When introducing genetic material into the target cell of a patient to prevent or cure a disease, one approach is to replace an otherwise mutated or missing gene with the correct coding sequence. Another is to inactivate or silence a mutant copy of the gene with a dominant negative or toxic effect (for example, using endonuclease/CRISPR-Cas9, ribozyme or antisense RNA). It is also possible to introduce therapeutically beneficial genetic material such as a ‘killer gene’ into tumours.

These three approaches were introduced by Prof. Isabelle Audo in one of her presentations at this year’s European Society of Retinal Specialists (EURETINA) Meeting on 3rd September in Hamburg, Germany, in the Session on “Inherited Retinal Diseases”. Prof. Audo is based at the Department of Genetics, Institut de la Vision, Paris, France.

However, there is another promising avenue available in gene therapy: optogenetics. In this case, the genetic material consists of light-sensitive proteins which can induce a biological process when exposed to light of a certain wavelength. This has potential in the progressive, inherited disease retinitis pigmentosa (RP), Prof. Audo explained.

The ongoing PIONEER Phase I/II study is a first-in-human dose escalation study that is investigating the optogenetics approach with the AAV2-based candidate GS030 (GenSight Biologics), which is delivered by a single intravitreal injection in the worst-seeing eyes of RP patients.

GS030 encodes the light-sensitive protein red-shifted channelrhodopsin. According to Prof. Audo, the gene is stimulated with an optoelectronic device consisting of a pair of engineered glasses, to transform an external light stimulus into a signal to activate the retinal ganglion cells and the retinal output is sent to the brain for image processing.

The clinical trial is being undertaken at is being at three sites in the United Kingdom (London), Paris (France) and United States (Pittsburg, Pennsylvania) and has enrolled 18 subjects between the ages of 18 and 75 with non-syndromic RP into three cohorts. Patients eligible for the study were affected by end-stage RP with no light perception or light perception levels of visual acuity. An extension cohort expanded the inclusion criteria by recruiting patients with hand motion and counting fingers levels of visual acuity.

The first cohort of patients (n = 3) received a dose of 5.0 x 1010 vector genomes, the second (n = 3) received 1.5 x 1011 vector genomes and the third cohort (n = 3) were administered with a dose of 5.0 x 1011 vector genomes. Dosing in these three cohorts has been completed and, following review by the independent Data Safety Monitoring Review Board, no safety issues were found. Based on this, the Board advised that the highest dose could be selected for the extension cohort, and one patient in this cohort is currently being reviewed in France.

In terms of efficacy data to date, Prof. Audo described by way of a video how a patient with late-stage RP in the second cohort partially recovered her visual function following treatment with a single dose. The patient had been diagnosed with RP 20 years prior to enrolment and, 12 months following injection in her worse-seeing eye, she could correctly locate objects of different sizes and contrasts on a white table in front of her, with a 57% success rate when wearing the light-stimulating goggles, versus 24% without the device.

The optogenetic candidate has been granted orphan drug designation in Europe and the United States.

Another company that is investigating the optogenetic approach in RP patients is Nanoscope Therapeutics. According to Prof. Audo, enrolment is complete in a Phase IIb trial, RESTORE, in 27 adult patients with a diagnosis of advanced RP.

In this trial, the experimental treatment is the ambient-light activatable multi-characteristic opsin MCO-010, delivered in a single intravitreal injection. There are two dose groups that comprise patients over the age of 18-years-old who have a confirmed diagnosis of advanced RP based on clinical examination, dilated fundus examination and genetic testing.

Enrolled patients had a best-corrected visual acuity worse than 1.9 LogMAR (Snellen equivalent of 20/1600), counts fingers/hand motion in the study eye and no better than 1.6 LogMAR (Snellen equivalent 20/800) in the fellow eye during screening. Patients also had the presence of retinal inner nuclear and nerve fibre layers detected on optical coherence tomography testing in the study eye during screening as determined by the investigator and confirmed by the sponsor or designee.

Patients will be assessed over 52 weeks and the primary outcome measures are the efficacy of a single intravitreal injection of vMCO-010 assessed by Y-Mobility test, and the type, severity and incidence of ocular and systemic adverse events, specifically those related to intravitreal injection of the candidate.

