Roth spots are retinal hemorrhages with a white or pale yellow center. They were first described in 1872 by Swiss pathologist Moritz Roth as a fundus finding in patients with infective endocarditis.
The incidence in infective endocarditis is only about 2% 1). However, they appear more frequently in hematologic diseases, occurring in about 90% of leukemia cases. They are a nonspecific fundus finding associated with various systemic diseases, and when present, investigation for the underlying cause is required.
The appearance of Roth spots has been reported in the following diseases4).
Roth spots are a non-specific finding associated with many systemic diseases. Infective endocarditis and hematologic diseases (such as leukemia, anemia, Evans syndrome) are common causes, and a systemic workup is necessary. For details, see the “Causes and Risk Factors” section.
Roth spots are usually asymptomatic. When the lesion is located away from the macula, patients rarely report subjective symptoms.
On fundus examination, they are observed as flame-shaped hemorrhages with a white center. The following findings are obtained with various ancillary tests.
The histological composition of the white center varies depending on the underlying disease. In infective endocarditis, it is mainly a fibrin thrombus surrounding a bacterial embolus; in hematologic diseases, it is primarily an accumulation of white blood cells (including leukemic cells). For details, see the “Pathophysiology” section.
The main diseases causing Roth spots are listed below.
Infectious Diseases
Infective endocarditis: A classic cause. The incidence is low, about 2%1). Septic emboli occlude retinal vessels in the setting of fever and bacteremia.
Other infections: Also reported in HIV infection, cytomegalovirus retinitis, and sepsis.
Blood Disorders
Leukemia: Most frequent, appearing in about 90% of cases. Vascular infiltration of leukemia cells and thrombocytopenia are involved.
Anemia: Occurs in iron deficiency anemia and pernicious anemia. It tends to develop when hemoglobin is below 6 g/dL4). When anemia and thrombocytopenia coexist, the incidence rises to 44%5).
Sickle cell disease (SCD): Vascular occlusion and chronic anemia are involved2).
Evans syndrome: A combination of autoimmune hemolytic anemia and immune thrombocytopenia. Ocular symptoms may be the initial manifestation in some cases5).
Other
Hypertensive and diabetic retinopathy: Involves vascular wall fragility and bleeding tendency.
Trauma/Terson syndrome: Roth spot-like findings have been reported as retinal hemorrhage associated with increased intracranial pressure3).
Collagen diseases: Diseases with vasculitis such as SLE.
Roth spots are a fundus finding, and identifying the underlying disease is more important than diagnosing the spots themselves. The following tests are combined to investigate the cause.
The table below shows the main recommended tests.
| Clinical Suspicion | Test | Purpose |
|---|---|---|
| Infective endocarditis | Blood culture, echocardiography | Confirmation of bacteremia and vegetations |
| General hematologic diseases | CBC, peripheral blood smear | Assessment of anemia, platelets, and blasts |
| Iron deficiency anemia | Serum iron, ferritin, TIBC | Evaluation of iron dynamics4) |
| Evans syndrome | Direct Coombs test (DAT) | Confirmation of autoantibodies5) |
Direct intervention for Roth spots themselves is usually unnecessary. Treatment of the underlying disease is the highest priority.
In cases where the lesion extends to the macula and causes vision loss, the following interventions may be considered 2).
If the underlying disease is treated effectively, Roth spots are often naturally absorbed within weeks to months. However, if the macula is involved, visual recovery may be incomplete.
The formation of Roth spots is explained by the following common pathophysiological chain.
Lesions form through a common pathway of capillary rupture → hemorrhage → fibrin thrombus formation2)5).
Anemia/hypoxia pathway: A marked decrease in Hb concentration (especially below 6 g/dL) causes chronic retinal hypoxia, leading to ischemic capillary damage and a tendency for bleeding 4). The incidence is significantly higher when thrombocytopenia is combined with anemia (44%) than with anemia alone 5).
The following table shows a comparison of representative cases.
| Disease | White-centered component | Hb/Platelets | Incidence |
|---|---|---|---|
| Endocarditis | Bacterial vegetation + fibrin | Variable | Approximately 2%1) |
| Leukemia | Leukemic cells | Decreased | Approximately 90% |
| Iron deficiency anemia | Fibrin | Hb<6 g/dL4) | Unknown |
| Evans syndrome | Fibrin + platelets | Both decreased5) | High frequency |
Alsalem et al. (2025) reported a case of unilateral Roth spots in a 35-year-old woman4). Chronic blood loss due to uterine leiomyoma led to iron deficiency anemia (Hb 5.7 g/dL) and thrombocytosis, with retinal hemorrhages and white centers appearing. After iron supplementation with ferric carboxymaltose and Mirena insertion, anemia improved and Roth spots resolved. This is a rare report showing that gynecological diseases can cause Roth spots.
Makri et al. (2024) reported a case of Terson syndrome after subarachnoid hemorrhage with Roth spot-like findings 3). The pathogenesis is thought to involve retinal hemorrhage and fibrin deposition due to increased intracranial pressure, contributing to the understanding of the mechanism of Roth spot appearance in a neuro-ophthalmological context.
Mazharuddin et al. (2022) reported multiple cases of Evans syndrome in which ocular symptoms (Roth spots, petaloid macular leakage) preceded the systemic diagnosis 5). Fluorescein angiography revealed petaloid macular leakage, indicating that ocular findings can be a clue to the discovery of hematologic disease.
Yes. In Evans syndrome, cases have been reported where patients first visited an ophthalmologist with complaints of decreased vision or fundus abnormalities, and subsequent workup led to the discovery of hematologic disease 5). This is an important example of how ophthalmologists can contribute to the detection of systemic diseases.
If the underlying disease is fully controlled, recurrence is rare, but they may reappear due to relapse of leukemia or exacerbation of chronic anemia. Regular fundus examination is recommended.
