‘Structure–function relationship’ in glaucoma: past thinking and current concepts

Abstract

An understanding of the relationship between functional and structural measures in primary open angle glaucoma (POAG) is necessary for both grading the severity of disease and for understanding the natural history of the condition. This article outlines the current evidence for the nature of this relationship, and highlights the current mathematical models linking structure and function. Large clinical trials demonstrate that both structural and functional change are apparent in advanced stages of disease, while, at an individual level, detectable structural abnormality may precede functional abnormality in some patients whilst the converse in true in other patients. Although the exact nature of the ‘structure-function’ relationship in POAG is still the topic of scientific debate and the subject of continuing research, this article aims to provide the clinician with an understanding of the past concepts and contemporary thinking in relation to the structure-function relationship in POAG.

Structural and functional assessment by hemispheric asymmetry testing of the macular region in preperimetric glaucoma

“…Garway-Heath demonstrated that the appearance of a functional reserve could be explained as a statistical artifact using log units for perimetric sensitivity and linear units for anatomical measurements [2]. Even now, a structure-function relationship remains controversial in the earliest stages of ''preperimetric'' glaucoma [3][4][5].…”

A view on glaucoma—are we seeing it clearly?

“…Advances in imaging technology now readily available to the clinic, like optical coherence tomography, infer the feasibility of objectively measuring structural progression in glaucoma. Yet the research community still struggles with the link between these structural assessments and how they impact on visual function; an excellent recent review is given by Malik et al 13 I suggest the most important measure for disease progression in glaucoma is the functionally relevant assessment of the visual field; it certainly ought to be a key determinant in assessing effectiveness of treatments in a clinical trial setting. Unfortunately, effective visual field assessment can be difficult and identifying changes in follow-up (progression) beyond the measurement variability is a well-known thorny issue.…”

The joint structure–function dynamics of glaucoma progression

“…Dynamic models have been developed for other chronic diseases [12,13] and this approach could be applied to glaucoma progression. Recent efforts in 3 this direction have been made and deserve attention. Schell et al [14] proposed a dynamic model to personalize the frequency of clinic visits for glaucoma patients based on each patient's historical intraocular pressure levels and their performance on visual field tests.…”

“…Determining how structural and functional data should be combined, however, is complicated by the fact that the relationship between structure and function is not well understood in glaucoma [3]. For example, while some studies suggested that structure and function were best defined by a curvilinear relationship [4][5][6], recent studies have demonstrated that the structure-function relationship may be linear when both measurements are expressed in linear units [7][8][9][10][11].…”