AMD: Untreated Sleep Apnea May Reduce Response to Bevacizumab

Veronica Hackethal, MD

April 14, 2016

People with untreated obstructive sleep apnea (OSA) and exudative age-related macular degeneration (AMD) may have decreased response to bevacizumab therapy, according to a study published in the April issue of Retina.

"The results of this interventional comparative case series suggest that untreated OSA may underlie nonresponsiveness to [vascular endothelial growth factor inhibitor (anti-VEGF)] treatment in a subset of patients with exudative AMD," write Shlomit Schaal, MD, PhD, from the University of Louisville, Kentucky, and colleagues.

"Compliance with [continuous positive airway pressure (CPAP)] therapy promoted a positive response to anti-VEGF treatment, a decrease in the macular volume and in the amount of subretinal fluid, and resulted in a significantly decreased need for frequent anti-VEGF injections," the authors add.

Bevacizumab and other VEGF inhibitors can slow the progression and improve visual outcomes in patients with AMD, Unfortunately, patients exhibit a broad range of responses to anti-VEGF therapy. Some show rapid improvement, but others fail to respond. Even after trying alternative approaches, such as higher dosage, more frequent injections, another type of drug, combination therapies with steroids, or photodynamic therapy, many nonresponders still do not improve.

OSA affects about 15% of the US population, yet remains underdiagnosed. As a systemic disease, OSA increases the risk for hypertension, coronary heart disease, stroke, congestive heart failure, and death. Past work by the same group has shown that anti-VEGF nonresponders with exudative AMD have significantly higher risk for OSA compared with responders.

In the current study, Dr Schaal and colleagues enrolled included patients with OSA who received treatment for nonretinal angiomatous proliferation, nonpolypoidal choroidal vasculopathy, or exudative AMD at the Retina Clinic of the University of Louisville. Researchers separated participants into two groups: untreated (n = 18) and regular CPAP users (n = 20).

Participants were bevacizumab-naive at baseline and received three intravitreal injections of bevacizumab (1.25 mg/0.05 mL) and a full clinical exam every 6 weeks. After the initial three injections, they were treated on a pro re nata regimen. They also received fluorescein angiography at baseline and ocular imaging, using optical coherence tomography at baseline and each follow-up visit. OSA was diagnosed using nocturnal diagnostic polysomnography in a hospital setting.

After an average follow-up of about 120 weeks, results showed significantly better visual acuity in the CPAP group compared with the untreated group (logarithm of the minimum angle of resolution, 0.3 ± 0.24 [20/40] vs logarithm of the minimum angle of resolution, 0.7 ± 0.41; P < .05).

The CPAP group also showed improved central retinal thickness compared with untreated patients (358 ± 95 μm to 254 ± 45 μm and 350 ± 75 μm to 322 ± 105 μm, respectively; P < .05 [20/100]).

In addition, CPAP users needed half the number of total injections of untreated patients (8 ± 7 total injections vs 16 ± 4 injections; P < .05).

Although both groups experienced improved visual acuity, the untreated group continued to show a constant pattern of high subretinal fluid. In contrast, CPAP users reached anatomical stability by 40 weeks. Starting from week 48, they also showed significantly better visual acuity compared with the untreated group.

The results suggest that patients with exudative AMD who do not respond to anti-VEGF therapy should be assessed for undiagnosed OSA, the authors note.

"It is quite possible that early screening for OSA and early intervention in nonresponders may yield better functional outcomes, and it [may] also have a major effect on the general health and well-being of patients," they write.

"Our findings reinforce the fact that treatment of eye diseases should be an integral part of a patient's general medical care," they conclude.

Larger, prospective trials are needed to confirm the results in more diverse populations.

The study was supported in part by a grant from Research to Prevent Blindness, Inc. The authors have disclosed no relevant financial relationships.

Retina. 2016;36:791-797. Abstract


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