Key to beating diabetes is better understanding for ophthalmologists

Health systems are challenged to provide appropriate care for the ever-increasing number of patients with diabetes and its complications, such as diabetic retinopathy and diabetic macular oedema.

Should NPDR patients be treated with anti-VEGF agents?

Dr Jennifer Sun explores the question of whether ophthalmologists should be using anti-VEGF agents to treat patients with nonproliferative diabetic retinopathy (NPDR)

Comparison of suitable naïve versus pretreated DMO patients

Dr Javier Zarranz-Ventura discusses the key highlights from his presentation on a clinical investigation of suitable naïve versus pretreated DMO patients, and what it means for future research.

Providing optimal care for patients with diabetic eye disease

Prof Tunde Peto discusses her presentation on providing the best virtual care for patients with diabetic eye disease at EURETINA 2021.

Optogenetic therapy for retinal degeneration shows potential of gene-independent therapeutic strategies

Dr José-Alain Sahel explains that optogenetics involves the use of artificial photoreceptors from specific retinal cells to restore vision by transferring a gene that encodes for a light-sensitive protein that causes neuronal cells to respond to light stimulation.

Brolucizumab injection improves vision in eyes with neovascular AMD

Dr Cristina Cristian noted that an injection of brolucizumab treatment in patients with neovascular age-related macular degeneration led to a median improvement in visual acuity (VA) of 10.5 letters and the drug was well-tolerated.

AI for nAMD: Capturing more information from OCT

Dr Anat Loewenstein discussed how artificial intelligence can optimize optical coherence tomography.

Exploring the clinical and humanistic burden of geographic atrophy

During a presentation at the EURETINA 2021 Virtual Congress, Dr Daniel Jones discussed GA and emphasized the need for additional study to gain a better understanding of the burden experienced by patients.

LIGHTSITE II study: Photobiomodulation treatment improves vision in eyes with dry AMD

During a presentation at the EURETINA 2021 Virtual Congress, Prof. Ben Burton detailed how dry AMD patients treated with photobiomodulation therapy have seen improvements in best-corrected visual acuity 9 months after treatment.

Worldwide pathological myopia discussed by panel

Dr Ramin Tadayoni discusses the myopia panel at the EURETINA 2021 virtual meeting.

Addressing roadblocks of treating peripheral hemorrhagic polypoidal choroidal vasculopathy

Treating the disease can be a challenge, and at the EURETINA 2021 Virtual Congress, Dr Chekitaan Singh discussed a case study detailing the care of a patient who had already lost vision in one eye from a similar issue.

Exploration of new biological treatments in posterior uveitis

Professor Quan Dong Nguyen speaks on the highlights of his presentation regarding new biological treatments of posterior uveitis.

Analysis of macula dystrophy classifications

Study investigates PCR risks associated with intravitreal injections for AMD

Dr Marta Belmonte-Grau discussed the potential risk for posterior capsular rupture during cataract surgery.

Role of anterior vitreous, managing retinal folds in retinal detachment cases

Dr Grazia Pertile discusses the highlights of her presentations on the management of retinal folds after retinal detachment and the role of the anterior vitreous as a cause of recurrent retinal detachment.

Articles

A post-conference guide for ophthalmologists after the conclusion of EURETINA 2021.

EURETINA 2021 Virtual Congress in review

Videos

UK researchers reported that photobiomodulation (PBM) (LumiThera Inc.) therapy in patients with dry age-related macular degeneration (AMD) resulted in significant improvements in the best-corrected visual acuity (BCVA) 9 months after treatment and that retreatment at intervals of 4 months provided consistent improvements in visual function and morphologic signs of dry AMD activity and maintenance of clinical outcome benefits, according to first author Ben Burton, an honorary professor at the University of East Anglia in Norwich, England.

The LIGHTSITE II trial, designed to assess the safety and efficacy of PBM in dry AMD, is being carried out in the UK, Germany, France, Spain, and Italy.

Burton, speaking at the EURETINA 2021 Virtual Congress, explained that this technology uses wavelengths of light to target cytochrome c oxidase of the mitochondrial respiratory chain to activate energy production and improve metabolic output.

By improving cellular activities, the anatomic and clinical endpoints benefit. PBM improves cellular activities that in turn positively impact the anatomic and clinical endpoints.

