Quantification of optic nerve axon loss associated with a relative afferent pupillary defect in the monkey

Objective: To quantify the amount of optic nerve axonal loss associated wit h the presence of a mild relative afferent pupillary defect (RAPD) in an ex perimental 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. I ntervals between treatments were 3 to 7 days over a period of 2 months. Pup illary responses to light stimulation were recorded with a monocular infrar ed television pupillometer. Two months after detection of an RAPD, 5 treate d and 4 control monkeys underwent euthanasia and enucleation. Histopatholog ic analysis and quantification of optic nerve axon counts using an image an alysis 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 sear i ncorporated the entire macula within the temporal vascular arcades. One eye had progressive vitreomacular traction with worsening of the RAPD to 1.8 l og units without further laser treatment. Histopathologic evaluation disclo sed 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 compare d with fellow eyes was 53.3% (95% confidence interval [CI], 45.0%-61.6%). T he average difference in axon counts between untreated pairs of optic nerve s was 12.8% (95% CI, 10.0%-15.6%). Optic nerve axon loss between pairs of e xperimental and control eyes was statistically significant (P<.001). Conclusion: In rhesus monkeys, an RAPD develops after an approximate unilat eral loss between 25% and 50% of retinal ganglion cells. Clinical Relevance: Owing to redundancy in the anterior visual pathways, un ilateral retinal ganglion cell loss may occur prior to the observation of a n RAPD. The presence of an RAPD measuring 0.6 log units implies that signif icant retinal ganglion cell injury has occurred.