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Editors Selection IGR 17-4

Basic Research: Are reflectance and thickness RNFL related?

Comment by Brad Fortune on:

47979 Reflectance decreases before thickness changes in the retinal nerve fiber layer in glaucomatous retinas, Huang XR; Zhou Y; Kong W et al., Investigative ophthalmology & visual science, 2011; 52: 6737-6742

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Huang et al. (1787) have performed an elegant study following from an impressive series of prior papers that began with theoretical work on optical properties of the vertebrate retinal nerve fiber layer (RNFL), evolved to empirical tests of their theoretical findings then advanced to their current work in experimental glaucoma. Their basic premise is that RNFL optical properties, including reflectance and birefringence, are highly dependent on intact axonal cytoskeletal components, which might become disrupted at an early stage after axonal injury and precede total axonal degeneration. If such a stage can be detected and measured in vivo, it might serve as a harbinger predicting subsequent irreversible axonal degeneration and warn the clinician to consider advancement of therapy.

This study was performed on retinas taken from Wistar rats two weeks after each rat had undergone translimbal photocoagulation of the trabecular meshwork in one eye to elevate intraocular pressure (to 41 ± 8 mmHg, approximately 30 mmHg above fellow control eye values on average). A customized method was used to obtain measurements of reflectance along RNFL bundles in both glaucomatous and control retinas. Measurements were exquisitely controlled for the well-documented geometrical dependence of reflectance and were compared to measures of bundle thickness obtained by confocal microscopy after the retinas had undergone immunohistochemical staining by markers present in RNFL axons (and other layers). The investigators were careful to register the locations for the two measurements, which revealed a strong linear relationship between reflectance and thickness. The slope of this relationship was reduced in retinal locations close to the optic nerve head (ONH); but was similar to fellow control eyes at farther eccentricities from the ONH. This finding indicates that reflectance per unit thickness was reduced in axon bundles nearest the ONH, supporting the notion that the source of RNFL reflectance becomes abnormal prior to RNFL bundle thinning (presumed cytoskeletal disruption, though the authors did not have strong evidence one way or the other on this latter point).

Reflectance per unit thickness was reduced in axon bundles nearest the ONH, supporting the notion that the source of RNFL reflectance becomes abnormal prior to RNFL bundle thinning

It will be interesting to learn from future studies whether at later stages the relative reflectance also diminishes in more peripheral RNFL bundle locations, whether this is predictive of ultimate axonal degeneration (e.g., using in-vivo measures), and perhaps most importantly, whether it represents a reversible stage.

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