The PBM treatment is delivered using a light delivery system (Valeda Light Delivery System, LumiThera Inc.), which is CE marked in the EU. A growing body of evidence, Burton noted, supports PBM in the 500- to 1000-nm wavelength spectrum as a novel treatment for dry AMD.

A total of 44 patients (53 eyes; 17 men, 27 women; mean age, 74.1 years) with dry AMD were enrolled.

However, this enrollment did not meet the original goal of 96 patients (144 eyes) because of the COVID-19 pandemic.

The study extended the positive findings of the LIGHTSITE I trial by treating earlier, intermediate dry AMD subjects with 3 rounds of PBM, Burton explained.

Patients, with vision ranging from 20/32 to 20/100 and no central geographic atrophy, were randomized to either PBM or sham using the Valeda Light Delivery System delivered 3 times weekly over 3 to 4 weeks. The light treatment is applied for 4 to 5 minutes/treatment/eye.

“PBM-treated eyes showed significant (p=0.02) improvement compared with baseline in the BCVA at 9 months in the modified intention-to-treat group (n = 51 eyes),” according to investigators. “The patients had sustained BCVA improvement at 9 months (p = 0.01) with an approximate gain of 4 letters in the PBM-treated group versus a 0.5 letter gain in the sham group (p=0.1) for patients that underwent all 27 PBM treatments (29 eyes).”

More than 33% of PBM-treated eyes gained 5 letters at 9 months. The AMD converted from dry to wet disease in 3.1% treated with PBM compared with 5.6% in the sham group and 4.8% in non-study eyes.

The investigators pointed out that that eyes at high risk for conversion to wet AMD, i.e., the fellow eye had exudative macular neovascularization, showed a 0% conversion rate after PBM treatment.

PBM treatment also was associated with no significant drusen growth at 9 months in contrast to the sham group.

A 44% decrease in growth of geographic atrophy after PBM was observed at 9 months.

No safety concerns or phototoxicity were associated with PBM.

Physicians and health systems are challenged to provide appropriate care for the ever-increasing number of patients with diabetes and its complications, such as diabetic retinopathy (DR) and diabetic macular oedema (DMO). Dr Tunde Peto, Professor of Clinical Ophthalmology, Queen’s University Belfast, Belfast, Northern Ireland, and Clinical Lead for Diabetic Eye Screening in Northern Ireland and Medical Retina Consultant, offered some practical advice to address some of these challenges.

Diabetes and DR: Making progress in the global epidemic

The Diabetic Retinopathy (DR) Barometer Study

 analyzed data from over 4,000 patients and 2,000 doctors worldwide showing just how difficult living with and managing diabetes can be. The study results showed that almost 40% of patients describe the long wait times for an appointment as a barrier to eye examinations. 

About 80% of responders said that diabetes and DR and DMO impacted their ability to function in daily life, making driving, working, and completing the most basic household tasks difficult to impossible. Twenty percent reported that their visual impairment resulting from DR and DMO made managing diabetes difficult; and 69% described days during which they experienced poor physical/mental health. 

These difficulties in some settings might be compounded by the fact that as high as 1 in 5 ophthalmologists said that they did not receive specific training in diagnosing DR and DMO; and 44% of care providers did not have or use written protocols for managing diabetic eye disease and related visual loss. 

Prof Peto believes education, timely diagnosis, and treatment are the key components for preventing visual loss and preserving vision. Working together with patients and patient organization and co-developing education material will raise awareness of the disease. Diabetic eye screening programs can significantly address the problems associated with late diagnosis of DR and DMO leading to timely treatment and consequently better quality of life.

Diabetes during pregnancy linked to high refractive error in offspring

Complications associated with diabetes develop over a long period and regular monitoring can identify most patients at a stage in which treatment is most beneficial. DR and DMO lend themselves to image-based monitoring.

Physicians have an excellent understanding of diabetes-related eye changes, starting with the Airlie House Classification of DR.

 Landmark studies such as the Early Treatment Diabetic Retinopathy Study and the Diabetes Control and Complications Trial established a good understanding of the disease process.

 DR classification has been based on the presence of characteristic features in the eye or color fundus imaging of microaneurysms, hemorrhages, vascular abnormalities, and new vessels, and for DMO on these changes and exudates and macular fluid.

