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Prof. Ioannis Pallikaris discusses his 2022 ESCRS presentation: "Peripheral Capsule Reconstruction And IOL Centration With The Fixoflex Ring".

Fixoflex ring: Prof. Pallikaris describes how to utilise the device during IOL implantation

The European Society for Cataract and Refractive Surgery (ESCRS) plans to welcome delegates to the Milano Convention Centre in Milan, Italy, for the fortieth time this year, and, judging by the preliminary online programme overview, there is a great variety of ophthalmology sessions on offer.

A range of symposia, programmes, video sessions and workshops will be on offer and are discussed in this brief preview article. There will also be a daily exhibition, enabling delegates to learn about the latest technological advancements in ophthalmology and providing networking opportunities.

editorial advisory board members about their anticipations for the Congress:

Prof. Dr Martin Dirisamer, FEBO, cornea consultant at University Munich, University Graz and Wels-Grieskirchen

Dr Frank Goes, consultant at the Goes Eye Center, Antwerp, Belgium

Dr Anastasios G. Konstas, Professor of Ophthalmology at Aristotle University of Thessaloniki, Thessaloniki, Greece

H. Burkhard Dick, Chair of Ophthalmology, University of Bochum, Germany

New this year are the “Cornea Day” and “Glaucoma Day” streams that are due to take place throughout the day. Cornea Day topics will include cataract surgery in patients with ocular comorbidities; ocular surface and anterior segment surgery; and developments in posterior lamellar keratoplasty, keratoconus and cross-linking, whilst Glaucoma Day will cover profiling glaucoma patients, hints for cataract surgeons who are considering MIGS, surgical complications and surgical controversies.

Prof Konstas remarks: “The Glaucoma Day format provides an enticing and practical platform aiming at both young as well as more senior ophthalmologists who have been many years in clinical practice. Attendees will gain greater insight into recent developments in glaucoma diagnosis and management. In particular, the surgical management of glaucoma has been revolutionized by the introduction of MIGS, which aim to meaningfully lower IOP with a better safety profile than traditional glaucoma surgery. Cumulative data suggest that MIGS offer tangible clinical benefits to selected glaucoma patients. The Glaucoma Day will cover the role and emerging potential of several novel antiglaucoma options enabling a better understanding of their future value in clinical practice.”

The Main Symposium to be held at the end of the afternoon will be on the topic of “Emerging Treatment Options for Corneal Endothelial Disease”. There will also be an IME Symposium with the title “Phaco complex cases.”

“A very promising symposium, a bunch of new treatment options for endothelial diseases are on the way, probably also with a paradigm shift (treatment options without need for transplants, cell injection, etc.) Mid-term and long-term data expected of DSO (Descemetorhexis only),” said Prof Dirisamer.

"A highlight for me will be the session on Cataract Surgery in the patient with ocular comorbidity", says Dr. Dick, and adds: "We're seeing patients with a variety of corneal afflictions which just a couple of years ago would have been called 'challenging', if not outright 'desolate'. Today, cataract surgery can in many cases benefit these patients - who value even moderate visual improvement - to an often astonishing degree."

Three instructional courses to be held at the end of the day will cover the topics of “Different Ways of Secondary IOL Implantation without Capsular Support”; “DALK: From Basic to Advanced”; and “Endophthalmitis after Cataract Surgery”. Finally, the Exhibition Hall will open at 13:00 on Friday and remain open until 18:00.

“It’s an exciting topic with several new approaches on the market (IOL, Yamane technique, etc.). I’m excited to hear more about the femto-second laser technology supporting this highly challenging procedure,” Prof. Dirisamer said.

“Assisting my colleagues in medical legal matters I am regularly confronted with endophthalmitis cases, so the topic ‘Endophthalmitis after cataract surgery’ and specifically the analysis of eventual differences between inpatient and outpatient surgery may be of practical use,” said Dr Goes.

Saturday sees the Opening Ceremony of the Congress take place at 10:00, which should provide attendees with a feel of what to expect during the yearly event. This is due to be followed at 11:00 by the Main Symposium on “Demystifying IOLS optics”.

“There is a strong need for a new and clear classification of different IOL’s and technologies on the market,” said Prof. Dirisamer.

Elsewhere, the “Young Ophthalmologists Programme” is running “Starting Phaco” which includes video cases submitted by young ophthalmologists. This programme also offers junior ophthalmologists the chance to network and pick up useful information.

"This is one of the most encouraging events of the meeting," according to Dr Dick, "since we all once again are going to recognize what a huge potential and bright future ophthalmology has - and needs to have given the demographic development in our countries - in these fine young colleagues!"

Prof. Konstas points out: “This session will offer a first-class introduction to all young ophthalmologists to the key steps and pitfalls of the surgical procedure that dominates daily clinical practice in our profession. Understanding the rules of engagement with this procedure is crucial to all junior ophthalmologists.”

