Ocular pathology of uncommon hematologic malignancies: a case series

<p>Abstract</p> <p>Introduction</p> <p>In general, ocular complications of hematologic malignancies such as leukemia are well documented. However, reports of ocular involvement in such diseases as lymphomatoid granulomatosis and chronic myelomonocytic leukemia are uncommon. Here we present cases of these two relatively rare hematologic malignancies demonstrating clinical and subclinical ocular involvement.</p> <p>Case Presentation</p> <p>In the first case, a 54-year-old man with a previous diagnosis of lymphomatoid granulomatosis presented with a new-onset conjunctival lesion while his systemic disease was thought to be in remission. A biopsy was taken that revealed heavy infiltrates of B and T cells at the site of the lesion. Molecular analysis confirmed that these cells were positive for both Epstein-Barr viral DNA and immunoglobulin heavy chain gene rearrangement, consistent with a manifestation of his systemic disease. In the second case, a 51-year-old man with chronic myelomonocytic leukemia died after a waxing and waning clinical course. Post-mortem studies revealed the presence of atypical monocytes in the choroidal and subretinal spaces, consistent with his previous diagnosis.</p> <p>Conclusion</p> <p>While ocular involvement in hematologic malignancies is not uncommon, these two cases describe involvement of the eye by two relatively rare neoplasms. We herein emphasize novel findings in each case, including conjunctival involvement as the first sign of recurrent lymphomatoid granulomatosis and the combination of subretinal and choroidal myelomonocytic leukemic infiltration. With the evolution of new antineoplastic therapies that may prolong life, these cases exemplify the importance of eye care in patients diagnosed with hematologic malignancies.</p

Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing

Abstract Recombinant adeno-associated viral (AAV) vectors are a promising gene delivery platform, but ongoing clinical trials continue to highlight a relatively narrow therapeutic window. Effective clinical translation is confounded, at least in part, by differences in AAV biology across animal species. Here, we tackle this challenge by sequentially evolving AAV capsid libraries in mice, pigs and macaques. We discover a highly potent, cross-species compatible variant (AAV.cc47) that shows improved attributes benchmarked against AAV serotype 9 as evidenced by robust reporter and therapeutic gene expression, Cre recombination and CRISPR genome editing in normal and diseased mouse models. Enhanced transduction efficiency of AAV.cc47 vectors is further corroborated in macaques and pigs, providing a strong rationale for potential clinical translation into human gene therapies. We envision that ccAAV vectors may not only improve predictive modeling in preclinical studies, but also clinical translatability by broadening the therapeutic window of AAV based gene therapies