Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma?

Primary open angle glaucoma (OAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and associated visual field loss. OAG is an emerging disease with increasing costs and negative outcomes, yet its fundamental pathophysiology remains largely undetermined. A major treatable risk factor for glaucoma is elevated intraocular pressure (IOP). Despite the medical lowering of IOP, however, some glaucoma patients continue to experience disease progression and subsequent irreversible vision loss. The scientific community continues to accrue evidence suggesting that alterations in ocular blood flow play a prominent role in OAG disease processes. This article develops the thesis that dysfunctional regulation of ocular blood flow may contribute to glaucomatous optic neuropathy. Evidence suggests that impaired vascular autoregulation renders the optic nerve head susceptible to decreases in ocular perfusion pressure, increases in IOP, and/or increased local metabolic demands. Ischemic damage, which likely contributes to further impairment in autoregulation, results in changes to the optic nerve head consistent with glaucoma. Included in this review are discussions of conditions thought to contribute to vascular regulatory dysfunction in OAG, including atherosclerosis, vasospasm, and endothelial dysfunction

Evaluation of Hemodynamic Parameters as Predictors of Glaucoma Progression

Purpose. To evaluate hemodynamic parameters as possible predictors for glaucoma progression. Methods. An 18-month randomized double-masked cohort study including 30 open-angle glaucoma patients receiving fixed-combination treatment with Dorzolamide/Timolol (DTFC) or Latanoprost/Timolol (LTFC) (n = 15 per group) was performed. Intraocular pressure (IOP), arterial blood pressure (BP), ocular and diastolic perfusion pressures (OPP, DPP), color Doppler imaging, pulsatile ocular blood flow analysis, scanning laser polarimetry, and Humphrey visual field evaluations were included. Results. Both treatments showed statistically similar IOP reduction. Six patients in DTFC and 7 in LTFC group met glaucoma progression criteria. DTFC group had higher OPP, DPP, and lower vascular resistivity indices as compared to the LTFC. Progressing patients had higher nerve fiber index, lower systolic BP, OPP, DPP, higher ophthalmic and central retinal artery vascular resistance, and lower pulse volume (P < .05; t-test). Conclusions. Structural changes consistent with glaucoma progression correlate with non-IOP-dependent risk factors

Update in intracranial pressure evaluation methods and translaminar pressure gradient role in glaucoma

Glaucoma is one of the leading causes of blindness worldwide. Historically, it has been considered an ocular disease primary caused by pathological intraocular pressure (IOP). Recently, researchers have emphasized intracranial pressure (ICP), as translaminar counter pressure against IOP may play a role in glaucoma development and progression. It remains controversial what is the best way to measure ICP in glaucoma. Currently, the ‘gold standard’ for ICP measurement is invasive measurement of the pressure in the cerebrospinal fluid via lumbar puncture or via implantation of the pressure sensor into the brains ventricle. However, the direct measurements of ICP are not without risk due to its invasiveness and potential risk of intracranial haemorrhage and infection. Therefore, invasive ICP measurements are prohibitive due to safety needs, especially in glaucoma patients. Several approaches have been proposed to estimate ICP non-invasively, including transcranial Doppler ultrasonography, tympanic membrane displacement, ophthalmodynamometry, measurement of optic nerve sheath diameter and two-depth transcranial Doppler technology. Special emphasis is put on the two-depth transcranial Doppler technology, which uses an ophthalmic artery as a natural ICP sensor. It is the only method which accurately and precisely measures absolute ICP values and may provide valuable information in glaucoma

The Difference in Translaminar Pressure Gradient and Neuroretinal Rim Area in Glaucoma and Healthy Subjects

Purpose. To assess differences in translaminar pressure gradient (TPG) and neuroretinal rim area (NRA) in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. Methods. 27 patients with NTG, HTG, and healthy controls were included in the prospective pilot study (each group consisted of 9 patients). Intraocular pressure (IOP), intracranial pressure (ICP), and confocal laser scanning tomography were assessed. TPG was calculated as the difference of IOP minus ICP. ICP was measured using noninvasive two-depth transcranial Doppler device. The level of significance P < 0.05 was considered significant. Results. NTG patients had significantly lower IOP (13.7(1.6) mmHg), NRA (0.97(0.36) mm2), comparing with HTG and healthy subjects, P < 0.05. ICP was lower in NTG (7.4(2.7) mmHg), compared with HTG (8.9(1.9) mmHg) and healthy subjects (10.5(3.0) mmHg); however, the difference between groups was not statistically significant (P>0.05). The difference between TPG for healthy (5.4(7.7) mmHg) and glaucomatous eyes (NTG 6.3(3.1) mmHg, HTG 15.7(7.7) mmHg) was statistically significant (P < 0.001). Higher TPG was correlated with decreased NRA (r = −0.83; P = 0.01) in the NTG group. Conclusion. Translaminar pressure gradient was higher in glaucoma patients. Reduction of NRA was related to higher TPG in NTG patients. Further prospective studies are warranted to investigate the involvement of TPG in glaucoma management