Dr Audo concluded by stating that in the future it should be possible to fine-tune the vectors to improve sensitivity and simulation and to target dormant cones to help restore vision.

Articles

Companies are exploring light-sensitive proteins method in patients with advanced disease.

Optogenetics approach could restore visual function in retinitis pigmentosa

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

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.

Countries included in the interim analysis of the survey.

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

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

At this year’s EURETINA in Hamburg, Germany, there were several engaging presentations during the Symposium Session that took place on the Friday, 2nd September on the important topic of artificial intelligence (AI) tools for fluid monitoring in neovascular age-related macular degeneration (nAMD).

Towards the end of the Symposium Session, Stela Vujosevic, head of the Medical Retina Service at the University Hospital, “Maggiore della Carità”, Novara, Italy, provided attendees with some practical guidance on handling the RetInSight Fluid Monitor, a Class IIa medical device that can be used to help support clinical decisions in the monitoring of patients with nAMD in Europe.

The fluid monitor is designed to identify, localise and quantify retinal fluid in routine OCT images. It assigns a label to each OCT pixel, denoting the fluid type as IRF, SRF or PED, and provides its location within the central 1-mm and 6-mm macular area. Fluid measurements are provided in nanolitres.

According to Dr Vujosevic, it is important to distinguish between the specific fluid compartments due to the differences in the impact on visual function and the dynamics of fluid resolution whilst patients are receiving different treatment regimens. She explained that the measurements and readouts of fluid activity enable ophthalmologists to monitor disease progression or response to treatment. The monitor is intended to be compatible with all leading OCT systems.

Dr Vujosevic went onto discuss that the AI-based software can be deployed by the OCT operator under the supervision of an eyecare specialist in the clinic environment, producing a concise and highly accurate real-time report containing patient results whilst the patient is on site. Benefits to patients include shorter waiting times for appointments, less inconvenience and lower cost associated with travelling and absence from work resulting from over-treatment, as well as a lowered risk of vision loss caused by under-treatment.

Meanwhile, eyecare specialists benefit from being able to monitor their patients long term for optimised and personalised treatment regimens, as well as having access to a more efficient workflow and one which enables them to see more patients.

Eyecare specialists benefit from being able to monitor their patients long term for optimised and personalised treatment regimens, as well as having access to a more efficient workflow and one which enables them to see more patients.

Fluid monitor utilises AI to identify, localise and quantify retinal fluid

Another speaker in the AI Symposium, Dr Gregor S. Reiter, Laboratory for Ophthalmic Image Analysis, Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria, took to the podium to highlight recent data from a prospective multicentre Phase 3 clinical trial using AI in nAMD.

The trial enrolled 290 patients with active nAMD with foveal intra- and/or subretinal fluid who were randomised into receiving AI-support or conventional, qualitative fluid assessment. The patients were aged 50 years or older and all had a best-corrected visual acuity (BCVA) better-than or equal-to 1.0 log MAR. 

In the BCVA-examiner blinded study, patients were randomised to undergo either conventional qualitative fluid assessment or AI-guided fluid assessment and the resulting impact on injection frequency was analysed.

According to Dr Reiter, the results demonstrated that fluid volumes can be precisely identified, localised and measured in real-time using AI. He said that treatment for nAMD is based on fluid volumes but also emphasised the importance of fluid dynamics.

He concluded by describing how automated tools such as these will enable precision medicine based on fluid guidance to enter real-world management of exudative disease, thus improving clinical outcomes whilst also providing savings in terms of healthcare resources.

According to Dr Gregor S. Reiter, the results from the multicentre Phase 3 clinical trial demonstrated that fluid volumes in patients with nAMD can be precisely identified, localised and measured in real-time using artificial intelligence.

Multicentre Phase 3 clinical trial using AI in nAMD identifies, measures fluid volumes in real time

In his presentation, “The fluid tool in clinical routine – Data from FRB! In Zurich”, Prof. Daniel Barthelmes, director of the Department of Ophthalmology at University Hospital Zurich, Switzerland, discussed a study that was designed to investigate the feasibility of analysing real-practice optical coherence tomography (OCT) imaging data using an established AI method.

