Ocular microcirculation measurement with laser speckle flowgraphy and optical coherence tomography angiography in glaucoma

Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.

To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma.

Purpose The purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients. Methods Two hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy. Results Age-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P < 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65). Conclusions Optical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG.