Volume 14, Number 32
Monday, August 11, 2014


In this issue: (click heading to view article)
######### Two-Year Results of Treating Neovascular AMD With Anti-VEGF
######### Affect of Omega-3 Supplementation + Anti-VEGF on Vitreal Levels of VEGF in Wet AMD
######### Link Between Systemic Medication and IOP in a British Population
######### Short-Term Effects of Restasis in Long-Standing Prosthetic Eye Wearers


Two-Year Results of Treating Neovascular AMD With Anti-VEGF

The following prospective cohort study evaluated the two-year visual acuity outcome of a treat-and-extend protocol of anti-vascular endothelial growth factor treatment in age-related macular degeneration.

In it, 120 AMD patients with choroidal neovascularization received three initial monthly ranibizumab or bevacizumab injections. Monthly injections were continued until there was no CNV activity (subretinal/intraretinal fluid, loss of more than five letters, or persistent/recurrent retinal hemorrhage). When there was no CNV activity, the interval to the next visit/injection was extended by two weeks to a maximum of 12 weeks. In the presence of CNV activity, this interval was shortened by two weeks. Main outcome measures included the percentage losing fewer than 15 letters and the mean VA change after 12 months and 24 months.

Mean baseline visual acuity was 51.2 ± 12.1 Early Treatment Diabetic Retinopathy Study scores. Mean visual acuity change from baseline was +9.5 ± 10.9 and +8.0 ± 12.9 letters after 12 months and 24 months, respectively, with, on average, 8.6 ± 1.1 visits/injections in the first year and 5.6 ± 2.0 in the second year. After 12 months and 24 months, 97.5% and 95.0% of patients, respectively, lost fewer than 15 letters.

It was concluded that the “inject-and-extend” protocol—with fewer injections and visits—delivered outcomes comparable to those of the pivotal clinical trials of monthly ranibizumab.


SOURCE: Abedi F, Wickremasinghe S, Islam AF, et al. Anti-VEGF treatment in neovascular age-related macular degeneration: a treat-and-extend protocol over 2 years. Retina. 2014;3498):1531–1538.


Affect of Omega-3 Supplementation + Anti-VEGF on Vitreal Levels of VEGF in Wet AMD

To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A levels in patients with wet age-related macular degeneration receiving intravitreal anti-VEGF treatment, investigators conducted this prospective, randomized, open-label, single center, clinical trial, consecutive interventional case series. They demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients.

The study included three cohorts with wet AMD and a control group with epiretinal membrane or macular hole (ERM/MH). The investigators randomized 20 wet AMD patients being treated with anti-VEGF to daily supplementation of antioxidants, zinc and carotenoids with (Group One, n=10) or without (Group Two, n=10) omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid). They compared these groups to an anti-VEGF treatment-naïve wet-AMD (Group Three, n=10) and an ERM/MH (Group Four, n=10) group. Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness (CFT). Patients with new submacular hemorrhage or any other treatment within three months were excluded. Final analyses included nine, six, seven and eight patients in Groups One to Four, respectively.

They found that in a multiple regression model, the VFQ-J11 score was significantly associated with corrected distance visual acuity in the better-seeing eye (better eye VA), and improvement in the VFQ-J11 score after cataract surgery was associated not only with improvement in the better eye VA, but also with improvement in the worse eye VA. Compared to one-eye cataract surgery, both-eyes surgery had a greater impact on VFQ-J11 score improvement.

According to the investigators, patients receiving omega-3s (Group One) had significantly lower levels of vitreal VEGF-A (141.11 ± 61.89 pg/mL) when compared to Group Two (626.09 ± 279.27 pg/mL, p=0.036) and Group Three (735.48 ± 216.43 pg/mL, p=0.013), but similar levels to Group Four (235.81 ± 33.99 pg/mL, p=0.215). All groups showed similar values for plasma VEGF-A and CFT measurements.

SOURCE: Rezende FA, Lapalme E, Qian CX, et al. Omega-3 supplementation combined with anti-VEGF lowers vitreal levels of VEGF in wet age-related macular degeneration. Am J Ophthalmol. 2014;Aug 1. [Epub ahead of print].

