Ophthalmology Month in Review: May 2024

In a pivotal month for ophthalmology, Srinivas R. Sadda, MD, was inaugurated as president of the Association for Research in Vision and Ophthalmology (ARVO), emphasizing future innovations and challenges in the field. Despite the phase 2 PAVIA trial's failure to meet its primary endpoint for vorolanib in diabetic retinopathy, other studies showed promise: metformin reduced the likelihood of geographic atrophy (GA) by 12%, and the HORNBILL study demonstrated safety and potential efficacy for BI 764524 in diabetic macular ischemia (DMI). Additionally, tarcocimab tedromer significantly improved diabetic retinopathy, and a novel virtual reality approach showed promise for assessing contrast sensitivity in patients with age-related macular degeneration (AMD).

Here are the top 7 stories in ophthalmology from May 2024.

ARVO President Srinivas R. Sadda, MD, Visualizes Ophthalmology's Future 🔒

At the end of ARVO 2024, president-elect Srinivas R. Sadda, MD, a professor of ophthalmology at the David Geffen School of Medicine, University of California, Los Angeles, and the director of the artificial intelligence (AI) lab at Doheny Eye Institute, became president of the organization for the 2024-2025 year.

In an exclusive interview with HCPLive, Sadda described what the position represents for him, how innovations and challenges have defined ophthalmology in recent years, and his plans for the future of ARVO during his term as president.

“I'm honored to be serving as president of ARVO. It's an organization I've been involved with for over 30 years. I came to my first ARVO as a medical student and it’s been instrumental in my career,” Sadda told HCPLive.

PAVIA: Duravyu Misses Primary Phase 2 Endpoint in Diabetic Retinopathy

Topline data from the phase 2 PAVIA trial revealed the vorolanib intravitreal insert failed to show improvement of ≥2-Diabetic Retinopathy Severity Scale (DRSS) levels by Week 36, missing its primary endpoint, in patients with non-proflierative diabetic retinopathy (NPDR).

“Although the trial did not meet the pre-specified primary endpoint, we are encouraged that DURAVYU continues to be well-tolerated and appears to reduce rates of NPDR progression at nine months. We plan to analyze the full 12-month data once it is available to gain the clarity needed to assess the future of DURAVYU as a potential treatment for NPDR,” said Jay Duker, MD, chief executive officer of EyePoint Pharmaceuticals.

Dimitra Skondra, MD, PhD: Protective Effect of Metformin in Geographic Atrophy

Metformin was linked to a reduction in new-onset coding of geographic atrophy (GA), according to research presented at ARVO 2024. Approximately 10,500 cases with GA, and 10,500 matched controls without GA, were identified and 10.9% and 12.2%, respectively, had been exposed to metformin.

Across the full sample, metformin reduced the likelihood of GA by 12%.

“I think metformin fits very well, it’s almost the perfect candidate for a non-invasive strategy to target patients when they’re earlier in the disease stage,” Dimitra Skondra, MD, PhD, University of Chicago told HCPLive. “It’s safe, affordable, and may help delay the process until they go to advantage stages of wet age-related macular degeneration (AMD) or GA in particular.”

HORNBILL: BI 764524 Meets Safety Endpoints in Diabetic Macular Ischemia

Data from the phase 1/2a HORNBILL study showed BI 764524 was well-tolerated after single and multiple-dose intravitreal administration in patients with diabetic macular ischemia (DMI). HORNBILL, the first-ever study investigating a treatment for DMI, met its primary safety endpoints, while also identifying early signs of potential efficacy with BI 764524 treatment.

“The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of, and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, Byers Eye Institute.

Deepak Sambhara, MD: Impact of CRT on Aflibercept 8 mg Outcomes in DME

Aflibercept 8 mg meaningfully improved best-corrected visual acuity (BCVA) and central retinal thickness (CRT) across baseline quartiles in eyes with diabetic macular edema (DME) in a posthoc analysis of the phase 2/3 PHOTON trial.

Those eyes with the thickest baseline CRT experienced numerically less fluid reaccumulation at 8 weeks after the last initial monthly dose of aflibercept 8 mg versus 2 mg aflibercept.

“That tells me as a treating retina specialist that folks with more swollen retinas at baseline have more circulating VEGF that needs to be suppressed,” Deepak Sambhara, MD, Eye Clinic of Wisconsin told HCPLive. “That also reiterates the importance of having a higher-dosed VEGF agent on the market that can contribute to that initial VEGF suppression, particularly in the more difficult-to-treat DME patient population.”

Tarcocimab Tedromer Shows Promise for Diabetic Retinopathy in GLOW1

Treatment with tarcocimab tedromer (KSI-301) achieved a significant ≥2-step improvement in the DRSS in 41% of patients with treatment-naive NPDR, meeting the primary end point of the Phase 3 GLOW1 study. By comparison, only approximately 1.4% of patients treated with sham injection experienced a ≥2-step improvement in DRSS.

Overall, the data showed a 29-times increase in the response rate ratio with tarcocimab treatment (P <.0001) administered at up to a 6-month interval.

“As a clinician, what is most relevant is the potential of 6-month dosing. The adoption of treatment has been historically limited, due to the high treatment burden, so having this extended interval option can make a significant difference in the treatment of this patient,” said Robert W. Wong, MD, Austin Retina Associates.

Deepayan Kar, PhD, MS: A Virtual Reality Approach to Contrast Sensitivity in AMD

A novel approach to evaluate contrast sensitivity using a novel virtual reality headrest showed promise for patients with AMD. A key function affecting the quality of life, contrast sensitivity trended to differentiate among different disease stages in AMD after being measured with the VR headset.

Investigator Deepayan Kar, PhD, MS, an ophthalmology biomarker scientist in translational development at Apellis Pharmaceuticals, noted the VR-based test remained objective and was efficiently administered across a wide age range and lens status during the study.

“We found that the test is feasible across a broad range of age groups and in our clinical study, the test could separate normal from disease eyes,” Kar told HCPLive. “The test has a small footprint, so it’s really easy to scale it up for clinics or trials.”