Evolution of Autoimmune Retinopathy in Stiff Person Syndrome: A Case Report.

PURPOSE: To report a case of autoimmune retinopathy (AIR) as the presenting feature of Stiff Person Syndrome (SPS) and assess its evolution. OBSERVATIONS: A 35-year-old man presented with progressive, chronic, vision loss. On initial examination, visual acuity measured 20/20 OD and 20/50 OS. Humphrey Visual Field testing (HVF) demonstrated decreased foveal threshold OU. Mild subfoveal ellipsoid zone loss was noted on Optical Coherence Tomography (OCT). Five years later the patient presented with painful lower extremity muscle spasms and stiffness and complained of increasing vision loss with difficulty distinguishing colors. OCT showed marked progression of ellipsoid zone loss. Scotoma were demonstrated on HVF and electroretinography demonstrated reduced responses consistent with bilateral severe maculopathy. Serum testing showed autoantibodies to the glutamic acid decarboxylase 65-kilodalton isoform (GAD65) at a high titer and a diagnosis of AIR in the setting of SPS was made. A systemic workup for malignancy was negative. The patient was treated with IVIG and transitioned to rituximab with improvement in systemic symptoms. CONCLUSIONS: and Importance: Unlike previous cases of AIR in the setting of SPS, vision symptoms and OCT changes presented years before the onset of muscle spasms. Etiologies such as SPS should be on the differential of unexplained retinopathy, even in the absence of systemic symptoms, especially when paraneoplastic etiologies are ruled out.

Risk Factors for Worsening Morphology and Visual Acuity in Eyes with Adult-Onset Foveomacular Vitelliform Dystrophy.

PURPOSE: To explore clinical risk factors and OCT features associated with worse visual acuity (VA), progression of disease, choroidal neovascularization (CNV), and atrophy in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD). DESIGN: Single-center, retrospective, observational cohort study. PARTICIPANTS: Patients seen at Duke Eye Center between January 2012 and May 2023 with a diagnosis of AOFVD confirmed via OCT and fundus autofluorescence. METHODS: Baseline and final-visit images from eyes with AOFVD were examined. Disease stage was assigned, and presence of atrophy or CNV was determined. Clinical and OCT features associated with progression to atrophy and CNV were determined using t tests and chi-square analysis. Correlation with lower VA was determined using linear regression. MAIN OUTCOME MEASURES: Association of clinical characteristics and OCT features with worse VA, progression of disease, CNV, and atrophy as determined by independent t tests, chi-square analysis, and linear regression (P < 0.05). RESULTS: One hundred one eyes (63 patients) met inclusion criteria for this study, with mean follow-up duration of 48 months (standard deviation, 31 months). Fifty-one percent of eyes progressed beyond baseline staging during follow-up; among baseline stage 1 eyes, incidence of atrophy was 0.068/person-year; incidence of CNV was 0.022/person-year. Risk factors for worse final VA were baseline presence of vitreomacular traction ([VMT], P = 0.006), ellipsoid zone attenuation (P = 0.02), and increased lesion height and width (P < 0.001). Predictors of progression include diabetes mellitus (P = 0.01), statin use (P = 0.03), presence of hyperreflective foci (P = 0.01), and increased lesion width and volume (P = 0.03 and P = 0.04, respectively). Predictors of atrophy include the baseline presence of VMT (P = 0.02), decreased choroidal thickness (P = 0.03), and greater maximal height, width, and volume of the lesion (P = 0.03, P = 0.02, and P = 0.009, respectively). Lower baseline VA (P = 0.03) and increased lesion volume (P = 0.04) were associated with CNV. CONCLUSIONS: Clinical and OCT imaging features at baseline may prove useful in stratifying patient risk for progression, atrophy, CNV, and worse VA. Features such as statin use, diabetes, baseline VA, and laterality should be accounted for. OCT features, such as lesion size, VMT, ellipsoid zone attenuation, choroidal thickness, and hyperreflective foci, may impart greater risk of poor outcomes. Future prospective analysis accounting for the time to development of atrophy and CNV is needed. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Glaucoma Fellows-in-Training Recent Surgery Trends.

