Glaucoma Diagnosis: from the Artisanal to the Defined

Abstract

In 400BC, Hippocrates wrote the first record of glaucoma. Since then, increasingly objective diagnostic techniques have enabled earlier detection of glaucoma and its progression, providing greater certainty in decision-making and early medical and surgical intervention.

Figure 1

An early iteration of the Helmholtz ophthalmoscope, 1852. Courtesy of the “Joint Library of Ophthalmology Moorfields Eye Hospital & UCL Institute of Ophthalmology”. (Used with permission.)

Figure 2

An 1854 illustration of a glaucomatous optic disc by Eduard Jaeger, drawn to depict protrusion and swelling, Jaeger’s interpretation of glaucomatous disc change. The image was originally published in his text, Ueber Staar und Staaroperationen (Wien) (Used with permission.)

Figure 3

AUROCs for the best parameters obtained using three objective, quantitative methods of structural assessment demonstrate the superiority of OCT (inferior average thickness, AUROC = 0.91) over scanning laser polarimetry with enhanced (TSNIT, AUROC = 0.87) or variable (TSNIT, AUROC = 0.81) corneal compensation. Originally published in Sehi M, Ume S, Greenfield DS. Scanning laser polarimetry with enhanced corneal compensation and optical coherence tomography in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 2007;48:2099-2014. (Used with permission.)

Figure 4

Visual field results (a) and OCT RNFL GPA reports (b) for a representative patient. These studies illustrate that, even when early abnormalities on VF or OCT are not statistically significant, one can be reasonably certain that real progression is occurring when changes are occurring in corresponding areas for both tests.

Figure 5

Data from a representative eye with glaucoma detectable on perimetric testing. The first and second columns display 6×6 mm en face angiograms from nonprojection-resolved OCTA and projection-resolved OCTA, respectively. The white arrows highlight the focal decrease in vessel density in a superior arcuate pattern in the superficial vascular complex (SVC) and all-plexus PR-OCTA images. The ganglion cell complex map (second image in third column) and visual field pattern deviation (third image in third column) demonstrate defects in corresponding locations. Of note, as might be expected, a corresponding decrease in vessel density was not found in the PR-OCTA for the intermediate capillary plexus (ICP) or deep capillary plexus (DCP). Originally published in Takusagawa HL, Liu L, Ma KN, et al. Projection-resolved optical coherence tomography angiography of macular retinal circulation in glaucoma. Ophthalmology. 2017;124:1589–1599. (Used with permission.)

Figure 6

Assessment of the relationships between perimetric visual function and (a) structural measures of the of retina and ONH (b) visual cortex activity as measured by MRI blood-oxygenation-level-dependent (BOLD) signal revealed that each of these relationships can be described by broken-stick (segmented) models. That is, this study demonstrated that functional impairment in terms of visual field progression occurs only after a “tipping point” in term of other measurements of glaucoma damage, and this finding holds true not only for measures of ocular structure (tipping points were 76.9 μm for RNFL [95% confidence interval (C.I.) = 67.9 to 86.0 μm], 59.6 μm for GCIPL (95% C.I. = 54.5 to 64.7 μm) and 0.81 for cup-to-disc ratio (95% C.I. = 0.79 to 0.83)), but also for measures of brain function (topping point was BOLD = 0.58% for upper visual field stimulation (95% C.I. = 0.34 to 0.82%) and BOLD = 0.61% for lower visual field stimulation (95% C.I. = 0.30 to 0.92%)). Red line represents the spline fit, and the black line represents the broken stick fit model. (*p < 0.05, **p < 0.01, ***p < 0.001: Davies’ test for statistically significant difference in slope between segments). Originally published in Murphy MC, Conner IP, Teng CY et al. Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma. Sci Rep. 2016;6:31464. (Used with permission.)