membrane or direct invasion from an external cutaneous lesion [231, 232].

Other rare T cell lymphomas, like natural killer (NK) neoplasms, also show marked vitritis but may additionally have serous retinal and choroidal detachments, while atypical findings like CRAO may be the initial presenting symptom of lymphoma in children [172, 233].

Controversies/Perspectives

Roth Spots

Confusion regarding Roth spots (RS), or whitecentered hemorrhages, seems to permeate throughout the medical community. This is partly due to a strong stereotype associating RS with subacute bacterial endocarditis, in addition to a lack of understanding of RS pathophysiology. Speculation persisted that these lesions may have also represented leukemic cells or nerve fiber layer injury. In fact, studies have shown that RS lesions are rather the result of platelet-fibrin thrombi formed as a result of capillary rupture probably from acute systemic insults [13, 146, 234].

In addition, RS can occur in a wide variety of clinical settings, ranging from ocular hypotony; to shaken baby syndrome; human immunodeficiency virus; intracranial hemorrhage; traumatic delivery; blood dyscrasias such as anemia, thrombocytopenia, and leukemia; anoxic or hypoxic states like carbon monoxide poisoning; and relative ischemic conditions such as diabetes mellitus, hypertension, and preeclampsia [236]. Therefore, although RS are most commonly due to emboli from subacute bacterial endocarditis, other traumatic, ischemic, or hemodynamic causes should be considered based on clinical context.

Anti-VEGF Therapy

neovascular disorders. Bevacizumab is commonly used as a treatment of neovascular glaucoma and is used by some as an adjuvant treatment in patients undergoing surgical repair of tractional retinal detachments due to proliferative diabetic retinopathy. Despite the evidence that VEGF plays an important role in proliferative sickle retinopathy (PSR), the data on the use of anti-VEGF agents is slim, with only two reported cases to our knowledge in the published literature.

There are theoretical and practical advantages and disadvantages to the use of anti-VEGF agents for PSR. One theoretically avoids the risk of choroidal neovascularization and retinal tear that is associated with argon laser photocoagulation. However, one set of complications is traded for another, as intravitreal injection is associated with a small, but definite, risk of endophthalmitis and also the risk that the rapid regression may be associated with traction or tractionrhegmatogenous detachment. In addition, the risk for potential systemic ischemic events associated with intravitreal anti-VEGF treatment should not be taken lightly in sickle cell patients, who already face an increased risk of stroke and other systemic ischemic events. Intravitreal injection can be useful in the setting of vitreous hemorrhage precluding laser treatment. In most cases, however, vitreous hemorrhage in PSR resolves spontaneously, and it is unclear if intravitreal treatment will make it go away any faster. Finally, intravitreal injection has the disadvantage of needing recurrent treatments, whereas photocoagulation effective ablates the area of treated retina.

Ultimately, judgment on anti-VEGF treatment of PSR should be reserved until there is reliable data in the form of controlled clinical trials. Until then, well-intended treatments with intravitreal bevacizumab or ranibizumab may in fact simply be shots in the dark.

Focal Points

Anemia

•Ischemic changes such as intraretinal hemorrhages, retinal edema, and CWS.

•Fundus manifestations more common with a hematocrit less than 30%, often with coexistent thrombocytopenia.

•Erythropoietin may help stimulate neovascularization.

Hemoglobinopathies

Sickle Cell

•Commonly with arteriolosclerosis and vascular tortuosity, rarely angioid streaks

•Proliferative: Sea-fan neovascularization, overall more common in HbSC disease

•Non-proliferative: Salmon patches, intraor preretinal hemorrhages, and black sunbursts, pre-hyperplasia secondary to subretinal hemorrhages

Thalassemia

•Degenerative RPE changes more common in thalassemia major and may be due to deferoxamine therapy

•Venous tortuosity, angioid streaks

Thrombotic Thrombocytopenic

Purpura/Hemolytic Uremic Syndrome

•Purtscher-like retinopathy

•Vascular occlusions

Myelodysplastic Syndrome

•Retinal and choroidal changes almost always due to cytopenia of one or more cell lines causing anemia, thrombocytopenia, and/or neutropenia

Myeloproliferative Neoplasms

Myelogenous Leukemia

•Recurrent, predominantly peripheral vascular injury and nonperfusion with possible neovascularization

Polycythemia Vera

•Hyperviscosity and thrombotic symptoms with vascular engorgement, NFL infarcts, and retinal hemorrhages

Essential Thrombocythemia

•Ischemic changes secondary to higher risk of thrombosis.

Leukemia

•Most commonly a retinopathy due to characteristic changes from anemia, thrombocytopenia, and hyperviscosity

•Patchy or diffuse choroidal involvement with direct infiltration that can extend subor intraretinally appearing as yellow-white infiltrates

•Roth spots

Lymphoma

Yellow retinal lesions in a patient with known lymphoma more often represent infection due to bacterial, fungal, CMV, or other viral causes.

B Cell

•Vitreoretinal type more common and associated with CNS lymphoma.

•Uveal type more associated with peripheral lymphomas.

•Metastasis from systemic lymphoma may

appear as unior multifocal yellow-white choroid lesions.

Hodgkin’s Lymphoma

•Rule out other etiologies as this is extremely rare.

Plasma Cell

•MGUS is essentially clinically undetectable. Waldenstrom

•CRVO-like appearance but bilateral, possible neurologic symptoms, and responds to plasmapheresis

•Sausage-link venous tortuosity

Multiple Myeloma

•Manifests mainly with retinal findings of anemia, less commonly hyperviscosity as most patients’ M-protein consists of the smaller IgG