Related Experiment Video
Updated: Jul 11, 2026
In Vivo Methods to Assess Retinal Ganglion Cell and Optic Nerve Function and Structure in Large Animals
Published on: February 26, 2022
Quantification of optic nerve axon loss associated with a relative afferent pupillary defect in the monkey
J B Kerrison1, K Buchanan, M L Rosenberg
1Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA. jkerrison@yahoo.com
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.
