Leukemic retinopathy is a general term for fundus lesions associated with leukemia. Some retinal findings are observed in 35–50% of all leukemia patients1), and intraocular infiltration of leukemic cells is reported to reach over 80% in some cases4).
It can occur in any type of leukemia, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic eosinophilic leukemia (CEL). Fundus findings may appear as the first sign of leukemia and serve as a diagnostic clue reflecting systemic disease activity3).
Not necessarily. Cases have been reported where fundus findings appear at the same time as the onset of leukemia or as the first sign3). Unexplained retinal hemorrhage or vision loss may lead to the discovery of a hematologic disease.
The main fundus findings are shown below.
| Finding | Characteristics | Severity Indicator |
|---|---|---|
| Venous dilation and tortuosity | Most common finding | Hyperviscosity, high white blood cell count |
| Roth spots | Flame-shaped hemorrhages with white centers (approximately 90%) | — |
| Retinal hemorrhages (multilayered) | Flame-shaped to dome-shaped | Thrombocytopenia |
| Cotton-wool spots | Findings of capillary occlusion | Indicates poor prognosis |
Dilation and tortuosity of retinal veins are the most common findings 1). Cases presenting with a central retinal vein occlusion (CRVO)-like appearance have also been reported 1). Roth spots (hemorrhages with white centers) are observed in approximately 90% of cases. Multilayered retinal hemorrhages are prominent in cases with thrombocytopenia 4), and the appearance of cotton-wool spots suggests a poor prognosis 3).
In hyperleukocytosis with WBC ≥200,000/μL, peripheral retinal ischemia and neovascularization may be observed 1). Some cases are complicated by optic disc edema 2).
The following OCT and OCTA findings have been reported.
Primary lesions
Definition: Changes due to direct infiltration of the retina and vitreous by leukemic cells.
Main findings: Retinal infiltrates, vitreous cell infiltration, optic nerve infiltration.
Characteristics: Can occur even with mild blood abnormalities.
Secondary lesions
Definition: Changes resulting from blood abnormalities such as anemia, thrombocytopenia, and hyperviscosity.
Main findings: Retinal hemorrhages, Roth spots, venous dilation and tortuosity, cotton-wool spots.
Features: Often correlate with abnormal blood test results.
When hemorrhage or edema involves the macula, central vision decreases rapidly. If the lesions are mainly in the periphery, subjective symptoms may be minimal. When optic disc edema is present, the central part of the visual field may become dark (central scotoma).
The development of leukemic retinopathy involves multiple hematologic abnormalities.
The diagnosis of leukemic retinopathy is made by combining fundus findings and blood tests.
If bilateral multiple retinal hemorrhages or Roth spots are observed, referral to hematology is necessary. Checking CBC (complete blood count) and peripheral blood smear is the first step3). Collaboration between ophthalmology and hematology prevents delays in diagnosis.
Treatment is selected based on the type and severity of leukemia and the extent of ocular symptoms. Systemic chemotherapy is the mainstay, and fundus findings often improve in response to systemic treatment.
Systemic Chemotherapy
CML: Tyrosine kinase inhibitors (TKIs) are first-line. Dasatinib has been reported to improve retinopathy2).
AML: Daunorubicin plus cytarabine (DA therapy) is standard.
CEL: Imatinib is considered effective 3).
Adjunctive cytoreduction: Rapid reduction of WBC with hydroxyurea is effective 1)3).
Leukapheresis
Leukapheresis: Selective removal of white blood cells via extracorporeal circulation.
Recommendation grade: ASFA (American Society for Apheresis) grade 2B 1).
Indications: Acute visual impairment due to hyperleukocytosis (WBC >200K).
Effect: Rapid visual recovery can be expected 1).
Ophthalmic Treatment
Pars plana vitrectomy (PPV): Performed in stages for massive non-absorbing hemorrhage 4).
Dexamethasone implant: Useful for cystoid macular edema (CME) 4).
Radiation therapy: May be performed for local infiltration into the orbit or eye 3).
The type of leukemia, main therapeutic agents, and indicators of visual improvement are shown below.
| Leukemia type | First-line drug | Indicator of visual improvement |
|---|---|---|
| CML | TKIs such as Dasatinib | Several weeks to months |
| AML | DA therapy | Improves after remission |
| CEL | Imatinib | Effective in some cases |
As leukemia goes into remission with systemic chemotherapy, many cases show improvement in fundus hemorrhage and edema, leading to visual recovery. However, it has been reported that decreased vascular density in the deep capillary plexus (DCP) is difficult to recover even after treatment 2). Extensive outer retinal damage (EZ loss) may result in poor visual prognosis.
This is a treatment in which blood is circulated outside the body to selectively remove white blood cells. It is used as a bridge until chemotherapy takes effect for emergency vision impairment caused by hyperleukocytosis (WBC >200,000/μL)1). ASFA recommends it as grade 2B.
The pathogenesis of leukemic retinopathy is broadly divided into primary and secondary mechanisms1).
Leukemic cells directly infiltrate the retinal blood vessels, parenchyma, and vitreous body, causing local tissue damage. A characteristic feature is that this can occur even when blood abnormalities are relatively mild.
Three factors—anemia, thrombocytopenia, and hyperviscosity—act in combination.
The deep capillary plexus (DCP) has lower perfusion pressure than the superficial capillary plexus (SCP) and is more susceptible to leukostasis. Even after treatment, the vascular density of the DCP is difficult to recover2), which affects long-term visual prognosis. Outer retinal damage (EZ loss) is thought to reflect photoreceptor damage due to chronic ischemia4).
Jamshidi et al. (2025) reported that in cases of leukemic retinopathy, OCTA can detect decreased vessel density in the deep capillary plexus before clinically apparent retinopathy appears 4). OCTA has potential as a tool for early detection of asymptomatic retinal lesions in leukemia patients.
Jamshidi et al. (2025) reported a case of severe leukemic retinopathy treated with staged vitrectomy 4). The effectiveness of a dexamethasone implant (Ozurdex) for residual cystoid macular edema (CME) after surgery was also demonstrated, leading to visual improvement 4). The combination of ophthalmic intervention and systemic treatment may contribute to improved prognosis.
