Longitudinal Changes in Retinotopic Rod Function in Intermediate Age-Related Macular Degeneration

Abstract

PURPOSE. Although impairment of rod function in the early stages of age-related macular degeneration (AMD) has been well recognized, data on longitudinal changes in rod function at multiple retinal locations remain limited. This study investigated the longitudinal changes in retinotopic rod function in eyes with intermediate AMD (iAMD). METHODS.Complete ophthalmic examination, multimodal imaging, and scotopic perimetry were performed at baseline and at 12-month follow-up. Perimetric scotopic retinal sensitivities for the 505-nm stimulus were repeatedly measured for 20 minutes after exposing to a single photobleach (~30%). The rod intercept time (RIT) and retinal sensitivity at seven retinal loci within the central 128 were ascertained. Using the 95% limit of measurement variability derived from the control eyes as a reference, the proportion of test points with a significant change in retinal sensitivity or RIT at follow-up was determined.RESULTS. Twenty iAMD and 6 control eyes were included. Decline in rod function was detected at 12-month follow-up in eyes with iAMD, but not in control eyes. Approximately 25% of test points in iAMD eyes showed a significant increase in RIT compared to 6% of test points with a decrease in RIT over the 12-month period (P < 0.001). Similarly, 40% of test points demonstrated a reduction in retinal sensitivity compared to the 7% of test points with an increase in retinal sensitivity at follow-up (P < 0.001).CONCLUSIONS. There are detectable retinotopic changes in rod function over 12 months in iAMD eyes, indicating an ongoing disease progression in rod impairment or loss with time.

Longitudinal Assessment of Rod Function in Intermediate Age-Related Macular Degeneration With and Without Reticular Pseudodrusen

“…A greater rod dysfunction at the paracentral macula has also been reported in the earlier studies by Flynn 13 and Pfau et al 43 When evaluating the RIT in our 30-minute testing protocol, we still found a large proportion of testing points in the RPD group that did not reach the rod intercept level after 30 minutes of dark adaptation. While slightly smaller than in our previous protocol where testing was only for 20 minutes (46%), 6 we still had about a third of all points in the RPD group not reaching the rod intercept level, and as such was uninformative to follow over time. Previously we have reported that RPD patients could take many hours to recover after bleach, with many test points not recovering after 24 hours of dark adaptation.…”

“…4,5,7 Our group has previously investigated rod function in AMD and we have reported worsening of RIT in intermediate AMD over 12 months within the central 68 of the macula. 6 However, our initial protocol only followed recovery over 20 minutes and we found that approximately 36% of test points did not reach the rod intercept level at baseline and thus we were unable to observe a worsening in function at these points. Therefore, we wished to further evaluate rod function over a 12-month period, allowing a longer 30 minutes recovery time and within the central 128 of the fovea, in a well characterized, clinically stable cohort, all with bilateral large drusen, subgrouped on the presence or absence of RPD, to further our understanding of the impact of RPD on longitudinal changes in rod function in eyes with intermediate AMD.…”

“…Rod function has been shown to be a promising biomarker to evaluate disease severity 1,2 and progression [3][4][5][6][7] in the early stages of AMD. Many cross-sectional studies have demonstrated that rod function is abnormal early in AMD 3,[8][9][10] and more recently it has been found that AMD cases with the additional phenotype of reticular pseudodrusen (RPD, also known as subretinal drusenoid deposits) have particularly poor rod function.…”

“…However, there are only a few reports on the longitudinal natural history of rod decline in the early stages of AMD, especially ones using modern multimodal imaging techniques to identify the presence of RPD and analyze the data of group with and without RPD separately. [4][5][6][7] A study by Jackson et al 4 reported an average worsening of 6.2 minutes of RIT in 19% of AMD patients in 12 months when both visual acuity and stage of intermediate AMD (iAMD) did not change. However, the study did not report on the presence of RPD in the study subjects.…”

Determining Optimal Test Parameters for Assessing Dark Adaptation in People With Intermediate Age-Related Macular Degeneration

“…Nguyen et al 38 in a study of retinotopic rod function showed that, while the effect of the disease was greatest in the central macula, as expected, there was a significant difference in RIT between controls and people with iAMD at the 128 location. Owsley et al 20 reported that, when RIT was evaluated at 118 eccentricity, 22 of 30 eyes (73.3%) with iAMD had an increase in RIT exceeding 1 minute over a follow-up period of 24 months, and 17 of 30 eyes (56.7%) had an increase exceeding 3 minutes.…”