Night vision testing at specific locations in the retina may help researchers pin down the point of transition from the eye’s normal aging to intermediate age-related macular degeneration (AMD).
Two decades ago, researchers at the University of Alabama at Birmingham found that rod-mediated dark adaptation (RMDA) worsened as patients developed early and intermediate AMD. Now, they have found that RMDA takes place more slowly close to the fovea than in areas farther away from the fovea, where rods are numerous and where subretinal drusenoid deposits (SDDs, also called reticular pseudodrusen) are prominent.1
“Our data show that AMD is potentially more addressable at early stages of disease than in geographic atrophy [GA], currently the only stage of non-neovascular AMD for which there is a regulatory endpoint,” said Christine Curcio, PhD.
WHERE IT BEGINS. (Left) Color fundus image of drusen. (Right) SDDs, seen via near-infrared reflectance. Rod-mediated dark adaptation tested at 5 degrees (bottom spot), where rods are sparse, slows more than at 12 degrees (top spot), where rods are numerous and SDDs begin.
Unmet clinical need. Despite evidence that RMDA worsens with AMD and that the area under the fovea plays a critical role in AMD progression, the goal of improving vision in patients with AMD remains largely unmet.
“We think RMDA testing could be used in clinical trials to track the ability of interventions to affect AMD progression at early stages,” said Cynthia Owsley, PhD, MSPH. She added, “We also believe that RMDA is the best functional test for validating imaging tests, which are likely to be favored clinically because they take less time than behavioral measures like RMDA.”
Study overview. This investigation was part of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2). The researchers examined RMDA (measured as rod intercept time) at 5 and 12 degrees in the superior retina of 438 adults (age, ≥60 years). Participants were recruited from three groups: those with early AMD (n = 129), those with intermediate AMD (n = 89), and those with normal macular health (n = 220).
One eye of each participant was tested with the AdaptDx (LumiThera) in a dark, light-tight room. The researchers also used multimodal imaging to identify SDDs, which start near 12 degrees in the superior retina.
Results. The results showed that rod intercept time was longer (i.e., poorer) at 5 degrees than at 12 degrees across all patient groups. In addition, differences in RMDA among groups were more pronounced at 5 degrees than at 12 degrees. In eyes with early and intermediate AMD, SDD presence was associated with slowed RMDA at 5 degrees. SDD presence at 12 degrees was associated with slowed RMDA only in eyes with intermediate AMD.
These findings “support a ‘center-surround model’ of deposit-driven AMD progression,” Dr. Curcio said. She added that RMDA slowing at 5 degrees could be attributed to mechanisms associated with the accumulation of soft drusen and their precursors under the macula lutea throughout adulthood.
Looking ahead. In a follow-up study, Dr. Owsley said, the ALSTAR2 researchers are planning to examine whether RMDA slowing at 5 degrees can predict AMD progression. As part of this investigation, they will correlate imaging findings with photoreceptor function.
—Christos Evangelou, PhD
1 Owsley C et al. Ophthalmol Science. 2023;3:100272.
Relevant financial disclosures: Dr. Curcio—Heidelberg Engineering: S; NIH: S. Dr. Owsley: Co-inventor of AdaptDx device; NIH: S.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Chen Horizon: C; UCB: C.
Dr. Curcio Apellis: C; Astellas: C; Boehringer Ingelheim: C; Character Biosciences: C; Genentech/Hoffman LaRoche: C; Heidelberg Engineering: S; NIH: S; Osanni: C; Regeneron: S.
Dr. Moheb None.
Dr. Owsley Co-inventor of AdaptDx device; Johnson & Johnson Vision: C; NIH: S.
Dr. Shahon None.
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