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Volume 13, Number 4
Monday, January 28, 2013
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JANUARY IS NATIONAL GLAUCOMA AWARENESS MONTH




In this issue: (click heading to view article)
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######### Vascular Considerations in POAG vs. NTG

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######### Use of Pharmacogenetics for Genes Associated with AMD
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######### Safety and Efficacy of Pazopanib in CNV
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######### Choroidal Thickness and Density of Drusen in RAP vs. AMD
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Vascular Considerations in POAG vs. NTG

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.

SOURCE: Mroczkowska S, Benavente-Perez A, Negi A, et al. Primary open-angle glaucoma vs. normal-tension glaucoma: the vascular perspective. JAMA Ophthalmol. 2013;131(1):36–43.



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Use of Pharmacogenetics for Genes Associated with AMD

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.

SOURCE: Hagstrom SA, Ying G, Pauer GJ, et al; Comparison of AMD Treatments Trials Research Group. Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT). Ophthalmology. 2013; Jan 21. [Epub ahead of print].

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Safety and Efficacy of Pazopanib in CNV

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.

SOURCE: Amparo F, Sadrai Z, Jin Y, et al. Safety and efficacy of the multitargeted receptor kinase inhibitor pazopanib in the treatment of corneal neovascularization. Invest Ophthalmol Vis Sci. 2013;54(1):537–544.






Choroidal Thickness and Density of Drusen in RAP vs. AMD

In the following observational case series, investigators compared choroidal thickness and extent and density of drusen between eyes with typical exudative age-related macular degeneration (AMD) and eyes with retinal angiomatous proliferation (RAP).

They included 24 eyes with typical exudative AMD and 20 eyes with RAP and measured subfoveal choroidal thickness using enhanced depth imaging optical coherence tomography (OCT). Additionally, they classified eyes into three groups according to the extent of drusen distribution in the fundus photograph. The study investigators estimated density of drusen based on OCT images of the fellow eye and defined the proportion of the length beneath the drusen per the entire length of the Bruch's membrane as the density of drusen. They compared subfoveal choroidal thickness, extent of drusen distribution and the density of drusen between typical exudative AMD and RAP.

According to the investigators, mean ± standard deviation subfoveal choroidal thickness in eyes with typical exudative AMD and eyes and RAP was 184.9 ± 68.5 µm and 139.0 ± 65.5 µm, respectively (p=.035). They found that the mean density of drusen was 0.06 ± 0.08 and 0.24 ± 0.12, respectively (p<.001). They also noted that in the typical exudative AMD group, 19, three and two eyes were included in the small extent group (less than one-third), intermediate extent group (one-third to two-thirds) and large extent group (more than two-thirds), respectively. In the RAP group, three, 14 and three eyes were included in each aforementioned group, respectively (p=.001).

To conclude, the thinner subfoveal choroidal thickness and greater extent and density of drusen in RAP than the typical exudative AMD may suggest compromised choroidal perfusion in the development of RAP.

SOURCE: Kim JH, Kim JR, Kang SW, et al. Thinner choroid and greater drusen extent in retinal angiomatous proliferation than in typical exudative age-related macular degeneration. Am J Ophthalmol. 2013; Jan 14. [Epub ahead of print].




