of malignant cells, with a peripheral smear showing sequelae of myelophthisis. Approximately 50% of patients with PMF show JAK2 mutations, while the remainder may have other mutations related to the JAK-STAT pathway or as yet unrecognized molecular etiologies [137–139]. The incidence is reported to be 1.5 per 100,000 individuals per year with median age being 67; the disease rarely occurs in children [111].

This disorder is more commonly associated with ocular adnexal involvement, such as extramedullary hematopoiesis with secondary effects related to immunosuppression from bone marrow transplantation, with a reported case of CMV retinitis [140] and hemorrhagic retinopathy due to anemia [141]. Otherwise, the literature is sparse, and treatment-related effects from supportive therapies such as prednisone, etanercept, or radiation may manifest.

Leukemias

Acute Myeloid Leukemia

This is a clonal proliferation of myeloid precursors that lack the ability to differentiate into mature forms resulting in the accumulation of immature or blast cells. It is the most common cause of leukemia in adults but comprises less than 10% of leukemias in children [142]. The incidence is approximately 3–5/100,000 individuals per year, with a median age of 65 years and slight male predominance [142]. It is classified based on World Health Organization (WHO) criteria into four groups: acute myeloid leukemia (AML) with recurrent genetic abnormalities, AML with myelodysplasia-related features, ther- apy-related AML and MDS, and AML not otherwise specified [143].

Lymphoid

Lymphoid neoplasms derive from T or B cell lineages and are classically grouped as deriving from lymphoid precursors, mature lymphocytes, or plasma cells. These can present as a mass, or

lymphoma, or have blood and bone marrow involvement (greater than 25% blasts) and be termed leukemia. Yet any lymphoma can evolve into leukemia, and sometimes, leukemia can present as an extramedullary mass; therefore, lymphoid neoplasms should be classified based on morphology, genetics, and immunophenotype rather than anatomic location [144].

The precursor B leukemias/lymphomas, tdt positive and cd3 negative, are more common in childhood and have an overall incidence of 2% per population with a male predominance [145, 146]. They typically present acutely as leukemias, commonly with central nervous system (CNS) and nodal involvement. In contrast, precursor T leukemia/lymphoma, cd3 and 7 positive, tends to affect young adult males who often have diffuse lymphadenopathy and a bulky mediastinal mass. There may be CNS involvement, especially if in the leukemic form.

The prevalence of leukemic ocular involvement in the literature varies from 9% to 90%, with one prospective study showing leukemic infiltration in 3% of patients, leukemia-related findings in 39%, and unrelated abnormalities in 20% [147, 148]. The characteristic findings of leukemia are the result of direct organ invasion, abnormal hematopoiesis, altered blood viscosity, or immune suppression. Within the choroid, leukemic infiltration is often perivascular but can be patchy or diffuse with increased thickness [149]. Cellular infiltration can also extend subretinally and intraretinally, appearing as yellow infiltrates that may resemble viral or fungal infections, especially in the immunosuppressed, or as perivascular sheathing and optic nerve infiltration. It has been speculated that infection may have a closer association with patients in remission with prior bone marrow transplantation (BMT) rather than those with newly diagnosed leukemia [150]. An analysis of patients with BMT showed a posterior segment complication rate of 12.8%, with 2% having developed infectious retinitis or endophthalmitis that had a temporal correlation showing that fungal infection typically occurred within 120 days of BMT while viral or parasitic infection generally arose much later [151].