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BJO Online First, published on December 2, 2014 as 10.1136/bjophthalmol-2014-305780 Clinical science
The role of retrobulbar and retinal circulation on optic nerve head and retinal nerve fibre layer structure in patients with open-angle glaucoma over an 18-month period Leslie Abrams Tobe,1 Alon Harris,1 Rehan M Hussain,1,2 George Eckert,1 Andrew Huck,1 Joshua Park,1 Patrick Egan,1 Nathaniel J Kim,1 Brent Siesky1 1
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA 2 Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan, USA Correspondence to Professor Alon Harris, Department of Ophthalmology, Indiana University School of Medicine, 1160 West Michigan Street, Indianapolis, IN 46202, USA;
[email protected] Received 7 July 2014 Revised 2 October 2014 Accepted 22 October 2014
ABSTRACT Background/aims Evidence suggests that vascular abnormalities play a role in the pathogenesis of openangle glaucoma (OAG) in some patients. This study aims to assess changes in retrobulbar and retinal blood flow over time in patients with glaucoma and examine their relationship to glaucomatous progression, as determined by retinal and optic nerve structure. Methods In this observational study, 103 patients with OAG were examined at baseline and 18 months followup. Retrobulbar blood flow was measured by colour Doppler imaging in the ophthalmic, central retinal and temporal posterior ciliary artery (TPCA) and nasal short posterior ciliary artery. Retinal capillary blood flow was measured by confocal scanning laser Doppler. Peripapillary retinal nerve fibre layer thickness was assessed by optical coherence tomography. Nonparametric Wilcoxon signed ranks tests were used to assess for any statistically significant changes between the baseline and 18-month visits for the retrobulbar and retinal flow, as well as the structural parameters. Results In general, retinal and retrobulbar blood flow parameters decreased over 18 months. Thinning of the optic disc rim and increase in cup area were associated with a higher resistance index (p=0.0334) and lower peak systolic velocity of TPCA (p=0.0282), respectively. A higher amount of retinal zero pixel blood flow correlated with a greater increase in cup/disc ratio (p=0.0170). Conclusions Reductions in retrobulbar and retinal blood flow over time were associated with structural glaucomatous progression, as indicated by retinal and optic nerve changes.
INTRODUCTION
To cite: Tobe LA, Harris A, Hussain RM, et al. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-305780
Primary open-angle glaucoma (OAG) is a multifactorial optic neuropathy characterised by progressive retinal ganglion cell death and visual field loss. Despite being one of the leading causes of impaired vision worldwide, the pathogenesis of OAG is not well understood. The only currently available management of OAG is based upon reduction of intraocular pressure (IOP). However, many studies have shown that some patients experience disease progression despite significantly lowered IOP.1–4 Over the past several decades, evidence has suggested that vascular pathologies play an important role in the aetiology and progression of OAG. Many population-based studies have found decreased retinal, choroidal and retrobulbar blood flow to be
associated with increased glaucoma prevalence and incidence.5–11 While the relationship between ocular blood flow and glaucoma is relatively well established, the nature of that relationship is not well understood. The reduced ocular blood flow seen in patients with OAG may be secondary to elevated IOP, retinal ganglion cell death or of primary vascular origin.6 7 Some theorise that decreased blood flow causes ischaemic insult to the optic disc and retina, which may play a role in the structural and functional damage that is characteristic of glaucoma.10 Others theorise that elevated IOP in glaucoma leads to tissue injury, thus obviating the need for blood flow to that region.11 While the mechanism is not well established, there is growing evidence that glaucomatous eyes have impaired blood flow. Previous studies have found decreased ocular blood flow to be correlated with glaucomatous structural and functional progression.12–14 However, these studies are small in number, often measure only one vascular bed, and many do not address the change in both parameters over time. The purpose of this study is twofold. First, this study will assess a large cohort of patients with OAG to see how ocular blood flow in both retrobulbar and retinal vessels, as well as optic nerve head (ONH) structure, changes over time. Second, this study will also assess how changes in ocular blood flow over time are related to glaucomatous structural progression over time.
METHODS A total of 103 patients with primary OAG were assessed at baseline and prospectively followed every 6 months thereafter for ocular perfusion and blood flow as well as markers of structural glaucomatous progression. A comparison of results at baseline and 18 months was performed. All patients signed an informed consent after explanation in accordance with the Declaration of Helsinki, and the study protocol was approved by both the clinical and reading centre Institutional Review Boards. The diagnosis of OAG was confirmed by a certified ophthalmologist. Exclusion criteria included the following: extensive Humphrey visual field damage consisting of either a mean deviation (MD)
