Reduced Central Cone Function Suggests Photoreceptor Degeneration in Stargardt

In the early and middle phases of Stargardt disease, functional degeneration appears to predominantly affect the cones, and changes in the temporal dynamics of the rods in affected regions demonstrated some retinal network alteration, according to research published in Investigative Ophthalmology & Visual Science.

For the study, the researchers used chromatic pupil campimetry (CPC) to map local functional degenerative changes of cones and rods in patients with Stargardt disease. 

A total of 19 patients (mean age, 36±8 years; 63% men and 37% women) with confirmed mutations in the ABCA4 gene and a clinical diagnosis of Stargardt disease as well as 12 age-matched control participants (mean age, 37±11 years; 17% men and 83% women) were included in the study. All participants underwent scotopic (rod-favoring protocol with blue stimuli) and photopic (cone-favoring protocol with red stimuli) CPC to evaluate the local retinal function in the central 30° visual field. Pupil constriction to local stimuli was analyzed in a gaze-corrected manner.

With scotopic CPC, the researchers found that the rod function of patients with Stargardt disease inside of the 30° visual field was not impaired relative to that of the control participants. The team noted a small, nonsignificant reduction in the center and slightly increased rod responses in the periphery among the patients compared with the control participants. They also reported a statistically significant faster pupil response onset time (∼ 40 ms) at all stimulus locations (0°, 6°, 12°, 20°, and 30°) in patients compared with control participants (P <.005 for all). 

With photopic CPC, the researchers found a significant reduction of the central cone function up to 6° in the patients compared with the control participants (0°: relMCA, 13±5% vs 25±5%; P <.001; and 6°: relMCA, 11±5% vs 19.0±4.5%; P <.01). They noted minor, non-significant reductions at 12°, 20°, and 30° in the patients relative to the control participants. The team did not observe differences in the temporal dynamics of the pupillary response between the groups.

“The functional analysis of the macular region in [Stargardt] disease indicates reduced central cone function, corresponding to photoreceptor degeneration. In contrast, the rod function in the central area was not affected,” according to the researchers. “[C]hanges in the rods’ time dynamics in affected regions indicate some level retinal network alteration up to the mid periphery, which should be considered in future therapeutic interventions.”

Limitations of the study included the relatively small study population and potential variability in the preferred retinal locus (PRL) in patients with Stargardt disease. The researchers noted the results did not change when removing 2 patients with PRL variation from the analysis.  

Reference

Stingl K, Hoyng C, Kempf M, et al. Evaluation of local rod and cone function in Stargardt disease. Invest Ophthalmol Vis Sci. 2022;63(3):6. doi:10.1167/iovs.63.3.6