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Sleep apnea and anti-VEGF treatment in AMD patients – a potential under-diagnosis of apnea may account for anti-VEGF non-responders

Collaborative clinical research conducted by teams from the University of Louisville, Kentucky and the Rambam Medical Centre, Haifa Israel, have proposed that treatment of exudative AMD patients with bevacizumab with a co-morbidity of untreated sleep apnoea may result in considerably less effective treatment. In comparison, AMD patients with sleep apnea, and who undergo continuous positive airway pressure (CPAP) therapy for their apnea, had improved anatomical and functional vision improvements when treated with bevacizumab. In addition, such patients required less injections than matched patients without CPAP treatment. Clinical management of such patients may improve the proportion of anti-VEGF responders if the observed effect is reproducible in larger numbers of individuals with a dual diagnosis of AMD and sleep apnea.


As many clinicians and academic papers have reported, not all AMD patients have the same response to anti-VEGF medication – as with many pharmacological treatments, some patients improve while others remain resistant. A number of studies estimate that up to 45% of patients may not receive a clinically meaningful benefit from anti-VEGF treatment, despite the considerable absolute numbers who show clear benefit. While many potential causes of non-response may exist, no previous epidemiologic studies have described a causal link between apnea and AMD however, in a previous study by the same research group an observation was noted that patients with exudative AMD who are non-responders to anti-VEGF therapy appeared to have a higher risk of sleep apnea when compared to patients who do respond to anti-VEGF therapy. To establish more definitive data on the question a small clinical study was designed to compare functional and anatomical responses to intravitreal bevacizumab in AMD patients with obstructive sleep apnea, with and without treatment with CPAP therapy.


Two groups consisting of 18 untreated and 20 treated apnea patients, all with exudative AMD, received intravitreal bevacizumab treatment for their AMD. Patients treated for their apnea required 8 ± 7 total injections during the study period while untreated apnea patients required 16 ± 4 injections (P< 0.05). In addition, the apnea treated group was reported to show statistically significant better visual acuity (LOGMAR, 0.3 ± 0.24, 20/40), when compared to the untreated group (LOGMAR, 0.7 ± 0.41; P<0.05). Finally, central retinal thickness appeared to improve in the treated apnea patients compared to the untreated apnea patients (358 ±95 um to 254 ± 45 um and 350 ± 75 um to 322 ± 105 um, respectively (P<0.05, 20/100)). While the study was conducted as a relatively small non-randomized comparative case series, the results suggest that a larger study is warranted to assess the potential benefits if the effects can be observed across a broader population. The authors of the study believe that sleep apnea may be considerably under-diagnosed in the older population and, as such, the disorder should be “specifically looked for in nonretinal angiomatous proliferation and nonpolypoidal exudative AMD patients who do not respond to repetitive anti-VEGF therapy.” The researchers conclude their study with the observation that, “[W]ith approximately 15% of the US population affected, timely recognition and identification of this underlying systemic condition in exudative AMD patients may enable preservation of sight and decrease injection burden.”