New public beta of MyVisionTest entoptic perimetry program A new, totally overhauled version of the original "video static" MyVisionTest entoptic perimetry vision testing program is in the works. A beta version of the new test is now available for users to evaluate.

Unlike earlier versions of the entoptic perimetry program, the new vision test is written in Flash. This change will make it technically easier for users to setup their computers and configure their web browsers to use the vision test.

The new program is essentially the same vision test, but with some enhancements. One significant change in that users can draw vision defects of any shape, rather than being limited to only round shapes. A new in-program help system is now present, allowing users to get assistance with using the program while using it. Finally, we have reinstituted full-screen mode, permitting the vision test to take full advantage of your computer monitor's real estate.

Give it a try and let us know what you think. Your feedback is very important to us. Please let us know about any bugs that you encounter. Your comments and suggestions for improvement are also welcome.

MyVisionTest version 4 - Public Beta   (change log)

Measuring vision recovery following Avastin therapy A new study finds that optical coherence tomography (OCT) subretinal fluid measurements correleted well with visual acuity recovery following Avastin therapy for neovascular age-related macular degeneration (AMD).

The advent of high-definition "spectral domain" OCT permits more detailed analysis of the anatomic changes in the retina than is possible with traditional "time domain" OCT. It has long been recognized that visual acuity improves following anti-VEGF therapy as the retinal thickness, as measured by conventional "time domain" OCT decreases. Recently, high-definition OCT has revealed that it is actually the decrease in subretinal fluid (SRF) that is important in vision recovery.

The current study attempts to correlate various measures of vision with various anatomic measurements using OCT and flourescein angiography following Avastin therapy for neovascular AMD.

Fifty eyes were treated with at least three injections of Avastin (bevicizumab) for neovascular AMD and followed for at least 6 months.

Vision outcomes included best-corrected ETDRS chart acuity, scored by best-line read (ETDRS line) and by total letters read (ETDRS letter), and two measures obtained from central acuity perimetry with 98% contrast targets, the best acuity within 6 degrees of fixation (BA6), and global macular acuity (GMA), representing a weighted average of multiple acuity measurements within a 10 degree radius of fixation.

The researchers found an association between EDTRS letter and BA6 with the change in SRF thickness. GMA was associated with the change in SRF thickness, CNV thickness, and in CNV fibrosis grade. No association was found between ETDRS line with any anatomic measurements.

The investigators conclude that acuity perimetry offers improved understanding of the relationship between vision and anatomic changes following anti-VEGF therapy. Furthermore, they state that it is not possible to predict vision based upon either OCT or fluorescein angiography findings.

Read more...
Eye. 2008 Nov 28. [Epub ahead of print]

Retinylamine Slows Progression of AMD-Like Condition in Mice An investigational drug called retinylamine slowed the progression of a condition in mice that is very similar to age-related macular degeneration (AMD) in humans.

The AMD-like condition was triggered in mice by disrupting the removal of all-trans-retinal from the retina.

Under normal conditions, the visual pigment 11-cis-retinylidene is converted by reaction with light to all-trans-retinylidene, releasing all-trans-retinal as a waste product. Although the retinals are essential to the visual cycle, they are also chemically reactive, and they and their by-products are toxic, so the visual cycle includes specific mechanisms for clearing them. All-trans-retinal has been associated with lipofuscin deposits in the retinal pigmented epithelium (RPE).

Lacking genes for two proteins that are critical for the clearance of all-trans-retinal from photoreceptors, the mice in the study developed severe retinal pigmented epithelium (RPE) atrophy at an early age. Specifically, the mice accumulated all-trans-retinal condensation products, a finding that directly links abnormal functioning of the visual cycle to RPE/photoreceptor degeneration.

The researchers noted that the genetically modified mice developed the AMD-like condition at an early age. Characteristic features including RPE/photoreceptor atrophy, drusen, basal laminar deposits, thickening of the Bruch's membrane, and choroidal neovascularization were seen in the first 2 to 3 months of life.

The researchers found that the severity of the condition could be made worse by exposing the animal to light. Importantly, it was discovered that treatment with the drug retinylamine decreased the severity of the degeneration.

