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Project

Ocular perfusion and vitreous influence on neuroretinal pathophysiology

This clinical doctoral research focuses on the intriguing field of ocular blood flow. The human eye is mainly perfused via branches of the ophthalmic artery. The most important branches for the retina and optic nerve are the central retinal artery (CRA) and the short posterior ciliary arteries (SPCAs), respectively. The retinal circulation arises from a single “end-artery”, the CRA, which supplies the inner layers of the retina. These are mainly the ganglion cells and their axons who are running together in the nerve fiber layer and form the optic nerve when exiting the eye. The SPCAs supply blood to the choroid which delivers oxygen to the outer layers of the retina and the optic nerve head. The outflow of the entire retinal circulation is provided by the central retinal vein (CRV). Any hypoperfusion or blockage of either in- or outflow has devastating consequences for the neuroretina. To study the retrobulbar circulation color Doppler imaging (CDI) is a validated and non-invasive method. To estimate blood flow in the choroid the choroidal thickness can be measured with optical coherence tomography (OCT). To assess the retinal circulation fundus oximetry, fluo-angiography and OCT-angiography are the methods of choice. Next to these technical investigations there is also the observation of spontaneous venous pulsations and the measurement of the ocular pulse amplitude (OPA). Many have investigated these vascular parameters separately, but their interplay remains a blank field both in health and in disease. One of the ocular diseases primarily linked to neurovascular abnormalities is glaucoma.

Glaucoma is a neurodegenerative disorder causing irreversible loss of retinal ganglion cells and leading to characteristic visual field defects and optic nerve head damage. It is currently the second leading cause of blindness. The main acknowledged risk factor for the development of glaucoma is an elevated intraocular pressure (IOP), but some patients appear to develop glaucomatous damage even with an IOP in the normal range. This observation prompted the question for other contributing factors in glaucoma pathophysiology. Flammer proposed in 1994 the vascular hypothesis stating that altered ocular blood flow could serve as an important risk factor. Researchers focused mainly on the arterial ocular perfusion, but the venous counterpart seems to have significant influence as well. For instance, the appearance of spontaneous venous pulsation at the optic nerve head is present in almost all healthy and only in half of glaucoma patients. Besides altered vascularization of the optic nerve head, glaucoma patients seem to suffer from altered regulation of retinal blood flow and are more prone to develop retinal vein occlusion (RVO). Next to the vascular hypothesis in glaucoma pathophysiology, there are also recent reports on patients presenting with visual field defects associated with vitreous traction to the optic nerve head. The vitreous is a gel-like structure most firmly attached posterior to the vitreous base, the optic disc and the macular region. With ageing a natural process of posterior vitreous detachment (PVD) occurs and, in some, traction to the fovea is exerted leading to macular disease and even macular hole formation. This disease is intensively studied and treatment options like enzymatic vitreolysis or surgical vitrectomy (whereby the vitreous is detached from the retina) are established. However, little is known about the effect of concomitant vitreous traction on the optic disc, affecting the papillary morphology and functioning of the ganglion cell axons. Therefore, next to the vascular hypothesis, this research project intends to investigate the vitreopapillary interface (VPI) in terms of diagnostic classification, pathophysiology and treatments options. Our research group has gained expert knowledge on enzymatic and surgical treatment of vitreomacular traction and its complications. This project thus expands the horizon by investigating if the same treatment modalities are indicated and can be applied for disease of the VPI.

Although mainly described as a separate disease entity, RVO is strongly linked to glaucoma. As mentioned, patients with glaucoma have significant more chance to develop a RVO and RVO in itself can be regarded as a strong cardiovascular risk factor correlated with the development of glaucomatous damage. On itself, RVO is the second most common retinal vascular disorder. Especially a central retinal vein occlusion (CRVO) renders the patient with a poor prognosis. Clogging of the only outflow pathway of the retinal circulation results in the formation of retinal edema, neovascularization, vitreous hemorrhages and neovascular glaucoma. Currently the treatment of this disease consists of counteracting the secondary complications of the ceased blood flow. To allow a paradigm shift in treatment strategy, this doctoral research is set to find, test and optimize a surgical approach for local intravenous administration of fibrinolytic drugs in order to remove the cause; the blood clot itself.

Date:1 Mar 2014 →  18 Sep 2017
Keywords:glaucoma, vitreous, ocular perfusion
Disciplines:Ophthalmology and optometry
Project type:PhD project