Retinal nerve fiber layer loss in glaucoma patients with a relative afferent pupillary defect

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.

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.

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 μm or greater, intereye 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.

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.