Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene

Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma

<p>Abstract</p> <p>Background</p> <p>CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated.</p> <p>Methods</p> <p>Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206) at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1) tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2) activation HLA-DR and memory CD45RO markers on CD4⁺/CD8⁺cells; and 3) real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis.</p> <p>Results</p> <p>Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8⁺cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup.</p> <p>Conclusion</p> <p>Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood.</p> <p>Clinical trial registration number</p> <p>NCT00086489</p

Jules Stein, MD Ophthalmologist, Entertainment Magnate, and Advocate for Vision

PurposeTo report the lifetime activities and accomplishments of Jules Stein, MD.DesignRetrospective review.MethodsAssessment of published and unpublished biographical material.ResultsJules Stein combined his love of music and medicine with organizational skills to achieve successive careers as a musician, an ophthalmologist, an entertainment magnate, and an advocate for vision. To preserve vision, he founded Research to Prevent Blindness, founded the Jules Stein Eye Institute at the University of California, Los Angeles, and led a multiyear campaign to establish the National Eye Institute.ConclusionsWith successive careers and extraordinary achievements, Jules Stein created an enduring legacy of benefits to ophthalmology, vision research, and the prevention of blindness

Bilateral Acquired Progressive Retinal Nerve Fiber Layer Myelination.

The authors present the multimodal imaging findings of an unusual case of bilateral acquired progressive myelination of the optic disc during a 10-year follow-up period in a hyperopic adolescent patient in the absence of an underlying ocular or systemic abnormality. Myelination of the left optic disc was noted at age 7 and of the right optic disc at age 13, but no other ocular or systemic abnormalities were identified. Cross-sectional optical coherence tomography (OCT) and en face OCT angiography confirmed the presence of myelination of the retinal nerve fiber layer and excluded other etiologic possibilities including an astrocytic hamartoma. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e147-e150.]

Bilateral Acquired Progressive Retinal Nerve Fiber Layer Myelination

The authors present the multimodal imaging findings of an unusual case of bilateral acquired progressive myelination of the optic disc during a 10-year follow-up period in a hyperopic adolescent patient in the absence of an underlying ocular or systemic abnormality. Myelination of the left optic disc was noted at age 7 and of the right optic disc at age 13, but no other ocular or systemic abnormalities were identified. Cross-sectional optical coherence tomography (OCT) and en face OCT angiography confirmed the presence of myelination of the retinal nerve fiber layer and excluded other etiologic possibilities including an astrocytic hamartoma. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e147-e150.]