Throughout the day, Clinical Research Symposia will be held on: “Digital Medicine – 6 Steps for a Better Future”; “Ocular Tissue Engineering”; “Advancement of IOL Optic – How Far Can We Go?” and last-but-not-least, on the very hot topic in ophthalmology at the moment: gene therapy.

“Gene therapy is certainly a hot topic, with huge chances of big changes in the treatment of genetic caused diseases,” explained Prof. Dirisamer.

"I'm so excited, especially in my function as the Chairman of the ESCRS Research Committee", exclaims Dr Dick, "since we hopefully will learn a lot in these sessions, that finally - finally! - we will be able to cure or at least influence to a hitherto unknown degree the course of terrible diseases, including Morbus Stargardt and Fuchs."

Prof. Konstas underlines: “the topic of gene therapy truly represents a hot topic! With recent advancements in the discovery of specific disease mechanisms, it is even conceivable that future therapies for ocular conditions like open-angle glaucoma will protect ganglion cells and the optic nerve and may even reverse long standing glaucomatous damage. This exciting prospect promotes gene therapy and genome editing into the forefront of ophthalmic research in the hope that it may in due course provide a real therapy instead of the current indirect therapeutic approach of IOP-lowering.”

A total of 28 instructional courses will be running throughout the day on Saturday. The majority of these are 90 minutes long and start at 08:30, 10:30, 14:00 and 16:00. Shorter one-hour courses begin at 14:30. Free Paper Sessions and Presented Poster sessions will also be taking place and the Exhibition Hall will be open from 09:00 to 18:00.

The Main Symposium, on “High Volume Cataract Surgery”, will take place at 11.00 on the Sunday. The JCRS Symposium will be held at 14:00 and a Video Symposium at 16:15 entitled “Surgical Complications: You Make the Call” is sure to draw curious ophthalmologists.Early evening sees the IIIC Symposium at 18:15 on “The Perfect Save: Challenging Cases Managed by International Experts”.

"I recommend this session for very personal reasons," Dr. Dick adds with a smile: "I had the great privilege to act as an editor of a fine new book at Springer, together with Jorge Alio and Bobby Osher, on how to overcome the challenges of complex and complicated cases in cataract surgery. It's so brand new, I even haven't received a copy of it myself! Hopefully I'll see it in 'Publishers Row' in the Exhibition Centre. This session deals with some of the situations that can be successfully treated with the techniques we describe in our book."

“The Main Symposium on ‘High volume cataract surgery’ may help us with how to cope with waiting lists, which have grown to more than a million eyes in some areas,” Dr Goes suggests.

Workshops on Visual Optics will be being held throughout the day, starting with “Visual Function – Visual Behaviour” at 08:30; “Ocular Biometrics/IOL Optics and Calculation” at 10:50 and finally “Imaging of the Human Eye” at 14:00.

Also at 14.00, a “Case Report” Session aims to delve into “Preoperatory Complications and Difficult Manoeuvres”. Meanwhile, there will be a Young Ophthalmologists Session at 16:30 on “Cataract and Corneal Issues”. A Practice Management Masterclass, on how ophthalmologists can optimise the patient experience, will also take place on the Sunday; the exact timings for this are yet to be confirmed.

A further 27 Instructional Courses will be held, starting at 08:30, 10:30, 14:00, 14:30 and 16:30. These cover a broad range of topics including “Corneal Regeneration Therapy and Surgery”, “Enhanced Monofocals and EDOF IOLs” and several aspects of cataract surgery.

Instructional Courses also continue with 33 taking place, again starting at 08:30, 10:30, 14:00 and 16:00. Topics covered include “The Art and Science of Personalizing Refractive Outcomes in Cataract Surgery and Beyond”; “When Cataract Meets Glaucoma”; “All You Need To Know About Contact Lenses as a Refractive Surgeon”; and “Phaco Nightmares and Worst Case Scenarios”.

Prof Konstas observes: “Of particular value in current practice would be the Course “When Cataract Meets Glaucoma”. While the chance of improving vision in glaucoma patients manifesting co-existent cataract has never been better, significant controversies still exist requiring further clarification. Emerging evidence however suggests that earlier cataract surgery in patients with glaucoma, especially those with exfoliative glaucoma, will benefit long-term outcomes.

The final day of the Congress starts at 08:00 with an Orbis Symposium on “Innovative Ophthalmology in Conflict Zones” and a concurrent Presbyopia Workshop titled “Is there a change in the paradigm of presbyopia correction?” The final Main Symposium of the ESCRS at 10:30 is on the eye-catching subject of “How Not to Be Surprised by Refractive Surprise”.

“Since refractive market is growing and cataract surgery is more and more turning into a refractive procedure, dealing with refractive surprises is becoming increasingly important. Further, patients demands are getting higher,” explained Prof. Dirisamer.

“Surprises following refractive surgery do happen and thus the best way to prepare for them, how to optimize their outcome and, of equal importance, how to deal with our patients when they occur is critical,” Prof. Konstas comments. “Unfortunately, many refractive patients have overly high expectations, which will not be met when a refractive surprise occurs. The Main Symposium will help us to optimize the outcome of these surprises.”

The Free Paper Sessions continue, as do a series of Wet Labs starting at 08:00 and 10:30.There will be a final twelve Instructional Courses starting at 08:30 and 10:30, including courses on “Tips and Tricks for Challenging Cataract Surgery” and “Ocular Trauma Assessment and Management”.

The Congress finishes with the ever-popular “Best of the Best” session starting at 12:45 which highlights the best parts of the meeting.

Articles

Members of the Ophthalmology Times Europe Editorial Advisory Board offer comments on the symposia they are most excited to attend at the 2022 ESCRS Congress in Milan, Italy.

Top ophthalmologists anticipate ESCRS sessions

Spanish investigators from the Ophthalmology Service, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, led by first author Fernando Ly-Yang, MD, reported the case of a 42-year-old man with monkeypox. The patient had HIV and presented with conjunctivitis.

The patient’s symptoms included lacrimation, pain, and photophobia of the left eye for 6 days. Facial maculopapular lesions developed on his face and foot on the 5th day after symptom onset. The patient had a fever and painful cervical adenopathy and was HIV positive.

The patient had not traveled recently or had contact with monkeypox cases. However, his boyfriend worked in a sex club and had a fever.

Slit-lamp examination of the affected eye showed ulcerations on the eyelid margin, mucoid discharge, and conjunctival whitish, serpinginous, infiltrative lesions with conjunctival thickening. The cornea was unaffected.

Dermatologic evaluation of the skin resulted in a clinical diagnosis with high suspicion for monkeypox.

Polymerase chain reaction testing of the conjunctiva and skin was positive for monkeypox and negative for herpes viruses.

The authors reported that the patient received systemic treatment with 600 mg tecovirimat every 12 hours and intravenous acyclovir 1 gram every 8 hours, and topical zinc sulfate every 8 hours on the skin lesions. Ocular topical treatment included the following drops administered 5 times daily: chlorhexidine 0.2%, ganciclovir 0.15%, moxifloxacin, and povidone iodine 1%.

During the second week of treatment, conjunctival pseudomembranes developed during the second week of treatment. The pseudomembranes were removed and and topical fluorometholone 4 times daily was started.

The skin lesions resolved first and the conjunctival lesions resolved after 4 weeks of treatment.

The authors pointed out that conjunctivitis has been reported in 23% of monkeypox cases, but generally the male patients are younger than 10 years and have other symptoms in contrast to the current patient who was 42 years and did not have systemic signs or symptoms.

“The presence of conjunctival inflammation could occur more often in immunocompromised individuals given that the patient was HIV positive or it could be due to the contiguous spread of the periocular skin lesions,” the investigators wrote.

The investigators also noted that it is unknown if monkeypox is secreted in tears during conjunctivitis. However, the smallpox virus is secreted in tears, and monkeypox is a similar virus. Therefore, conjunctivitis may transmit the disease.

“A case of monkeypox in a patient with HIV with conjunctivitis is documented,” investigators concluded. “Conjunctivitis associated with monkeypox might present before skin lesions and may be a way of transmitting the disease.”

Ly-Yang F, Miranda-Sánchez A, Burgos-Blasco B, et al. Conjunctivitis in an individual with monkeypox. 

. Published Online September 7, 2022. doi:10.1001/jamaophthalmol.2022.3743

Spanish investigators hypothesise that conjunctivitis plays a role in disease transmission.

Monkeypox may be linked with conjunctivitis

Patients who present for cataract surgery are increasingly younger and more active and are therefore interested in a greater degree of spectacle independence without the limitations of standard monofocal IOLs. The loss of intermediate vision may have a particular impact on these patient’s lives, as they spend more time in front of computers and smart ‘phones.

To provide a balance between distance and near vision, the use of monofocal IOLs to produce a monovision set-up has been well established. Although we often see a high level of patient satisfaction with this approach, monovision has its limitations, including tolerance issues due to anisometropia, loss of binocular stereoacuity and asthenopia.

 The lens increases depth of focus through induction of positive spherical aberration.

By using Rayner’s RayOne EMV IOL (RAO200E; 

), my patients are achieving an extended depth of vision without the limitations of standard monofocal IOLs or the side effects associated with diffractive multifocal IOLs. The lens offers an extended depth of field via controlled positive spherical aberration, which can be used with and without monovision to increase the patient’s range of focus.

This lens has a non-diffractive optic and is therefore not expected to produce the side effects that are usually associated with diffractive IOLs such as night vision disturbance and loss of contrast. Although a high level of spherical aberration may induce night vision disturbances when certain thresholds are exceeded, there is a therapeutic range of spherical aberration in which night vision disturbances are not experienced because they are effectively filtered and processed by the brain.

