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Quantification of Optic Nerve Axon Loss Associated With a Relative Afferent Pupillary Defect in the Monkey
John B. Kerrison, MD;
Kelvin Buchanan, DVM;
Michael L. Rosenberg, MD;
Robert Clark, PhD;
Kurt Andreason, MD;
Daniel V. Alfaro, MD;
Hans E. Grossniklaus, MD;
Lisa A. Kerrigan-Baumrind, MS;
Danielle F. Kerrigan, BS;
Neil R. Miller, MD;
Harry A. Quigley, MD
Arch Ophthalmol. 2001;119:1333-1341.
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.
From the Wilmer Ophthalmological Institute, Johns Hopkins Hospital,
Baltimore, Md (Drs Kerrison, Miller, and Quigley and Mss Kerrigan-Baumrind
and Kerrigan); Uniformed Services University of Health Sciences, Bethesda,
Md (Drs Kerrison, Rosenberg, Andreason, and Alfaro); Armed Forces Radiobiology
Research Institute, Bethesda (Dr Buchanan); New Jersey Neuroscience Institute,
JFK Medical Center, Edison (Drs Rosenberg and Clark); and the Department of
Ophthalmology, Emory University School of Medicine, Atlanta, Ga (Dr Grossniklaus).
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