Retinylamine is a visual cycle inhibitor. It acts on a protein found in the RPE called RPE65. This protein is involved in the conversion of all-trans-retinol to 11-cis-retinal during the visual cycle. In effect, it slows the flow of all-trans-retinal.

These findings provide direct evidence that aberrant production of toxic condensation by-products of the visual cycle in mice can lead to rapid, progressive retinal degeneration. The investigators state that their research findings suggests that retinylamine could halt the progression of AMD in humans if treatment were started early enough.

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J Biol Chem 2008;283:26684-26693

Meta-analysis confirms Lucentis safety Lucentis (ranibizumab) appears safe in the treatment of wet age-related macular degeneration (AMD), according to an analysis of 4 large clinical trials.

Dr David Boyer presented these findings at the 2008 Joint Meeting of the American Academy of Ophthalmology (AAO) and the European Society of Ophthalmology (SOE).

Several clinical trials have evaluated the safety of Lucentis using differing dosing and treatment schedules. In the current analysis, Dr Boyer analyzed data from the MARINA, ANCHOR, PIER, and SAILOR trials, including 3701 patients receiving a total of 28,547 Lucentis injections. Trials were 2 years in duration, with the exception of the SAILOR trial cohort 1, which was 1 year in duration. Dr. Boyer and colleagues assessed safety outcomes, including the incidence of ocular and nonocular adverse events.

Incidence of intraocular inflammation was somewhat higher for Lucentis-treated patients compared with the sham or photodynamic therapy, respectively, in the MARINA (15.9% vs 10.6%) and ANCHOR trials (14.4% vs 3.5%).

The rates of serious endophthalmitis per injection was very low, ranging from 0% to 0.06% for 2 years of treatment with Lucentis compared with 0% in patients in the control groups.

In the Lucentis group vs control group, respectively, the incidence of cataracts per patient was comparable in the MARINA trial, 15.5% vs 15.7%, but was higher with Lucentis in the other trials: 18.4% vs 10.5% in the ANCHOR trial and 13.3% vs 8.1% in the PIER trial. Incidence of cataracts was 5.7% in the 1 year SAILOR trial.

For nonocular adverse events, the rate of blood clots was 2.7% after year 1 in all 4 studies combined and 4.1% after year 2 in 3 studies combined.

In addition, there was a non-significant difference towards a higher rate of stroke in the Lucentis group vs the control group, whereas no such trend was observed for heart attack or arterial thrombotic events overall.

Dr Boyer said, "In my opinion, the only new finding from the analysis was that it showed a higher rate of ocular inflammation in the ranibizumab treated patients treated monthly in the 2-year MARINA and ANCHOR trial vs the 1 year SAILOR cohort 1."

"There are no safety signals that should deter physicians from using ranibizumab for patients with neovascular AMD," Dr Diana Do, of Johns Hopkins University, said.

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Medscape

Fewer injections for wet AMD: Clinical trial update Medscape has assembled updates on several ongoing clinical trials into new drugs and dosing strategies that were presented at the 2008 Joint Meeting of the American Academy of Ophthalmology and the European Society of Ophthalmology held in November. Below is a synopsis of information presented.

LEVEL Study

The LEVEL study is evaluating the ability of Macugen (pegaptanib) to maintain initial visual gains provided by previous AMD treatments. Because Macugen is a selective anti-VEGF inhibitor, it is thought that it may pose a lower risk for systemic side efects, such as heart attack or stroke, in patients at risk for these conditions.

Macgen was given every 6 weeks for 1 year after successful treatment with previous therapy, which included Avastin (bevacizumab) in 36% of the study group and Lucentis (ranibizumab) in 42%. During the maintenance phase, patients received Macugen and additional booster therapy at the discretion of the treating investigator.

Of the 568 patients, 88% completed 1 year of maintenance with Macugen. Visual acuity and central retinal thickness were maintained at week 54. No serious side effects were encountered.

SUSTAIN Study

The SUSTAIN study was designed to assess the safety and efficacy of Lucentis in wet AMD using a guided, individualised, as-needed, dosing schedule.