In fact, while treating patients who had problems with night vision and loss of contrast in low light, which were common in patients with very small optical zones who had undergone laser surgery in the 1980s and 1990s, Prof. Dan Reinstein found that some degree of spherical aberration was therapeutic.

 At these levels of spherical aberration, depth of field was increased, but no night vision disturbances were experienced by the patient.

Visual ranges of standard monofocals, standard monovision and "modified monovision". 

In my patients who receive this lens, my goal is to produce “modified monovision”. The additional controlled spherical aberration produces superior distance vision in the non-dominant eye and superior near vision in the dominant eye compared with what could be achieved with a standard monofocal IOL in a “standard monovision” setup (

I usually target plano in the dominant eye, and I choose a target refraction of −1.50 D in the non-dominant eye. This target for the non-dominant eye is consistent with an offset my colleagues and I have already used successfully in the settings of PRESBYOND and LASIK,

 which also combines spherical aberration induction and monovision.

The outcomes achieved with this strategy avoid patient intolerance and the other drawbacks seen with standard monovision. This approach provides a broad range of spectacle independence across the visual range, and the wide range of functional vision achieved allows for a better range of refractive error tolerance, without glare and halos or drop in contrast.

In patients who have already had corneal laser refractive surgery, I am sometimes hesitant to use this lens since they will likely already have a raised level of corneal spherical aberration. Raising it further may risk exceeding the therapeutic level. In these patients, I explain that their eyes already have increased depth of focus due to their previous laser treatment and that standard monofocals can be used to achieve “modified monovision”.

My patient interactions begin by establishing their daily visual needs and asking what they hope to achieve with their cataract surgery. In those with substantial cataracts, I explain that any option will result in improved quality of vision.

Beyond this initial expectation, the question then becomes the amount of spectacle independence that they hope to achieve with surgery. I review both monofocal and multifocal options and explain the potential limitations to multifocal IOLs such as the potential impact on night vision and loss of contrast.

I first discuss the option of standard monofocal vision with one eye set for near vision and one eye set for distance vision, without synergy between eyes, which is tolerated by about two-thirds of our patients. I explain that intermediate vision is not likely to be covered in this scenario.

I then discuss the concept of “modified monovision” as a strategy to overcome these limitations, with one eye set to predominantly manage distance vision and one eye to predominantly manage near vision but working in synergy to provide a better depth of field and some degree of intermediate vision that is independent of spectacles.

I feel that it is important to under-promise and over-deliver, and the fact that multiple strategies currently exist to improve vision in patients undergoing cataract surgery suggests that no solution is perfect for every patient. I explain to all patients that no presbyopic treatment can guarantee complete independence from glasses. For instance, most patients will continue to require spectacles for reading the small print of medicine bottles or watching live performances at far distances.

Overall, I have aimed for a target vision goal of −1.50 for the reading eye and have yet to find a patient needs follow-up laser surgery to address anisometropia. However, I do explain to my patients that a LASIK enhancement is a safe option to reduce the myopia if they do not tolerate it.

In contrast, if a patient does not tolerate a multifocal IOL then only lens exchange will remedy the situation. Overall, I have seen excellent levels of patient satisfaction in those who have received the RayOne EMV with this goal of modified monovision, and I have been very pleased with the results so far.

Suggestions for those new to modified monovision

Surgeons who are not comfortable attempting a modified monovision setup and who do not typically manage presbyopia may still see promising results with a standard plano target with this lens. This is because the depth of field offered will likely enable the patient to read text of a reasonable size in good light.

As the surgeon develops confidence, with patient experience, they may begin to target some myopia in the reading eye to increase the range of spectacle independence achieved.

Mr Alastair Stuart, BMBS, BMedSci, FRCOphth, PGDip CRS, Cert LRS

Mr Stuart completed his ophthalmology training in London and the South of England, UK, culminating in a corneal fellowship at Moorfields Eye Hospital followed by a fellowship in refractive surgery at the London Vision Clinic. He joined Optegra as a cataract and refractive surgeon in December 2021. He is a key opinion leader and consultant for both Rayner and Carl Zeiss Meditec, from which he receives payment for scientific reports and presentations.

Pseudophakic monovision: a clinical guide

2. Barrett GD. Consistently the best of both worlds: modest monovision as a strategy for balancing near and far vision.

3. Reinstein DZ, Archer TJ, Couch D, et al. A new night vision disturbances parameter and contrast sensitivity as indicators of success in wavefront-guided enhancement. 

4. Reinstein DZ, Couch DG, Archer TJ. LASIK for hyperopic astigmatism and presbyopia using micro-monovision with the Carl Zeiss Meditec MEL80 platform.

