Researchers compared and contrasted the presence of ocular and systemic vascular function in patients with newly diagnosed and previously untreated primary open-angle glaucoma (POAG) vs. those with normal-tension glaucoma (NTG) and comparable early-stage, functional loss. They found that patients with POAG or NTG exhibit similar alterations in ocular and systemic circulation in the early stages of their disease process.

The researchers assessed the systemic vascular function of 19 patients with POAG, 19 patients with NTG and 20 healthy individuals serving as controls using 24-hour ambulatory blood pressure monitoring, peripheral pulse-wave analysis and carotid intima-medial thickness. They also assessed retinal vascular reactivity to flicker light using dynamic retinal vessel analysis (Imedos, GmbH).

Compared with controls, patients with POAG and those with NTG exhibited similarly increased nocturnal systemic blood pressure variability (p=.01), peripheral arterial stiffness (p=.02), carotid intima-media thickness (p=.04) and reduced ocular perfusion pressure (p<.001). On dynamic retinal vessel analysis, the researchers noted that both glaucoma groups exhibited steeper retinal arterial constriction slopes after cessation of flicker (p=.007) and a similarly increased fluctuation in arterial and venous baseline diameter (p=.008 and p=.009, respectively) compared with controls.

These findings highlight the importance of considering vascular risk factors in both conditions and raises questions about the current separation of the two conditions into distinct clinical entities.

The authors of the following clinical trial sought to evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis, Genentech) or bevacizumab (Avastin, Genentech) for neovascular AMD.

They recruited 834 (73% of 1,149 patients participating in the Comparison of AMD Treatments Trials (CATT) through 43 CATT clinical centers and genotyped each patient for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1) and rs2230199 (C3) using TaqMan SNP genotyping assays (Applied Biosystems). The authors compared genotypic frequencies with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size and mean number of injections administered. They evaluated differences in response by genotype with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, p≤0.01 was considered statistically significant.

The study authors did not identify any statistically significant differences in response by genotype for any of the clinical measures studied. Specifically, they found no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size) or the number of injections. Furthermore, a step-wise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing.

In conclusion, although specific alleles for CFH, ARMS2, HTRA1 and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy.

To evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV), 20 eyes of 20 patients with stable CNV were enrolled in this prospective, open-label, noncomparative study and treated with topical pazopanib 0.5% for three weeks, and followed for 12 weeks.

The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves; (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend; (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end; and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels.

No severe adverse events were reported following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week three (p=0.02 and 0.01, respectively); and NA, IA and VL statistically significantly decreased at week 12 (p=0.03, 0.04, and <0.01, respectively). Additionally, visual acuity maintained without changes after the 12-week follow-up.

This preliminary study suggests that topical treatment with pazopanib 0.5% is safe, well-tolerated and may have a role as an alternative for the treatment of CNV.