The study aimed to determine the impact of subretinal fluid (SRF), intraretinal fluid (IRF) and pigment epithelium detachment (PED) on visual acuity outcomes at 12 and 48 months after starting anti-VEGF treatment.

The patients enrolled onto the study were treatment naïve and had nAMD, an average age of 78.9 years, and had had no prior treatment. A total of 209 eyes were analysed during the trial.

The Vienna Fluid monitor, an AI-based method for detecting and quantifying retinal fluid, was used to analyse OCT volume scans for SRF, IRF and PED from routine clinical practice and the effect of post-loading phase fluid volumes on visual acuity outcomes.

The study determined that the volume of fluids present was correlated with visual acuity outcomes and that the Vienna Fluid monitor is a more accurate method of assessing the volume of fluid present. Prof. Barthelmes explained that it is imperative to control the volume of fluid to improve patient outcomes, and this should be reflected in a change to the treatment paradigm.

He concluded by stating that the AI tool allows for more precise measurements in real time which can be utilised to improve treatment benefits in daily clinical practice. Patients with high IRF volumes after the loading phase are at risk of losing vision during the maintenance phase. Patients with high macular fluid volumes receive more injections compared to those with low volumes. For SRF and PED, this increased number of injections can prevent vision loss, however, for IRF the increase in injections does not compensate for loss in visual acuity.

Automated quantitative fluid analyses are enabling personalised treatments, better patient outcomes.

How, when and why to use AI in the clinical management of nAMD

RGX-314 provided 2-Step or more improvement in diabetic severity in Phase 2 Altitude study analysis

A gene therapy evaluated for diabetic retinopathy (DR), RGX-314 (REGENXBIO), may provide sustained clinical outcomes for treating DR. A major advantage is that this treatment can be administered once into the suprachoroidal space in an office setting, which markedly reduces the treatment burden, according to Dr Mark Barakat.

The Phase 2 Altitude study, an open-label, randomized, controlled, dose-escalation evaluation of RGX-314. It was conducted at 18 retina practices nationally and evaluated the efficacy, safety, and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector (Clearside Biomedical) in patients with moderately severe/severe non-proliferative diabetic retinopathy (NPDR) or mild PDR.

Using this treatment, an adeno-associated virus 8 vector delivers a transgene for a soluble anti-vascular endothelial growth factor (VEGF) fab which is designed to provide continuous anti-VEGF therapy.

First analysis of gene therapy for RPE65 inherited retinal dystrophies shows good safety, efficacy

French researchers, led by Dr Isabelle Audo reported that voretigene neparvovec (VN) (Luxturna, Spark Therapeutics), used to treat patients with a RPE65-related inherited retinal dystrophy, showed good safety and efficacy at the 1-year time point of the LIGHT Study.

 gene and loss of gene function causes photoreceptor dysfunction and degeneration, leading to blindness. VN is the first gene therapy for this patient population.

The LIGHT study, Dr Audo described, is a descriptive, non-interventional study in which VN was administered at a dose of 1.5 x 1011 vector genomes that were delivered in a total subretinal volume of 0.3 ml.

Both eyes of the patients were treated on separate days and at least 6 days apart. Follow-up examinations were conducted at 1, 3-, 6-, 12- and 24-months following gene therapy in the second eye. At these time points, the investigators evaluated the treatment efficacy and safety and collected the patients’ postoperative experience.

EURETINA leadership discusses what to expect at the 2022 Congress, outlines Women in Retina programme

Dara Conlon, Executive Vice President of EURETINA, and Prof. Anat Loewenstein, General Secretary of EURETINA, discuss some key features of this year's Congress.

Managing silicone oil-related complications following vitreoretinal surgery

Vision loss associated with a silicone oil endotamponade in vitreoretinal surgery is a rare yet underreported complication, but it is becoming increasingly important as technical refinements of the surgical procedure progress along with the increasing visual expectations of individual patients. Historically, silicone oil tamponade has been used in complicated cases of vitreoretinal surgery with a significantly reduced visual prognosis. Recurrent retinal detachments and proliferative vitreoretinopathy (PVR) retinal detachments and giant retinal holes have always been the main indications when considering silicone oil tamponades. European investigators describe how they address complications.