In “modified monovision”, which can be achieved with a new IOL, one eye predominantly manages distance vision and the other near vision—as with standard monovision—but the extended depth of field provides a degree of intermediate vision that is independent of spectacles.

A new lens option for enhanced monovision performance

Taking place from 16–20 September 2022, and following the success of last year’s congress, the 40th ESCRS will again be a face-to-face event but supported by a virtual conferencing platform that will allow the sessions to also be streamed.

At the time of going to press, the ESCRS had not released the full, in-depth programme, however, a range of symposia, programmes, video sessions and workshops will be on offer and are discussed in this brief preview article. There will also be a daily exhibition, enabling delegates to learn about the latest technological advancements in ophthalmology and providing networking opportunities.

New for 2022 is the ESCRS iNovation Day. The agenda for iNovation Day includes discussions on the most urgent clinical needs and the use of technology to address them, along with perspectives from the European investment, regulatory and research communities. In parallel to this, the World Society of Paediatric Ophthalmology will be holding their Subspecialty Day.

Also new this year are the “Cornea Day” and “Glaucoma Day” streams that are due to take place throughout the day. Cornea Day topics will include cataract surgery in patients with ocular comorbidities; ocular surface and anterior segment surgery; and developments in posterior lamellar keratoplasty, keratoconus and cross-linking, whilst Glaucoma Day will cover profiling glaucoma patients, hints for cataract surgeons who are considering MIGS, surgical complications and surgical controversies.

At 16:00 there will be an IME Symposium on Presbyopia IOLs and at 17:00 a Video Symposium on the topic of “Challenging Cases”.

A three-part Refractive Surgery Didactics Course will be ongoing on Saturday. The first session at 08:30 covers diagnostic techniques; the second session at 10:45 is entitled “Therapeutic Techniques: Intraocular Surgery”; and the final session at 14:00 covers “Therapeutic Techniques: Corneal Surgery”.

Monday morning has two Main Symposia, beginning with the Heritage Lecture at 10:30 and followed at 11:00 by a session entitled “Where Are We in Intracorneal Implantation?” An IME Symposium on the subject of “3D Cataract Microscope Visualisation” will be held at 13:00.

A Video Session on “Getting Into Trouble” should provide delegates with some useful tips on overcoming surgical challenges at 14.00. Throughout the day there will be the opportunity to attend Practice Management workshops and the Free Paper Sessions and Presented Poster Sessions continue to run.

At 16:15 the CSCRS Symposium will be held on the subject of “The Patient Journey in Cataract Surgery.” There will also be an ISRS Symposium at 18:15 to end the day.

Taking place from 16–20 September 2022, and following the success of last year’s congress, the 40th ESCRS will again be a face-to-face event but supported by a virtual conferencing platform that will allow the sessions to also be streamed. 

Congress of the ESCRS reaches milestone age

If left untreated, diabetic macular oedema (DMO) and diabetic retinopathy (DR) can lead to severe visual impairment. It is therefore imperative to understand the challenges clinicians and their patients routinely encounter in the management of these conditions, according to Prof. Anat Loewenstein, who spoke in a “Late Breakings” Session at the European Society of Retinal Specialists (EURETINA) Meeting on 2nd September 2022 in Hamburg, Germany.

Prof. Loewenstein is based at the Department of Ophthalmology, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel. She is co-chair of the Bayer-sponsored Barometer Programme, which is conducting a global survey of patients, physicians and clinic staff to identify these challenges, and the opportunities to improve outcomes for patients. This interim analysis included data from 16 countries across North America, South America, Europe, Africa, the Middle East and the Asia-Pacific region (see

Countries included in the interim analysis of the survey.

 (Image courtesy of The Barometer Programme, which is sponsored by Bayer.)

Patients were asked to complete an anonymous questionnaire which delved into their experiences with obtaining a diagnosis, attending appointments and receiving treatment. Their personal characteristics were collected and they were asked about opportunities where they felt better support could have been provided.

In addition, patients with DMO were asked about their adherence to treatment. Physicians and clinic staff were asked to complete similar questionnaires and the two types of responses were compared in order to obtain an idea as to where the patient and clinician experiences converged or diverged.

In total, 2,546 surveys were completed in the interim analysis, comprising 275 providers (those administering and/or prescribing anti-VEGF treatment), 558 clinic staff (those interacting with patients butnot administering or prescribing anti-VEGF treatment), 1,073 patients with DMO and 640 patients with DR.

Within the analysis, no statistical comparisons were planned or performed, and the data was reported descriptively. Differences between responses of adherent and non-adherent DMO patients were determined by subtracting the percentage of non-adherent patients from the percentage of adherent patients answering each possible response of any individual question on the survey.

According to Prof. Loewenstein, the results showed that patients did not feel they had sufficient information to help them understand their treatment or their disease. More than half (55%) of DMO patients did not know how many more treatments they would have in the following 12 months and 50% did not know how long treatment would last.In contrast, 85% of providers reported always or regularly discussing how long treatment might be required for, highlighting a potential disconnect in physician-patient communication.

