Prevalence of cerebrotendinous xanthomatosis among patients diagnosed with early-onset idiopathic bilateral cataracts: final analysis.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.

Dual phenotype: co-occurring Leber congenital amaurosis and familial exudative vitreoretinopathy: a case report.

PURPOSE: To report the concurrent presentation and management of IQCB1-associated Leber Congenital Amaurosis and NDP-associated Familial Exudative Vitreoretinopathy (FEVR). MATERIALS AND METHODS: A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described. RESULTS: Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone. CONCLUSIONS: The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring.

Long-Term Anatomic and Visual Outcomes of Planned Preterm Delivery and Treatment of Norrie Disease.

We previously reported that planned preterm delivery at 34 weeks gestational age provided an opportunity to treat Norrie disease in the vasoproliferative phase, prevented infantile retinal detachment, and preserved functional vision without further treatment after infancy. Although retinal vascularization did not proceed postnatally, after 8 years of follow-up, the retinas remained attached, and rudimentary foveal development was observed by optical coherence tomography. Best corrected visual acuity gradually improved to 20/80 with both eyes, and visual fields and real-world visual performance were remarkably functional. Global development progressed appropriately, and no long-term sequelae of premature delivery were observed. [Ophthalmic Surg Lasers Imaging Retina 2022;53:464-467.].

Alternative Biologic Therapy in Children Failing Conventional TNFα Inhibitors for Refractory, Noninfectious, Chronic Anterior Uveitis.

PURPOSE: A significant number of children with noninfectious, chronic anterior uveitis (CAU) fail to respond to conventional therapy; however, successful alternative biologic treatments (ABT) have not been well described. This study aims to review the clinical and treatment characteristics of children with CAU who require ABT. DESIGN: Retrospective, nonrandomized clinical study. METHODS: Setting: Tertiary center. STUDY POPULATION: Children with noninfectious CAU. OBSERVATION PROCEDURES: Clinical characteristics, uveitis course, complications, and treatment were compared among patients treated with methotrexate (MTX) monotherapy, conventional TNFα inhibitors (cTNFi), and ABT for >3 months. MAIN OUTCOME MEASURE: Success of ABT (abatacept, tocilizumab, and/or golimumab) in children failing conventional treatment. RESULTS: Of the 52 children with CAU, 75% had juvenile idiopathic arthritis. CAU was controlled in 15 children receiving MTX monotherapy, 28 receiving cTNFi, and 9 receiving ABT (n = 1, abatacept; n = 3, tocilizumab; n = 5, golimumab). Patients in the ABT group had a greater number of total ocular complications per person before ABT than those in the control groups (3.4 vs 0.7 [MTX], P < .001, and 1.5 [cTNFi], P < .001, respectively). In all 9 children on ABT, treatment led to control of CAU and topical glucocorticoids tapered to ≤2 drops/d with no new ocular complications. CONCLUSIONS: In this study, alternative biologics (abatacept, golimumab, and tocilizumab) were useful for treating CAU in children who fail MTX and cTNFi therapy. Patients who were controlled on ABT had more disease activity, ocular complications, and anti-cTNFi neutralizing antibodies (before ABT) than those managed with conventional therapy. Larger studies are required to confirm these findings.

Survey of practice patterns for the management of ophthalmic genetic disorders among AAPOS members: report by the AAPOS Genetic Eye Disease Task Force.

To better understand AAPOS member pediatric ophthalmologists' knowledge and needs regarding genetic eye disorders, the AAPOS Genetic Eye Disease Task Force developed a 16-question survey that was circulated to national and international AAPOS members. Responses to questions on practice patterns, baseline knowledge, and educational interests regarding patients with suspected ophthalmic genetic disorders were collected. A majority of respondents (93%) evaluate patients with suspected genetic disorders. Knowledge gaps were present in heritability of certain conditions, genetic testing strategies, and referral to clinical trials. Most respondents expressed interest in further education in these areas. A model for care is proposed as a first step in the education process.

Gene therapy for RPE65-related retinal disease.

Significant discoveries in the etiology and pathogenesis of inherited retinal diseases (IRDs) have been made in the last few decades. Of the large number genes that cause IRDs, bi-allelic mutations in RPE65 lead to Leber Congenital Amaurosis type 2 (LCA 2), and can also result in phenotypes described as severe early childhood onset retinal dystrophy (SECORD) and Retinitis pigmentosa 20 (RP20). Following the publication of the successful Phase-III clinical trials of gene augmentation surgery for RPE65-related IRDs with voretigene neparvovec, the FDA approved the commercial use of this pharmacologic agent in December 2017. In this perspective, ongoing and completed gene therapy trials for RPE65-related dystrophies are reviewed and challenges in patient selection, counseling and informed consent, as well as financial considerations of commercial treatment are discussed.

Surgical management of lens subluxation in Marfan syndrome.

PURPOSE: To review the literature on the surgical management, describe a simplified surgical technique, and to report the postoperative clinical course of ectopia lentis removal in patients with Marfan syndrome. METHODS: The medical records of patients with a clinical diagnosis of Marfan syndrome and clinically significant lens subluxation were retrospectively reviewed. Patients underwent lens extraction by a single surgeon via a simplified anterior segment approach. The pre- and postoperative best-corrected visual acuity, biometric measurements, intraocular pressure, and incidence of surgery-related complications were reviewed. RESULTS: A total of 42 eyes of 22 patients were included. Mean postoperative follow-up was 4.9 ± 2.9 years (range, 1-10 years). Average age at surgery was 10.2 ± 9.2 years (range, 2-37 years), with 18 patients (36 eyes) ≤ 18 years of age. The average preoperative best-corrected visual acuity was 20/80, and the average postoperative best-corrected visual acuity at last follow-up was 20/25, with an average improvement of 6 lines on the Snellen chart. All eyes had a best-corrected visual acuity > 20/30 at last follow-up with aphakic correction. One eye of 1 patient developed a retinal detachment following blunt trauma. No other intra- or postoperative complications were reported. CONCLUSIONS: Anterior lensectomy and limited vitrectomy with aphakic correction is safe and provides a consistent visual outcome in patients with lens subluxation secondary to Marfan syndrome. This is especially important in pediatric patients, in whom long-term follow-up for iris- and scleral-fixated intraocular lenses is limited.