PURPOSE: The volume of microinvasive glaucoma surgery (MIGS) has increased dramatically in recent years, from 31 059 in 2013 to 69 420 in 2018. We investigated the impact of this trend on trainees by determining the proportion of glaucoma surgeries performed by fellows-in-training comprised by MIGS, trabeculectomies, and aqueous shunts. DESIGN: Retrospective analysis. PARTICIPANTS: Fellows-in-training at Glaucoma Fellowship Programs certified by the Association of University Professors of Ophthalmology Fellowship Compliance Committee (AUPO-FCC) METHODS: We analyzed aggregate summaries of surgeries performed by fellows as reported to the AUPO-FCC from the academic years (AYs) beginning in 2014 through AY 2020. Each report lists the average number of procedures performed per surgery type per fellow. We combined these averages to create a sum "average number surgeries performed" across glaucoma surgeries and computed the proportion that each surgery type (MIGS, trabeculectomies, and aqueous shunts) represented within the total average number of surgeries performed per year. MAIN OUTCOME MEASURES: Average number of procedures performed for each surgery type as well as the proportion that each surgery type (MIGS, trabeculectomies, and aqueous shunts) represented within the total average number of procedures performed per year. RESULTS: Average number of MIGS performed is significantly greater in later years compared with earlier years (P < 0.001). The average number of trabeculectomies performed between AYs 2014 and AY 2020 ranged from 21.8 to 31.9 and decreased, on average, by - 0.80 year-to-year. The average number of aqueous shunts performed between AY 2014 and AY 2020 ranged from 44.7 to 49.5, with an average increase of + 0.8 year-to-year. The total average number of procedures performed (across all 3 surgical subtypes) increased on average by + 4.8 procedures each year. CONCLUSIONS: Since 2014, fellows are performing increasing numbers of MIGS procedures, whereas the total number of trabeculectomies and aqueous shunt surgeries performed each year remain similar, resulting in a net increase in total number of procedures performed per fellow each year. This suggests the increase in MIGS is not associated with a substantial decline in trabeculectomies or aqueous shunts performed by glaucoma fellows. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Small Molecule Antipsychotic Aripiprazole Potentiates Ozone-Induced Inflammation in Airway Epithelium.

Inhaled ground level ozone (O3) has well described adverse health effects, which may be augmented in susceptible populations. While conditions, such as pre-existing respiratory disease, have been identified as factors enhancing susceptibility to O3-induced health effects, the potential for chemical interactions in the lung to sensitize populations to pollutant-induced responses has not yet been studied. In the airways, inhaled O3 reacts with lipids, such as cholesterol, to generate reactive and electrophilic oxysterol species, capable of causing cellular dysfunction and inflammation. The enzyme regulating the final step of cholesterol biosynthesis, 7-dehydrocholesterol reductase (DHCR7), converts 7-dehydrocholesterol (7-DHC) to cholesterol. Inhibition of DHCR7 increases the levels of 7-DHC, which is much more susceptible to oxidation than cholesterol. Chemical analysis established the capacity for a variety of small molecule antipsychotic drugs, like Aripiprazole (APZ), to inhibit DHCR7 and elevate circulating 7-DHC. Our results show that APZ and the known DHCR7 inhibitor, AY9944, increase 7-DHC levels in airway epithelial cells and potentiate O3-induced IL-6 and IL-8 expression and cytokine release. Targeted immune-related gene array analysis demonstrates that APZ significantly modified O3-induced expression of 16 genes, causing dysregulation in expression of genes associated with leukocyte recruitment and inflammatory response. Additionally, we find that APZ increases O3-induced IL-6 and IL-8 expression in human nasal epithelial cells from male but not female donors. Overall, the evidence we provide describes a novel molecular mechanism by which chemicals, such as APZ, that perturb cholesterol biosynthesis affect O3-induced biological responses.