Ophthalmology Month in Review: January 2024

The end of 2023 marked a historic, milestone year for the field of ophthalmology, from landmark updates in the therapeutic pipeline to transformative developments for clinical practice. With the initial month of 2024 concluded, the field is poised to embrace these developments and enter a new era. Before 2024 makes its mark on history, January provides a glimpse of what’s to come this year.

For our January 2024 month-in-review, the HCPLive Ophthalmology editorial team highlights 8 top stories in our ophthalmic coverage, exploring the impact of social determinants of health, the latest updates to the ophthalmic pipeline, and the critical influence of local environments on eye health. Stay turned for more on the trends shaping the field in 2024.

Social Determinants of Health

Sex, Gender Analysis Insufficient in Ophthalmology Clinical Trials

An analysis of pivotal ophthalmology clinical trials linked to US Food and Drug Administration (FDA) drug approvals over 20 years found greater integration of sex and gender is critical to improving trial validity. Across 85 trials representing 34 drug approvals, more than three-quarters were shown to conflate sex and gender, while more than two-thirds lacked any sex- and gender-based analyses.

“This cross-sectional analysis of clinical trials associated with FDA approval of ophthalmic drugs demonstrated marked conflation of sex and gender terminology, underreporting of sex and gender assessment methods, and inattention to sex- and gender-based analysis,” wrote the investigative team.

Socioeconomically Disadvantaged Children Experience Gaps in Vision Screening

Recent cross-sectional data highlighted the key gaps in the vision screening pathway among school-aged children belonging to historically vulnerable groups in the US. At each stage of the pathway, socioeconomically disadvantaged children were less likely to receive screening, more likely to undergo failure screening, and less likely to receive care from an eye care specialist

“The cumulative effect of each step along the pathway may contribute to the racial, ethnic, and socioeconomic disparities in visual outcomes that are already evident by adolescence,” investigators wrote.

Study Identifies Genetic Variants in African Ancestry Linked to Glaucoma Risk

A multicohort genome-wide association study (GWAS) among people with African ancestry added new insight into genetic variants with pathophysiological significance for primary open-angle glaucoma. The GWAS detected 46 genome-wide risk loci significantly associated with glaucoma. Further replication and post-GWAS analyses found two previously underdefined variants and one previously associated variant as potentially causal for glaucoma.

“Our current treatments for this blinding disease are inadequate, and precision medicine could be applied if we more clearly understood the full pathophysiology of this inherited neurodegeneration,” corresponding author Joan O’Brien, MD, explained in a statement.

Pipeline News

AR-15512 for Dry Eye Disease Achieves Primary Endpoint in Phase 3 COMET Trials

Topline results from the phase 3 COMET trials indicate the novel topical drug candidate, AR-15512, achieved its primary endpoint as a treatment for the signs and symptoms of dry eye disease (DED). AR-15512 is an investigational product and has not been submitted to the FDA for approval. Alcon has stated its plan to file the New Drug Application for AR-15512 in mid-2024.

“A key gap in dry eye medications is rapid speed of onset,” Edward Holland, MD, a professor of ophthalmology at the University of Cincinnati, said in a statement. “AR-15512 demonstrated this important achievement in both pivotal efficacy and safety studies and it represents a first-in-class candidate for chronic dry eye.”

Michael B. Gorin, MD, PhD: Interim TEASE-3 Trial Data in Stargardt Disease

Interim data from the TEASE-3 trial showed oral gildeuretinol (ALK-001) slowed the progression of Stargardt disease, the most common form of inherited macular degeneration in children and adolescents, for up to 6 years. To learn more, the HCPLive Ophthalmology editorial team spoke with Michael B. Gorin, MD, a professor in the departments of ophthalmology and human genetics at the David Geffen School of Medicine at UCLA.

“We could find evidence of early Stargardt changes with microperimetry or imaging, but they were completely asymptomatic. From a vision standpoint, they were functioning completely normally,” Gorin told HCPLive. “Those children who have been on this drug have managed to maintain a high level of vision and have developed almost no atrophy at all.”

