a safer alternative to trabeculectomy, but more evidence is needed to understand how the subconjunctival MIGS procedures compare and where they fit into the algorithm for glaucoma surgical care, Henny J Beckers MD, PhD told delegates.

“Trabeculectomy remains the gold standard, but we look forward to results from randomised controlled trials of the subconjunctival MIGS procedures that are underway,” Dr Beckers said.

Currently, there are two options in the subconjunctival MIGS category—the XEN® Gel Stent (Allergan) and the PRESERFLO™ MicroShunt (Santen). Dr Beckers first reviewed five studies of the XEN stent. Those studies reported data from two-to-three years of follow-up for patients undergoing the MIGS procedure alone or combined with phacoemulsification. Mean IOP across the studies ranged from approximately 20 to 23 mmHg at baseline and reduced to between approximately 13 and 15 mmHg at last follow-up. However, needling rates were high (43% to 62%), and the reoperation rate in the three studies ranged from 12% to 26%.

Dr Beckers then reviewed findings from five published studies reporting outcomes from follow-up periods of up to five years after MicroShunt surgery. In these trials, mean IOP ranged from approximately 20 to 25 mmHg at baseline, reduced to approximately 11 to 14.5 mmHg after one year, and sustained over time in the studies with longer follow-up. Needling rates ranged from 5% to 18%, and the reoperation rate ranged up to 13.5%.

HEAD-TO-HEAD TRIALS

Dr Beckers and colleagues compared the two subconjunctival MIGS procedures and reported their results in a retrospective study.i Summarising the results, she said the XEN and PRESERFLO showed similar efficacy.

“Although IOP was lower in the MicroShunt group at all timepoints, the difference between groups was not statistically significant for most comparisons,” she said.

For both procedures, complications were mostly mild and selflimiting, consisting of early hypotony and early microhyphaema. Stent curling was only reported in the XEN group and is a feature of the device’s material, Dr Beckers explained.

The XEN group had a higher rate of bleb needling than the MicroShunt group and a lower rate of glaucoma filtration surgery, but the differences were not statistically significant. Transscleral cyclophotocoagulation was performed significantly more often after the XEN procedure.

COMPARISONS WITH TRABECULECTOMY

The ongoing Gold-Standard Pathway Study is a US-based multicentre trial comparing XEN implantation and trabeculectomy. Recruitment was just completed with 162 participants enrolled.

Data from one year of follow-up are available from a twoyear study that randomised 527 patients 3:1 to surgery with the MicroShunt or trabeculectomy.ii Mean IOP at baseline was

21.1 mmHg in both groups. At one year, mean IOP was 11.1 mmHg in the trabeculectomy group and 14.3 mmHg in the MicroShunt group.

“The MicroShunt result is inferior to trabeculectomy, but the trabeculectomy results are very good in this study. The 58 participating investigators in the study perhaps were very skilled with trabeculectomy, whereas many had no experience with the MicroShunt procedure. There may be a learning curve effect for the MicroShunt outcomes, and we will see if that is true in further studies,” Dr Beckers said.

As another potentially confounding issue, the MicroShunt group included a significantly higher proportion of Black patients, a demographic at increased risk for failure after blebforming surgery. In addition, both surgeries were performed using mitomycin-C (MMC) 0.2 mg/mL for two minutes.

“Now there is debate over whether a higher dose of MMC may improve the results of the MicroShunt surgery. Recently published studies found a trend to better IOP reduction using a concentration of 0.4 mg/mL. However, the reduction in medication use in the head-to-head comparison of the MicroShunt and trabeculectomy was also significantly better in the trabeculectomy group,” Dr Beckers said.

There were more postoperative interventions in the trabeculectomy group, although laser suture lysis procedures account for most of the difference. After excluding those procedures, the postoperative intervention rates were similar in the two groups.

Adverse events related to IOP were more common in the trabeculectomy group that had higher rates of hypotony and increased IOP requiring treatment in the early postoperative phase. After three months of follow-up, IOP was slightly higher in the MicroShunt group.

“The more predictable postoperative course (however, with fewer possibilities of early intervention) with the MicroShunt may also help explain why it was associated with higher IOPs than trabeculectomy over the later follow-up period,” Dr Beckers noted.

