Identification and Management of a Novel PRDM5 Gene Pathologic Variant in a Family With Brittle Cornea Syndrome.

PURPOSE: The aim of this study was to report a novel PRDM5 pathologic variant and ophthalmic findings in a family with 3 children diagnosed with brittle cornea syndrome (BCS). Histopathologic findings and surgical outcome of a child with BCS who underwent full-thickness corneal transplant are described. METHODS: This is an observational case report of a nonconsanguineous Laotian family with 3 siblings diagnosed with BCS. Data collected included visual acuity, cycloplegic refraction, slit-lamp biomicroscopy, dilated fundus examination, corneal pachymetry, corneal topography, and general medical findings. Targeted testing through PRDM5 gene sequencing with copy number variation detection was conducted. RESULTS: The 3 siblings included a 12-year-old boy and 8- and 6-year-old sisters, all of whom presented with myopia, blue-tinted sclerae, thin corneas, and variable corneal scarring. All 3 affected children were found to be homozygous for the PRDM5 gene variant c.1117_1123delinsTTTAATGCTTACAAATGTTTG p.Asp373Phefs*57. Coding sequences of PRDM5 and ZNF469 genes were sequenced in their entirety, and this was the only pathologic variant present in this family. The youngest affected sister developed persistent hydrops with severely decreased vision and underwent penetrating keratoplasty. Histopathology revealed severe corneal thinning, diffuse absence of Bowman layer, and ruptured Descemet membrane scrolls. CONCLUSIONS: Three siblings with clinical signs of BCS, including corneal thinning, myopia, and blue sclerae, were found to have a novel PRDM5 gene pathologic variant. This pathologic variant has not been previously reported, although 1 downstream nonsense pathologic variant has been reported as pathogenic. The similar phenotypes in all affected patients support the pathogenicity of this variant. Surgical management of BCS presents unique challenges due to severe tissue fragility.

Geographic and socioeconomic access disparities to Phase 3 clinical trials in ophthalmology in the United States.

BACKGROUND/OBJECTIVE: To identify geographic and socioeconomic variables associated with residential proximity to Phase 3 ophthalmology clinical trial sites. METHODS: The geographic location of clinical trial sites for Phase 3 clinical trials in ophthalmology was identified using ClinicalTrials.gov. Driving time from each United States (US) census tract centroid to nearest clinical trial site was calculated using real traffic patterns. Travel data were crosslinked to census-tract level public datasets from United States Census Bureau American Community Survey (ACS). Cross-sectional multivariable regression was used to identify associations between census-tract sociodemographic factors and driving time (>60 min) from each census tract centroid to the nearest clinical trial site. RESULTS: There were 2330 unique clinical trial sites and 71,897 census tracts. Shortest median time was to retina sites [33.7 min (18.7, 70.1 min)]. Longest median time was to neuro-ophthalmology sites [119.8 min (48.7, 240.4 min)]. Driving >60 min was associated with rural tracts [adjusted odds ratio (aOR) 7.60; 95% CI (5.66-10.20), p < 0.0001]; Midwest [aOR 1.84(1.15-2.96), p = 0.01], South [aOR 2.57 (1.38-4.79), p < 0.01], and West [aOR 2.52 (1.52-4.17), p < 0.001] v. Northeast; and tracts with higher visual impairment [aOR 1.07 (1.03-1.10), p < 0.001)]; higher poverty levels [4th v.1st Quartile of population below poverty, aOR 2.26 (1.72-2.98), p < 0.0001]; and lower education levels [high school v. Bachelor's degree or higher aOR 1.02 (1.00-1.03), p = 0.0072]. CONCLUSIONS: There are significant geographic and socioeconomic disparities in access to ophthalmology clinical trial sites for rural, non-Northeastern, poorer, and lower education level census tracts, and for census tracts with higher levels of self-reported visual impairment.

The risk of uveitis due to prostaglandin analogs in pediatric glaucoma.

PURPOSE: To examine the incidence of uveitis in children prescribed prostaglandin analogs (PGAs) for glaucoma. METHODS: In this dual-center cohort study, the medical records of consecutive patients <18 years old treated with a PGA between January 1, 2012, and December 31, 2018, were reviewed retrospectively. Patients with all forms of glaucoma, including those with a prior history of uveitis, were included. Patients who had been on a PGA prior to their first recorded visit were excluded. Patient charts were reviewed for new or recurrent uveitis during the first year of PGA therapy. RESULTS: A total of 103 children (147 eyes) were included, with a total PGA exposure of 1,352 child-months. Ninety-eight children (142 eyes) tolerated the PGA without an episode of uveitis. Five patients with a documented prior history of uveitis experienced a unilateral episode of uveitis. A review of their medical records identified prescribed or unscheduled decrease in topical steroids or immunosuppressive medication as the most likely cause of uveitis recurrence. CONCLUSIONS: This study provides further evidence that PGAs are unlikely to induce uveitis in children being treated for glaucoma and suggests that this may also be true in those with a history of uveitis. We are unable to evaluate whether PGAs make recurrence more likely or the tapering of steroids more difficult.

Persistent epithelial defect after photorefractive keratectomy in a patient with autism.

Refractive surgery has been performed under general anesthesia on pediatric and neurobehaviorally challenged adults without reported loss of vision or serious complications. Persistent epithelial defect (PED) is a rare complication of photorefractive keratectomy (PRK) in the general refractive surgery population. We report a case of PED following PRK under general anesthesia for high myopia in a man with autism and ocular history of juvenile open-angle glaucoma and dry eye syndrome.