Blood Pressure, Flow and More…
Vascular Changes in Experimental Glaucoma
Dr. Verena Prokosch started her talk by posing the question, whether the vascular changes preceded the ganglion cell loss or were they completely independent of intraocular pressure (IOP). In animal models, a change in vessel calibre has been shown with elevated IOP. Additionally, elevated IOP has also been shown to induce molecular changes, Crystallin, H2S (downregulation), CRMP5 and Beta-III Tubulin (upregulation). This suggests that remodelling of vasculature occurred both morphologically as well as functionally, in response to IOP.
She also mentioned that NOX2 was expressed in ganglion cell layer and adjacent vasculature as a stress marker after elevated IOP in vivo. In addition to the existing therapeutic strategies, Dr Prokosch talked about Hydrogen Sulphide (H2S), a vasoactive agent, which when injected in vivo and in vitro was found to have a neuroprotective effect. She concluded that vessel changes at functional, morphological, as well as molecular level, are likely to have a bearing on the glaucoma.
Blood Pressure – A Risk Factor for Glaucoma?
The relationship between blood pressure and glaucoma risk is complicated. Dr. Henry Marshall talked about a U-shaped association between blood pressure and Primary Open Angle Glaucoma, wherein both low and high BP had a detrimental effect. Dr. Marshall quoted the PROGRESSA study which highlighted the relationship between cardiovascular disease and retinal thinning in glaucoma suspects and manifest cases.
Structural phenotyping was done into no structural thinning, predominantly peripapillary retinal nerve fibre layer (pRNFL) thinning, predominantly Macular Ganglion cell-inner plexiform layer (mGCIPL) change and both pRNFL and mGCIPL changes. It was seen that the group with mGCIPL change had a high prevalence of hypertension and anti-hypertensive use. Longitudinal progression also showed that there was a strong association between mGCIPL thinning and history of hypertension. The PROGRESSA study highlighted that hypertension may be an important risk factor for glaucomatous progression. Additional, inputs from Ambulatory Blood pressure monitoring and OCT Angiography may add more insight as regards the actual area of concern, small vessels or ocular perfusion pressure.
OCT Angiography of Ocular Blood Flow: Pros and Cons
Abnormalities of the circulation of the optic nerve head, retina and/or choroid have been suggested to have a role in the etiolopathogenesis of glaucoma.
Dr. Jaewan Choi stated that the OCT-Angiography (OCT-A) showed better structure-function relationship in moderate-to-advanced glaucoma in terms of circumpapillary capillary density (cpCD), macular capillary density(mCD) and Choroidal microvascular dropout (CMVD). Mean rate of cpCD change was significantly higher in moderate-to-advanced glaucoma stage than in early glaucoma, with no difference in circumpapillary retinal nerve fibre layer (cpRNFL) thickness. Additionally, less floor effect occurs with Capillary density thickness than the cpRNFL thickness.
Dr. Choi advocated the use of OCT-A as a monitoring tool in eyes with moderate-to-advanced glaucoma, as the association between mCD and cVFS was significantly stronger than the association between average mGCIPL thickness and cVFS, whereas this association was not found in early glaucoma. CMVD was associated with progressive cpRNFL thinning and visual field progression.
Dr. Choi cited several limitations of OCT-A, viz., limited diagnostic ability, difficulty in getting reliable images, absence of normative database and no automated change analysis. He suggested the need to focus on the Foveal avascular zone (FAZ) as it is extremely vulnerable to ischaemic insult. Early glaucoma patients have been shown to have irregular FAZ borders with lower FAZ circularity index, while advanced glaucoma patients have enlarged FAZ size or increased FAZ perimeter. Diagnostic accuracy of FAZ circularity perimeters has been found to be similar to cpRNFL and mGCIPL. He concluded by posing a question, “Do some types of glaucoma begin from the breakdown of the capillary system of macula?”. Dr. Choi suggested that the OCT-A derived normal vascular findings such as CMVD or FAZ related variables may give additional value for future research.
Using OCT to access Retinal Oxygenation – Implications for Glaucoma Specialists
Dr. Yali Jia, an ophthalmic imaging expert, talked about a spectroscopic optical coherence tomography (OCT) instrument using visible-light band (Vis-OCT). Vis-OCT can measure vascular oximetry by virtue of higher resolution and contrast than standard IR-OCT. Dr Jia paired Vis-OCT with a novel algorithm to extract the blood oxygen saturation in retinal capillaries in a preclinical model and found that at elevated IOP there was an increased oxygen extraction. Results from rat model have shown that vascular perfusion remained steady until IOP >70 mm Hg. Arterial oxygen saturation (sO2) remained steady while venous sO2 dropped gradually as IOP increased. Arterial flow reversal occurred at high IOP levels while Total retinal blood flow (TRBF) reduced as IOP rose above 40 mmHg. Dr. Jia highlighted that the Oxygen metabolism was maintained until IOP >40 mm Hg. However, she mentioned that currently the chief limitations of using this technology were expensive light sources and poor penetration below RPE.
Translating Blood Flow Research into Clinical Practice
Dr. Vital Paulino Costa talked about the multifaceted relationship between blood pressure, ocular perfusion pressure (OPP) and open angle glaucoma. The dynamics between OPP and nocturnal systemic hypotension (nocturnal dip) influence the development and/or progression of glaucoma. He quoted the Egna Neumarket Study and Proyecto VER, which have shown that lower the diastolic perfusion pressure, higher the risk of glaucoma. The Barbados study has also shown that the risk factors for glaucoma included low diastolic perfusion pressure, low systolic perfusion pressure as well as low Mean perfusion pressure.
Dr. Paulino Costa cited one of his studies where they monitored 24-hour OPP of 29 POAG patients and 24 controls, none of them was using systemic antihypertensives, and found an increase in IOP and a dip in BP early in the morning. He showed another study which analysed data from the Duke Glaucoma Registry, and found that when adjusted for mean IOP during followup, for each 10 mm Hg lowering in Mean Arterial Pressure (MAP) and Mean Diastolic Arterial Pressure (DAP) there was a significant faster rate of glaucoma progression.
He cited the Systolic blood pressure intervention trial (SPRINT), which supported aggressive treatment of hypertension. In this study, lower incidence of cardiovascular endpoints was noted with intensive BP control, which led the American College of Cardiology to revise the safe limits of BP to 130/80 mm Hg. Dr. Paulino Costa suggested that ophthalmologists must remain in contact with cardiologist. His concluding remarks were that achieving target BP was as essential as achieving target IOP, to address both cardiovascular events and glaucoma progression.