There was no statistically significant difference between groups in endothelial cell loss after one year.

“Overall, the first results indicate the MicroShunt appears to be slightly less effective than trabeculectomy. However, it is a more controlled procedure—with proper case selection it can provide an IOP in the low teens, and it usually shows excellent visual rehabilitation.”

This presentation was made at the 39th Congress of the ESCRS in Amsterdam.

Henny J Beckers MD, PhD, is a glaucoma specialist and cataract and glaucoma surgeon at the University Eye Clinic Maastricht, the Netherlands. henny.beckers@mumc.nl

Less invasive approaches promising, but more data needed to guide evidence-based decisions.

Cheryl Guttman Krader reports

Ab Externo Shunt Procedure Finds a Niche Between MIGS and Trabeculectomy

Microinvasive bleb-forming surgery merges safety of MIGS with better efficacy. Cheryl Guttman Krader reports

The PRESERFLO™ MicroShunt (Santen) is not a replacement for trabeculectomy, but it might be a real game-changer in the realm of glaucoma surgery and a good fit for many patients and surgeons, according to Joseph F Panarelli MD.

“I believe that at least initially, the MicroShunt will bridge a substantial gap between patients who could have microinvasive canal-based surgery and those who need traditional trabeculectomy. The IOP-lowering outcomes may be better with trabeculectomy, but I think they will be more reproducible with the MicroShunt and will improve with refinements to the surgical technique and postoperative management. Therefore, the MicroShunt might be a nice procedure to learn for surgeons who want efficacy-like outcomes of trabeculectomies but do not perform a large volume of those procedures,” he said.

Dr Panarelli also highlighted the postoperative stability and recovery after MicroShunt surgery.

“Often these patients are very happy because they regain visual acuity much more quickly than after trabeculectomy, and they have a much smoother postoperative course. I think when surgeons start performing this procedure, they will see other nuances that will make them want to do it more and more.”

EFFICACY AND SAFETY OUTCOMES

Implanted in an ab externo procedure, the MicroShunt drains aqueous humour from the anterior chamber to the subconjunctival/sub-Tenon’s space in a regulated manner. Dr Panarelli described the procedure as microinvasive blebforming surgery.

He reviewed results from two years of follow-up in the pivotal international trial that randomised 891 patients 3:1 to the MicroShunt or trabeculectomy. Eligible patients had primary open-angle glaucoma with uncontrolled IOP 15 to 40 mmHg on maximum tolerated glaucoma medication. Dr Panarelli highlighted two characteristics of the study population.

“About one-third of patients had a preoperative IOP <18 mmHg, and that is a tough group for getting a low final IOP. In addition, an appreciable subset of patients (about 15%) had severe glaucoma. These are patients who need very substantial IOP-lowering,” he said.

Surgical success, defined by a ≥20% reduction in diurnal IOP without increasing medications, was achieved in 64% of patients randomised to trabeculectomy and 51% of those in the MicroShunt group. Mean IOP was 21 mmHg at baseline in both groups and s was 13.9 mmHg in the MicroShunt group and 10.7 mmHg in the trabeculectomy group. The average daily number of medications for the trabeculectomy and MicroShunt groups was 0.9 and 0.4, respectively.

“Keep in mind this was a really experienced group of trabeculectomy surgeons who participated in the study, but I think the MicroShunt did quite well for a new procedure,” Dr Panarelli said.

There were few serious postoperative complications in either group. Adverse event rates were generally similar between groups other than hypotony. Persistent hypotony and early bleb leaks were more common after trabeculectomy. Notably, rates of cataract progression, corneal oedema, hypotony maculopathy, and change in endothelial cell density were similar in the two groups. Rates of bleb needling, introduction of glaucoma medications, reoperations, and other glaucoma surgeries were all higher in the MicroShunt group.

The study was presented at AAO 2021 in New Orleans, Louisiana, USA.

Joseph F Panarelli MD is the Chief, Division of Glaucoma Services, New York University Grossman School of Medicine, USA.

joepanarelli@gmail.com

“Often these patients are very happy because they regain visual acuity much more quickly than after trabeculectomy, and they have a much smoother postoperative course.”

Paediatric Myopia Control Gains New Contact

A potential practice opportunity opens as products gain regulatory approval.

Cheryl Guttman Krader reports

Controlling myopia progression in children has not yet become part and parcel of the care offered by most ophthalmologists, and those who have entered this space are most likely to prescribe compounded low-dose atropine. However, because paediatric myopia is a growing and important public health issue with new and emerging contact lens options available for its management, myopia control represents both a valuable service and a practice opportunity, said Michael X Repka MD, MBA.

CONTACT LENS OPTIONS

Contact lens-based strategies for myopia control aim to eliminate the peripheral hyperopic defocus believed to stimulate axial elongation. These strategies do so by either optical design or peripheral cornea remoulding, i.e., orthokeratology.

Focusing on the United States market, Dr Repka said the FDA approved a single product within each of the two categories for myopia control. They include the dual-focus MiSight® 1 day (CooperVision®) single-use contact lens. Reflecting the characteristics of the patient population enrolled in the clinical trial supporting its regulatory approval, MiSight lenses are indicated for children 8 to 12 years of age with spherical equivalent myopia -0.75 to -4.00 D and <1.00 D astigmatism. It is recommended to be worn at least 10 hours per day, 6 days per week.

The FDA-approved orthokeratology product—ACUVUE® Abiliti™ Overnight Therapeutic Lenses (Johnson & Johnson Vision)—is a gas permeable lens worn nightly for two weeks with the use of soft contact lenses during the day.

The ACUVUE Abiliti 1-Day Soft Therapeutic Lens for Myopia Management (Johnson & Johnson Vision) is pending FDA approval. It is approved in Canada for slowing myopia progression in children ages 7 to 12 years with a spherical equivalent myopia -0.75 D to -4.50 D and ≤1.00 D astigmatism.

The Biofinity® Contact Lens (CooperVision), which is approved only for vision correction, was studied for myopia control in a prospective trial that randomised children ages 7 to 11 years with -0.75 to -5.00 D sphere and <1.00 D astigmatism to a single-vision lens or a multifocal lens with a +1.50 or +2.50 D add power. The results showed the high add power lens significantly reduced the rate of myopia progression and axial eye growth compared to the single vision control.

PRACTICAL ISSUES AND UNANSWERED QUESTIONS

Clinicians should be aware there can be a mismatch between the relatively modest effect contact lens interventions have for controlling myopia progression and patients’ (and parents’) potentially high expectations for outcomes. In addition, although the rate of infectious disease complications with these modalities is unknown, Dr Repka suggested that because of the importance of proper lens care and hygiene, the contact lens intervention may be more appropriate for older versus younger children.

At the same time, however, he added intervening even earlier than the currently approved minimum ages of 7 or 8 years may be desirable considering evidence that the younger the age of myopia onset, the greater its eventual severity.

Dr Repka also suggested optimising outcomes may necessitate combination therapy but noted there are no data at this time to support its effectiveness.

The study was presented at AAO 2021 in New Orleans, Louisiana, USA.

Michael X Repka MD, MBA, is a Professor of Ophthalmology at Johns Hopkins University, Baltimore, Maryland, USA. mrepka@jhmi.edu

A Growing Change in Paediatric Ocular Biometry

Study could offer new basis for monitoring refractive error development in children. Roibeárd

O’hÉineacháin reports

Eyes appear to mature differently in boys and girls, according to a study by Franziska G Rauscher PhD and associates that won first prize in the 39th ESCRS Congress poster competition in Amsterdam, the Netherlands.

“These data may serve as normative values for assessing eye growth in central European children and will provide a basis for monitoring refractive error development,” the study’s authors noted.

The study involved 1,907 children aged 4 to 17 years examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Diseases), a population-based study in Leipzig, Germany.

The children participating in the study underwent optical biometry of their right eyes with the LENSTAR® LS 900 (HaagStreit) to determine axial length, central corneal thickness, flat and steep corneal radii, aqueous depth, lens thickness, and vitreous depth.

