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Objective: To quantify the amount of optic nerve axonal loss associated with the presence of a mild relative afferent pupillary defect (RAPD) in an experimental monkey model., Methods: The right macula of 5 rhesus monkeys (Macaca mulatta) was treated with concentrically enlarging diode laser burns until an RAPD was detected using a transilluminator light and measured with neutral density filters. Intervals between treatments were 3 to 7 days over a period of 2 months. Pupillary responses to light stimulation were recorded with a monocular infrared television pupillometer. Two months after detection of an RAPD, 5 treated and 4 control monkeys underwent euthanasia and enucleation. Histopathologic analysis and quantification of optic nerve axon counts using an image analysis system were performed., Results: No RAPD was observed despite an estimated ganglion cell loss of up to 26%. A 0.6 log unit RAPD was present in 5 monkeys when the laser scar incorporated the entire macula within the temporal vascular arcades. One eye had progressive vitreomacular traction with worsening of the RAPD to 1.8 log units without further laser treatment. Histopathologic evaluation disclosed complete loss of the normal retinal architecture within the macula. The average fiber loss for the 4 treated eyes with 0.6 log unit RAPDs compared with fellow eyes was 53.3% (95% confidence interval [CI], 45.0%-61.6%). The average difference in axon counts between untreated pairs of optic nerves was 12.8% (95% CI, 10.0%-15.6%). Optic nerve axon loss between pairs of experimental and control eyes was statistically significant (P<.001)., Conclusion: In rhesus monkeys, an RAPD develops after an approximate unilateral loss between 25% and 50% of retinal ganglion cells., Clinical Relevance: Owing to redundancy in the anterior visual pathways, unilateral retinal ganglion cell loss may occur prior to the observation of an RAPD. The presence of an RAPD measuring 0.6 log units implies that significant retinal ganglion cell injury has occurred.

Objectives: To assess the validity and reproducibility of quantitating relative afferent pupillary defects with the swinging flashlight test, using a 3-second pause technique, and to compare this grading system with that using neutral density filters., Design: We prospectively studied patients with relative afferent pupillary defects by using the swinging flashlight test with a standardized illumination time of 3 seconds (pause time) for each eye. Each relative afferent pupillary defect was graded as follows: grade I, a weak initial constriction and greater redilatation; grade II, initial stall and greater redilatation; grade III, immediate pupillary dilatation; grade IV, immediate pupillary dilatation following prolonged illumination of the good eye for 6 seconds; grade V, immediate pupillary dilatation with no secondary constriction. The grades on the individual resident evaluations were compared with those on the group evaluations, and the grading system was compared with the neutral density filter grading system., Setting: Neuro-ophthalmology service of an urban teaching hospital., Study Participants: A total of 119 patients., Results: There was a good correlation in all grades between individual resident and group evaluations, with an overall 78% agreement. The five grades had corresponding values in neutral density filter log units: grade I, 0.4; grade II, 0.7; grade III, 1.1; grade IV, 2.0; and grade V, infinity., Conclusions: The 3-second pause technique for the swinging flashlight test is a reliable method for the detection and quantitation of relative afferent pupillary defects. The grading system can be compared with the neutral density filter grading system, and each grade has a corresponding value in log units.