High Blood Pressure, High Cholesterol May be Associated With Retinal Vascular Disease
High blood pressure and high cholesterol levels appear to be risk factors for retinal vein occlusion, a condition that causes vision loss, according to a report in the Archives of Ophthalmology.

Paul R.A. O'Mahoney, of the Royal College of Surgeons in Ireland, and colleagues conducted a meta-analysis of 21 previously published studies involving 2,916 individuals with retinal vein occlusion and 28,646 control participants without the condition. The researchers pooled data from all the studies and estimated the population-attributable risk, or the percentage of cases of retinal vein occlusion that could be attributed to hypertension, diabetes and hyperlipidemia.

Of patients with retinal vein occlusion, 63.6% had hypertension, compared with 36.2% of controls; those with high blood pressure had more than 3.5 times greater odds of having retinal vein occlusion. High cholesterol levels were more than twice as common among patients with retinal vein occlusion than in those without (35.1% vs 16.7%), and those with high cholesterol levels had an approximately 2.5-fold higher risk of retinal vein occlusion. Diabetes was slightly more prevalent among those with retinal vein occlusion than among those without (14.6% vs 11.1%).

"The pronounced population attributable risk percentage for hypertension (nearly 50%), hyperlipidemia (20%) and diabetes mellitus (5%) in persons with retinal vein occlusion, if causal, would mean that treatment of these diseases might be important in the primary and secondary prevention of retinal vein occlusion," the study's authors wrote. "Accordingly, we recommend that an assessment of blood pressure and both fasting lipid and glucose levels be routinely performed in adults with any form of retinal vein occlusion."

In addition, "those who treat patients with systemic hypertension, diabetes mellitus, and hyperlipidemia should consider that each poses a risk not only to cardiovascular health but also to ocular health," they concluded.

SiRNA Therapies Could Have Harmful Side Effects
Gene silencing may have potentially harmful effects in humans, according to research by Jayakrishna Ambati, MD, a researcher at the University of Kentucky.

Dr. Ambati and colleagues believe that short interfering RNA (siRNA), thought by many to have the capability to interfere with specific disease-causing genes and prevent them from being expressed, functions generally and may adversely affect blood vessel growth in a variety of organs. This research was published in Nature.

"My lab made the surprising discovery that siRNAs, including those in clinical trials, do not enter cells, or trigger RNA interference (RNAi)," Dr. Ambati said. "Rather, we found that they generically, regardless of their sequence or target, bind a receptor known as TLR3 on cell surfaces and block blood vessel growth in the eye, skin, and a variety of other organs."

Although the blocking of blood vessel growth is beneficial in wet age-related macular degeneration (AMD) and other diseases, it may be detrimental if it affects other organs, Dr. Ambati said.

"RNA interference does, of course, exist," he said. "It is just that siRNA functions differently than commonly believed—not via RNA interference."

The implications of this research are that researchers must understand how siRNAs work, and approach clinical trials of siRNA with great caution, Dr. Ambati said. The next steps are to better understand the generic mechanism of siRNA that inhibits blood vessel growth and to discover how to render it useful in creating treatments. Dr. Ambati's team will also work to refine siRNAs to potentially achieve precise gene targeting.

Radiation Combo Therapy for AMD Shows Promise
Patients treated with bevacizumab (Avastin, Genentech) in combination with brachytherapy for AMD showed marked improvement in mean visual acuity, according to a recent company-sponsored study.

NeoVista, Inc., (Fremont, CA) released the 1-year results from an ongoing nonrandomized, multicenter, feasibility study of 34 patients who received a single treatment of epiretinal brachytherapy in combination with two injections of bevacizumab. One dose was delivered prior to or simultaneous with radiation delivery, and another 1 month later. After 12 months follow-up, patients experienced a mean improvement in visual acuity of 10 letters using the Early Treatment Diabetic Retinopathy Study (ETDRS) test. The study also found that 94% of patients lost fewer than 15 letters, 39% percent gained 15 or more letters, and 12% gained 30 or more letters. Additionally, 76% of patients did not require additional injections of bevacizumab throughout the year.

"As more data are collected and analyzed surrounding this one-time surgical procedure, we're continuing to see the potential of the concomitant approach to treat wet AMD," said Jeffrey S. Heier, MD, a retinal specialist and consultant for NeoVista. "Unlike previous attempts with radiation therapy, NeoVista has developed a means of delivering targeted beta radiation to choroidal neovascular membranes with minimal penetration, resulting in little effect on the surrounding healthy tissue," he said.