Girls presented with 0.63 mm shorter eyes than boys at four years of age. However, in this cross-sectional data set, girls’ eyes elongated at a similar rate to boys, reaching the same axial length about four years after the boys. The study’s authors noted in the girls, axial length increased from 21.6 mm at four years old to 23.4 mm by 17 years. The yearly increase was statistically significant up to age 14 (0.174 mm per year). In the boys, axial length increased from 22.2 mm at four years to 23.9 mm at 17 years, but the yearly increase (0.178 mm per year) was statistically significant only up to age 10.

Lens thickness decreased in girls from 3.75 mm at four years to 3.47 mm at 10 years with no further statistically significant change

between 10 and 17 years. Lens thickness decreased in boys from 3.73 mm at four years to 3.44 mm at 10 years. Lenses reached their minimum thickness at 11 years in girls and 12 years in boys.

Central corneal thickness (CCT) in girls did not change statistically significantly between four and seven years of age but increased significantly between seven and 10 years of age with no significant increase thereon. In boys, the CCT did not change statistically significantly between four and 17 years. The overall mean CCT was 550 µm in girls and 554 µm in boys. In girls, corneal curvature was somewhat flatter at age four compared to age 10, whereas it remained constant in boys.

Aqueous and vitreous depths increased at the same rate in boys and girls. At age 17, aqueous depth was 3.06 mm for girls and 3.20 mm for boys, and vitreous depth was 16.29 mm in girls and 16.62 mm in boys. The aqueous depth increase matched the lens thickness decrease from four to 10 years of age. All dimensions of the optical ocular components closely correlated with axial length.

Dr Rauscher and her associates published their findings in the May 2021 issue of Ophthalmic and Physiological Optics i iRauscher et al, Ophthalmic Physiological Optics. 2021; 41(3): 496–511.

Franziska Rauscher PhD is a Vision Scientist at the Institute for Medical Informatics, Statistics, and Epidemiology (IMISE), Leipzig University, Germany. franziska.rauscher@medizin.uni-leipzig.de

Do you have ideas for any stories that might be of interest to our readers?

THOMAS KOHNEN European Editor of JCRS

JCRS HIGHLIGHTS

CAPSULORHEXIS IRREGULARITIES MAY HAVE LIMITED IMPACT

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The effect of capsulorhexis irregularities on the postoperative position and orientation of an IOL is mathematically relevant but optically neutral, according to the authors of a computational study using a finite model of the crystalline lens and zonule. The researchers used the model to simulate cantered, decentred, circular, and elliptic rhexes and calculated the capsular bag stress, IOL rotation, tilt, decentration, and vaulting these induced. They found that as rhexis eccentricity increased, the stress difference between the zand x-axes increased. They noted anterior capsulorhexis irregularity and/or eccentricity significantly increased IOL tilt, decentration, rotation, and vaulting, but with only a negligible optical effect. However, stress asymmetry may influence postoperative biologic processes of capsular bag shrinkage, they added. T Rossi et al., “Influence of anterior capsulorhexis shape, centration, size, and location on intraocular lens position: finite element model”, 48 (2): 222–229.

SWEPT-SOURCE OCT AND PENTACAM POSTERIOR CORNEA MEASUREMENTS NOT INTERCHANGEABLE

SS-OCT-based biometry and the Scheimpflug-based topography cannot be used interchangeably to measure K flat, K steep, J0, and J45 values of the posterior corneal surface, a new study suggests. It showed that in 59 eyes of 59 myopic patients who were candidates for refractive surgery, the IOLMaster 700® (ZEISS) provided significantly flatter K flat and K steep values and J0 and J45 values than the Pentacam® HR (OCULUS) with mean differences of 0.49 D, 0.53 D, 0.04 D, and 0.05 D, respectively. The study’s author noted that as the Pentacam serves as the gold standard, the IOLMaster 700 may tend to underestimate the amount of posterior corneal curvature. B Kose, “Agreement between swept-source optical biometry and Scheimpflug-based measurements of posterior topography corneal curvature”, 48(2): 185–189.

