Topographic rod function in intermediate age-related macular degeneration

Abstract

Background Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the elderly. In the early stages of disease, dark adaptation problems are more significant for patients than visual acuity impairment. For decades, studies of rod function related to dark adaptation issues suggested that rod function could be useful as a functional marker for differentiating AMD severity and monitoring disease progression. However, there remains many unanswered questions about how best to investigate rod function in the early stages of AMD.

Earlier studies were not able to phenotype AMD cases to the extent we can today as they relied only on colour fundus photographs to determine AMD subgroups. We now have the opportunity to look at different AMD phenotypes using multimodal imaging techniques. These advances have added clarity to the phenotyping of AMD, as high-risk features such as reticular pseudodrusen (RPD), hyperreflective foci (HRF), and nascent geographic atrophy (nGA) can now be identified.

At the same time as the advances in detecting anatomical changes were made, instruments that could measure rod function in a more thorough way were improving. Previously, instruments measured rod function at only a single retinal location, or could only detect large losses in sensitivity due to a lack of dynamic range. Recent advances have seen perimeters that are able to measure rod function at multiple locations in the one setting and also have a larger dynamic range to detect subtle rod dysfunction. I have used one of these new tools in my studies.

Aims Two-color dark-adapted chromatic perimeter (DACP) is a novel device, designed and manufactured in Melbourne, Australia. It was first used in 2015 when I commenced my PhD. This perimeter measures rod function at multiple locations with sufficiently large range of stimulus intensities to detect subtle changes seen in early AMD. My thesis aimed to investigate the ability of the DACP to reliably detect and record rod sensitivities. I then utilized this new perimeter to investigate the ability of rod function to act as a robust functional biomarker that could be used to determine AMD disease severity and to monitor disease progression, and to compare rod function in AMD cases to normal control participants. I was also able to separate my AMD cohort into those with or without RPD, a high-risk AMD phenotype, to investigate the impact of this phenotype on rod function. Both static and dynamic rod functional changes were recorded at baseline visits and then again at 6- and 12-months. The results of this study will contribute to our understanding of functional loss in AMD and help clinicians and researchers when designing research protocols aiming to evaluate rod functional impairment before vision loss.

Methods This study was conducted between 2015 and 2018 at the Macular Research Unit, Centre for Eye Research Australia. During that time, three main studies were completed. An initial assessment of test-retest reliability of the DACP was followed by a cross-sectional study comparing the severity of rod dysfunction based on point wise sensitivity (PWS) and point wise sensitivity difference (PWSD) of two color sensitivities. AMD cases were divided into an AMD group with traditional drusen only and an RPD group, and rod function was evaluated at multiple ring eccentricities within 24º of the central macula. A further 12-months evaluation of static (PWSD) and dynamic rod functional changes (rod intercept time (RIT) and rod recovery rate (RRR)) within the central 12º was conducted in participants with intermediate AMD with and without RPD as well as normal control eyes.

Results The DACP did not have ceiling or floor issues during the intrasession and intersession testing, with a coefficient of repeatability of ± 5 dB. Intermediate AMD (iAMD) with the presence of RPD was found to be associated with poorer rod function compared with iAMD without RPD and normal control eyes, but only within the central macular 8º. Rod dysfunction was more significant if the eyes were prebleached before undertaking the sensitivity measurements. In a longitudinal study, dynamic rod functional changes, ie. RRR, was the only parameter that changed over 12 months, and only in the iAMD without RPD group. Change was found only at the peripheral 12º ring eccentricities.

Conclusion The DACP offers a great opportunity to evaluate topographic rod function when eyesight is still normal. The findings from this study support that concept of rod function being impaired in the early stages of AMD. The presence of RPD in cases of iAMD were associated with further reductions in rod function. Measuring dynamic rod function offers a more sensitive functional marker in determining severity of AMD within the central 8 degrees of the macula, but changes over time were only detected at more peripheral locations. Longer follow-up will be beneficial to determine how rod function deteriorates over time and correlates with progression to vision loss.