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The eyes are a window to the brain. Researchers performed a nationwide cohort study of the risk of retinal disease in patients with bipolar disorder.
“Mr Jerry” is a 52-year-old Caucasian male with a 25-year history of bipolar I disorder, whose most recent episode involved depression with psychotic features. Eighteen months ago, he had surgery to repair a detached retina (non-traumatic) after noticing an acute worsening of vision in his right eye over a 1-week period. Six months later, he was in a motor vehicle accident that resulted in a traumatic macular hole in the same eye that required surgical repair. He also has persistent corneal edema of his right eye. He is not a candidate for further surgery, given overall poor visual potential. His visual impairments are a contributing factor to his depression. As he is outpatient psychiatric, how would you address his concerns?
The brain and the retina develop from the same neuroectodermal tissue.1 As a result, retinal pathology may parallel changes in the brain.2 A recent study of patients with bipolar disorder found abnormalities in retinal arterioles and venules.3 One case-control study investigated ocular disease in bipolar disorder, finding an association with glaucoma, but not retinal disease.4 However, the incidence of retinal disease in bipolar disorder has not been investigated in a longitudinal cohort study.
The Current Study
Fang and colleagues5 investigated the association between retinal disease and bipolar disorder in a nationwide cohort study. They utilized the Taiwan National (Longitudinal) Health Insurance Database. The authors included patients aged 12 years and older with ICD-9 bipolar disorder confirmed by board-certified psychiatrists at least twice between 2001 and 2009. Cohort members had no history of retinal diseases before enrollment. Patients with bipolar disorder were matched 1:4 with controls (who had no history of ICD-9 mood or psychotic disorders) based on age, sex, residence, income, and comorbidities (medical and ophthalmological).
The primary outcomes were 5 non-degenerative retinal diseases: retinal detachment, primary retinopathy, diabetic retinopathy, hypertensive retinopathy, and retinal vascular complications. The risk of retinal disease was estimated using conditional Cox regression analyses, adjusting for the aforementioned covariates, as well as psychotropic medications.
The cohort consisted of 73,271 patients with bipolar disorder and 293,084 controls. The mean subject age was 38, 44% were male, and the mean follow-up duration was 6.7 years. Patients with bipolar disorder had a significantly higher incidence rate of any retinal disease versus controls (1.3% versus 0.5%), as well as each of the 5 individual retinal diseases. The mean age at diagnosis of any retinal disease was almost 3 years earlier in patients with bipolar disorder.
After controlling for covariates, patients with bipolar disorder were 2.4 times more likely to develop retinal disease than controls (HR=2.43, 95% CI 2.14-2.75). The HRs for individual retinal diseases ranged from 2.26 to 3.46. The magnitude of cumulative exposure to psychotropic medications was not associated with the development of any retinal disease in patients with bipolar disorder.
The authors concluded that patients with bipolar disorder had a higher risk of retinal detachment, retinopathy, and retinal vascular complications, after controlling for covariates. Patients with bipolar disorder were diagnosed with retinal disease at a younger age than the well-matched controls. Psychotropic medications used in the treatment of bipolar disorder were not associated with the incidence of retinal disease.
The primary study strength was the use of a population-based cohort with linkage to national data registers. The selection of hospitalized patients provides a reasonable indicator of illness severity. Study limitations included the exclusion of diabetic and hypertensive retinopathy as well as degenerative retinal diseases, which could lead to underestimation of the risk of retinal disease; that data on medications cannot account for potential nonadherence; and that many retinal problems can be mostly symptomatic until advanced stages.
The Bottom Line
This study demonstrates that patients with bipolar disorder have an increased incidence of non-degenerative retinal disease, independent of psychotropic medications. Psychiatrists should be aware of ocular disease risks in this patient population.
Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
1. London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013;9(1):44-53.
2. Silverstein SM, Rosen R. Schizophrenia and the eye. Schizophr Res Cogn. 2015;2(2):46-55.
3. Appaji A, Nagendra B, Chako DM, et al. Retinal vascular abnormalities in schizophrenia and bipolar disorder: a window to the brain. Bipolar Disord. 2019;21(7):634-641.
4. Liu CH, Kang EY, Lin YH, et al. Association of ocular diseases with schizophrenia, bipolar disorder, and major depressive disorder: a retrospective case-control, population-based study. BMC Psychiatry. 2020;20(1):486.
5. Hsu TW, Bai YM, Tsai SJ, et al. Risk of retinal disease in patients with bipolar disorder: a nationwide cohort study. Psychiatry Clin Neurosci. 2022;76(4):106-113.