The study includes 531 individuals with either new-onset choroidal neovascularization (CNV) that had never been treated or patients that had completed the ANCHOR trial that were then recruited into this study.

The data presented was of 69 of the new-onset category patients. Patients received 3 fixed monthly injections of Lucentis in the initial phase and then returned every 4 weeks in the maintenance phase for a total study period of 12 months.

The average number of injections given was 2.3 (range: 0 to 7) in the maintenance phase, indicating that only minimal doses are needed when using a flexible dosing schedule.

At month 3 and month 12, the change in visual acuity from baseline was within 15 letters for approximately 74% and 71% of patients, respectively, indicating that as-needed treatment maintained visual acuity.

The investigators conclude that their results indicate that flexible dosing based on predefined treatment criteria with monthly monitoring results in fewer injections overall without sacrificing effectiveness.

CLEAR-IT 2 Study

The CLEAR-IT 2 study is a phase 2 clinical trial of a new drug for the treatment of wet AMD called VEGF-Trap-Eye. This drug works very similarly to existing therapies, such as Lucentis, but it appears to have a longer duration of action. Like Lucentis, it is administered by intravitreal injection. VEGF-Trap-Eye is still undergoing evaluation and is not yet commercially available, but is expected be released very soon.

The CLEAR-IT 2 study was designed to assess responses at 12 weeks to a range of VEGF-Trap-Eye doses administered monthly and quarterly. The durability of as-needed dosing response was also measured out to 1 year. One-year results from the study were presented at the meeting.

A total of 159 patients were randomized to 1 of 5 equal groups: 0.5 mg or 2 mg VEGF-Trap-Eye every 4 weeks for 12 weeks; or 0.5, 2, or 4 mg every 12 weeks.

Responses to the drug were assessed at the conclusion of the initial 12-week fixed-dosing period. A mean improvement in visual acuity of 5.7 letters and a reduction in central retinal thickness to 119 µm was noted for all groups combined. For those patients dosed every 12 weeks the effect was not as robust as with monthly dosing.

Patients received, on average, about 2 additional injections over the 40-week as-needed dosing phase following a 12-week fixed-dosing period. Of the patients, 19% received no additional injections after week 12. Treatment was generally well tolerated and no serious adverse events occured.

"These findings were very encouraging and exciting because they suggest that VEGF-Trap-Eye produces at least similar results to those of standard care," said study author Quan Dong Nguyen of Johns Hopkins University. "We are also very encouraged by the long duration of action of the drug," he said.

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Medscape

Role of integrins in proliferative diabetic retinopathy This article investigates the role of integrins in proliferative diabetic retinopathy, and concludes that they represent a potential target for the development of new drug therapies for the disease. Integrins have also been identified as playing a role in the pathogenesis of choroidal neovascularization.

Proliferative diabetic retinopathy involves the growth of neovascular blood vessels and asociated fibrous tissue over the surface of the retina and optic nerve head and into the vitreous cavity. These proliferative vessels are abnormally permiable and leak fluid into the retina. They are also prone to hemorrhage. The retinal edema and vitreous hemorrhage and their sequlae that frequently arise from proliferative diabetic retinopathy is responsible for much of the blindness attributed to diabetes.

Integrins are a class of cell surface receptors that play a key role in the regulation of numerous key processes, including cell proliferation, migration, and differentiation. Integrins bind with various components in the extracellular matrix, including basement membrane proteins. Integrin binding produces changes in cell physiology and behavior, including angiogenesis. Hence, changes in the extracellular matrix can promote or deter angiogenesis because of integrin activity.

Several integrin subtypes have been identified in the endothelium of neovascular vessels in patients with proliferative diabetic retinopathy. Recent research has identified two integrin subtypes, alpha-v beta-3 and alpha-v beta-5, as key regulators of proliferative diabetic retinopathy. Antagonists of alpha-v beta-3 have been shown to suppress angiogenesis without harming pre-existing blood vessels in research animals. This subtype has also been identified in human choroidal neovascular membranes.

The authors conclude that integrins appear to play a key role in regulating angiogenesis and may be a promising target for new drug therapies for proliferative diabetic retinopathy and choroidal neovascularization.

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Can J Ophthalmol. 2008;43:683-688