Diabetic macular edema: Treatment overview

“With advances in imaging technologies, we now have the opportunity to refine these and add further disease features to match our current understanding of the disease, its progression, and the potential response to treatment. Diabetes-related blindness still increases by 8% annually, so working with patients, care givers, public health agencies, and the healthcare sector, our patients with diabetes will have a better chance of retaining their vision and live a productive life,” Prof Peto concluded.

1. Cavan D, Makaroff L, da Rocha Fernandes J, et al. The Diabetic Retinopathy Barometer Study: Global perspectives on access to and experiences of diabetic retinopathy screening and treatment. Diabetes Res Clin Pract 2017;129:16-24; DOI: 10.1016/j.diabres.2017.03.023

2. Wu L, Fernandez-Loaiza P, Sauma J, et al. Classification of diabetic retinopathy and diabetic macular edema. 

3. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 1991;98:786–806.

Diabetes Control and Complications Trial Research Group

 S, Lachin J, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med1993;329:977-86; doi: 10.1056/NEJM199309303291401

Geographic atrophy (GA) imposes a heavy clinical and humanistic burden on patients with dry age-related macular degeneration (AMD), according to first author Dr Daniel Jones an employee of Apellis Pharmaceuticals.

Jones discussed the topic at the EURETINA 2021 Virtual Congress.

According to Jones, this advanced form of dry AMD, which has the potential to cause irreversible blindness, currently has no approved treatment and clinicians have no ways to prevent or slow progression, estimate the risk, or determine patient prognosis.

The estimated incidence of GA in the US is about 1.9/1000 and in older patients that rate increases to 4.3/1000.

It has been estimated that from 12% to 20% of GA cases end up with severe loss of vision, which severely impacts patients’ ability to care for themselves, perform chores, and navigate successfully outside the home without assistance.

Jones and colleagues undertook a literature review from January 1, 2015, to August 11, 2020, to assess the clinical and humanistic burden of GA already reported. They searched databases (PubMed, Embase, and Cochrane Library) during those dates as well as conference abstracts for 2019 to 2020.

The investigators found that in addition to the 12% to 20% of patients with GA who have severe loss of vision, almost a third of patients lose a minimum of 2 lines of vision during a 2-year period.

Compared with patients without GA, the vision-related function and health-related quality of life are poor in patients with GA, according to Jones.

The investigators noted that the results of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), a tool that is often used to measure patient quality-of-life parameters, has found that patients with GA have significantly lower NEI VFQ-25 composite scores and lower subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision versus individuals without GA, Jones said.

GA naturally impacts patient independence, and the inability to continue to drive is a particular concern for patients.

It also is associated with increased anxiety and depression, likely because patients lose the ability to take care of themselves and decreased vision prevents them from performing their daily tasks.

An important finding concerns ease of mobility.

“Patients are more likely to experience falls and fractures as a result of their impaired vision;

 study reported that 9% of patients with GA had a fall or fracture during a 12-month period,” Jones explained.

Based on these findings, the investigators concluded that GA imposes significant clinical and humanistic burdens on this patient population and loss of vision has a detrimental effect on many aspects of patients' lives.

The researchers emphasized the need for additional study to gain a better understanding of the GA burden experienced by patients.

A team of investigators in the UK has found that 1 injection of brolucizumab (Beovu, Novartis) treatment can result in a median improvement in visual acuity (VA) of 10.5 letters.

The investigators also found that the drug was well tolerated by patients with neovascular age-related macular degeneration (nAMD), according to first author Dr Cristina Cristian from the Department of Ophthalmology at Leeds Teaching Hospitals National Health Service Trust.

The drug was approved recently in the UK for treating nAMD. An advantage found in clinical trials was that the results achieved with injections at 8- or 12-week intervals were non-inferior to treatment with aflibercept (Eylea, Regeneron Pharmaceuticals Inc.) administered every 8 weeks.

According to Cristian, speaking at the EURETINA 2021 Virtual Congress, the advantages of 12-week dosing is a reduction in the number of patient visits and injections.

This is particularly important during the COVID-19 pandemic when maintaining social distancing is key to health and safety.