A similar proportion (41%) of patients with DR reported not receiving any information about what to expect with their treatment and this aligned with 53% of DMO/DR providers stating that their clinic did not have sufficient educational material to give to patients regarding their condition or what to expect from treatment. Most patients with DMO, DMO/DR providers and clinic staff (65%, 85% and 89%, respectively) said that they felt it was either extremely or very important to have better educational material available for patients.

When analysing the differences between adherent and non-adherent patients, the survey found that compared with non-adherent patients, adherent patients found travelling to the clinic easier; did not consider the number of appointments for DMO to be overly burdensome; felt that their physician understood the challenges of managing their condition and gave them enough time to ask questions; and felt more comfortable talking to their doctor about their condition and asking for support to help manage it.

From the clinician questionnaires, it became apparent that only 26% of providers and 20% of clinic staff considered themselves fully trained in how to avoid jargon when speaking with patients; 29% and 37%, respectively, said that they would like better training in this area.

Only 40% of providers considered themselves trained to an expert level in using anti-VEGF treatment and just 15% considered themselves experts on the contraindications of anti-diabetic medicines. Finally, 43% of providers rarely or never discussed where to find more information on DMO/DR or support services associated with the conditions.

Prof. Loewenstein concluded by stating that this survey is the largest such initiative undertaken to gather unique insights from multiple perspectives on the challenges and opportunities for managing both conditions, and highlighted the need for accessible educational materials for patients to improve access to information, education and guidance. In addition, there is a need for training resources on DMO/DR for clinicians in order to help them to better communicate with their patients.

Prof. Loewenstein said: “Gaining perspectives from patients and clinicians alike will support identifying barriers and possible opportunities to optimise care, hopefully informing and shaping practice and policy not only at a global level, but at national and clinic levels too.” She added that with survey submission drawing to a close, the primary analysis of the survey planned for 2023 is anticipated to provide much more detailed and systemic information which should help to improve the treatment process and outcomes for patients and inform clinical guidelines.

Prof. Loewenstein is a consultant to Allergan, Bayer, Beyeonics, Forsight Labs, Notal Vision, Novartis and Roche.

Data highlights need for educational materials and training resources in DMO and DR.

Interim global survey analysis reveals opportunities to improve patient outcomes

Dr Arshad M. Khanani, clinical associate professor of Sierra Eye Associates, University of Nevada, Reno, Nevada, United States, announced 12-week interim results of BEHOLD, a proof-of-concept Phase 2a study investigating the candidate UBX1325, a novel senolytic approach for previously-treated patients with diabetic macular oedema (DMO) in the “Late Breakings” session at this year’s European Society of Retinal Specialists (EURETINA) Meeting on 2nd September in Hamburg, Germany.

Dr Khanani began his presentation by describing how senescent cells accumulate in areas of disease activity in DMO and wet AMD, releasing mediators (growth factors, pro-fibrotic factors and inflammatory factors) that drive the pathology of these two diseases.

UBX1325, which is in development by the company Unity Biotechnology, is a small-molecule inhibitor of Bcl-xL, a member of the Bcl-2 family of apoptosis-regulating proteins. According to the company, it is designed to inhibit the function of proteins that senescent cells rely on for survival.

The Phase 2a study was undertaken in previously-treated patients with DMO. Patients enrolled had to have 73-20 ETDRS letters, an OCT with residual retinal fluid central subfield thickness (CST) of at least 300μm and at least two injections of anti-VEGF therapy in the preceding 6 months with the last injection occurring 3-6 weeks prior to randomisation.

They were then randomised to receive either a single 10-μg injection of UBX1325 or a placebo injection. Patient demographics were well-balanced between both arms of the study.

Safety and efficacy data were analysed at 12 and 18 weeks following randomisation. Rescue criteria were an increase in CST of +75 μm from the lowest value and/or a decrease in best-corrected visual acuity (BCVA) of 10 ETDRS letters from the highest value.

Safety and tolerability were one of the primary endpoints of the BEHOLD study, the others being visual acuity by BCVA, macular oedema as assessed on optical coherence tomography by CST and the proportion of patients receiving rescue.

There were 65 patients enrolled in the 12-week arm of the study and 54 patients in the 18-week arm. BCVA and CST analyses were performed by mixed model repeated measures (MMRM). This methodology takes post-rescue data into account so that the analyses reflect the treatment effect and not the effects of anti-VEGF rescue.

Patients treated with UBX1325 had a mean increase of 4.7 letters compared with 1.3 letters in the control group (

 = 0.1148). At the 18-week time point, treated patients gained 6.1 letters, compared with 1.1 letters in the control group with (

 = 0.0368). According to Dr Khanani, the improvements in BCVA were durable and robust across a range of disease severity.

