All things considered, is geographic atrophy treatment ready for widespread use?
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Yes, but risks and benefits need to be thoroughly discussed
I do think that complement therapy can be considered for many patients with geographic atrophy, but the risks and benefits need to be thoroughly discussed with the patient.
For many years, we have seen our patients with geographic atrophy (GA) progressively lose vision and visual function, and we have not been able to offer them any effective treatments. With the FDA approval of pegcetacoplan and avacincaptad pegol earlier this year, we finally have treatments that we can offer to patients to slow progressive GA growth.
However, patients need to have appropriate expectations before starting treatment. Patients often hope for visual improvement or perpetual preservation of central vision, looking for signs of improvement on follow-up visits. I have found that the patients who are most interested in proceeding with treatment are those who have demonstrated GA growth over the last few years and have noticed increasing visual scotomas in their daily lives. Problems with reading, driving, dark adaptation and increasing distortion are common symptoms. A lot of these patients have lost vision in the other eye due to central GA or neovascular age-related macular degeneration, although some of my monocular patients are also more cautious about treating their better eye.
Although we as retina specialists are concerned about the safety profile of these new therapies, and rightly so, the main reservations my patients have raised about treatment have centered around the increased risk for choroidal neovascularization in treated eyes and the increased visit burden associated with GA therapy.
I am happy that we have new treatment options to offer our patients, and I have been informing all my patients with GA about these therapies. Many of them are eager to proceed with treatment, but thorough education and counseling are always necessary to make sure that the patient is truly informed and ensure proper expectations.
Margaret A. Chang, MD, MS, is a retina specialist at Retina Consultants Medical Group, Sacramento, California.
Not yet, and more real-world data are required
“We are going to treat you with frequent injections to make you less worse in a year or 2 years.”
If this sounds familiar, it should because it was essentially our argument from the Macular Photocoagulation Study era for treatment of exudative macular degeneration. In the advancement of our field, not all treatments or surgeries are meant to be the widespread panacea for the blinding conditions of our time. The iterative breakthroughs that help evolve our fields are often the bricks upon which the road to a true revolution is built. While it is exciting to have validated clinical trial designs and metrics for geographic atrophy and pharmacologic interventions for this unmet need, especially despite early trial setbacks, the magnitude of clinical benefit vs. the amount of treatment burden is a moment of pause for widespread use.
Despite the slowing of vision loss observed in the clinical trials, the increased rate of conversion to exudative macular degeneration in a portion of those treated is another reminder that there are consequences to targeting the complement cascade that are not fully understood. Furthermore, when one considers the recent safety signal with pegcetacoplan with occlusive retinal vasculitis, we need to study this issue further to see if this is specific to pegcetacoplan vs. a potential consequence of targeting the broader complement pathway.
Clinical trials help establish efficacy of an intervention in a highly selected population that does not reflect the complexity of the real world. When it comes time to extend those results, particularly with new pharmacologic agents or targeting of novel pathways, caution is prudent. One needs only look to our recent past with brolucizumab to see an example in which the clinical trial did not fully encapsulate the adverse events, particularly with intraocular inflammation, when it came time for broader use in the real world. So, while we all have motivated monocular patients whose contralateral eyes may have lost the battle to geographic atrophy, upon whom it is reasonable to embrace the new science of complement inhibition, I think more real-world data are required before we are ready for widespread use of pegcetacoplan or avacincaptad pegol.
Rajiv E. Shah, MD, is an assistant professor of ophthalmology at Wake Forest University School of Medicine, Winston-Salem, North Carolina.
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