A condition in which systemic anemia causes bilateral retinal hemorrhages is called anemic retinopathy1.
The World Health Organization (WHO) defines anemia as follows: hemoglobin (Hb) concentration ≤13 g/dL in adult men and ≤12 g/dL in adult women, and hematocrit (Ht) ≤39% in adult men and ≤36% in adult women. The diagnosis requires anemia meeting these criteria on blood tests.
In many cases, it is discovered incidentally when an ophthalmological examination is requested during treatment for systemic anemia. Patients rarely visit with ocular symptoms as their chief complaint, and opportunities for ophthalmologists to become actively involved mainly arise from referrals by internists.
Representative causative diseases include hematologic disorders such as aplastic anemia, sickle cell disease, leukemia, multiple myeloma, and macroglobulinemia (Waldenström macroglobulinemia). Among these, multiple myeloma and macroglobulinemia may also involve increased blood viscosity in addition to anemia, and are sometimes classified into the adjacent clinical category of hyperviscosity retinopathy.
Mild anemia rarely causes retinal hemorrhages. They are more likely to occur in severe anemia or blood disorders accompanied by thrombocytopenia (such as leukemia or aplastic anemia) 2. The presence of retinal hemorrhages must be confirmed by fundus examination and cannot be determined solely by the severity of blood test results.
Retinal hemorrhages associated with anemia are often asymptomatic. They are frequently discovered when an ophthalmic examination is requested during treatment for a systemic disease.
However, when bleeding occurs in the macula, the following subjective symptoms may appear.
Findings confirmed by fundus examination or fundus photography are central to diagnosis.
Characteristics of Fundus Hemorrhage
Distribution of hemorrhage: Scattered throughout the retina, mainly in the posterior pole, bilaterally.
Hemorrhage morphology: blot-shaped, round, or oval, varying in size.
Depth of hemorrhage: Intraretinal hemorrhage is most common, but subretinal and preretinal hemorrhages also occur.
Characteristics: Lesions are more concentrated in the posterior pole compared to diabetic retinopathy.
Associated fundus findings
Roth spots: Hemorrhagic spots with a white center. Appear in severe anemia, infective endocarditis, and leukemia.
Pallor of the retina and optic disc: Generalized pallor of tissues due to anemia.
Hard exudates and soft exudates: Reflect deposition of exudates and microinfarctions of the nerve fiber layer.
Retinal artery narrowing, venous dilation, and tortuosity: Vascular morphological abnormalities due to changes in blood circulation.
Bilateral and posterior pole-predominant distribution is the most important fundus finding characterizing this disease. This is thought to reflect that capillaries in the macula, which has high metabolic activity, are susceptible to hypoxic injury.
Roth spots are a characteristic fundus finding with a white center within a hemorrhagic spot. The white center is thought to be formed by accumulation of fibrin and leukocytes 3. In leukemia, accumulation of tumor cells (leukocytes) may also be the center. It is not specific to anemic retinopathy and also appears in infective endocarditis, leukemia, and sepsis, so when Roth spots are confirmed, systematic differential diagnosis of the underlying disease is necessary 4.
Roth spots are hemorrhagic spots with a white center, observed as a fundus finding in severe anemia, infective endocarditis, and leukemia. The white center is thought to reflect accumulation of fibrin and white blood cells (or tumor cells in leukemia). Since it is not specific to anemic retinopathy, systematic differential diagnosis of the underlying disease is required when Roth spots are present.
The causative diseases of anemic retinopathy are diverse, with hematologic disorders being central.
It is thought that reduced oxygen supply to the retinal tissue due to anemia causes breakdown of the vessel wall.
In addition, if thrombocytopenia (due to leukemia, aplastic anemia, etc.) is present, the hemostatic mechanism (primary hemostasis) is impaired, further significantly worsening the bleeding tendency.
The diagnosis of anemic retinopathy is made by combining a blood test to confirm systemic anemia and a fundus examination to confirm retinal hemorrhage. Although no official diagnostic criteria have been established, the diagnosis is made when the following two conditions are met.
Hb level and platelet count are important predictors of fundus findings. In severe cases with Hb <8 g/dL and platelets <50×10⁹/L, the rate of fundus hemorrhage is significantly higher2. When Hb 8.95 g/dL is used as a threshold, the sensitivity for predicting anemic retinopathy is 85.8%, and specificity is 68.9%1.
| Test | Purpose / Key Findings |
|---|---|
| Fundus examination / fundus photography | Confirmation of bilateral posterior pole retinal hemorrhages (dot, round, or oval), Roth spots, and optic disc pallor (first choice) |
| Blood tests (CBC, Hb, Ht) | Assessment of anemia severity and type, confirmation of platelet count |
| OCT (Optical Coherence Tomography) | Assessment of presence and severity of macular edema, and localization of intraretinal and subretinal hemorrhages |
Fundus examination is the first-line test; when performed under mydriasis, it allows detailed observation from the posterior pole to the periphery. OCT is useful for quantitative evaluation of macular edema and longitudinal monitoring of treatment response.
It is important to differentiate from diseases that cause bilateral retinal hemorrhages. Diabetic retinopathy and hypertensive retinopathy are the main differential diagnoses.
The key points for differentiation are: (1) presence or absence of anemia on blood test, (2) hemorrhage morphology (blot/round vs. linear), and (3) posterior pole predominant distribution.