Link Between Systemic Medication and IOP in a British Population

The authors of the population-based, cross-sectional study below sought to determine the association between systemic medication use and intraocular pressure in a population of older British men and women.

They included 7,093 participants from the European Prospective Investigation into the Cancer–Norfolk Eye Study. Exclusion criteria were a history of glaucoma therapy (medical, laser or surgical), IOP asymmetry between eyes of >5 mmHg and missing data for any covariables. The mean age of participants was 68 years (range, 48 to 92) and 56% were women.

The study authors used the Ocular Response Analyzer to measure IOP. They took three readings per eye and considered the best signal value of the Goldmann-correlated IOP value. They asked participants to bring all of their medications and related documentation to the health examination, and these were recorded by the research nurse using an electronic case record form. The medication classes examined were angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, alpha-blockers, beta-blockers, calcium channel blockers, diuretics, nitrates, statins, insulin, biguanides, sulfonylureas, aspirin and other nonsteroidal anti-inflammatory drugs. They authors examined associations between medication use and IOP using multivariable linear regression models adjusted for age, sex and body mass index. Models containing diabetic medication were further adjusted for glycosylated hemoglobin levels. Mean IOP of the right and left eyes were the main outcome measures.

The authors noted that use of systemic beta-blockers (–0.92 mmHg; 95% CI, –1.19, –0.65; p<0.001) and nitrates (–0.63 mmHg; 95% CI, –1.12, –0.14; p=0.011) were independently associated with lower IOP. Additionally, the observed associations between statin or aspirin use with IOP were no longer significant after adjustment for beta-blocker use.

This is the first population-based study to demonstrate and quantify clinically significant differences in IOP among participants using systemic beta-blockers or nitrates. Lower IOP observed in participants using statins or aspirin was explained by concurrent systemic beta-blocker use. The study findings may have implications for the management of glaucoma patients with comorbidity, and may provide insight into the pathophysiologic processes underlying IOP.

SOURCE: Khawaja AP, Chan MP, Broadway DC, et al. Systemic medication and intraocular pressure in a British population: the EPIC-Norfolk Eye Study. Ophthalmology. 2014;121(8):1501–1507.


Short-Term Effects of Restasis in Long-Standing Prosthetic Eye Wearers

Long-standing prosthetic eye wear induces ocular surface inflammation. In this prospective, interventional case series, Korean researchers investigated the short-term effects of topical cyclosporine A 0.05% (Restasis) in patients with ocular discomfort resulting from long-standing prosthetic eye wear.

They enrolled patients who were unilateral prosthetic eye wearers over a period of five years at a single institution from March to July 2013. They instructed subjects to instill Restasis b.i.d. and took measurements pre-treatment and after one and three months of treatment. Outcome measures were the ocular symptom score, the lid margin abnormality score, the Schirmer test and the tear meniscus amount, using Fourier-domain optical coherence tomography.

In total, 20 consecutive patients (mean age: 60.1 years, eight males, 12 females) were included. They researchers found that ocular symptoms were improved after treatment for one month in all patients (ocular symptom score pre-treatment 76.83 vs. 46.75 after treatment; p<0.001). They also noted that there was no statistically significant difference in lid margin abnormality score or tear meniscus amount. Furthermore, the Schirmer test results were improved after treatment for three months (pre- and after treatment, 6.70 vs. 11.40; p<0.001).

To conclude, Restasis showed a satisfactory effect in long-standing prosthetic eye wearers. Ocular symptoms were markedly relieved in all subjects after treatment for one month.

SOURCE: Han JW, Yoon JS, Jang SY. Short-term effects of topical cyclosporine A 0.05% (Restasis) in long-standing prosthetic eye wearers: a pilot study. Eye. 2014; Aug 1. [Epub ahead of print].