Most of the adverse events were related to the vitrectomy procedure (eg, retinal tear, retinal detachment, subretinal hemorrhage).

Another trial evaluating the safety and efficacy of the epiretinal beta radiation therapy delivered concomitantly with ranibizumab is underway, according to a company news release.

FDA Discussion of Implantable Telescope Postponed
Review of the investigational Implantable Miniature Telescope (IMT; VisionCare Ophthalmic Technologies, Inc., Saratoga, CA) by the US Food and Drug Administration (FDA) Ophthalmic Devices Advisory Panel, has been postponed, according to the company.

VisionCare requested the postponement to allow time for the submission of additional long-term clinical data and review of data by the FDA.

Makers of Xibrom Subpoenaed Over Promotional Practices
Ista Pharmaceuticals, Inc. (Irvine, CA), reported that is had received a subpoena from the US Attorney's Office in Buffalo requesting the production of documents regarding the company's promotional, educational, and other activities relating to Xibrom 0.09% (bromfenac sodium ophthalmic solution).

The company issued a statement saying that it plans to fully cooperate in responding to the subpoena.

FAME Trial to Continue Without Change
Two phase 3 clinical trials, known collectively as FAME (Fluocinolone Acetonide in Diabetic Macular Edema) will continue under the current protocol, following a review of safety and efficacy by an independent data safety monitoring board.

FAME consists of two, duplicate, double-masked, randomized, multicenter studies that are following 956 patients implanted with Medidur (Alimera Sciences, Alpharetta, GA) in the United States, Canada, Europe, and India for 36 months. Medidur is a tiny, injectable insert, being studied as a way to deliver fluocinolone acetonide to the retina for up to 3 years for the treatment of diabetic macular edema. Using a 25-gauge injector system, medical professionals inject the Medidur insert into the vitreous through a minimally invasive procedure, according to the company.

"As of this latest data safety monitoring board review, we continue to be on track for regulatory submissions in early 2010," said Alimera Chief Executive Officer Dan Meyers, in a company press release.

Hormone Use May Lower Risk of Macular Degeneration
Women who take postmenopausal hormones appear to have a lower risk of developing advanced stages of AMD, especially if they had also taken oral contraceptives in the past, according to an article in the Archives of Ophthalmology.

Diane Feskanich, ScD, and colleagues assessed estrogen-related factors such as postmenopausal hormone use, past use of oral contraceptives, ages at first period and menopause, and childbirth history in approximately 75,000 postmenopausal women involved in the Nurses' Health Study. Between 1980 and 2002, 554 of the women in the study developed early AMD, and 334 women developed neovascular AMD.

"Current postmenopausal hormone users had a notable 48% lower risk of neovascular AMD compared with those who had never used postmenopausal hormones, although risk did not decline linearly with longer durations of use," the authors wrote. "Risk was lowest for postmenopausal hormone users who had used oral contraceptives in the past."

In contrast, risk of early AMD was 34% higher among current postmenopausal hormone users and oral contraceptive use was not associated with early AMD risk. The higher risk of early AMD among postmenopausal hormone users was unexpected, the authors said. It was also in apparent conflict with the observed inverse association for neovascular AMD. Additionally, the authors found that women who had given birth had a 26% lower risk of early AMD.

"Taken together, these findings suggest a role for estrogen in the pathogenesis of AMD that requires further research in specific early and late signs of the disease," they concluded.

VEGF Trap-Eye Maintains VA Gains at 32-Weeks
VEGF Trap-Eye (Regeneron, Tarrytown, NY) dosed on an as-needed dosing schedule maintained the statistically significant gain in visual acuity originally achieved after an initial, 12-week, fixed-dosing phase of a phase 2 study for neovascular AMD, according to a presentation at ARVO.

Across all dose groups in the study population, the 6.6 mean letter gain in visual acuity achieved vs baseline at the week-16 evaluation, following 12 weeks of fixed-dosing, was maintained out to week 32 using as-needed dosing. The decrease in retinal thickness was also maintained for all dose groups combined at week 32 (137 µm mean decrease vs baseline; P<.0001).

