Axon Content of the Circumpapillary Nerve Fiber Layer in Experimental Glaucoma
In brief
OCT model differed by 25 axons on average, but estimates varied widely
In 22 monkeys with experimental glaucoma, a location-adjusted model estimated optic nerve axon counts from OCT scans, with a mean difference of just 25 axons from counts obtained after death. However, individual estimates had very wide limits of agreement, so the model's accuracy for a given eye remains uncertain; validation in people is also needed.
- Journal
- Investigative ophthalmology & visual science (Q1)
- Published
- 2 November 2026
- Study design
- Cross-sectional study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Anish Kharal, Mitchell Sullivan, Nimesh Bhikhu Patel
- PMID
- 42975102
- DOI
- 10.1167/iovs.67.13.8
Why clinicians should know about it
- Picked for Histology (paper of the day, 4 November 2026): Serial-block-face EM and quantitative axon histomorphometry
Abstract
PURPOSE: To determine axonal content from optical coherence tomography (OCT)-derived circumpapillary retinal nerve fiber layer (RNFL) measures using histologically informed models in a non-human primate experimental glaucoma model. METHODS: Unilateral experimental glaucoma was induced in 22 animals (mean age, 6.1 ± 1.9 years; 10 females) who were monitored with OCT. At varying stages of neuropathy, animals were euthanized and perfusion fixed. For RNFL histology, circumpapillary tissue (∼0.75 × 0.75 mm) from six equally spaced regions was obtained and processed for serial block face scanning electron microscopy in five animals. A single high-resolution image of the block face was used to quantify axon size (cross-sectional area) and non-axonal tissue area within the RNFL. Using the 95% limits of the histological data as a starting point, models for estimating axon count from OCT RNFL area were optimized and compared to total retrobulbar optic nerve axon counts in 22 animals. RESULTS: The mean circumpapillary RNFL thickness of control eyes was 112 ± 6 µm, and it was 70 ± 24 µm in eyes with experimental glaucoma. Axon size and non-axonal area varied across the circumpapillary regions (F5, 31 = 9.06 and F5, 36 = 3.94, respectively; both P < 0.01), but did not differ between the two eyes (F1, 22 = 0.59, P = 0.45 and F1, 15 = 2.10, P = 0.17). The optimized model for estimating axon content from the circumpapillary RNFL profile had good agreement with the retrobulbar axon count (mean difference = 25; 95% limits of agreement, -334,239 to 334,289). CONCLUSIONS: The axon size distribution and non-axonal area in the circumpapillary RNFL are similar between healthy and stable glaucomatous eyes. Building on this, a location-specific model is proposed that estimates axon content from the circumpapillary RNFL profile after accounting for regional variability in axonal and non-axonal components.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.