Diagnosis is possible with fundus examination alone, and OCT is not mandatory. However, when hemorrhage or edema is suspected in the macula, OCT is useful for evaluating the cause of vision loss and for follow-up. Confirmation of the presence and extent of macular edema also aids in assessing the efficacy of medical treatment.
There is no effective ophthalmic treatment for fundus hemorrhage associated with anemia. The main treatment is medical management of the underlying anemia. Medical drug therapy according to the cause of anemia is necessary, and fundus hemorrhage is expected to improve with successful treatment of the causative disease.
Treatment is provided by internists or hematologists depending on the underlying cause of anemia.
The effects of medical treatment are periodically monitored through fundus examinations.
There are no effective ophthalmic treatments (eye drops, intravitreal injections, lasers, etc.). The main treatment is medical management of the underlying cause of anemia by an internist. Ophthalmology primarily plays a role in regularly monitoring the degree of retinal hemorrhage and its impact on the macula, and evaluating the effectiveness of medical treatment through fundus findings.
The basic mechanism by which anemia causes retinal hemorrhage is insufficient oxygen supply to retinal tissue due to decreased blood hemoglobin concentration. It is thought that reduced oxygen supply to retinal tissue due to anemia leads to breakdown of blood vessel walls.
When hemoglobin that carries oxygen decreases, retinal tissue is placed in a state of chronic hypoxia. Under this hypoxic environment, the following changes occur in a chain reaction.
In leukemia, aplastic anemia, and other conditions, platelet count is markedly reduced due to impaired bone marrow function. Platelets are responsible for primary hemostasis (sealing of bleeding sites by platelet aggregation), so when thrombocytopenia is present, hemostasis becomes difficult even with minor vascular injury.
Therefore, when thrombocytopenia is added to hypoxia-induced vessel wall fragility, retinal hemorrhages tend to occur frequently and become severe. In aplastic anemia and leukemia, these two bleeding-promoting factors act together.
Roth spots are a characteristic finding with a white center within a hemorrhagic spot. The composition of the white center varies depending on the underlying disease.
The morphology of fundus hemorrhage varies depending on its depth.
The predominance in the posterior pole is thought to reflect the high metabolic activity and rich capillary network of the macula, making it susceptible to hypoxic injury.
In multiple myeloma and macroglobulinemia, abnormal production of M protein and IgM markedly increases blood viscosity. Elevated blood viscosity reduces retinal venous flow velocity and increases the risk of thrombosis, leading to venous dilation, tortuosity, and hemorrhage. This condition is sometimes described as “hyperviscosity retinopathy” in association with anemic retinopathy. Menke et al. have shown that retinal changes in Waldenström macroglobulinemia occur at lower serum IgM and serum viscosity levels than previously reported thresholds 5.
In cases of severe bone marrow dysfunction such as aplastic anemia, multilayered intraretinal, preretinal, and subretinal hemorrhages may occur, sometimes complicated by serous retinal detachment. In pediatric cases, acute bilateral vision loss may be the presenting symptom, and vitrectomy may be considered 6.
When anemia improves, retinal hemorrhages gradually resolve. However, this process takes time, often requiring several months for complete disappearance.
Visual prognosis varies greatly depending on the success of treatment for the underlying disease and the extent of macular involvement.
Regular fundus examinations should be performed in conjunction with internal medicine follow-up to monitor improvement in systemic condition. Since fundus hemorrhages may recur if the underlying disease relapses or worsens, continuous follow-up is important even after remission.
If the anemia is improved by treating the underlying disease, retinal hemorrhage gradually resolves. However, it often takes several months for complete resolution. If the hemorrhage involves the macula (center of vision), visual impairment may persist even after the hemorrhage clears. Regular fundus examinations are important for follow-up.
If the underlying disease relapses or worsens, retinal hemorrhage may reappear. In chronic diseases such as leukemia or aplastic anemia, remission and relapse may alternate. It is important to continue systemic management by an internist and ophthalmologic follow-up simultaneously.
Venkatesh R, Gurram Reddy N, Jayadev C, Chhablani J. Determinants for Anemic Retinopathy. Beyoglu Eye J. 2023;8(2):97-103. PMID: 37521879 ↩ ↩2
Carraro MC, Rossetti L, Gerli GC. Prevalence of retinopathy in patients with anemia or thrombocytopenia. Eur J Haematol. 2001;67(4):238-244. PMID: 11860445 ↩ ↩2
Ling R, James B. White-centred retinal haemorrhages (Roth spots). Postgrad Med J. 1998;74(876):581-582. PMID: 10211348 ↩
Gurnani B, Tivakaran VS. Roth Spots. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. PMID: 29494053 ↩
Menke MN, Feke GT, McMeel JW, Branagan A, Hunter Z, Treon SP. Hyperviscosity-related retinopathy in waldenstrom macroglobulinemia. Arch Ophthalmol. 2006;124(11):1601-1606. PMID: 17102008 ↩
Jiang X, Shen M, Liang L, Rosenfeld PJ, Lu F. Severe retinal hemorrhages at various levels with a serous retinal detachment in a pediatric patient with aplastic anemia–A case report. Front Med (Lausanne). 2023;10:1051089. doi: 10.3389/fmed.2023.1051089 ↩
