Patients with Dry Age-Related Macular Degeneration are at Higher Risk for Sleep Apnea

Research Article

Austin J Clin Ophthalmol. 2018; 5(3): 1098.

Patients with Dry Age-Related Macular Degeneration are at Higher Risk for Sleep Apnea

Hackett NJ, Lauren NM, Garg PG, Gill MK, Lyon AT and Mirza RG*

Northwestern University Department of Ophthalmology and Feinberg School of Medicine, USA

*Corresponding author: Rukhsana G. Mirza, Northwestern University Department of Ophthalmology and Feinberg School of Medicine, 645 N Michigan Avenue, Suite 440, Chicago, IL 60611

Received: October 22, 2018; Accepted: December 03, 2018; Published: December 10, 2018


Objective: To explore the association between disordered sleep and agerelated macular degeneration (AMD).

Design: A prospective nonrandomized observational study.

Subjects: Patients from 3 retina specialists at a tertiary academic hospital.

Methods: One hundred patient volunteers with AMD were recruited, 50 nonexudative and 50 exudative. Nonexudative AMD patients were further divided into subgroups based on the presence or absence of geographic atrophy. Exudative AMD patients were further divided into treatment responsive versus resistant based on resolution of intraretinal and subretinal fluid at 3 months. Demographic information was obtained from the electronic medical record. Patients completed 3 surveys on disordered sleep that screened for symptoms of insomnia, general sleep quality, and sleep apnea to assess the relationship between type of AMD and scores on metrics of sleep quality and disordered sleep.

Main Outcome Measures: Symptoms of sleep apnea, symptoms of insomnia, symptoms of general sleep disturbance.

Results: Patients with dry AMD displayed significantly more symptoms of sleep apnea compared to wet AMD (36% vs 16%, p=0.023). Dry AMD patients without geographic atrophy displayed more symptoms of sleep apnea compared to those with geographic atrophy (41.9% vs 0%, p=0.016). Rates of sleep apnea across all AMD subtypes in the study group were higher than estimated population norms. Patients did not differ significantly on assessments of insomnia or general sleep quality.

Conclusions: AMD and sleep apnea appear to be associated, most strongly between patients with dry AMD. There is perhaps a further delineation among those with and without geographic atrophy, with the association favoring the latter.

Keywords: Age-related macular degeneration; Macular degeneration; AMD; Sleep apnea; Sleep quality; Ophthalmology; Retina; Low-vision


Age-related Macular Degeneration (AMD) is a chronic, progressive eye disorder that affects the elderly. It is the leading cause of blindness in industrialized nations and the third most common cause of blindness worldwide [1]. Advanced AMD is divided into two subcategories: “dry” (nonexudative) and “wet” (exudative). The dry type is more common, accounting for 85-90% of cases, while the wet type is responsible for greater than 80% of severe visual loss or blindness in patients with AMD [2]. In addition, AMD is known to be associated with decreased quality of life, with patients reporting increased rates of depression and decreased ability to perform activities of daily living such as reading and driving [3]. Furthermore, a recent article reported an association between decreased duration of sleep and exudative AMD as well as higher sleep medication use in these subjects [4].

Sleep dysfunction has been the subject of significant study in recent years. Poor sleep quality has been associated with increases in several organic deleterious health outcomes such as hypertension, diabetes, obesity, heart attack, and stroke [5]. Visual pathology is not exempt from this relationship. One study found higher rates of sleep disturbance in the visually impaired elderly as defined by frequent awakenings, difficulty falling back asleep, and subjective poor sleep quality [6]. Among blind patients, those with no light perception suffered from worse sleep disturbance [7]. Blindness is associated with disruption of circadian rhythms, presumably by interruption of visual signals required for sleep cycle regulation in the suprachiasmatic nucleus [8]. It has also been shown that obstructive sleep apnea (OSA), a sleep disorder characterized by periods of nighttime respiratory disturbances and hypoxia, may hinder the response to anti-VEGF therapy in patients with exudative AMD; this occurs presumably by interrupting the microcirculation of the retina and optic nerve [9]. The reader should note that two directions of the relationship between sleep and vision are mentioned here. On the one hand, visual impairment seems to have an effect on sleep quality. In most studies sleep quality is a subjective measure, determined by how well a person sleeps through the night and how tired they feel the next day. On the other hand, we find a specific disorder of sleep, OSA, mediating visual damage via repeated hypoxia. With respect to the latter relationship, the literature is unclear on whether sleep quality is associated with severity of disease in AMD. One study of sleep quality found no association with severity, visual acuity, or disease staging of AMD and sleep disturbance [10], while another suggested a link between obstructive sleep apnea and exudative AMD [11]. To our knowledge, there has not been a study that characterizes the overall sleep quality in patients with AMD compared with the general population nor one that compares wet and dry macular degeneration. Given known data that patients with impaired vision suffer from sleep disorders [6,7], we hypothesized that patients with AMD would differ from the general population when assessed with assays for overall sleep quality, insomnia, and obstructive sleep apnea as endpoints. Furthermore, we also hypothesized that we may observe a variance in sleep quality between subjects with the two different subtypes of AMD, wet and dry. As a secondary outcome, we analyzed any differences among patients with and without geographic atrophy in the dry AMD group and good responders to treatment versus incomplete responders in the wet AMD group.