  • OPHTHOTECH INITIATES EXPANSION STUDIES TO FURTHER EVALUATE FOVISTA THERAPY IN WET AMD PATIENTS. Ophthotech Corp. has initiated the first of several planned expansion trials, in addition to the ongoing Fovista combination therapy Phase III clinical program. Ophthotech says these trials will investigate the potential role of Fovista combination therapy in reducing subretinal fibrosis, addressing suboptimal treatment response and reducing treatment burden in wet age-related macular degeneration patients receiving anti-vascular endothelial growth factor monotherapy. The first expansion trial is a Phase IIa open-label study investigating the potential role of anti-platelet derived growth factor therapy in combination with anti-VEGF therapy in reducing subretinal fibrosis in wet AMD patients. For further information, click here.

  • NICOX AND BAUSCH + LOMB TO CO-PROMOTE LATANOPROSTENE BUNOD IN UNITED STATES. In 2010, Nicox S.A. licensed latanoprostene bunod, a nitric oxide-donating prostaglandin F2-alpha analog, to Bausch + Lomb, a division of Valeant Pharmaceuticals International Inc. Under the licensing agreement, Nicox had an option to co-promote latanoprostene bunod products in the United States, and the company has notified Bausch + Lomb of its intentions to exercise that option. Latanoprostene bunod is in Phase III clinical development for the potential treatment of glaucoma and ocular hypertension and, according to Valeant, could be launched in the United States in 2016, pending approval from the FDA. Nicox and Bausch + Lomb will now start negotiating a co-promotion agreement to be signed at a later date. Want to know more? Visit www.nicox.com.

  • ALLERGAN-VALEANT SITUATION CONTINUES TO BOIL. Allergan Inc. recently filed a lawsuit against Valeant Pharmaceuticals International Inc., Pershing Square Capital Management L.P. and its principal, William A. Ackman, alleging that Valeant, Pershing Square and Mr. Ackman violated the federal securities laws prohibiting insider trading, engaged in other fraudulent practices, and failed to disclose legally required information. The complaint alleges that between February 2014 and April 2014, Pershing Square purchased Allergan stock and securities then valued at more than $3.2 billion from unknowing Allergan stockholders while fully aware of Valeant’s nonpublic takeover intentions, thereby securing for itself and depriving the selling stockholders of value appreciation worth approximately $1.2 billion upon Valeant's announcement of its initial offer on April 22, 2014. Allergan is seeking, among other remedies, a declaration from the court that Pershing Square and Valeant violated insider trading and disclosure laws, and an order rescinding Pershing Square's purchase of the Allergan shares it acquired illegally. For additional details of the complaint, click here.

    Valeant Pharmaceuticals International Inc. and Pershing Square responded to Allergan's lawsuit, stating that it makes baseless claims about Valeant and Pershing Square regarding the tender offer rules. Most recently, two proxy advisory firms backed a campaign by Pershing Square to persuade Allergan shareholders to call for a special shareholder meeting. Allergan has commented that these recommendations do not change the fact that Valeant's offer is grossly inadequate, substantially undervalues Allergan, creates significant risks and uncertainties for Allergan stockholders and is not in the best interests of the company and its stockholders.

  • NIH AWARDS ORAYA THERAPEUTICS WITH SMALL BUSINESS TECHNOLOGY TRANSFER GRANT FOR GOLD NANOPARTICLES DEVELOPMENT. In a recent press release, Oraya Therapeutics Inc. reported that it has been awarded a $215,500 Small Business Technology Transfer Grant from the National Institutes of Health to investigate how Oraya Therapy, a low-voltage stereotactic radiotherapy, and gold nanoparticles can further enhance the treatment of wet age-related macular degeneration. Under the grant, scientists at Oraya will collaborate with scientists at Dana-Farber Cancer Institute to develop a novel approach to treating wet AMD that utilizes the intravenous delivery of gold nanoparticles to target neovascular endothelial cells, the key therapeutic target associated with wet AMD.

  • ABB OPTICAL NAMED EXCLUSIVE U.S. DISTRIBUTER FOR ALDEN OPTICAL. Alden Optical announced that it has named ABB Optical Group as its exclusive distributor partner effective September 1, 2014. As of this date, all new orders for Alden Optical lenses will be placed either directly with Alden or via ABB Optical. Alden says its current distribution network will continue to service all customer orders initiated prior to September 1, 2014 for all transactions relating to Alden’s policies and warranties.

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