New Treatments for macular degeneration

New Treatments for macular degeneration

“In the United States alone, as many as 11 million people have age-related macular degeneration (AMD).

When I was a student at Pennsylvania College of Optometry (now Salus University), there was little we could do to help prevent our patients’ vision loss from age-related macular degeneration (AMD). I did my low vision/vision rehabilitation residency at the Feinblom Vision Rehabilitation Center.  

At the time, low-vision devices were one of the few options to enhance patients’ vision for those suffering from AMD. Treatments began to crop up that could stabilize visual acuity. Available treatments were limited to wet AMD. The Wet form makes up a small minority of the total cases of AMD. 

“The American Macular Degeneration Foundation estimates that around 10-15% of people with AMD have the wet subtype.

The first treatment for wet macular degeneration was laser photocoagulation

The Macular Photocoagulation Study Group demonstrated that laser treatment of extrafoveal choroidal neovascular membranes lesions was beneficial in preventing or delaying large losses of visual acuity for at least 5 years.

Other treatments were developed, which included surgical removal of the choroidal neovascular membrane and photodynamic therapies. The latter involved the intravenous infusion of a photosensitive drug. 

The second step involved activating the drug by nonthermal light at a specific wavelength5,6   This damage may lead to platelet activation and subsequent thrombosis and occlusion of choroidal neovasculature within the treated area.

Vascular endothelial cell growth factor was targeted with a revolutionary new approach. 

Anti-VEGF biologics such as Avastin, Eylea and Lucentis allow for functional improvement and normalization of macular morphology with reductions in intra- and subretinal fluid, hyperreflective material and pigment epithelial detachments.

These agents are still in wide use today. However, these injections often involve multiple sessions spread out over months.  Patients may need help with follow-up.  Other patients may fail to respond appropriately to anti-VEGF therapies. New implantable anti-VEGF release systems have been recently developed.  However, this is a more invasive procedure and may stimulate inflammation.  

Vabysmo, recently approved, has a dual mechanism of action simultaneously targeting VEGF and angiopoietin-2. Blockade of these two main drivers of angiogenesis might be more effective in preventing expansion of the neovascular complexes and thus recurrence.

 The main limitation of all the above therapies is that they only address wet macular degeneration. The majority of patients with macular degeneration have the dry type.

National Institutes of Health funded AREDS to study macular degeneration.

The original AREDS study was launched in 1996. This study showed that a dietary supplement formulation: 

  • 500 mg of vitamin C
  • 400 international units of vitamin E
  • 2 mg copper, 80 mg zinc
  • 15 mg beta-carotene) 

could significantly slow the progression of AMD from moderate to late disease.

Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for the development of NV AMD but not for central geographic atrophy.9 These results are consistent with the original recommendations that persons with intermediate or advanced AMD in one eye should consider taking the AREDS formulation.

However,  people who smoked and took the beta-carotene containing AREDS formulation had a significantly higher risk of lung cancer than expected.

Another study, AREDS2, began in 2006. Chew and colleagues compared the beta-carotene formulation to one with 10 mg lutein and 2 mg zeaxanthin instead.11  At the end of the five-year study period, the researchers concluded that lutein and zeaxanthin did not increase the risk for lung cancer.

 One of the conclusions from the AREDS 2 study is that the lutein/zeaxanthin combination was an appropriate and effective substitute for the original formula. Formulations based on the AREDS studies are readily available over the counter.

Treatment of geographic atrophy-associated dry macular degeneration

The FDA recently approved (February 2023) intravitreal injection pegcetacoplan for treating geographic atrophy-associated dry macular degeneration.12  The regulatory approval is based on positive data from the Phase III OAKS and DERBY trials conducted across a broad and representative population of GA patients.

 Syfovre (brand name for pegcetacoplan) is a C3 and C3 inhibitor. This complement inhibitor decreases inflammation, phagocytosis, and cell membrane disruption. The eventual benefit would be to reduce retinal cell death and associated geographic atrophy.  

Reduction of geographic atrophy was shown in the OAKS and DERBY studies. It also showed increasing effects of treatment over time, with up to 36% lesion growth reduction occurring between months 18 and 24. However, wet AMD is a potential adverse effect of pegctacolan use.

Iveric Bio company also has an injectable product (avacincaptad pegol)  for geographic atrophy. This is a C5 complement inhibitor that met its primary endpoints in the GATHER2 study. This product is up for possible FDA approval in August 2023.

Up until recently, viable treatments have been limited to the less common wet form of AMD. Now that there are current and developing therapies for both types, it is essential for eye care practitioners to get up to date with these new and existing therapies. There is renewed hope for the millions of people suffering from AMD and we have an important role to discuss these new developments with our patients.

Written by: Dr David Jupiter, Optometrist


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