Purpose To evaluate outer retinal structural abnormalities in patients with visual deficits following closed globe blunt ocular trauma (cgBOT). Methods Nine subjects with visual complaints following cgBOT were examined between 1 month post-trauma and 6 years post-trauma. Spectral domain optical coherence tomography (SD-OCT) was used to assess outer retinal architecture, while adaptive optics scanning light ophthalmoscopy (AOSLO) was used to analyze photoreceptor mosaic integrity. Results Visual deficits ranged from central scotomas to decreased visual acuity. SD-OCT defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. AOSLO revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss. Conclusions We observe persistent outer retinal disruption in subjects with visual complaints following cgBOT, albeit to a variable degree. AOSLO imaging allows assessment of photoreceptor structure at a level of detail not resolvable using SD-OCT or other current clinical imaging tools. Multimodal imaging appears useful for revealing the cause of visual complaints in patients following cgBOT. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various trauma.

Devic's disease is often considered as a variant of multiple sclerosis (MS). However, evidence suggests that Devic's disease may be distinct from MS. Devic's disease can coexist with connective tissue diseases, particularly Sjögren's disease, but this association is rare with MS. Diagnosis of Sjögren's disease in patients with neurological symptoms is often difficult. During early stages of Sjögren's disease, patients may not fulfill all criteria for Sjögren's disease. A high percentage of patients with Sjögren's disease have inflammatory infiltrates in minor salivary glands, and this may be a reliable indicator of early or subclinical disease. We show high prevalence (80%) of salivary gland inflammation in Devic's disease and longitudinally extensive transverse myelitis (LETM). We diagnosed 16 patients with Devic's disease, and 2 of these satisfied criteria for Sjögren's disease as did 2 of 9 patients with LETM. Anti-SSA/B titers were infrequently elevated. Although most did not satisfy criteria for Sjögren's disease. 9 of 12 Devic's disease patients and 7 of 8 LETM patients had severe salivary gland inflammation. Thus: (1) patients with Devic's disease or with LETM who have positive labial biopsies but do not satisfy criteria for Sjögren's disease could have subclinical Sjögren's diseases. Alternatively, (2) as patients with Devic's disease have elevated titers of several autoantibodies, so there may exist a set of antibodies that react with antigens in minor salivary glands and cause inflammation. Minor salivary gland biopsy is more sensitive than anti-SSA/B serology in providing histological evidence for possible Sjögren's disease with CNS lesions.

BackgroundIpilimumab, a humanized CLTA-4 antibody is a standard therapy in the treatment of advanced melanoma. While ipilimumab provides an overall survival benefit to patients, it can be associated with immune related adverse events (IrAEs).Case presentationHere we describe a patient treated with ipilimumab who experienced known IrAEs, including hypophysitis, as well as a profound vision loss due to optic neuritis. There are rare reports of optic neuritis occurring as an adverse event associated with ipilimumab treatment. Furthermore, the patient experienced multiple complications from high dose steroids used to manage his IrAEs.ConclusionsThis case highlights the need for recognition of atypical immune mediated processes associated with newer checkpoint inhibitor therapies including ipilimumab.

Background: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. Methods: A survey was distributed through the secure electronic data collection tool REDCap to neuroophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. Results: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/ 31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven

Lessons Learned Hyperfractionation of lutetium‐177 (177Lu)‐J591 for patients with metastatic castration‐resistant prostate cancer did not appear to have any additional advantage over the single dose 177Lu‐J591 or fractionated two‐dose 177Lu‐J591 therapy. Definite conclusions were challenging because of the small sample size of this study, and so further studies are needed to evaluate the viability of the hypothesis. On the basis of available data, a registration study of 177Lu‐J591 (also known as TLX591) is planned and will use the two‐dose fractionation schedule (Telix Pharma Q3 2019 update https://telixpharma.com/news-media/). Background Phase I and II single‐dose studies of lutetium‐177 (177Lu)‐J591, a radio‐labeled antibody binding prostate‐specific membrane antigen (PSMA), demonstrated safety and efficacy with dose response. Modest dose fractionation of 177Lu‐J591 (2 doses) has less myelosuppression per similar cumulative dose, allowing higher doses to be administered safely. We hypothesized that additional dose fractionation would allow a higher cumulative dose, potentially with less toxicity and more efficacy. Methods Men with progressive metastatic castration‐resistant prostate cancer and adequate organ function were enrolled. 177Lu‐J591 was administered at 25 mCi/m2 every 2 weeks until the emergence of related grade 2 toxicity. 177Lu‐J591 imaging was performed and circulating tumor cell (CTC) counts were measured before and after treatment along with standard monitoring. Results Six subjects in a single cohort, with a median age of 68.6 years, were enrolled. Patients received three to six doses (cumulative 75−150 mCi/m2). Two (33%) patients had >30% prostate‐specific antigen (PSA) decline and three (50%) had CTC count decline. Two (33%) experienced grade (Gr) 4 neutropenia (without fever), three (50%) had Gr 4 thrombocytopenia (without hemorrhage), and two (33%) required platelet transfusions. Following hematological improvement, two patients developed worsening cytopenia during prostate cancer progression; bone marrow biopsies revealed infiltrative tumor replacing normal marrow elements without myelodysplasia. Targeting of known disease sites was seen on planar imaging in all. Conclusion Hyperfractionation of 177Lu‐J591 is feasible but does not seem to have significant advantages over the two‐dose fractionation regimen.