FDA, Tarsier Pharma Reach Agreement on Phase 3 Trial of TRS01 Eye Drops

Tarsier Pharma has received agreement from the FDA under a Special Protocol Assessment (SPA) for the Tarsier-04 phase 3 trial investigating TRS01 eye drops (Dazdotuftide) for non-infectious uveitis, including uveitic glaucoma. An SPA agreement with the FDA signals concurrence with the adequacy and acceptability of the protocol design for a study intended to support a future marketing application.

“The SPA agreement with the FDA provides a clear regulatory path for TRS01,” said Daphne Haim-Langford, PhD, CEO of Tarsier. "The approved protocol of the upcoming Tarsier-04 trial was designed to replicate the TRS4Vision trial, with revised endpoints that are aimed to emphasize the benefit/risk profile of TRS01, based on lessons learned from the TRS4Vision trial."

Environmental Exposure

More Nighttime Outdoor Artificial Light May Increase Wet AMD Risk

New data revealed higher levels of nighttime residential outdoor artificial light were associated with an increased risk of incident wet age-related macular degeneration (AMD), which remained after adjustment for individual- and area-level risk factors. Using population-based data in South Korea, the population-based, case-control study showed the association between light exposure and wet AMD followed a nonlinear pattern and became more pronounced at higher levels of outdoor artificial light.

“These findings align with the increasing body of evidence that emphasizes the negative impact of outdoor artificial light at night on health, further implicating outdoor artificial light at night as a potential risk factor for wet AMD,” wrote the investigative team.

Green Space May Reduce the Risk of Childhood Myopia Development

Overall green space morphology was associated with a decreased relative risk of myopia over a two-year period among school-aged children, according to a recent prospective cohort study in China. An analysis of satellite images found a well-arranged green space, including larger areas, better connectivity, increased aggregation, lower fragmentation, and a shorter distance between green patches was linked to slower disease progression.

“Principal component analysis of 7 relevant landscape metrics demonstrated an association with smaller increases in school myopia prevalence and incident myopia at the individual level, suggesting that the landscape structure as a whole was negatively associated with myopia development,” wrote the investigative team.

References

1. _{Iapoce C. Sex, gender analysis insufficient in ophthalmology clinical trials. HCP Live. January 19, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/sex-gender-analysis-insufficient-ophthalmology-clinical-trials.}
2. _{Iapoce C. Socioeconomically disadvantaged children experience gaps in vision screening. HCP Live. January 26, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/socioeconomically-disadvantaged-children-experience-gaps-vision-screening.}
3. _{Iapoce C. Study identifies genetic variants in African ancestry linked to glaucoma risk. HCP Live. January 19, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/study-identifies-genetic-variants-african-ancestry-glaucoma-risk.}
4. _{Iapoce C. AR-15512 for Dry Eye disease achieves primary endpoint in phase 3 comet trials. HCP Live. January 12, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/ar-15512-achieves-primary-endpoint-phase-3-comet-trials-dry-eye-disease.}
5. _{Iapoce C. Michael B. Gorin, MD, Phd: Interim tease-3 trial data in Stargardt Disease. HCP Live. January 9, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/michael-gorin-md-phd-interim-tease-3-trial-data-stargardt-disease.}
6. _{Iapoce C. FDA, Tarsier Pharma Reach Agreement on Phase 3 trial of TRS01 eye drops. HCP Live. January 16, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/fda-tarsier-pharma-reach-agreement-phase-3-trial-trs01-eye-drops.}
7. _{Iapoce C. More nighttime outdoor artificial light may increase wet AMD risk. HCP Live. January 16, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/more-nighttime-outdoor-artificial-light-may-increase-wet-amd-risk.}
8. _{Iapoce C. Green space may reduce the risk of childhood myopia development. HCP Live. January 4, 2024. Accessed February 1, 2024. https://www.hcplive.com/view/green-space-may-reduce-risk-childhood-myopia-development.}