Cristian and her colleagues conducted a retrospective observational study to assess the efficacy and the risk profile of brolucizumab intravitreal injections in patients with an insufficient response to aflibercept characterized by persistent disease activity and unstable VA despite frequent therapy or disease control but a heavy treatment burden.

The charts of 35 patients (age range, 66-93 years; 51% women) with nAMD who were treated with brolucizumab from April 2020 to April 2021 were reviewed.

For all patients, the best-corrected VA, central retinal thickness, and intraocular pressure were measured; all patients underwent a complete ophthalmic examination at baseline and the last follow-up after the brolucizumab injection.

The patients received a total of 102 injections of brolucizumab; they had received from 3 to 62 previous aflibercept injections (median, 17; median injection interval, 6 weeks).

The median VAs before and after the brolucizumab injection were 57 and 67.5 letters, respectively; the respective central retinal thickness measurements were 337 μm and 436 μm.

The investigators reported that the treatment was well tolerated with no adverse events.

“The median VA improvement after the first injection was 10.5 letters despite the median increase in the central retinal thickness of 112.5 μm after the first dose of brolucizumab,” Cristian concluded. “No intraocular inflammation or vascular retinitis was detected in this case series.”

She also advised that conclusions about long-term results cannot be drawn.

In a presentation at the EURETINA 2021 Virtual Congress, Dr Cristina Cristian noted that an injection of brolucizumab treatment in patients with neovascular age-related macular degeneration led to a median improvement in visual acuity (VA) of 10.5 letters and the drug was well-tolerated.

Worldwide pathological myopia discussed by panel at EURETINA 2021

In a presentation at the EURETINA 2021 Virtual Congress, Dr Anat Loewenstein discussed optimizing optical coherence tomography (OCT) and how physicians can determine with even more accuracy precisely what is happening in patients’ eyes with neovascular age-related macular degeneration (nAMD) because of the potential afforded by application of artificial intelligence (AI).

Loewenstein is professor and director of the Department of Ophthalmology at Tel Aviv Medical Center, the Sidney A. Fox Chair in Ophthalmology, and vice dean, Sackler Faculty of Medicine, Tel Aviv University, Israel.

OCT is a major step forward in patient diagnosis, treatment, and monitoring but shortcomings remain. For example, physicians routinely make qualitative assessments of the presence and degrees of intraretinal/subretinal fluid and pigment epithelial detachments, but these are not precise assessment that are likely to result in poor inter-grader agreement and intra-grader consistency; OCT also provides the central subfield thickness, but the retinal fluid and neural tissue are not considered separately.

As Loewenstein pointed out, In neovascular AMD, it is important to distinguish between retinal fluid localization in the intraretinal and subretinal compartments and their volumetric information for informing retreatment decisions and predicting visual outcomes.

One technology to quantify OCT data, according to Loewenstein, is the Notal home-based OCT Analyzer (NOA), a machine learning algorithm that distinguishes normal morphologic features from elevated or distorted contours to quantify macular fluid of OCT volumes. The NOA quantifies intraretinal/subretinal fluid on Spectralis and Cirrus spectral-domain OCT devices. Both algorithms display their respective fluid output in nanoliters, which allows repeatable measurements and precise monitoring of disease activity.

“Recent advances in machine learning and deep learning have resulted in development of software that can process routinely acquired spectral-domain OCT data and precisely determine the location and volumetric information of macular fluid within different tissue compartments,” she said.

The software then can automatically generate multiple quantitative metrics related to macular fluid variables that may provide substantial advantages to research and clinical practice.

According to Loewenstein, using volume instead of thickness, separating fluid volume from neural tissue volume, distinguishing between intraretinal and subretinal fluid and monitoring dynamics over time might improve OCT’s ability to predict visual acuity changes.

• Because of the importance of OCT in assessing nAMD parameters, for which the fluid volumes in the retina are generally the key biomarkers, the availability of software that can analyze them quantitatively, automatically, and at scale is paramount.

• In practice, the ability to extract quantitative metrics of exudative activity from OCT scans is an important advantage over qualitative descriptions.

• By eliminating low intra-grader consistency and inter-grader agreement, exudative activity can be compared more meaningfully between sequential visits and visits that are widely separated of the same patient, or between patients, regardless of the individual physicians’ discretion.