Additionally, patients treated with UBX1325 maintained their retinal structure better than patients in the control group. UBX1325 was found to be well tolerated, had a favourable safety profile and showed no signs of intraocular inflammation.

Dr Khanani pointed out that the 6.1-letter game from baseline was a clinically meaningful outcome and better treatment based on a new mechanism of action that shows sustained improvement in BCVA and stability of CST whilst also reducing injection frequency would be of great value for DMO patients. He added that the candidate is currently being evaluated in a Phase 2 study, ENVISION, in nAMD patients, with data from this expected to be presented at “future meetings”.

12-week interim results of BEHOLD, a proof-of-concept Phase 2a study investigating the candidate UBX1325, provides a positive outlook for a novel senolytic approach for previously-treated patients with diabetic macular oedema.

Positive interim data in Phase 2 BEHOLD trial investigating UBX1325 in DMO patients

Optic neuritis (inflammation of the optic nerve) arises from numerous causes including infections (e.g. herpes zoster and Lyme disease), vaccines’ adverse events and autoimmune diseases.

 Optic neuritis is, for example, the presenting symptom in about 20% of multiple sclerosis (MS) cases.

 Acute optic neuritis also characterises neuromyelitis optica spectrum disorder (NMOSD), a rare but severe autoimmune disease.

In at least 70–80% of NMOSD cases, immunoglobulin G (IgG) autoantibodies to the water channel protein aquaporin-4 (AQP4) are detectable in the serum and play a relevant role in disease pathogenesis.

Many of the remaining cases arise from autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG). As the name suggests, oligodendrocytes as well as myelin sheaths express MOG.

 These cases should now be diagnosed as a separate disease entity, MOGAD (myelin oligodendrocyte glycoprotein antibody associated diseases).

Although NMOSD is rare, ophthalmologists 

optometrists need to remain aware of it as a potential differential diagnosis. Early diagnosis and rapid treatment maximise the chances that patients will fully recover their vision.

 As “time is retina,” this article aims to reduce the delay to diagnosis by reminding ophthalmologists 

 optometrists about NMOSD’s ocular hallmarks.

NMOSD is rare: the incidence is between 0.4 and 2 per 1,000,000 person-years and the prevalence 0.5 to 4 per 100,000.

 Ethnicity largely accounts for the variation.

 AQP4-NMOSD is more common in people of Afro-Caribbean descent than in other ethnic groups.

Several human leukocyte antigen (HLA) alleles and other polymorphisms seem to be associated with the risk of developing NMO. The particular HLA alleles depend on the population studied.

 So, as with other autoimmune diseases, genetic predisposition seems to be influential in determining NMOSD risk.

Age at presentation can help differentiate NMOSD from MS. The peak age of diagnosis for MS is between 25 and 35 years of age whereas, in European studies, the median age at onset for AQP4-NMOSD and MOGAD was 40 and 31 years, respectively.

 As a rule of thumb, the age of onset is about a decade later in NMOSD than in MS.

Moreover, MOGAD is the most common neuroinflammatory disease in children.

Most autoimmune diseases are more common in females than males. Indeed, females account for between 70% and 90% of relapsing AQP4-NMOSD cases.

 MOGAD, in contrast, shows little sex-related epidemiological difference.

 The incidence and prevalence of NMOSD will probably increase over the next few years, reflecting greater awareness, improved differential diagnosis, earlier diagnosis and better treatments.

NMOSD is characterised by attacks of acute optic neuritis and transverse myelitis (inflammation of the spinal cord).

 The spinal cord involvement offers another point of differentiation from MS. Long spinal cord lesions that extend over three or four vertebral segments, which are very rare in MS, often show on magnetic resonance imaging (MRI) of people with AQP4-NMOSD.

In some cases, the autoimmune attack involves the brain stem, and spinal cord lesions can extend into the medulla oblongata.

 The optic nerve often shows longitudinally extensive lesions on MRI, occasionally involving the chiasm.

 In contrast, MS tends to cause short lesions.

AQP4 is expressed predominately by astrocytes, which have numerous roles including regulating the development and permeability of the blood–brain barrier. Increased permeability of the blood–brain barrier may allow IgG to access the central nervous system (CNS).

Astrocytes also contribute to information processing, dispose of old and damaged organelles and modulate neurotransmitter levels in the CNS.

 AQP4 regulates changes in the extracellular volume that modulate the concentration of solutes and, in turn, neuronal electrical activity. As such, AQP4 modulates neuronal transmission and excitability.

In people with NMOSD, the autoimmune attack on AQP4 produces dysfunctional astrocytes and can cause astrocyte death. The autoimmune attack also triggers bystander inflammation, whichexposes other, usually hidden, autoantigens and can damage oligodendrocytes and neurons.

So, testing for IgG targeting AQP4 offers a highly specific serum test for AQP4-NMOSD. Indeed, the antibody assay allows the diagnosis of AQP4-NMOSD at the first event.

