Linking structure and function in glaucoma

Abstract

The glaucomas are a group of relatively common optic neuropathies, in which the pathological loss of retinal ganglion cells causes a progressive loss of sight and associated alterations in the retinal nerve fiber layer and optic nerve head. The diagnosis and management of glaucoma are often dependent on methods of clinical testing that either, 1) identify and quantify patterns of functional visual abnormality, or 2) quantify structural abnormality in the retinal nerve fiber layer, both of which are caused by loss of retinal ganglion cells. Although it is evident that the abnormalities in structure and function should be correlated, propositions to link losses in structure and function in glaucoma have been formulated only recently. The present report describes an attempt to build a model of these linking propositions using data from investigations of the relationships between losses of visual sensitivity and thinning of retinal nerve fiber layer over progressive stages of glaucoma severity. A foundation for the model was laid through the pointwise relationships between visual sensitivities (behavioral perimetry in monkeys with experimental glaucoma) and histological analyses of retinal ganglion cell densities in corresponding retinal locations. The subsequent blocks of the model were constructed from clinical studies of aging in normal human subjects and of clinical glaucoma in patients to provide a direct comparison of the results from standard clinical perimetry and optical coherence tomography. The final formulation is a nonlinear structure-function model that was evaluated by the accuracy and precision of translating visual sensitivities in a region of the visual field to produce a predicted thickness of the retinal nerve fiber layer in the peripapillary sector that corresponded to the region of reduced visual sensitivity. The model was tested on two independent patient populations, with results that confirmed the predictive relationship between the retinal nerve fiber layer thickness and visual sensitivities from clinical perimetry. Thus, the proposed model for linking structure and function in glaucoma has provided information that is important in understanding the results of standard clinical testing and the neuronal losses caused by glaucoma, which may have clinical application for inter-test comparisons of the stage of disease.

Association between retinal neuronal degeneration and visual function impairment in type 2 diabetic patients without diabetic retinopathy

“…Similar results have been reported previously [8,30,31]. Our finding of macular GCC loss could be explained by the loss of retinal ganglion cells and axons prior to the thinning of the RNFL [32,33]. In addition, the superior region of the macular is more susceptible to initial diabetic damage than the other regions.…”

Assessment of rates of structural change in glaucoma using imaging technologies

“…2 A complete assessment of rates of disease progression requires both structural and functional measures, as it is known that many patients seem to progress by one method and not the other. [3][4][5][6] Although functional outcomes have an unquestionable relevance to patients, it has been shown that structural changes can often precede functional losses and be an earlier marker of deterioration. More importantly, a recent study showed that structural changes observed on optic disc stereophotographs are predictive of future functional losses and, therefore, carry clinically relevant prognostic information.…”

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset

“…Generally speaking, quantitative metrics of visual performance reflect the extent of both injury and protection that can only be inferred by morphologic analyses; moreover, functional alterations are often seen in glaucoma in the absence of gross changes in retinal cell structure [45,46], resulting in nonlinear structure-function relationships [47,48]. In our model, impairments in visual function and performance to levels of about 70-75 % of fellow eye controls, concomitant with optic nerve axon integrity and soma survival on the order of 80-85 % of fellow eye controls, are indicative of mild-tomoderate injury after 3 weeks of sustained IOP elevation.…”