NEW EDOF LENS

A new, nondiffractive presbyopia-correcting IOL, the DFT015 (Alcon), appears to provide superior intermediate and near vision and noninferior distance vision compared with an aspheric monofocal IOL of similar design—SN60WF (AcrySof™ IQ)—according to the results of a new study. In the randomised, controlled, double-blind trial that involved 282 patients, 62.7% of those randomised DFT015 IOL achieved a monocular distance corrected intermediate visual acuity of 0.2 logMAR or better at month six, compared to only 33.1% in the SN60WF group. In addition, both the DFT015 and SN60WF IOL groups achieved a mean binocular corrected and uncorrected distance visual acuity of <0.0 logMAR. The binocular defocus curve indicated that patients with DFT015 IOL achieved ≤0.0 logMAR visual acuity from a defocus +0.50 D to -0.50 D, <0.1 logMAR out to -1.50 D, and <0.2 logMAR VA out to -2.00 D (50 cm). C Bala et al., “Multicountry clinical outcomes of a new nondiffractive presbyopia-correcting IOL”, 48(2): 136–143.

Not Quite Finished Training

Quigley

Life is for living—and not just for ophthalmology training. But anyone who goes through the training knows living is moulded around it, with its sometimes onerous requirements, for a while. Within training, there are the mandatory components, exams, logbooks, etc., but also an indistinct collection of activities you know you should engage in to improve your chances of progressing to the Consultant post you want. That includes different flavours of pursuing further development in research, management, or teaching. The training job, wonderful as it is, gobbles away precious time. Sometimes though, life bites back.

Galway-Dublin-SligoDublin-Cork-Dublin-who knows? Postgraduate training in most medical specialties in Ireland involves moving around and working in different units. It helps to have an understanding and sympathetic partner—and to give them good notice this is what to expect.

“I may be relocating for a while. Six months, a year?” And then there are the lesser day-today incursions at home. “Sorry about this, there’s an online teaching session that I have to attend tonight. Can I disappear into the study? I’ll do bedtime if my Zoom session finishes on time. Oh, and I have a mandatory assignment for my online management course that I have to submit by the end of the week. I better take a couple of hours at the weekend to work away at that, if that’s ok for you to be on duty?”

But we must acknowledge that any career can be demanding on family life; it helps to think relatively. When the job starts to feel burdensome, I imagine being called in to do appendectomies or deliver babies in the middle of the night. And then what about the non-medical alternative, working away, doing long hours unhappily at a dull desk job to pay the bills?

Despite the demands inherent in training, I can see now that this has been the comfortable career stage, working in teams with a motivated Consultant who is backing us up and supporting our learning, surgical and otherwise. I am not so far now from qualifying, and I see the real world looming. With that certificate of completion of training, we are to be let loose, looking for gainful employment.

I had imagined, optimistically in retrospect, finishing training shortly. But having babies and training through the COVID-

19 pandemic does not lend to as full a logbook as I might otherwise have, and those events also reduce opportunities for networking professionally. I am discovering this as I apply for fellowship training. After another protracted job application and interview results in generous feedback, but no job offer, I pause. I attempt to reorient with my values. One kernel exists that can quieten any anxiety about where I’m going or what I’m aiming for at any particular time: love. Thinking about expressing love and how that looks in caring for people, whether that be removing a cataract or a skin tumour, or looking after a distressed person in the ED, has a definite calming effect. It does not matter so much, then, about career or speed of completion of training; I am doing good in fulfilling work, and as a trainee or not, that matters.

At the start of training, when I was fresh to ophthalmology, I remember a steep learning curve. The job was challenging, and I was not proficient, needing to take advantage of helpful colleagues to show me how to do anything and everything. I remember willing myself to visualise the retina through a 90 D; eventually, the glimpses turned into steady images and progressed to detailed pictures—oh there, a retina tear! Patients, Consultants, and Registrars in Galway where I started out—thank you.

Now, training is going to make room for life for a difference. At work, I am walking slower, avoiding the stairs, taking the lift. I have been released from doing on-calls. I am operating— doing cataracts mainly—holding out from scrubbing in for long procedures, as I need to mobilise to stay comfortable. I am 35 weeks pregnant and counting.