Hair cortisol may act as molecular biomarker for retinitis pigmentosa patients

Dr Milagros Mateos and colleagues from the Department of Ophthalmology of Clinical University Hospital of Valladolid and the Institute of Applied Ophthalmobiology, University of Valladolid, Valladolid, Spain, reported that the concentration of cortisol in hair may be an effective biomarker associated with chronic stress in patients with retinitis pigmentosa.

The authors explained that patients with RP experience greater levels of stress and anxiety than individuals in the general population and that the level of stress can be measured easily and non-invasively in hair. The stress is associated with the progressive and unpredictable and variable vision loss associated with the disease.

Link discovered between retinitis pigmentosa and increased risk of primary open-angle glaucoma

Retinitis pigmentosa and primary angle-closure glaucomaare genetic diseases with similar genetic variants and pathophysiology between them. The investigators explained that elevated angle-closure-related intraocular pressure (IOP) may aggregate the visual impairment in patients with retinitis pigmentosa, so they wanted to determine if patients with retinitis pigmentosa have a significantly higher risk of PACG development. This knowledge may facilitate for early intervention in these patients.

Music creates soothing effect for babies during retinopathy of prematurity examinations

Researchers from Turkey reported that the introduction of white noise and music had a beneficial effect during examinations of preterm infants with retinopathy of prematurity (ROP).

The investigators conducted a 1-year study from August 2020 to August 2021 to determine how white noise and classical music affected pain and physiologic parameters while examining infants with ROP in a neonatal intensive care unit.

Ninety preterm infants were included and evenly and randomly divided into three groups: the control group, the white noise group, and the classical music group.

The infants’ responses to pain were evaluated using the Premature Infant Pain Profile.

Visual symptoms after COVID-19 suggest retinal involvement

Retinal involvement following a COVID-19 infection is rare but can happen after severe infections in immunocompetent individuals, according to Dr Yusar Asad and colleagues from the Vitreoretinal Services, Centre for Sight, Delhi, India.

The research team conducted a retrospective review of consecutive patients presenting with retinal manifestations attributable to COVID-19 between May 2020 and June 2021.

A synopsis of the findings presented at EURETINA 2022 for ophthalmologists and retina specialists.

EURETINA 2022 in review: A showcase of retinal revelations in Hamburg

Researchers from Turkey reported that the introduction of white noise and music had a beneficial effect during examinations of preterm infants with retinopathy of prematurity (ROP). The lead author, Dr Mediha Tok Cevik is from Department of Ophthalmology, Sişli Hamidiye Training and Research Hospital, Istanbul, Turkey; she was joined in this study by coauthors Dr Ustabas Yildiz and Dr Sadik Görkem Cevik from the Department of Ophthalmology, Yuksek Ihtisas Education and Training Hospital, Bursa, Turkey.

Effects on pain and physiologic parameters 

During and after the examination, Dr Cevik reported the positive beneficial effects of the interventions on the infants’ responses.

Before the examination, the heart rates, oxygen saturation levels, and pain scores in the 3 groups did not differ significantly.

During the examination, the peak mean heart rates in the white noise group, 181.17 ± 15.76/minute and the classical music group, 173.30 ± 20.66/minute, were lower than that in the control group, 189.63 ± 63.39/minute. After the examination, the respective peak mean heart rates were 150.10 ± 17.03/minute, 146.67 ± 18.17/minute, and 158.57 ± 19.95/minute.

During the examination, the respective oxygen saturation values were higher in the white noise and classical music groups, 93.60 ± 3.87/minute and 95.73 ± 2.52/minute, compared with the control group, 92.50 ± 3.51/minute. After the examination, the respective values were similar, 97.83 ± 1.93/minute, and 98.27 ± 1.82, and 94.70 ± 3.32/minute.

Likewise, during the examination, the pain scores were higher in the control group compared with the white noise and classical music groups, 12.27 ± 1.70, 9.70 ± 3.02, and 11.2 ± 2.28; the same was true after the examination, with respective values of 7.00 ± 1.68, 3.60 ± 2.11, and 3.77 ± 1.83.

The white noise and classical music listened to by the preterm infants during ROP examinations clearly had positive effects on pain and heart rate and oxygen saturation values.

