Case of the Month | April 2022

Case of the Month
April 27, 2022

The Case

The patient was a 60-year-old man who was found on routine examination to have cotton-wool spots and hemorrhages in both eyes. He was diagnosed with acute promyelocytic leukemia (PML) for which he received recently induction therapy of all-trans retinoic acid and arsenic trioxide. He had no acute visual complaints. The fundus findings were discovered on routine, annual examination for Best disease. The past medical history is remarkable also for testicular cancer treated 14 years previously with orchiectomy and hormone treatment.

What most likely accounts for the fundus findings?

The patient had cotton-wool spots and intraretinal hemorrhages in both eyes, right greater than left.  He had pancytopenia after induction of treatment for the PML, including a hematocrit of 28, and this likely accounted for the hemorrhages and cotton-wool spots. Other considerations include leukemic infiltrates or direct effects from the therapeutic agents. When seen 3 weeks later, the blood counts were much better, in part because of transfusions, and the hemorrhages and cotton-wool spots had largely resolved.

Regarding the diagnosis of Best disease, our patient’s presentation was atypical. Best disease typically presents in childhood with yellowish lipofuscin material under the neurosensory retina. The material breaks up (and there is “scrambled egg” appearance on the way to resolution of the neurosensory detachment), and eventually there is atrophy of the underlying neurosensory retina and retinal pigment epithelium. Frequently, a neovascular membrane develops, which without anti-VEGF treatment typically evolves into a deep fibrous scar. This patient at age 60 has subretinal fluid that was nonreflective on OCT, which is consistent with an adult-onset vitelliform macular dystrophy after its initial vitelliform presentation.

Best disease results from mutations in the VMD2 gene, which codes for a protein called bestrophin. This protein appears to be involved in the movement of chlorine ions into and out of retinal cells. With respect to adult onset vitelliform macular dystrophy, mutations of VMD2 and RDS genes account for about 25% of cases, and the source of the rest is unknown.

Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. New England Journal of Medicine 2013;369: 111-121.

Case Photos

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The patient had cotton-wool spots and intraretinal hemorrhages in both eyes, right greater than left.  He had pancytopenia after induction of treatment for the PML, including a hematocrit of 28, and this likely accounted for the hemorrhages and cotton-wool spots. Other considerations include leukemic infiltrates or direct effects from the therapeutic agents. When seen 3 weeks later, the blood counts were much better, in part because of transfusions, and the hemorrhages and cotton-wool spots had largely resolved.

Regarding the diagnosis of Best disease, our patient’s presentation was atypical. Best disease typically presents in childhood with yellowish lipofuscin material under the neurosensory retina. The material breaks up (and there is “scrambled egg” appearance on the way to resolution of the neurosensory detachment), and eventually there is atrophy of the underlying neurosensory retina and retinal pigment epithelium. Frequently, a neovascular membrane develops, which without anti-VEGF treatment typically evolves into a deep fibrous scar. This patient at age 60 has subretinal fluid that was nonreflective on OCT, which is consistent with an adult-onset vitelliform macular dystrophy after its initial vitelliform presentation.

Best disease results from mutations in the VMD2 gene, which codes for a protein called bestrophin. This protein appears to be involved in the movement of chlorine ions into and out of retinal cells. With respect to adult onset vitelliform macular dystrophy, mutations of VMD2 and RDS genes account for about 25% of cases, and the source of the rest is unknown.

Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. New England Journal of Medicine 2013;369: 111-121.

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