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Original Investigation
June 20, 2019

Characterization of Retinopathy Among Patients With Yellow Fever During 2 Outbreaks in Southeastern Brazil

Author Affiliations
  • 1Hospital São Geraldo e Centro de Telessaúde/Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
  • 2Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
  • 3Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Brazil
  • 4Departamento de Oftalmologia e Otorrinolaringologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
JAMA Ophthalmol. 2019;137(9):996-1002. doi:10.1001/jamaophthalmol.2019.1956
Key Points

Question  Is retinopathy observed in patients with yellow fever?

Findings  In this cross-sectional study of 64 patients who had received a confirmed diagnosis of yellow fever during 2 recent outbreaks in Southeastern Brazil, 13 patients (20%) had retinopathy, with the most common retinal findings being retinal nerve fiber layer infarct, superficial hemorrhage, and grayish outer retinal lesions. Elevated serum aspartate aminotransferase, total bilirubin, arterial lactate, and serum creatinine levels as well as disease severity and low platelet counts were associated with retinopathy in these patients.

Meaning  Retinopathy can be observed among patients with yellow fever but may be overlooked, especially if more severe disease precludes careful ophthalmoscopic examinations.


Importance  Yellow fever still threatens people in endemic areas, and besides conjunctival icterus, little is known about the ocular changes that occur in these patients.

Objective  To characterize retinal changes in patients with confirmed yellow fever during 2 recent outbreaks of the disease in Minas Gerais, Southeastern Brazil.

Design, Setting, and Participants  This cross-sectional, observational study conducted at a single referral center for infectious diseases in Southeastern Brazil collected data between January 2017 and February 2018 from 94 consecutive patients with suspicion of yellow fever who were eligible for the study.

Main Outcomes and Measures  Patients underwent ophthalmic examination. Clinical findings, laboratory results, and occurrence of retinopathy and death during hospitalization were reported, including age, sex, comorbidities, disease severity, serum aspartate aminotransferase level, total bilirubin level, serum creatinine level, arterial lactate level, international normalized ratio, and platelet count at hospital admission.

Results  In total, 64 patients were included who had received a confirmed diagnosis of yellow fever, with a median (interquartile range) age of 47 (38-56) years, and 12 patients (19%) were women. Twenty eyes (16%) of 13 patients (20%) had retinopathy at the same time as yellow fever. The most common fundus changes among the 20 eyes were retinal nerve fiber layer infarcts (11 [55%]), superficial hemorrhages (7 [35%]) and grayish deep lesions (6 [30%]), possibly at the level of the outer retina or choroid. Aspartate aminotransferase levels higher than 3000 U/L (odds ratio [OR], 14.2; 95% CI, 3.5-77.8; P < .001), total bilirubin levels higher than 2.3 mg/dL (OR, 20.0; 95% CI, 4.4-159.7; P < .001), serum creatinine levels higher than 2.0 mg/dL (OR, 8.2; 95% CI, 2.1-36.0; P = .003), arterial lactate levels higher than 17.1/mg/dL (OR, 4.6; 95% CI, 1.1-19.0; P = .03), platelet count lower than 94 × 103/μL (OR, 7.8; 95% CI, 1.8-59.9; P = .004), and classification of disease as severe (OR, 11.7; 95% CI, 2.0-301.0; P = .003) were associated with retinopathy. Arterial hypertension, diabetes, international normalized ratio, and death were not associated with retinopathy.

Conclusions and Relevance  Retinopathy was present in 20% of patients with yellow fever and appeared to be associated with more severe systemic disease. Retinal nerve fiber layer infarcts and superficial hemorrhages, but not the grayish deep lesions, resembled those associated with other flavivirus (eg, dengue virus) infections. The clinical relevance of these findings may warrant further investigation.