The authors commented, “In the study, we found that the non-pharmacologic techniques used during ROP examinations reduced preterm infants’ pain scores and peak heart rates, and they had higher oxygen saturation values. We think that the frequent use of musical methods such as listening to white noise and classical music during painful interventions such as ROP examinations for infants is effective in pain management and the regulation of physiologic parameters. More randomized controlled trials should be devoted to this topic.”

The white noise and classical music listened to by the preterm infants during ROP examinations showed positive effects on pain and heart rate and oxygen saturation values.

French researchers, led by Dr Isabelle Audo reported that voretigene neparvovec (VN) (Luxturna, Spark Therapeutics), used to treat patients with a RPE65-related inherited retinal dystrophy, showed good safety and efficacy at the 1-year time point of the LIGHT Study. 

Dr Audo is professor of ophthalmology in the Department of Genetics at Institut de la Vision, and coordinator of the National rare disease centre at Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris.

The efficacy was assessed by measuring the visual acuity (VA), full-field stimulus threshold (FST), and visual fields (VF). A maze platform was used that showed a typical street that patients may encounter during daily activities. Patients were instructed to follow the path under four lighting conditions of 2, 7.5, 50, and 500 lux and avoid obstacles and walls. Their mobility was assessed using the percentage of preferred walking speed and the time to completion of the course completion time.

The investigators also collected patient/parent comments about the visual experience.

Twelve patients (6 adults, 6 children; age range, 4-35 years) were included. 

Eleven had a diagnosis of Leber congenital amaurosis and one had retinitis pigmentosa. All have undergone bilateral surgeries.

At the 1-month evaluation, Dr Audo reported that the FST had median decrease of -33.2 decibels (dB) (-33.7; -19.8) dB, which remained stable until the last assessment. The VFs and VAs did not change significantly. 

She also reported that the percentage of preferred walking speed at 2 lux and at high speed, 1 month after surgery had a median increase of 63.9% (47.8%; 88.5%) and the course completion time decreased by 47.23% ( -58.50 %; -41.16 %). These improvements continued over time.

At least one adverse effect related to surgery occurred in all patients and only 1 was serious, i.e., a retinal detachment. Seven patients had at least one adverse effect related to VN, all of which were not serious and did not require treatment. Chorioretinal atrophy was observed in both eyes of 5 patients and was considered to be possibly related to surgery and VN.

The patients’ comments highlighted three categories described by Kay et al. 2021 mentioned by more than 50% of the patients: visual function symptoms, impact on vision dependent activities of daily living, and coping mechanisms and visual aids, providing more insight into their postoperative experience.

Dr Audo said, “This experience with VN showed significant post-treatment improvements in FST from month 1. Adding a mobility test to assess the evolution of functional vision in their routine follow-up protocol in addition to the FST allows this study to gain further insight into the efficacy of VN during the first postoperative year. The patients’ mobility also improved from the first month after surgery for all patients.”

She also mentioned that in the 5 patients in which chorioretinal atrophy developed after VN treatment, the FST improved compared to baseline and remained stable over the long-term follow-up (between 12- and 24-months post VN treatment).

At the 1-month evaluation, the full-field stimulus threshold had median decrease of -33.2 decibels (dB) (-33.7; -19.8) dB, which remained stable until the last assessment. Visual fields and visual acuity did not change significantly.

The study included 20 eyes of 17 patients. All COVID-19 infections were confirmed by reverse transcriptase polymerase chain reaction. All other causes of retinal involvement were eliminated by systemic work-ups.

Dr Asad reported that the patients presented with vascular involvement such as venous stasis retinopathy, central retinal vein occlusion (unilateral/bilateral), branch retinal artery occlusion, and anterior ischemic optic neuropathy as well as opportunistic infections like endogenous endophthalmitis, candidemia retinitis, and subretinal abscess in orbital mucormycosis.

“A whole spectrum of manifestations following COVID-19 infections in an otherwise immunocompetent patient presenting at a tertiary care centre have been documented,” the investigators reported.

They advised that clinicians should be aware of this spectrum of retinal involvement after COVID-19 infections and emphasized the importance of a fundus evaluation. “While it is rare, it is important that these diseases can develop in a patient with visual symptoms,” Dr Asad commented.

Investigators advised that clinicians should be aware of this spectrum of retinal involvement after COVID-19 infections and emphasized the importance of a fundus evaluation.