Development of a Dark Adaptation Protocol for Use in AMD Clinical Trials

Abstract

Purpose: About 20% of AMD patients exhibit significant worsening of dark adaptation (DA) over 12 months. This finding supports the potential use of DA as an endpoint in AMD clinical trials. To increase acceptance of DA, it is desirable to reduce the test duration for patients with AMD. The purpose of this project was to develop a new protocol that reduces test duration by 50% compared with our previous standard protocol.

Methods: Eleven patients with AMD had their DA measured with three different dark protocols. Each measurement occurred on a different day. Protocol #1 was the previous standard. It utilized a 58,000 scotopic cd/m² sec bleaching flash at a test location of 5^o inferior visual field (VF). Protocol #2 used an 18,000 scotopic cd/m² sec bleaching flash located at 12^o inferior VF. Protocol #3 used a 4,500 scotopic cd/m² sec bleaching flash located at 12^o inferior VF.

Results: Protocol #1 (previous standard) produced the slowest DA and longest test duration. Protocol #3 produced the fastest DA and shortest test duration. Protocol #2 produced an intermediate DA speed and test duration. On average, participants exhibited a ~55% reduction in test duration for protocol #2 compared with protocol #1. For a typical AMD patient, protocol #1 produced a rod intercept of 17.5 minutes which was reduced to 7.8 minutes by Protocol #2. Protocol #3 produced a very fast recovery of dark adaptation consistent with a rod intercept of 3.1 minutes. For Protocol #3, four of 11 participants had rod intercepts less than 3.1 minutes. It was concluded that Protocol #3’s DA functions were too fast to allow for the possibility of a significant improvement in DA performance in response to intervention. Thus, Protocol #2 was selected as the preferred new protocol.

Conclusions: DA measurement in response to a moderate 18,000 scotopic cd/m² sec bleaching flash located at 12^o inferior to the fixation light produces a wide range of rod intercept values from about five minutes to 35 minutes across the range of AMD severity from early AMD to high-risk AMD. This protocol is under further evaluation in a natural history study and an intervention study. Further test duration reduction may be possible if the population of interest is restricted to high-risk AMD patients.

Keywords: 412 age-related macular degeneration