Ocular Paraneoplastic Syndromes: A Critical Review of Diffuse Uveal Melanocytic Proliferation and Autoimmune Retinopathy

Abstract

Background: Dozens of paraneoplastic syndromes affect the visual system ranging from conjunctival pemphigoid to encephalopathy of the occipital cortex. The most profiled ocular syndromes are bilateral diffuse uveal melanocytic proliferation (BDUMP) and the autoimmune retinopathies. Purpose: To review the critical features of these 2 entities then concentrate on advancements in treatment made within the last 10 years. Study Design: Literature review with structured data abstraction. Results: Major insights into pathogenesis have been wanting. Plasmapheresis appears to improve vision in a substantial proportion of patients with BDUMP. The number of clinical variables that influence visual outcome in paraneoplastic retinopathies combined with the variety of local and systemic treatment options makes interpretation of clinical effectiveness difficult. Conclusions: The rarity of these disorders makes randomized clinical trials unlikely. It may be time for a clinical professional organization to use a modified Delphi method to establish a consensus algorithm for the diagnosis and management of retinal paraneoplastic syndromes to augment clinical communications and clinical trials.

Retinopathy in a Patient With IgM MGUS: Causal Association or an Epiphenomenon?

“…Carbonic anhydrase II is an essential metallo-enzyme for the regulation of acid-base balance and energy homeostasis in human cells. Antibodies against carbonic anhydrase II have been reported in both autoimmune-and cancer-associated retinopathy including hematological cancer (7). In our patient a direct activity of the monoclonal IgM against retina antigens was not tested.…”

“…The presence of anti-retinal antibodies should be interpreted in the context of other findings, due to lack of specificity and a universally accepted detection technique across laboratories. Indeed, it has been reported that anti-retinal antibodies may be found in up to one third of healthy individuals (7). In cases of cancer-associated retinopathy, antibodies against tumor-related antigens present cross-reactivity with retinal antigens, and these auto-antibodies target retinal cells and induce apoptosis (7).…”

“…Indeed, it has been reported that anti-retinal antibodies may be found in up to one third of healthy individuals (7). In cases of cancer-associated retinopathy, antibodies against tumor-related antigens present cross-reactivity with retinal antigens, and these auto-antibodies target retinal cells and induce apoptosis (7). In turn, damaged photoreceptor cells may release arrestin-enolase complexes which are processed by resident antigen-presenting cells and induce the production of anti-arrestin and anti-enolase autoantibodies.…”

Management of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP)—A Case Report

“…Gass's "leopard spots", characterizing the reticulated ocular fundus pattern, are colloquially known as the "gyrate pattern". While the reticulated depigmentation pattern is characteristic of BDUMP, its diagnostic specificity is tempered by its occurrence in other bilateral conditions such as metastatic cancer, leukemic choroidal infiltration, and lymphoma, all of which can manifest bilaterally [3].…”

“…It is theorized that either a substance secreted by the tumor or an antibody stimulated by the tumor triggers the benign proliferation of choroidal melanocytes [5]. Extensive discussions on the pathologic correlates of BDUMP have been documented in nearly 100 cases [3], underscoring the ongoing efforts to unravel its intricacies.…”