 Again, this differs from MS, in which neurologists typically wait for MRI-confirmed dissemination in time and space following optic neuritis or another element of the clinically isolated syndrome before diagnosis.

Ophthalmologists should bear in mind that the sensitivity and specificity of cell-based assays for IgG targeting AQP4 are much better than for other techniques such as enzyme-linked immunosorbent assay.

Oligodendrocytes, which produce myelin, and neurons do not express AQP4.

 Between 10% and 40% of NMOSD patients who are negative for IgG targeting AQP4 in the best cell-based assay have IgG autoantibodies to MOG, which is expressed on the surface of oligodendrocytes and the outside of myelin sheaths.

MOG accounts for only 0.05% of CNS myelin proteins.

 Nevertheless, the autoimmune attack can still cause clinically significant demyelination.

 It is important to bear in mind that the clinical phenotype of MOGAD only partly overlaps with that of AQP4-IgG-NMOSD.

There is some evidence of remyelination and other repair mechanisms, predominantly in animal and 

 Although it is an area of active research, drawing conclusions about the clinical relevance to humans would be premature. Moreover, compensatory mechanisms seem to be more common in MS than NMOSD.

Less commonly, other conditions, including sarcoidosis, infections, connective tissue disorders and paraneoplastic neurological disorders, can be associated with or trigger NMOSD.

An increasing number of risk factors are associated with the likelihood of developing NMOSD. Smoking may adversely affect NMOSD progression and severity, for example. Low vitamin D levels are common in people with NMOSD, although whether this predisposes to NMOSD or is secondary to neurological disability is unclear.

Acute infections (usually respiratory) precede about one-third of NMOSD attacks. Moreover, the gastrointestinal microbiota in NMOSD seems to differ from that in healthy controls and MS patients.

 seems particularly enriched in people with NMOSD compared with healthy controls. Whereas MS patients also showed higher 

 populations, the increase was of marginal statistical significance and, unlike in NMOSD, no longer remained significant after multiple comparisons.

These observations raise the prospect that molecular mimicry (environmental and other proteins expressing epitopes similar to those on AQP4) may contribute to NMOSD.

 For instance, the epitope for AQP4 in NMOSD is homologous with a sequence expressed by 

24The altered gastrointestinal microbiota may also regulate cellular and humoral immunity, such as the relative abundance of T cell subpopulations.

NMOSD is a multi-system disorder: 52% of patients with AQP4-NMOSD and 34% of those with MOGAD show transverse myelitis on presentation, which can cause symptoms that range from mild sensory abnormalities to bladder, bowel and erectile dysfunction and to very severe quadraparesis (weakness in all four limbs).

Cerebral involvement can result in headache, intractable vomiting or persistent hiccups.

 In addition, MOGAD can trigger impaired consciousness, altered behaviour, psychiatric symptoms (e.g. depression), neuropsychological deficits (e.g. poor attention and memory) and epileptic seizures.

Optic neuritis is also common in people with NMOSD: 50% of patients with AQP4-NMOSD and 74% with MOGAD show optic neuritis alone or with other symptoms at presentation.

The ocular changes associated with NMOSD vary widely. Acute optic neuritis can be mild, causing, for example, hazy vision and poor high-contrast visual acuity as assessed by a Snellen chart. Some people find that the optic neuritis affects only low-contrast visual acuity or colour vision. Many people with NMOSD report scotomas.

In most people, optic neuritis can progress to complete, uni- or bilateral functional blindness.

Even after treatment for the attack, recovery from optic neuritis is usually poorer in AQP4-NMOSD than in MOGAD or MS.

 Bilateral optic neuritis is more common in MOGAD than AQP4-NMOSD and MS. Over time, however, optic neuritis will affect both eyes in AQP4-NMOSD.

The ocular phenotypes of AQP4-NMOSD and MOGAD differ. For example, optic neuritis in people with AQP4-NMOSD predominantly affects the posterior optic nerve and often encompasses the chiasma.

 Optic neuritis associated with MOGAD more frequently involves the anterior optic nerve and can present as papillitis or papilloedema.

However, optic neuritis in people with MOGAD can cause posterior lesions, retinal haemorrhages or macular stars. In such cases, ophthalmologists 

optometrists should consider the possible differential diagnoses.

Pain is among the most common and debilitating NMOSD symptoms.

 Between 62% and 91% of NMOSD patients experience central neuropathic pain.

Ocular pain, pain on eye movement or both often precedes or accompanies optic neuritis. Indeed, 86% of patients with optic neuritis due to MOGAD reported pain when they move their eyes.

Early diagnosis helps minimise the impact on visual acuity. Optical coherence tomography (OCT) can detect optic nerve damage, sometimes even before symptoms become clinically apparent.

Symptoms of acute optic neuritis resulting from the disease can resolve in treated rapidly.