Retinal Nerve Fiber Layer Loss in Glaucoma Patients with a Relative Afferent Pupillary Defect

PURPOSE. To assess the amount of structural loss (retinal nerve fiber layer [RNFL] thickness loss, macular thickness [MT] and volume [MV] measured by optical coherence tomography [OCT]) and functional loss (visual acuity [VA], visual field mean deviation [MD], brightness sensitivity, and red perception) necessary for a relative afferent pupillary defect (RAPD) to manifest in patients with glaucoma. METHODS. In this case-control study, 50 glaucoma patients were prospectively enrolled: 25 with RAPD and 25 without. The presence of an RAPD was determined and quantified using the swinging-flashlight test, with neutral-density filters. A separate examiner, masked to the pupillary findings, assessed participants for brightness sense, red perception, VA, MD, RNFL thickness, MT, and MV. RESULTS. Differences in RNFL thickness (P < 0.0001), brightness sense (P = 0.0007), red perception (P = 0.030), and MD (P < 0.0001) were found between control and RAPD patients, but not in visual acuity or macular OCT parameters. An absolute difference in RNFL thickness of 14.6 mu m or greater, inter-eye difference of 9.5 dB or greater, and brightness of less than 64% in the weaker eye, were all associated with 100% specificity of RAPD presence. When RNFL thickness was reduced to 83% of the less advanced eye, the sensitivity and specificity of RAPD presence were 72% (95% confidence interval [CI], 0.51-0.88) and 100% (95% CI, 0.86-1.00), respectively. CONCLUSIONS. An RAPD was clinically detected in all participants in whom RNFL thickness decreased to 83% of that in the less advanced eye. Subjective brightness is the most accurate clinical surrogate for detecting an RAPD in patients with primary open-angle glaucoma. (Invest Ophthalmol Vis Sci. 2010;51:5049-5053) DOI:10.1167/iovs.09-4216