Leukemia and the relationship between disease subtypes and ocular manifestations

A new study¹ from India, reported in the British Journal of Ophthalmology increased the knowledge base about the ophthalmic manifestations of leukemia, in that the type of leukemia, ie, acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), and certain ophthalmic manifestations, such as epiretinal membranes (ERMs) and submacular hemorrhages, can help determine the disease remission and visual outcomes, according to the investigators led by Dhwanee Agarwal, MD, from the LV Prasad Eye Institute, GMR Varalakshmi Campus, and the Anant Bajaj Retina Institute.

Leukemia is divided into acute and chronic types and subdivided into 2 forms, myeloid and lymphoid.² The 4 main types of leukemia are acute lymphocytic leukemia (ALL), AML, chronic lymphocytic leukemia (CLL), and CML,³ the investigators explained.

Leukemic retinopathy was first reported in 1861 and was later shown to have protean manifestations,⁴ the investigators explained.

“Ophthalmic involvement has been proposed to be due to direct infiltration of leukemic cells (anterior segment uveal infiltration, orbital infiltration, and neuro-ophthalmic signs of central nervous system involvement like cranial nerve palsies, disc edema, or disc infiltration); secondary changes in the retina and choroid due to anemia, thrombocytopenia, and hyperviscosity syndrome; opportunistic infections like viruses (cytomegalovirus, herpes, mumps), bacteria, or fungi (Candida, Aspergillus); or rarely drug-related complications,^4-12” they enumerated.

However, it is noteworthy that in spite of the multisystem involvement, “ophthalmic manifestations are often the first clue to leukemia diagnosis, highlighting the importance of a detailed ophthalmic evaluation.^7,13 Not only does it help establish the primary diagnosis, but it can also be a reliable marker of relapse and prognosis,^14-16” they explained.

Specifically, Agarwal and colleagues pointed out that patients with macular hemorrhages have a five-fold relative risk of intracranial hemorrhage,¹⁷ and the presence of retinal infarction, leopard spots, and leukemic infiltrates is associated with a poor prognosis.¹⁶

“Hence, a high suspicion of leukemia is more important in cases of unexplained ophthalmic manifestations to establish an early diagnosis,” they emphasized.

Multicenter study of ophthalmic manifestations in leukemia and results

The retrospective study included 244 patients (378 eyes) (mean patient age, 34.9 ± 22.1 years; range, 1-88 years) who had been diagnosed with leukemia between January 2016 and 2024. The investigators collected data that included demography, leukemia type, ophthalmic manifestations, imaging modalities, treatment modalities (ocular and systemic), treatment outcome (relapses or remission), and final visual acuity. The most common subtypes of leukemia were ALL seen in 58% of patients and CML in 20%. The acute forms manifested earlier in life and were more aggressive, the investigator reported.

In addition, there were more manifestations in the posterior segment than the anterior segment, ie, 64% compared with 52%, respectively.

They also found that the myeloid types of leukemia were more often associated with hemorrhagic manifestations, whereas the lymphoid types were associated with non-hemorrhagic manifestations.

“Univariate analysis showed that the presence of ERMs (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.012-0.951, p=0.04), submacular hemorrhages (OR, 0.091; 95% CI, 0.010-0.763, p=0.027), and type of leukemia, ie, AML (OR, 3.195; 95% CI, 1.697-6.012, p<0.000) and CML (OR, 6.39; 95% CI, 3.130-13.041, p<0.000) were associated significantly with poor visual outcomes. Multivariate analysis revealed that AML (OR, 2.769; 95% CI, 1.392-5.507, p=0.004,) and CML (OR, 7.313; 95% CI, 3.326-16.074, p<0.000) were independent predictors of poor visual outcome,” Dr. Agarwal and colleagues reported.

The investigators summarized their findings:

“Our study elicited numerous salient observations, such as the pediatric population has predominantly acute forms of leukemia, whereas the elderly population has more chronic forms. Non-hemorrhagic manifestations in the anterior and posterior segments are more common in the lymphoid forms, whereas the posterior pole was more often involved in the myeloid forms. Hemorrhagic manifestations were significantly present in myeloid forms. CLL had the most indolent course and the least ocular involvement. We also discerned the need for prompt diagnosis and an early and aggressive approach in the treatment-naïve patients for better clinical outcomes. Our analysis revealed a relationship between disease remission and leukemia type (AML, CML) and ocular manifestations (ERM, submacular hemorrhage). Therefore, the pattern recognition of ocular findings plays a significant role in the diagnosis, treatment, and prognosis of leukemia,” they emphasized.

Agarwal was joined in this study by Mudit Tyagi, MD, the LV Prasad Eye Institute, Smt Kanuri Santhamma Centre for Vitreoretinal Diseases; and Rajeev Pappuru, MD, and Vishal Raval, MD, both from the LV Prasad Eye Institute, Anant Bajaj Retina Institute.

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