  • FDA ACCEPTS IND FOR OPTINA TO TREAT DME. According to a news release from Ampio Pharmaceuticals Inc., the FDA has accepted the company's IND for Optina for the treatment of diabetic macular edema (DME). The drug is based on a low dose of the weak androgen, low molecular weight, very lipophilic steroid danazol. The FDA granted Optina 505(b)(2) status last year; drugs designated under this pathway can be approved on a single trial. Ampio plans to commence enrollment in a clinical trial in the first quarter of 2013. The trial is designed to evaluate the safety and efficacy of oral Optina compared with placebo given over a period of 12 weeks in adult patients with DME. Patients will be randomized to receive one of two doses of Optina (0.5 mg per BMI and 1.0 mg per BMI per day) or placebo. The primary endpoint is improvement in visual acuity (VA). Secondary endpoints include measurements of changes in VA and central macular thickness in treated patients compared to placebo, as well as safety and tolerability of the two Optina doses.
  • OMEROS COMPLETES COLLECTION OF SAFETY DATA FOR PHASE III TRIAL OF OMS302. Omeros Corp. successfully completed the 90-day safety database lock in the second of its two pivotal Phase III clinical trials evaluating OMS302 in patients undergoing IOL replacement surgery. OMS302 is a proprietary combination of ketorolac and phenylephrine and is added to standard irrigation solution used during ophthalmological procedures to maintain intraoperative mydriasis and reduce postoperative pain and irritation resulting from cataract and other lens replacement surgery. The multicenter, double-blind trial enrolled 416 patients randomized 1:1 to receive either OMS302 or placebo. Safety data were collected through postop day 90 and OMS302 was well-tolerated. Omeros reports that the incidence of adverse events was similar between the two treatment groups, and the adverse event profile was similar to that seen in prior OMS302 clinical trials. Additionally, no safety concerns have been identified in the OMS302 clinical development program. Results from this study are expected to be presented at an upcoming major ophthalmology meeting, as well as published in a leading peer-reviewed ophthalmology journal. Further information is available at www.omeros.com.
  • ALCON LAUNCHES NEW NSAID FOR THE TREATMENT OF PAIN AND INFLAMMATION ASSOCIATED WITH CATARACT SURGERY. Alcon recently announced the launch of ILEVRO Suspension, a new once-daily treatment option for pain and inflammation associated with cataract surgery. The company notes that in two double-masked, randomized clinical trials, ILEVRO Suspension demonstrated superior clinical efficacy compared to its vehicle. Inflammation resolved at day 14 in 65% of ILEVRO Suspension patients vs. 32% of patients on vehicle and pain resolution rates in ILEVRO Suspension-treated patients were 86% compared to 46% on vehicle. Read more here.
  • NEW LINE OF VITREORETINAL DEVICES AND INSTRUMENTS FROM FCI OPHTHALMICS. FCI Ophthalmics has introduced a new line of devices and instruments designed to provide retina surgeons with high-performance products for vitreoretinal procedures. The products begin with a wide selection of disposable laser probes, fiber optic probes and laser illumination sources that can connect to any manufacturer's vitreoretinal power supply, but a range of instruments and hand-pieces made from lightweight and durable titanium in several gauges are also available, including Retilock, a one-step, self-retaining trocar system for easy access to the posterior segment. Other products in the vitreoretinal launch include: single-use and reusable backflush handles and reservoirs for passive and active aspiration; disposable PFCL and subretinal cannulas, scleral buckling components, vitrectomy lenses and Invitria – Intravitreal Injection Assistant. Additional information can be obtained by calling (800) 932-4202 or by emailing info@fci-ophthalmics.com.
  • NICE PUBLISHES FINAL GUIDANCE ON ILUVIEN FOR DME. pSivida Corp. recently reported that the United Kingdom's National Institute for Health and Clinical Excellence (NICE) has published final guidance indicating that ILUVIEN is not cost effective for the treatment of chronic diabetic macular edema (DME) considered insufficiently responsive to available therapies. This final guidance is consistent with the final draft guidance issued on November 29, 2012. pSivida's licensee for ILUVIEN for DME, Alimera Sciences Inc., reported that it will pursue a Patient Access Scheme (PAS) for ILUVIEN for DME that is intended to allow treatment decisions to be based on patient need, rather than cost. According to Alimera, the PAS is currently under review by the Patient Access Schemes Liaison Unit at NICE. If approved by the Department of Health, the PAS will be available to the Appraisal Committee for review and consideration. Read more here.
  • SANTEN LAUNCHES NEW IOL CUSTOMIZED FOR JAPANESE EYES. Santen Pharmaceutical Co. Ltd. has announced the launch of Eternity Natural Uni, a novel, single-piece IOL, and its dedicated injector system, Accuject UniFit. The new Eternity Natural Uni is based on the established Eternity material platform, which, according to Santen, offers several advantages in long-term clarity and stability. The hybrid acrylic IOL features an advanced haptic design to provide superior intracapsular stability in eyes, along with predictable vaulting. For a product overview and other additional information, click here.



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