Modern treatments for neovascular age-related macular degeneration may stop and even reverse vision loss. Drugs injected directly into the eye are designed to stop abnormal blood vessel growth from the macula area of retina that provides central vision.

AREDS 1

The AREDS Study was the first to demonstrate that specific nutritional supplements could slow intermediate and late AMD progression. It involved 4,757 people aged 55-88 years with either AMD, cataracts or both and their researchers divided them into categories based on whether or not there were drusen present – category one had none while category 2 included both small drusen as well as intermediate ones (63 to 124 microns in diameter).

Study results also demonstrated that diets rich in antioxidant vitamins were key factors in lowering the risk of advanced AMD. The original AREDS formulation contained 500 mg of vitamin C, 400 IU vitamin E, 15 mg beta carotene 15 mg beta carotene 15, zinc oxide 80 mg zinc oxide 80 mg and 2 mg copper which greatly decreased progression to advanced AMD by 25%-30% as well as central vision loss by 19%.

In a follow-up study, the research team tested whether adding lutein and zeaxanthin to the AREDS formula would enhance its results, and whether omega-3 fatty acids could further decrease progression to advanced AMD. They discovered that adding these two nutrients significantly decreased progression to neovascular AMD while decreasing geographic atrophy risk by 22% – as well as significantly decreasing risk for progression to advanced AMD whether intake levels of these nutrients are high or low.

AREDS2 was conducted with 4,203 individuals who either had intermediate AMD in both eyes, advanced AMD in one eye but early AMD in the other, or interme- diate AMD in both eyes but early AMD in another. It sought to answer several outstanding questions regarding nutritional supplementation’s efficacy in lowering risk of advanced AMD; these included whether adding lutein/zeaxanthin/DHA/EPA supplements to an already effective antioxidant formula such as vitamins C, E beta-carotene zinc formulation would further decrease progression; researchers wanted to also determine whether eliminating beta-carotene/reducing zinc could further decrease progression risk further; additionally they wanted to establish whether either further lowering either of the risk factors would make further reduction even greater; or whether eliminating beta-carotene/reducing zinc would further lower risk further reduction of progression into advanced AMD progression.

AREDS 2

The National Eye Institute recently conducted the AREDS 2 Study as the latest research trial to reduce vision loss caused by age-related macular degeneration. This randomized, double-blind trial examined the effects of supplementing original AREDS formulation with additional nutrients such as lutein and zeaxanthin as well as omega-3 long-chain polyunsaturated fatty acids; researchers then tested how adding these supplements affected vision loss when compared against placebo; in addition, beta carotene and zinc dose reduction was evaluated against placebo as well.

The results of the AREDS study revealed that antioxidant vitamins significantly decreased risk of progression to advanced AMD; however, which combination of nutrients provided the greatest protection is yet unknown. AREDS2 trial conducted a multiyear clinical investigation to study various combinations of vitamins and supplements on 4,203 people between 50-85. Participants were randomly assigned either the AREDS formula, or its variation with added lutein and zeaxanthin but without beta-carotene (AREDS2). This study showed that adding these nutrients did not increase its benefits compared to its original formulation; however, removing beta-carotene did reduce progression to advanced AMD rates.

New research demonstrates that the presence of reticular pseudodrusen increases the risk of progression to late-stage AMD at simplified severity scale levels, particularly at simplified severity scale levels. The conclusions are based on both color fundus photographs graded using color fundus grader and deep learning grading of fundus autofluorescence images; multivariate analyses were then performed, accounting for factors such as drusen size, pigment abnormalities and geographic atrophy in their analyses.

The AREDS2 study was sponsored by the National Eye Institute, with participants from clinics across the United States being recruited into it. Participants either took either the original AREDS supplement (containing vitamin C, E, zinc and copper) or an updated formulation containing DHA and EPA as omega-3 fatty acids) provided in their daily supplement dose – those taking an updated formulation had an approximately 30% lower risk of geographic AMD than those who used only traditional remedies alone.

CATT

The CATT study was the first large-scale clinical trial designed to compare two drugs used to treat wet AMD, one of the leading causes of blindness among older adults. Its goal was to find out whether one drug was superior and which treatment schedule proved more successful; until now doctors used either bevacizumab or ranibizumab to treat wet AMD but weren’t sure which would provide optimal results; now thanks to CATT’s results they know which ones they should prescribe their patients.

The study involved more than 1100 wet AMD patients who were randomly assigned bevacizumab (Avastin) or ranibizumab (Lucentis). For the first year, they attended monthly visits for evaluation and treatment; at the end of year one, they were either continued receiving a monthly dose or switched over to variable dosing, where bevacizumab would only be prescribed when there was active neovascularization present.

After two years of follow up, the CATT study concluded that both drugs produced similar vision gains; these findings were published in Ophthalmology journal. Unfortunately, vision gains did not last over time and some eyes continued to experience permanent blindness due to morphologic changes that could potentially cause permanent blindness.

CATT also studied the effect of various dosing schedules. By the end of their investigation, investigators concluded that PRN dosing led to slightly fewer serious adverse events than monthly dosing but this difference wasn’t statistically significant. Ophthalmologists and their patients will benefit greatly from knowing about long-term vision results and morphologic change through this CATT follow up study.

At CATT, a central grading center provided reliable, timely, and systematic grading of color photographs and OCT scans submitted for study participation. Grading was carried out by trained and certified ophthalmologists using standardised protocols; additionally, the FPRC supported study goals by providing image resources for recruitment meetings, presentations, publications.

EYP-1901

EyePoint Pharmaceuticals’ groundbreaking work brings us closer to an ideal world where losing vision due to retinal diseases will no longer be a worry. EYPT, located in Watertown, Massachusetts is dedicated to improving outcomes for patients suffering from serious retinal disorders by administering therapeutic agents through its proprietary bioerodible Durasert technology that provides sustained intraocular drug delivery. EYP-1901 combines vorolanib (a patent protected tyrosine kinase inhibitor) with Durasert and may reduce injection frequency over time for managing such diseases.

At a phase 1 DAVIO clinical trial, vorolanib combined with Durasert technology demonstrated promising safety and efficacy results. The trial was designed to assess its efficacy for previously treated wet age-related macular degeneration (nAMD), including participants treated with anti-VEGF therapy who displayed evidence of choroidal neovascularization at enrollment.

At the eight-month visit, no serious adverse events were recorded; instead, mild adverse reactions similar to anti-VEGF injections were experienced by most participants. Furthermore, OCT analysis demonstrated stabilization in visual acuity and central subfield thickness (CST).

Results also demonstrated that 76% of eyes did not require additional anti-VEGF therapy up to six months post implant initiation – representing an important reduction in treatment burden. Now, the study is progressing with an objective of demonstrating safety and efficacy across a wider patient population.

Retinal experts discuss the latest advancements in neovascular AMD, including faricimab’s clinical trials YOSEMITE and RHINE. Nathan Steinle, MD; Adrienne Scott, MD, FACS; Carl Regillo, MD, FACS, FASRS; and Prethy Rao MD discuss managing DME as well as new technologies like OCT angiography which could impact treatment options.

Mizuho Securities analyst Graig Suvannavejh maintained his Buy rating for EYPT stock on February 5. As a result, EYPT shares spiked more than 6% higher during morning trading on this news.