Inner plexiform layer offers early-stage glaucoma biomarker

Reviewed by Dr Zeinab Rozita Ghassabi and Dr Joel Schuman.

A sub-layer of the inner plexiform layer (IPL) holds promise as a potential biomarker to aid detection of early glaucomatous changes, according to Dr Zeinab Rozita Ghassabi, a post-doctoral research fellow, and Dr Joel Schuman. Both are based at the Department of Ophthalmology, New York University Langone Health, New York, United States.

Dr Ghassabi said that animal studies have determined glaucomatous changes start in dendrites and then develop in the ganglion cells and axons. Visible-light optical coherence tomography (vis-OCT) has been especially valuable in this research because the technology enables multiple sub-layers of the IPL to be visualised more easily.

“Vis-OCT has higher axial resolution compared with conventional OCT,” she explained.

Conventional systems are limited to axial resolutions of about 3–4 μm, in contrast to vis-OCT with an axial resolution in vivo of about 1.8 μm in air and 1.3 μm in the eye.

Dr Ghassabi and her colleagues tested the potential of the IPL sub-layers as glaucoma biomarkers using vis-OCT compared with conventional biomarkers such as the retinal nerve fibre layer (RNFL) and the ganglion cell layer. They used a prototype instrument, the Aurora X1 vis-OCT system (Opticent), which utilised a three-dimensional speckle-reduced raster scanning protocol focused on the superior fovea. The study population comprised nine healthy subjects and six patients with glaucoma.

Glaucoma biomarker study results

The healthy subjects (who had an average age of 47 years) and glaucoma patients (average age: 63 years) had respective RNFL thicknesses of 96.43 and 64.6 μm, which differed significantly (P = 0.002). Respective mean deviation values were –1.55 and –19.4 decibels, a difference that also reached significance (P = 0.002, Wilcoxon test).

OCT facilitates visualisation of multiple sub-layers of the IPL. (Images courtesy of Dr Zeinab Rozita Ghassabi)

Vis-OCT showed that the IPL has three sub-layers. In subjects who were healthy and in those with glaucoma, the total IPL values were 39.44 and 35.5 μm (P = 0.002, linear regression adjusted for age), respectively.

Dr Ghassabi noted that the thickness of sub-layer 1 did not differ between the two groups. The thickness of sub-layers 2 and 3, however, did differ significantly. With sub-layer 2, the values were 17.17 versus 14.36 μm, respectively (P = 0.003, linear regression adjusted for age); and with sub-layer 3, the thicknesses were 11.29 versus 10.29 μm (P = 0.045, linear regression adjusted for age).

Analysis showed a strong correlation between the thickness of sub-layer 2 and the mean deviation. “The IPL is a layer of synapses between the bipolar, amacrine and retinal ganglion cells and can be divided into on and off sub-laminae and five strata,” Dr Ghassabi said. “The five layers that were visible on vis-OCT images were correlated with five morphologic strata: S1 to S5.”

The patients with glaucoma had moderate and advanced disease. The thinning of sub-layer 2 that was observed was associated with a decrease in the distance between sub-layers 2 and 4 in the patients with glaucoma. This thinning was not observed in the healthy subjects.

“This finding corroborated the hypothesis that retinal ganglion cells with dendrites stratified in the off sub-laminae may be damaged,” Dr Ghassabi commented. According to the investigators, IPL sub-layer 2 seems to have high potential as a clinical glaucoma biomarker. However, future analysis of early-stage glaucoma in a larger study is needed."

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Zeinab Rozita Ghassabi, MD

E: zeinab.ghassabi@nyulangone.org

This article is adapted from Dr Ghassabi’s presentation at the 2021 American Glaucoma Society’s virtual annual meeting. Dr Ghassabi has no financial interest in this subject matter.

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