Predicting retinal tissue oxygenation using an image-based theoretical model

Impaired oxygen delivery and tissue perfusion have been identified as significant factors that contribute to the loss of retinal ganglion cells in glaucoma patients. This study predicts retinal blood and tissue oxygenation using a theoretical model of the retinal vasculature based on confocal microscopy images of the mouse retina. These images reveal a complex and heterogeneous geometry of vessels that are distributed non-uniformly into multiple distinct retinal layers at varying depths. Predicting oxygen delivery and distribution in this irregular arrangement of retinal microvessels requires the use of an efficient theoretical model. The model employed in this work utilizes numerical methods based on a Green's function approach to simulate the spatial distribution of oxygen levels in a network of retinal blood vessels and the tissue surrounding them. Model simulations also predict the blood flow rates and pressures in each of the microvessels throughout the entire network. As expected, the model predicts that average vessel PO2 decreases as oxygen demand is increased. However, the standard deviation of PO2 in the vessels nearly doubles as oxygen demand is increased from 1 to 8 cm3 O2/100 cm3/min, indicating a very wide spread in the predicted PO2 levels, suggesting that average PO2 is not a sufficient indicator of oxygenation in a heterogeneous vascular network. Ultimately, the development of this mathematical model will help to elucidate the important factors associated with blood flow and metabolism that contribute to the vision loss characteristic of glaucoma

Optic nerve head morphology in glaucoma patients of African descent is strongly correlated to retinal blood flow

BACKGROUND/AIMS: To examine the relationship between change in optic nerve head (ONH) morphology and retinal blood flow in patients with open-angle glaucoma (OAG) of African (AD) and European descent (ED) over 3 years. METHODS: 112 patients with OAG (29 AD; 83 ED) underwent assessment of ONH morphology using Heidelberg retinal tomography (HRT-III), and retinal blood flow using confocal scanning laser Doppler. Repeated-measures analysis of covariance was used to compare baseline and 3-year measurements, and Pearson correlations were calculated to evaluate the relationships. RESULTS: In OAG patients of AD, change in superior mean retinal blood flow was strongly, negatively correlated with change in cup/disc (C/D) area ratio (r=-0.78, p=0.020) and cup area (r=-0.75, p=0.0283) and strongly, positively correlated with change in rim area (r=0.74, p=0.0328) over 3 years. In OAG patients of AD, change in inferior mean retinal blood flow was strongly, negatively correlated with changes in C/D area ratio (r=-0.88, p=0.0156) and linear C/D ratio (r=-0.86, p=0.0265) over 3 years. In OAG patients of ED, these correlations were weak and did not reach statistical significance. DISCUSSION: OAG patients of AD may have a stronger vascular component to their glaucoma pathophysiology than patients of ED

Vascular considerations in glaucoma patients of African and European descent

Glaucoma is the leading cause of blindness in individuals of African descent (AD). While open-angle glaucoma (OAG) disproportionately affects individuals of AD compared with persons of European descent (ED), the physiological mechanisms behind this disparity are largely unknown. The more rapid progression and greater severity of the disease in persons of AD further raise the concern for identifying these underlying differences in disease pathophysiology between AD and ED glaucoma patients. Ocular structural differences between AD and ED patients, including larger optic disc area, cup:disc ratio and thinner corneas, have been found. AD individuals are also disproportionately affected by systemic vascular diseases, including hypertension, cardiovascular disease, stroke and diabetes mellitus. Abnormal ocular blood flow has been implicated as a risk factor for glaucoma, and pilot research is beginning to identify localized ocular vascular differences between AD and ED OAG patients. Given the known systemic vascular deficits and the relationship between glaucoma and ocular blood flow, exploring these concepts in terms of glaucoma risk factors may have a significant impact in elucidating the mechanisms behind the disease disparity in the AD population