In this double-masked, prospective, randomized, multicenter, phase 2 trial, 157 patients were randomized to five dose groups and treated with VEGF Trap-Eye in one eye. Two groups initially received monthly doses of 0.5 or 2 mg of VEGF Trap-Eye for 12 weeks, and three groups received quarterly doses of 0.5, 2, or 4 mg at baseline and week 12. Following the initial 12 weeks, dosing was based upon the physician assessment of the need for retreatment, as well as safety, retinal thickness, and visual acuity. These data represent the week-32 analyses from the 52-week study.

Patients receiving monthly doses of VEGF Trap-Eye, either 0.5 or 2 mg, for 12 weeks followed by as-needed dosing achieved mean improvements in visual acuity of 8.0 (P<.01 vs baseline), and 10.1 letters (P<.0001 vs baseline), respectively. Mean decreases in retinal thickness were measured at 141 µm and 162 µm at week 32, respectively.

After the last fixed-dose administration at week 12, patients from all dose groups combined required, on average, only one additional injection over the following 20 weeks to maintain the visual acuity gain established during the initial dosing period. Moreover, 97% of patients who received 2 mg of VEGF Trap-Eye for 12 weeks did not require redosing at week 16; this may indicate the feasibility of an 8-week dosing schedule, according to the company.

"Due to its high affinity for all isoforms of VEGF-A and P1GF, potent mediators of blood vessel overgrowth in AMD, as well as its long residence time in the eye, it is anticipated that VEGF Trap-Eye may be able to be dose at a frequency less than once a monthÉ without compromising visual acuity," according to the study's primary investigator, Quan Dong Nguyen, MD. "These emerging phase 2 clinical data seem to support the concept of durability of VEGF Trap-Eye."

VEGF Trap-Eye treatment was also associated with a reduction in the size of choroidal neovascular membranes, according to the company.

Positive Results Announced for Visudyne Combination Therapy
Combination therapy of verteporfin (Visudyne, QLT, Vancouver, Canada) followed by bevacizumab in patients with subfoveal choroidal neovascularization secondary to AMD, reduced by half the number of treatments required during the first 6 months of treatment to gain a similar visual acuity compared with bevacizumab monotherapy, according to an investigator-sponsored phase 2 study. Additionally, 30% of patients treated using the combination therapy required only a single combination treatment compared with bevacizumab monotherapy, with which all patients required additional treatments, QLT announced.

Michael Potter, MD, FRCSC, investigator-sponsor of the verteporfin and bevacizumab clinical trial, which was supported by QLT, presented the results at the 31st Annual Macular Society Meeting.

"At 6 months, virtually all patients treated with the Visudyne combination therapy gained visual acuity with half the number of treatments required with [bevacizumab] monotherapy," Dr. Potter said in a QLT press release.

Rehabilitation May Improve Visual Function
A low-vision rehabilitation program that includes a home visit, counseling, assistive devices such as magnifiers, and assignments to practice using them appears to significantly improve vision in veterans with diseases of the macula, according to a report in the Archives of Ophthalmology.

"Low vision, chronic visual impairment that limits everyday function, is one of the 10 most prevalent causes of disability in America," the authors wrote.

Joan A. Stelmack, OD, MPH, of the University of Illinois at Chicago College of Medicine, and colleagues studied 126 patients (average age, 78.9; 98% male) with low vision and diseases affecting the macula who were eligible for Veterans Affairs services between November 2004 and November 2006. Participants were randomly assigned to one of two groups.

In one group, patients received a low-vision rehabilitation program incorporating a low-vision examination, counseling, assistive devices such as magnifiers and five weekly sessions provided by a low-vision therapist to teach use of the assistive devices and other adaptive strategies. They were also assigned homework to ensure that they used the devices outside of rehabilitation.

The other group was placed on a wait list for the rehabilitation program and received no treatment for 4 months, an average amount of time for veterans to wait to receive such services.

After 4 months, the 64 patients in the treatment group had received an average of 10.46 hours of face-to-face low-vision rehabilitation and experienced a significant improvement in all aspects of visual function, including reading ability. Among the 62 patients in the group that did not receive rehabilitation, vision and functional ability declined over the 4-month follow-up.

"Significant improvements in functional ability for mobility, visual information processing, visual motor skills and overall ability also were seen in the treatment group; small losses in these functions were observed in the control group," the authors wrote.

"At least 10 hours of low-vision therapy, including a home visit and assigned homework to encourage practice, is justified for patients with moderate and severe vision loss from macular diseases," they concluded.

"Because the waiting-list control patients demonstrated a decline in functional ability, low-vision services should be offered as early as possible," the study's authors wrote.