Kraker, Jessica A.

ABSTRACT Stickler syndrome is most commonly caused by variants in COL2A1 and COL11A1 genes. The purpose of this study was to describe genetic variants and phenotypes in COL2A1 and COL11A1 Stickler syndrome. We performed a retrospective genotype–phenotype evaluation of COL2A1 and COL11A1 Stickler syndrome subjects. Thirty‐two subjects with COL2A1 and 13 subjects with COL11A1 Stickler syndrome were last seen in clinic at a mean age of 17.2 ± 13.1 and 12.6 ± 3.8 years, respectively ( p = 0.08). We found that 50% of COL2A1 subjects had lattice degeneration, whereas 8% of the COL11A1 subjects had lattice degeneration ( p = 0.015). The most common type of variant for COL2A1 Stickler syndrome was a premature termination codon (12 out of 18 families, 67%); and the most common types of variants for COL11A1 Stickler syndrome were glycine missense variants (4 out of 10 families, 40%) and splice site variants (4 out of 10 families, 40%). There was a higher rate of lattice degeneration in COL2A1 patients compared with COL11A1 patients, a finding that could be influenced by a trend towards older age at last follow‐up in the COL2A1 group.

Purpose: To evaluate the role of women physicians in thyroid eye disease (TED) research and clinical care and describe relevance for academic medicine and patient access. Methods: A cross-sectional study of TED-related publications indexed on PubMed in 2000, 2010, and 2020, and of completed or currently active clinical trials was conducted. Author, journal, and principal investigator (PI) characteristics were noted. Author/PI gender was determined from institutional profile or subsequently via a previously described Google-based algorithm. American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS), American Board of Ophthalmology (ABO), and American Thyroid Association (ATA) information was obtained via direct communication. Trends in participation of men and women were evaluated. Results: A total of 444 manuscripts (61 from 2000; 117 from 2010; 266 from 2020) were included. The percentage of women as first and senior authors increased from 2000 to 2020 (p < 0.0001 and p = 0.0003, resp.). First author gender distribution was near equal in 2020 (52.6% men, 47.4% women [p = 0.39]), whereas senior authors remained mostly men (68.0% men, 32.0% women [p < 0.0001]). As of 2020, the gender imbalance of senior authors was greater on multidisciplinary author teams (74.8% men, 25.2% women) compared with single specialty author teams (62.2% men, 37.8% women). Of the 98 TED-related clinical trials included, 34 had women PIs (35%). The percentage of women as members in ASOPRS, ABO, and ATA all increased significantly from 2000 to 2020, but remained disproportionately men in 2020 (all p < 0.0001). Conclusion: Gender-based discrepancies persist in TED research, especially among senior authors, who determine research direction, and on multidisciplinary teams, which reflect the preferred model of care. Further efforts are required to determine whether these findings affect patients with TED.

Purpose: We describe a case of nontraumatic macular hole in a pediatric patient associated with numerous epiretinal lesions throughout the macula. Methods: A healthy 9-year-old girl presented to retina clinic with several months of blurry vision in the right eye. Clinically, there was a full-thickness macular hole with serous detachment and white epiretinal tufts. Spectral-domain optical coherence tomography confirmed the presence of the full-thickness macular hole with hyperreflective epiretinal proliferations in the right eye and an unremarkable left eye. Systemic workup was negative. After a short period of observation, the patient underwent vitrectomy with internal limiting membrane peel and 14% C3F8 gas tamponade in the right eye. Multiple intraoperative samples were sent for further testing, which were also negative. Results: At 1- and 12 months/1 year postoperative visits, examination showed successful closure of the full-thickness macular hole with resolution of the subretinal fluid and improved VA. Conclusion: Nontraumatic macular holes in pediatric patients warrant systemic and ocular workup, including fluorescein angiography and laboratory testing. Good anatomic and visual outcomes are generally seen with spontaneous and surgical closures of macular holes in this age group. Early vitrectomy with histologic analysis of ocular samples should be considered in pediatric macular hole cases associated with vitreoretinal traction, especially those with epiretinal abnormalities.

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficient levels and/or activity of glycosaminoglycan (GAG)-degradative enzymes. MPS are characterized by accumulation of the mucopolysaccharides heparan sulfate, dermatan sulfate, keratan sulfate, or chondroitin sulfate in tissues. We report the case of a 38-year-old woman with a history of joint restriction and retinitis pigmentosa who developed bivalvular heart failure requiring surgery. It was not until pathological examination of surgically excised valvular tissue that a diagnosis of MPS I was made. Her musculoskeletal and ophthalmologic symptoms, when placed in the context of MPS I, painted the diagnostic picture of a genetic syndrome that was overlooked until a diagnosis was made in late middle age.