Ophthalmology Month in Review: June 2023

The ophthalmology month in review for June 2023 features important updates to the pipeline, the latest news in diabetic eye diseases from the 83rd Scientific Sessions of the American Diabetes Association, and the promise of artificial intelligence in detecting ophthalmic conditions.

Pipeline News

Updates to the pipeline have continued to remain a hot topic in 2023 in ophthalmology and June was no different. Trial results indicated the promise of an oral agent for diabetic retinopathy and confirmed the efficacy of a therapy for patients with thyroid eye disease (TED). The US Food and Drug Administration (FDA) declined to approve the biologics license application (BLA) for aflibercept 8 mg for the treatment of retinal diseases.

FDA Issues Complete Response Letter for Aflibercept 8 mg as AMD, DME Treatment

Late last month, the FDA filed a Complete Response Letter (CRL) in response to Regeneron’s biologics license application (BLA) for aflibercept 8 mg, a treatment for wet age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy (DR).

The CRL was said to pertain “solely” due to an ongoing review of findings from a third-party filler inspection and the company’s statement indicated no issues with the therapy’s clinical efficacy or safety, trial design, labeling, or drug substance manufacturing. The FDA requested no additional clinical data or trials. The BLA was supported by positive phase 3 data from the PULSAR trial for wet AMD and the PHOTON trial for DME.

Phase 4 Trial Data Supports Efficacy of Teprotumumab-trbw for Thyroid Eye Disease

Recently released phase 4 clinical trial data reinforce the efficacy of teprotumumab-trbw (TEPEZZA®) in patients with TED, regardless of disease activity or duration. The data were presented at the Endocrine Society Annual Meeting and announced by Horizon Therapeutics in a release. The trial findings followed an update to the teprotumumab-trbw indication language approved by the FDA in April, indicating the therapy's use in all patients with TED regardless of disease activity or duration.

Phase 2 ZETA-1 Trial Suggests Promise of APX3330 in Diabetic Retinopathy

Research presented at the 83rd Scientific Sessions of the American Diabetes Association suggested the promise of APX3330,  a non-invasive, oral, novel, small molecule inhibitor of Ref-1, for patients with diabetic retinopathy. Results from the phase 2 ZETA-1 trial suggest the primary endpoint was not met, with nearly 8% of eyes with diabetic retinopathy showing ≥2-step improvements in the diabetic retinopathy severity scale (DRSS).

However, the findings showed APX3330 was associated with a statistically significant reduction in binocular ≥3-step worsening after 24 weeks.  Study investigators suggested APX3330 may be a promising, non-invasive oral treatment option for preventing the risk of disease progression in patients with nonproliferative diabetic retinopathy who are otherwise monitored and untreated.

Diabetic Eye Diseases

Empagliflozin Associated with Reduced Risk of Diabetic Retinopathy Progression in T2D

Results from EMPRISE suggest the initiation of empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, may reduce the risk of diabetic retinopathy progression in adults with type 2 diabetes (T2D). Empagliflozin was associated with a 23% reduction in the risk of diabetic retinopathy progression, compared with Dipeptidyl peptidase 4 inhibitors (DPP4i), and a similar risk of nonproliferative diabetic retinopathy onset.

“Our data suggest that the initiation of empagliflozin may be beneficial in patients with diabetic retinopathy,” presenting investigator Helen Tesfaye, PharmD, MSc, from the division of pharmacoepidemiology at Brigham and Women’s Hospital, Harvard Medical School, said at ADA 2023. “These results may be helpful when weighing the potential risks and benefits of various glucose-lowering agents in adults with T2D and diabetic retinopathy.”

Prevalence of Diabetic Retinopathy Lower at Younger Age in Youth with T2D

Youth with type 2 diabetes (T2D) with younger age and shorter disease duration experience a lower prevalence of diabetic retinal diseases, including diabetic retinopathy, according to data presented at ADA 2023. The analysis of 3 academic health centers suggested youth with diabetic retinopathy had a longer duration of diabetes and higher hemoglobin A1c at the time of the diabetic eye exam. Results were in contrast with the prevalence of diabetic retinal diseases reported in youth from the Treatment Options for T2D in Adolescents and Youth (TODAY) study.

Prevalence of Diabetic Retinopathy in US Remains High, Expected to Increase

The prevalence of diabetic eye diseases remains high and is expected to grow in the coming decades due to the increasing burden of diabetes, according to a recent analysis. In the US, 9.6 million people had diabetic retinopathy (approximately 1 in 4 people with diabetes) and 1.84 million people had vision-threatening diabetic retinopathy (approximately 1 in 20 people with diabetes) in 2021. The updated estimates could help inform the allocation of public health resources and interventions to those populations at the highest risk.

Artificial Intelligence

Debates surrounding artificial intelligence continue to permeate public debate, but promising data has indicated its potential in medicine, including new study results presented at ADA 2023.

Artificial Intelligence May Predict Risk of Diabetic Retinopathy Progression

Data presented at ADA 2023 suggested the accuracy and feasibility of using machine learning models to identify the progression of diabetic retinopathy using ultra-widefield images. The AI model predicted correct labels for approximately 91% of study images, or the labels showed greater progression than the original labels.

“Currently, estimating the risk of diabetic retinopathy progression is one of the most important yet difficult tasks for physicians when caring for patients with diabetic eye disease,” study investigator Paolo S. Silva, MD, co-chief of telemedicine at Beetham Eye Institute, Joslin Diabetes Center, said in a statement. “Our findings show that potentially, the use of machine learning algorithms may further refine the risk of disease progression and personalize screening intervals for patients, possibly reducing costs and improving vision-related outcomes.”

Autonomous Artificial Intelligence Improved Adherence to Diabetic Eye Disease Testing

At ADA 2023, new research suggested autonomous artificial intelligence systems improved testing adherence for diabetic eye diseases across primary care clinics. A comparison of clinics that deployed artificial intelligence systems and those that did not suggest the increase in overall adherence rates at artificial intelligence sites was significantly greater (P <.001), even after controlling for potential confounders. The investigative team from the Wilmer Eye Institute noted the deployment of AI systems also improved access and equity, particularly those patient populations that are traditionally disadvantaged.

Artificial Intelligence Systems Inconsistent in Detecting Diabetic Retinopathy

A direct comparison of 3 independent AI systems showed differing prevalences of diabetic retinopathy, suggesting inconsistencies when applying these tools to those without preexisting diabetes. The data, presented at ADA 2023, were collected from the first direct comparison of 3 independent artificial intelligence companies when simultaneously assessing retinal images from ≥10,000 individuals. The investigative team noted that the AI systems perform well in diagnosing moderate retinopathy, but were unreliable when it came to diagnosing mild retinopathy.

New Insight

New Insight: The Journey to a Drug Approval with Cedric Francois, MD, PhD

The newest episode of New Insight with Veeral Sheth, MD was an important one. On the heels of the first geographic atrophy (GA) drug approval in February with pegcetacoplan injection (SYFOVRE), Sheth sat down with Cedric Francois, MD, PhD, the co-founder and chief executive officer/president of Apellis Pharmaceuticals.

The experts discussed the landmark approval of pegcetacoplan injection as the first-and-only treatment for GA and Francois’ feelings on the launch of the therapy into the real-world setting. They discussed the timeline of the company’s work and the journey that it takes from the beginning to introducing it in the clinical setting, as well as the challenges faced along the way. As well, the experts discussed the uptake of the therapy and the ever-changing treatment landscape.

For more episodes of New Insight, visit our show page and be sure to subscribe to our channel on Spotify, Apple Podcasts, and YouTube.