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 Controversy of Myopia as a Risk Factor for Glaucoma: a Mathematical Approach

poster abstractPurpose: to quantify how individual variations in anatomical parameters often associated with myopia (e.g. longer ocular axial length (OAL), reduced scleral thickness (ST), lamina cribrosa diameter (LCD) and thickness (LCT)) affect retinal blood flow (RBF) and its sensitivity to ocular perfusion pressure (OPP). Methods: A mathematical model is used to calculate RBF through central retinal artery (CRA), arterioles, capillaries, venules, and central retinal vein (CRV). The flow is time-dependent, driven by systemic pressure and regulated by variable resistances to account for nonlinear effects due to (1) autoregulation (AR), and (2) lamina cribrosa effect on CRA and CRV. The latter is a nonlinear function of intraocular pressure (IOP), cerebrospinal fluid pressure (CSF) and OAL, ST, LCD, and LCT. RBF is computed as the solution of a system of five non-linear ordinary differential equations. The system is solved for different OPP values, obtained by varying independently IOP and mean arterial pressure (MAP), with and without AR. Results: Four representative eyes are compared: Eye 1 (OAL=24mm, ST=1mm, LCD=3mm, LCT=0.4mm), Eye 2 (OAL=28mm, ST=1mm, LCD=3mm, LCT=0.4mm), Eye 3 (OAL=24mm, ST=0.7mm, LCD=2mm, LCT=0.2mm), Eye 4 (OAL=28mm, ST=0.7mm, LCD=2mm, LCT=0.2mm). The model predicts that the cardiac cycle RBF average (RBFav) for eyes with smaller LCD and LCT is notably less than in normal eyes when IOP is elevated and without AR (c). Without AR and reduced MAP, the four eyes show similar RBFav reductions (d). With AR, anatomical changes do not induce notable changes in RBFav, (a) and (b). Conclusions: Reduced LCD and LCT, often associated with myopia, seem to affect RBFav more than elevated OAL. RBFav reductions magnify when AR is impaired, and this might reduce IOP safe levels for eyes with reduced LCD and LCT. These findings suggest that a combination of anatomical and vascular factors might cause certain myopic eyes to be at higher risk for glaucomatous damage than others

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