The bump is big now. Some patients, especially women, comment. “Best of luck with your baby!” One woman called out after I finished her cataract. Most patients don’t say anything. I am confident that one man, when I was doing indirect PRP laser, felt the baby kick. I was lasering that awkward superior retina, leaning in from the side of the table, pressed up close to the man who was lying still, sub-Tenon’s block and sedation in. I fired at the blank retinal canvas at 12 o’clock. At that moment, the baby jabbed out a foot towards the patient, a gentle kick. Neither of us said anything. Life is due to take over from training soon, for a while.

Despite the demands inherent in training, I can see now that this has been the comfortable career stage, working in teams with a motivated Consultant who is backing us up and supporting our learning, surgical and otherwise.

Clare

Considering Economic and Social Issues Affecting Your Practice

By Howard Larkin

As currently practiced, femtosecond laser-assisted cataract surgery (FLACS) is not cost effective compared with manual phacoemulsification surgery, according to three large European randomised clinical trials. FLACS would have to nearly double operating theatre productivity and/or dramatically reduce its per-patient costs to become cost competitive, according to Alexander C Day PhD, FRCOphth.

When introduced in Europe nearly a decade ago, many potential benefits were touted for FLACS over manual phaco. These included more-accurate capsulotomy positioning, shape, and size; better IOL centration; less lens tilt and fewer higher order aberrations; and lower phacoemulsification energy leading to less endothelial loss.

In the real world, however, these theoretical benefits have not translated into meaningfully better patient outcomes in three large European randomised controlled clinical trials (RCT), Dr Day said in a presentation at the 39th Congress of the ESCRS in Amsterdam.

In the largest RCT comparison to date, the French multicentre FEMCAT study involving 907 patients, researchers did not find any significant differences in intra- or postoperative complications, visual outcomes, or patient-reported outcomes.

The UK multicentre FACT study, involving 785 patients, found only a one-letter advantage in binocular corrected distance visual acuity after one year favouring the FLACS group. This was statistically but not clinically significant, Dr Day said, and there was no difference in endothelial cell loss.

And the UK single-centre St Thomas’ study involving 400 patients found only a slight difference in posterior capsule tears favouring FLACS, 3% versus none, though this may be a statistical anomaly, Dr Day said.

“What have we learned from the large European RCTs? There is no difference or very little difference in outcomes between the two techniques,” he said.

EFFICIENCY AND COSTS

Whatever marginal improvements FLACS may provide come at a high cost in both resources and money. One is surgical theatre time. Both the FACT and St Thomas’ studies showed slightly shorter surgery times for FLACS but longer overall procedure times of four to five minutes due to added time for laser treatment, Dr Day reported.

So, if the outcomes are similar and theatre productivity is no better, the cost of the equipment and fees associated with manual phaco and FLACS must be considered, Dr Day said. Focusing on capsulotomy alone, the cost of a cystotome or rhexis forceps or bent insulin needle for manual procedures is less than £10

compared to a £100–150 click fee per FLACS procedure—not to mention the £250,000 for the FLACS platform.

Using the incremental cost-effectiveness ratio (ICER) per quality of life-adjusted year (QALY) gained gives a more global look at cost-effectiveness, Dr Day said.

“For something that gives a small incremental improvement, it is going to be hard to justify a higher price.”

Applying this measure to FACT study data, FLACS costs a mean of £167.62 more per patient for a gain of 0.001 QALYs. This translates to an ICER for FLACS of £167,620—or more than eight times the threshold ICER value of £20,000 per QALY that UK authorities consider cost effective.

“Very clearly, you can see FLACS is not cost effective in the UK National Health Service,” he noted.

Similarly, micro-costing analysis of the FEMCAT data revealed FLACS was more expensive than manual phaco by a mean of €305 and less effective by three percentage points, Dr Day said. Looking at the cost-effectiveness, this translates to an ICER savings of €10,703 per additional patient who had manual phaco cataract surgery.

“In all sensitivity analyses, FLACS was more expensive and less effective than phacoemulsification surgery,” he added.

IMPROVING COST-EFFECTIVENESS

For FLACS or any future technique to be cost effective, it needs to be cheaper, increase productivity, and/or improve outcomes for the short- and long-term, Dr Day said. In one economic model, FLACS could be less expensive than manual phaco if the number of surgeries per theatre list increased by more than 100% or if the cost per procedure reduced by 70%.

