CPAP Turns in Mixed Results for Patients With Diabetic Eye Disease

Long-term use of continuous positive airway pressure (CPAP) slowed the progression of eye disease in sleep apnea patients with non-proliferative diabetic retinopathy, a small randomized study showed, but patients who adhered to the intervention ended up with more retinal microhemorrhages.

In the single-center trial, the group assigned to a year of CPAP atop usual care had a significant reduction in the number of eyes with hard exudates (49.1% at baseline to 29.8% at 52 weeks), while the usual-care alone group experienced no change (41.5% to 43.9%) — a 27.1% between-group difference (P=0.035).

Yet in a per-protocol analysis, adequate adherence to CPAP (at least 4 hours per night) was associated with a “surprising” increase in the number of retinal microhemorrhages (adjusted difference of 6.0, 95% CI 0.6-11.5, P=0.029), reported Francisco García-Rio, MD, PhD, of the Hospital Universitario La Paz in Madrid, and colleagues.

That rise in retinal microhemorrhages was “directly related to the level of pressure used, which reinforces the need for an optimal pressure setting and closer clinical monitoring,” the researchers wrote in Annals of the American Thoracic Society.

While not definitive by any means, García-Rio’s team suggested that the increase could in part be due to an increase in intraocular pressure (IOP) driven by CPAP, a previously reported association.

“It is possible to speculate whether repeated IOP elevations during CPAP use might trigger greater mechanical irritation on the small retinal vessels, favoring wall deformations or the generation of microhemorrhages,” they wrote.

An estimated 9.6 million Americans are living with diabetic retinopathy, according to a recent study, and nearly 1.8 million have vision-threatening diabetic retinopathy. And while OSA is more common in patients with diabetic retinopathy, the potential benefit of apnea suppression on retinal disease progression has been unclear.

It might be prudent to ask patients with diabetic retinopathy about signs and symptoms of sleep apnea, said Garvin Davis, MD, of Houston Methodist Hospital, who was not involved in the study. He noted that CPAP has been shown to improve hypertension and glycemic control, both of which can independently improve retinopathy.

“Perhaps in addition to controlling their hypertension and blood glucose, we might recommend referral to sleep specialists to help manage their sleep apnea with CPAP machines,” he told MedPage Today. “It seems reasonable that improving a systemic problem such as sleep apnea that causes oxidative stress would also improve retinopathy.”

From 2016 to 2020, the open-label RetinAS trial randomized 83 patients with sleep apnea and mild-to-moderate non-proliferative diabetic retinopathy at a single center in Spain. The trial’s primary endpoint was change from baseline in the percentage of eyes with retinal exudates and in the number of retinal microhemorrhages at 52 weeks.

Baseline characteristics were similar: participants had an average age of about 65 years, approximately one-third were women, and their mean apnea-hypopnea index was 33 events per hour. Nearly 70% had hypertension and they had diabetes for an average 15-17 years, with an HbA1c of about 8%. A total of 79 and 67 eyes were available for analysis in the CPAP and control group, respectively.

At baseline, patients in the CPAP group had a median 12 retinal microhemorrhages while those in the usual-care alone group had a median of 9 microhemorrhages.

In contrast with the findings on hard exudates, no significant reduction was seen with CPAP when it came to the percentage of eyes with soft exudates (14.0% at baseline to 5.3% at 52 weeks). In the control group, no difference was seen for soft exudates either (19.5% to 17.1%, respectively).

In terms of other secondary outcomes, CPAP was associated with improvements in sleepiness, sleep-related quality of life, and glycemic control, as well as decrease in retinal thickness, though this did not lead to improvements in visual acuity or IOP.

No significant difference in serious adverse event rates were seen between the CPAP and control groups (9.3% vs 17.5%); four deaths occurred during the study, with three in the control arm.

Limitations included a higher than estimated drop-out rate and that a single ophthalmologist evaluated patients for microhemorrhages and retinal exudates.

Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow

Disclosures

This study was supported by funding from the Spanish Society of Pneumology and Thoracic Surgery.

No disclosures were reported. Davis reported no disclosures.

Primary Source

Annals of the American Thoracic Society

Source Reference: García-Sánchez A, et al “CPAP effect on progression of retinal disease in patients with sleep apnea and non-proliferative diabetic retinopathy: a randomized clinical trial” Ann Am Thorac Soc 2023; DOI: 10.1513/AnnalsATS.202304-296OC.

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