Leukemic retinopathy is a general term for fundus lesions associated with leukemia. It is a malignant tumor caused by clonal proliferation of leukocytes or upstream hematopoietic stem cells, leading to systemic infiltrative lesions. Leukemic retinopathy is the most common ocular complication seen ophthalmologically, occurring in approximately 70% of all leukemia patients. It is observed in both acute and chronic leukemia, but is particularly frequent during relapse of acute leukemia. Intraocular infiltration of leukemic cells can reach over 80% in some cases 4).
Leukemia is clinically classified into non-lymphocytic and lymphocytic types, each further divided into acute and chronic forms. Ocular findings are more common in acute leukemia. 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 indicator reflecting systemic disease activity 3).
Not necessarily. Cases have been reported where fundus findings appear at the same time as the onset of leukemia or as the initial sign 3). Unexplained retinal hemorrhage or sudden vision loss may lead to the discovery of a hematologic disorder. Since fundus findings can also indicate relapse, regular ophthalmologic follow-up is important.
Many patients are often asymptomatic in the early stages. Symptoms appear in the following situations.
Infiltration of leukemic cells around retinal blood vessels leads to vascular occlusion, presenting the following findings.
| Finding | Characteristics | Indicator of Severity |
|---|---|---|
| Venous dilation and tortuosity (sausage-like changes) | Most common finding. Accompanied by caliber variation. | Hyperviscosity, high white blood cell count |
| Vascular sheathing | Indicates infiltration of the vessel wall | Direct infiltration |
| Roth spots | Retinal hemorrhage with a white center | Characteristic finding |
| Retinal hemorrhage (multilayered) | Flame-shaped to dome-shaped | Thrombocytopenia |
| Cotton-wool spots | Findings of capillary occlusion | Suggests poor prognosis |
| Elevated lesions | Due to leukemic cell infiltration | Direct infiltration |
| Neovascularization | Appears in severe ischemia | Severe ischemia |
In extreme leukocytosis with WBC ≥200,000/μL, peripheral retinal ischemia and neovascularization may be observed 1). Cases presenting with a CRVO-like appearance have also been reported 1).
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.
Features: Can occur even with relatively 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.
Ocular complications of leukemia are not limited to the retina. The following findings due to leukemic cell infiltration of the anterior segment may be observed.
Infiltration into the orbit or retrobulbar hemorrhage leads to the following symptoms. Rarely, the lacrimal gland is also infiltrated.
In chronic leukemia, retinal microaneurysms, retinal ischemia, retinal hemorrhages, retinal elevation lesions, retinal neovascularization, and papilledema may also occur.
When hemorrhage or edema involves the macula, central visual acuity decreases rapidly. If peripheral lesions are predominant, subjective symptoms may be minimal. When papilledema is present, the central visual field may become dark (central scotoma). If pseudohypopyon or proptosis occurs, eye pain and photophobia may appear.
The development of leukemic retinopathy involves a combination of hematologic abnormalities.
Ocular findings can serve as indicators for initiating systemic treatment and prognosis, so the diagnostic role of ophthalmology is important. If recurrence in organ tissues is suspected, bone marrow recurrence is predicted within weeks to months, requiring re-evaluation by hematology.
Ocular findings can be an indicator for initiating systemic treatment and determining prognosis in leukemia. Fundus findings may be the first sign of the disease or suggest relapse in organs and tissues, and can provide clues to predict bone marrow relapse within weeks to months. When an ophthalmologist detects abnormalities, it is important to promptly inform the hematology department and proceed with further evaluation.
If bilateral multiple retinal hemorrhages or Roth spots are observed, referral to hematology is necessary. CBC (complete blood count) and peripheral blood smear examination are the first steps 3). If pseudohypopyon is present, anterior segment infiltration due to leukemia should be suspected, and systemic evaluation is needed. Collaboration between ophthalmology and hematology prevents delays in diagnosis.