Data collection

This prospective nonrandomized observational study was approved and monitored by the Institutional Review Board of Northwestern University, Feinberg School of Medicine. A total of 100 patients were included, 50 with nonexudative macular degeneration and 50 with exudative macular degeneration. These patients were further divided into subgroups based on the presence or absence of geographic atrophy for dry AMD. The wet AMD group was divided into good responders to anti-VEGF (resolution of intraretinal and subretinal fluid at 3 months) versus incomplete responders. Incomplete responders were defined as having persistent fluid of any type on optical coherence tomography (OCT) after 3 injections of an anti-VEGF agent.

All patients were from the Northwestern Ophthalmology Department. Patient inclusion criteria were the diagnosis of AMD and age 55-100; patients with a diagnosis of other retinal disease or findings were excluded from the study. The best-corrected visual acuity of each patient was recorded in both eyes at the time of their study visit. Patients were given a survey that included demographic information (age, gender, previous diagnosis of depression or sleep apnea, working status, smoking status and previous cataract surgery) as well as 3 assessments of sleep quality. These were the Patient- Reported Outcomes Measurement Information System (PROMISTM) Short Form Sleep Disturbance questionnaire, the Insomnia Severity Index (ISI), and the Berlin Questionnaire for obstructive sleep apnea (OSA). Each have been validated for their use as measures of sleep disturbance [12,13], insomnia [14], and risk of sleep apnea [15], respectively. The PROMIS questionnaire is an 8-item Likert-scale form derived from surveys of the general population (mean age 52) and study data (mean age 44) [13] that assesses the “[p]erceptions of sleep quality, sleep depth, and restoration associated with sleep [16].” Scores are converted to T-scores with a mean of 50 and standard deviation (SD) of 10, where higher scores represent more severe sleep impairment. The ISI is a 5-item Likert-scale form with scores ranging from 0-28, with scores greater than 8 representing subhthreshold or greater degrees of insomnia [14]. Lastly, the Berlin sleep questionnaire is a 10-item questionnaire that identifies patients as having a high or low risk of OSA based on assessments of sleep behaviors (e.g. snoring) as well as the presence of hypertension and obesity [15]. Three assessments were used in order to distinguish general sleep disturbances from sleep apnea.

Statistical analysis

All analyses were performed using SPSS version 21 (IBM Corporation, Copyright 2012). Age and visual acuity of the better and worse eye were compared between wet and dry, as well as the 4 subcategories (dry without geographic atrophy, dry with geographic atrophy, wet treatment responsive, and wet treatment resistant) using two-sided t-tests for equality of means. Gender, working status, presence and treatment status of depression, presence and treatment status of obstructive sleep apnea (OSA), smoking status, and prior cataract surgery were compared across these categories using chisquared tests and Fisher’s exact test where appropriate.


100 patients were enrolled in the study. 50 had the diagnosis of exudative AMD, and 50 had nonexudative AMD. Patients were further divided into subgroups of 1) dry AMD with no geographic atrophy (n=43), 2) dry AMD with geographic atrophy (n=7), 3) wet AMD treatment responsive (n=36) and 4) wet AMD treatment resistant (n=14). Table 1 shows the demographic information of the population. Among the dry AMD group, non-geographic atrophy patients were significantly younger than geographic atrophy. Among the wet AMD group, the mean ages were equivalent. Geographic atrophy patients had significantly worse best corrected visual acuity on average than all other subgroups (mean logMAR 0.491). Gender, tobacco use, depression, working status, previous OSA diagnosis, and cataract surgery did not differ significantly between subgroups. Not shown in the tables were treatment status of OSA patients. Of the eight patients with wet AMD and OSA, 1 used CPAP treatment.