• Quantitative metrics may result in better recordkeeping and visualization of exudative activity; the values from each visit can be recorded facilitating graphs of fluid volume plotted over time based on changes in treatment intervals, drugs, and doses.

• AI methods allow assessments and comparisons to be made separately for intraretinal/subretinal fluid and pigment epithelial detachments.

• Not all exudative activity is equal regarding visual prognosis and determining retreatment decisions.

• Future studies may lead to refined retreatment protocols possibly incorporating more nuanced approaches according to fluid compartment/volume.

• Algorithms that identify and quantify fluid types should help facilitate these approaches.

“AI tools may lead to more tailored treatment, ideally so that individuals achieve optimal visual outcomes with as few injections and visits as possible,” Loewenstein concluded. “This might help address some of the shortfall in visual outcomes that has consistently been observed between real-world practice and clinical trials.”

Loewenstein is a consultant to Notal Vision.

During a presentation at the EURETINA 2021 Virtual Congress, Dr Anat Loewenstein discussed how artificial intelligence can optimize optical coherence tomography.

Gene replacement therapies for inherited retinal degenerations have shown promise in experimental disease models and are being tested in RPE65-associated Leber congenital amaurosis (approved in 2017) and Leber hereditary optic neuropathy, among others.

In addition to this research, Dr José-Alain Sahel and colleagues are involved in another line of research to benefit patients with inherited retinal degenerations with the hope of avoiding the challenges posed by gene replacement therapies, i.e., extensive genetic heterogeneity and dominant transmission.

“Gene-independent strategies could offer promising treatment avenues for these blinding diseases,” Sahel, chairman of the Department of Ophthalmology, and director of the University of Pittsburgh Medical Center Eye Center University of Pittsburgh, said during a presentation at the EURETINA 2021 Virtual Congress.

According to Sahel, cones are critical to vision and preserving them may save vision in patients with inherited retinal degenerative diseases. The focus of his team’s work, rod-derived cone viability factor, promotes cone survival by stimulating aerobic glycolysis.

In previous work, Sahel, with Saddek Mohand-Said, MD, and Thierry Léveillard from the Institut de la Vision, Paris, demonstrated in a murine model of retinitis pigmentosa that rod transplantation delayed cone loss, which depends on functioning rod photoreceptor cells. These finding could benefit patients with retinitis pigmentosa and other inherited retinal diseases (trial in preparation by SparingVision).

Optogenetics involves use of artificial photoreceptors from specific retinal cells to restore vision by transferring a gene that encodes for a light-sensitive protein that causes neuronal cells to respond to light stimulation (GS030, GenSight Biologics). This technology combines gene therapy and a medical device to restore retinal light sensitivity by modifying and training retinal ganglion cells to act as photoreceptor, Sahel explained.

The PIONEER Study is the first trial to test how GS030 optogenetic therapy works in 9 patients with end-stage retinitis pigmentosa. Patients received 1 intravitreal injection in the eye with the worse vision. The primary endpoint was the safety and tolerability of the treatment at the 1-year timepoint.

The study also is evaluating he effects of 3 doses of the treatment. Three patients were injected with the lowest dose in March 2019, 3 with the medium dose in February 2020, and 3 with the highest dose in June 2020 and June 2021.

The injections are part of the combined therapy that includes the use of goggles that project light onto the retina. An extension cohort is planned for the end of 2021. Thus far, the therapy has been well tolerated up to 2.5 years after the intravitreal therapy. The most frequent adverse event was anterior chamber or intermediate intraocular inflammation that responded to steroids in 5 of the 9 patients.

Sahel reported that 1 patient had partial recovery of visual function after this treatment.

 He was the only one who could perform training during the COVID-19 pandemic. Others are now training. There is some hope that this treatment can benefit patients with many types of retinal degenerations included age-related macular degeneration.

1. Sahel J-A, Boulanger-Scemama E, Pagot C, et al. Partial recovery of visual function in a blind patient after optogenetic therapy

 Nature Med 2021;27:1223-9; https://doi.org/10.1038/s41591-021-01351-4

During a presentation at the EURETINA 2021 Virtual Congress, Dr José-Alain Sahel explains that optogenetics involves the use of artificial photoreceptors from specific retinal cells to restore vision by transferring a gene that encodes for a light-sensitive protein that causes neuronal cells to respond to light stimulation.