Treatment is selected according to the type and severity of leukemia and the degree of ocular symptoms. Systemic chemotherapy is the mainstay, and fundus findings often improve in response to systemic treatment. Systemic chemotherapy may not adequately reach the ocular region, and radiation therapy may be combined.
Systemic Chemotherapy
CML: Tyrosine kinase inhibitors (TKIs) are first-line. Dasatinib has been reported to improve retinopathy 2).
AML: Daunorubicin + cytarabine (DA therapy) is standard.
CEL: Imatinib is considered effective 3).
Adjunctive cytoreduction: Rapid reduction of WBC with hydroxyurea is effective1)3).
Leukapheresis
Leukapheresis: Selective removal of white blood cells via extracorporeal circulation.
Recommendation grade: ASFA (American Society for Apheresis) grade 2B1).
Indications: Acute visual impairment due to extreme leukocytosis (WBC >200K).
Effect: Rapid visual recovery can be expected1).
Ophthalmic Treatment
Radiation therapy: For iris infiltration, leukemic retinopathy, and secondary glaucoma, 2.5 Gy × 5 days is reported to induce remission. For optic nerve infiltration causing vision loss, higher doses of 7–20 Gy are used.
Photocoagulation: Performed for significant retinal ischemia.
Vitrectomy (PPV): Performed in stages for non-absorbing massive hemorrhage4).
Dexamethasone implant: Useful for cystoid macular edema (CME)4).
The type of leukemia, main therapeutic drugs, and local ocular treatments are shown below.
| Leukemia type | First-line drug | Visual improvement target |
|---|---|---|
| CML | TKIs such as Dasatinib | Several weeks to several months |
| AML | DA therapy | Improves after remission |
| CEL | Imatinib | Effective in some cases |
As leukemia goes into remission with systemic chemotherapy, retinal hemorrhages and edema often improve, and vision recovers in many cases. However, it has been reported that decreased vascular density in the deep capillary plexus (DCP) is difficult to recover even after treatment 2). If outer retinal damage (EZ loss) is extensive, visual prognosis may be poor. Radiation therapy for optic nerve infiltration may be effective for vision loss.
It is a treatment that selectively removes leukocytes by circulating blood outside the body. It is used as a bridge until chemotherapy takes effect for emergency visual impairment due to hyperleukocytosis (WBC >200,000/μL) 1). ASFA recommends it as grade 2B.
The pathogenesis of leukemic retinopathy is broadly divided into primary and secondary types 1).
Leukemic cells directly infiltrate the retinal vessels, parenchyma, and vitreous, causing local tissue damage. A characteristic feature is that it can occur even when blood abnormalities are relatively mild. Infiltration of leukemic cells around retinal vessels leads to vascular occlusion, resulting in dilation, tortuosity, and ischemia of retinal veins.
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. After treatment, vascular density in the DCP is difficult to restore 2), which affects long-term visual prognosis. Outer retinal damage (EZ loss) is thought to reflect photoreceptor damage due to chronic ischemia 4).
Immunosuppression predisposes to opportunistic infections (e.g., CMV retinitis, herpetic keratitis). Various ocular complications arise from intensive chemotherapy, radiation therapy, and hematopoietic stem cell transplantation.
In recent years, the number of long-term survivors after hematopoietic stem cell transplantation has increased, and management of post-transplant ocular complications has become more important.
Among ocular complications associated with graft-versus-host disease (GVHD), dry eye is the most common. In refractory cases, it can lead to corneal melting and perforation, requiring strict dry eye management.
The following complications are observed:
For GVHD-related dry eye, artificial tears, steroid eye drops, cyclosporine eye drops, and tacrolimus eye drops are used in combination. It is important to concurrently evaluate meibomian gland dysfunction, punctal occlusion, and conjunctival pseudomembrane formation, and in severe cases, not to miss signs of corneal melting or perforation.
Post-transplant ophthalmological follow-up requires regular combination of dry eye evaluation (Schirmer test, tear break-up time measurement), slit-lamp examination, and fundus examination.
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.