Increasing theatre productivity may be the most promising route, Dr Day said. Since only about half of surgeons’ time in theatre is devoted to actual surgery, increasing the use of other health professionals to do tasks such as writing operating notes and adding staff to move patients in and out more quickly might approximately double productivity. Switching to immediate sequential bilateral cataract surgery might also help, he added.

Still, significant numbers of FLACS are undertaken, mostly in private settings where cost-effectiveness is not a big issue, Dr Day said. But the question remains as to how new technologies can be implemented when the current manual phaco is highly cost effective.

Alexander C Day PhD, FRCOphth, is a consultant ophthalmic surgeon at Moorfields Eye Hospital, London, UK, and honorary senior lecturer at the University College London Institute of Ophthalmology, UK. alex.day@ucl.ac.uk

Doubling FLACS cost-effectiveness might make it more competitive with manual phaco.

INDUSTRY NEWS

Alcon Acquires Hydrus MIGS Stent Maker

Alcon reported it completed its acquisition of Ivantis®, the developer of the Hydrus® Microstent. The company noted that Ivantis associates, including manufacturing and sales, are immediately integrated into Alcon to ensure continuity for new and existing customers. The company says it plans to bring the Hydrus Microstent to more international markets and prioritize its ongoing evidence-based research.

“We believe this transaction will further strengthen our global surgical portfolio and help provide a platform for more growth in the glaucoma space. As we welcome Ivantis associates into Alcon, we look forward to introducing Hydrus Microstent on a broader, global scale in the near future to help even more patients see brilliantly,” said David Endicott, CEO of Alcon, in a press release.

Recent conference reports of the five-year HORIZON study results demonstrated clinically meaningful and statistically significant clinical benefits over the full five years, including sustained reduction in medication use and the need for invasive secondary glaucoma surgery. The safety profile was also sustained through the five-year follow-up, the company says.

“The visual field data recently showcased at the American Academy of Ophthalmology annual meeting showed Hydrus Microstent as the first MIGS device to demonstrate a reduced rate of visual field loss compared to cataract surgery alone,” said Ike Ahmed MD, FRCSC, University of Toronto, Canada, in a press statement.

CONTINUED GROWTH PROJECTED IN OPHTHALMOLOGY

Industry consulting firm Research and Markets released a new forecast predicting the next five years in the ophthalmology marketplace. The study reports the size of the global ophthalmology market estimated at USD 52.07 billion in 2020, was expected to reach USD 55.28 billion in 2021, COVID notwithstanding. The firm projects the market will grow at a compound annual growth rate of 6.52% to reach USD 81.05 billion by 2027.

In another study, the US-based Refractive Surgery Council (RSC) reported US laser vision correction procedure volume for the third quarter of 2021 at 190,911, marking a year-to-date increase of 48 percent over 2020. This was the top-performing third quarter since RSC began tracking LASIK, SMILE, and PRK procedures in 2015.

“Most refractive surgeons offer more than one laser vision correction procedure because while one particular procedure may not be the right option for a given patient, that patient may be a terrific candidate for an alternative procedure,” said Richard Lindstrom MD, founder and attending surgeon emeritus, Minnesota Eye Consultants.

RSC’s procedure volume report is based on utilization data gathered from the industry’s leading refractive device manufacturers, providing a valuable market performance indicator for the sector.

↙LAST CALL

MARCH

12th Annual Congress on Controversies in Ophthalmology: Europe (COPHy EU)

24 – 26 March

Virtual

APRIL

American Society of Cataract and Refractive Surgery Annual Meeting

22 – 26 April Washington, DC

MAY

ARVO

1 – 4 May Denver, Colorado, USA

JUNE

15th European Glaucoma Society Congress

4 – 7 June

Athens, Greece

SEPTEMBER

ESCRS 40th Congress of the ESCRS

16 – 20 September

Milan, Italy See

The ASCRS Annual Meeting is scheduled to be held in Washington, DC.

10 Issues per year. 6 Subspecialties. 25 Years. 169 Countries. A European focus. A global perspective. EUROTIMES.ORG/SUBSCRIBE