Ophthalmic findings in Alström syndrome.

IMPORTANCE: Alström syndrome is a rare genetic disorder characterized by retinopathy and has life-threatening complications. Alström syndrome is frequently misdiagnosed or confused with other early childhood disorders with retinopathy.  Understanding the spectrum of ocular manifestations of Alström syndrome is essential for ophthalmologists to recognize the cause and institute-appropriate care for this disorder that requires multidisciplinary attention. OBJECTIVE: To quantify and summarize the common ocular findings of Alström syndrome. DESIGN: Case series, clinical exam data obtained from 2015 to 2023. SETTING: Semiannual multidisciplinary Alström syndrome clinics (2015-2023) at the Greater Baltimore Medical Center (GBMC), organized by Alström Syndrome International (ASI). PARTICIPANTS: Forty-eight patients (38 children, 10 adults) with a known diagnosis of Alström syndrome participated in the semiannual multidisciplinary Alström syndrome clinics. Patients apply to be seen and are accepted based on need and capacity. INTERVENTION(S) OR EXPOSURE(S): Not applicable. MAIN OUTCOME(S) AND MEASURE(S): Clinical ocular findings. RESULTS: Participants in this study had a median age of 8 years (15 months to 42 years). Visual acuity and progression of vision loss varied. The youngest patient who was legally blind was 2 years old. The oldest patient who maintained useful vision was 7 years old. All patients 8 years old or older were legally blind. Nystagmus (94%, 45 of 48) and photophobia (73%, 35 of 48) were the most common first presenting ocular symptoms in childhood. Retinal vascular attenuation (91%, 40 of 44) and retinal internal limiting membrane changes (68%, 30 of 44) were the most commonly documented retinal findings in both children and adults followed by optic nerve (ON) pallor and retinal pigment epithelium (RPE) mottling. Less than half of the children had ON pallor (38%, 14 of 37) and RPEmottling (38%, 14 of 37), while all adults had these two findings (100%, 7 of 7). Retinal pigment clumps were not common in children (11%, 4 of 37), while common in adults (86%, 6 of 7). CONCLUSIONS AND RELEVANCE: Knowledge of these ocular findings is key to promptly recognize Alström syndrome. The ocular phenotype of Alström syndrome is largely dependent on age, suggesting that low vision interventions and potential gene-based therapeutics should target children with this disorder.

Question: What are the common ocular findings in Alström syndrome?Findings: In this case series study that included 48 patients with Alström syndrome, common ocular findings were retinal vascular attenuation and retinal internal limiting membrane changes documented in both children and adults. Optic nerve (ON) pallor and retinal pigment epithelium (RPE) mottling were relatively less common.Meaning: Knowledge of these clinical findings is essential to recognize this potentially vision- and life-threatening condition and to guide the optimal timing for receiving gene-based treatment in the future.

Advancing health equity in pediatric eye care: the role of school-based vision programs, research, advocacy, community engagement, and medical education.

Disparities in access to pediatric vision care for school-age children remain a pressing issue in the United States. School-based vision programs (SBVPs) are regarded as a means to advance health equity, especially for disadvantaged students. While SBVPs can be beneficial, these programs are only part of the solution. Interdisciplinary collaborations are needed to strengthen the pediatric eye care delivery system and advocate for broader access to needed eye services. This discussion will frame the role of SBVPs in conjunction with research, advocacy, community engagement, and medical education to advance health equity in pediatric eye care.

Depression, Anxiety, and Stress in Parents of Patients With Retinoblastoma.

PURPOSE: To assess depression, anxiety, and stress in parents of patients with retinoblastoma and to evaluate the impact of unifocal vs multifocal retinoblastoma. METHODS: A cross-sectional, self-reported psychological assessment of parents of patients with retinoblastoma at a tertiary care ocular oncology center was performed. The Beck Depression Inventory-II (BDI), Beck Anxiety Inventory (BAI), The Parental Stress Index 4-Short Form, and a retinoblastoma Knowledge Assessment questionnaire were administered. Descriptive statistics for outcomes and comparative analyses were made. RESULTS: There were 138 parents of children with retinoblastoma (unifocal: n = 77, multifocal: n = 61). Overall, parents displayed mild, moderate, or severe depression (BDI) (n = 37, 26.7%); mild, moderate, or severe anxiety (BAI) (n = 49, 35.8%), and stress scores within normal limits (n = 138, 100%). A comparison (unifocal vs multifocal) revealed parents of children with multifocal retinoblastoma with severe depression (1.4% vs 10.2%, P < .02), and no differences in anxiety or stress. Factors associated with moderate or severe parental depression included previous history of depression (30.0% vs 3.9%, P < .001) and factors for moderate or severe anxiety included previous history of depression (33.3% vs 8.6%, P < .001), parent highest level of education at high school or less vs college or beyond (29.2% vs 10.9%, P = .031), and parental report of "child developmental delay" (31.5% vs 11.3%, P = .019). CONCLUSIONS: The majority of parents displayed minimal depression (73.3%), anxiety (64.2%), or stress (100%). However, severe depression is more often found in those whose children have multifocal disease, and previous history of depression and less education can impact psychological function. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Strabismus in cerebral palsy: when and why to operate.

Cerebral palsy (CP) is the most common physical disability in children. Orthoptists and ophthalmologists who care for children with CP know that strabismus is a common feature. This paper reviews the literature on strabismus in patients with CP, and then provides summary data and recommendations for management of these patients. The incidence of strabismus in patients with CP, especially in patients with spastic diplegia, is much higher than in neurologically normal children. Esotropia is the most common ocular misalignment. CP patients with strabismus benefit from nonsurgical treatment and should be treated promptly. Strabismus surgery should be considered in CP patients for psychosocial reasons as well as for potential successful ocular realignment and restoration of binocular vision. The literature is lacking in a long-term natural history study, prospective strabismus surgery studies, and long-term outcome studies of strabismus management in patients with CP.

Ocular manifestations of autism in ophthalmology.

PURPOSE: To highlight the ocular manifestations of autism spectrum disorders in a retrospective chart review of the Greater Baltimore Medical Center (GBMC) among children in the pediatric ophthalmology practice setting. DESIGN: Retrospective chart review. Forty-four patients diagnosed with an autism spectrum disorder (ASD) between January 2007 and October 2011 were examined by an orthoptist, orthoptic student, and a pediatric ophthalmologist. RESULTS: Fifty-two percent of patients with ASD at GBMC were found to have an ocular abnormality, with 41% having strabismus, 27% with significant refractive error, 7% with anisometropia, and 11% with amblyopia. CONCLUSION: The prevalence of strabismus, amblyopia, and anisometropia were found to be higher among patients with ASD seen at the GBMC pediatric ophthalmology practice than in the general population.

Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance.

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.

Repeat probing for treatment of persistent nasolacrimal duct obstruction.

Repeat probing of the nasolacrimal duct is one treatment option for children with persistent symptoms of nasolacrimal duct obstruction (NLDO) following an initial probing. The authors conducted a prospective, multicenter study in which 20 subjects age 6 to <48 months underwent a repeat probing for symptomatic NLDO and had follow-up visits 1 month and 6 months after surgery. Treatment success was defined as the absence of all three clinical signs of nasolacrimal duct obstruction-epiphora, increased tear lake, and mucous discharge. Repeat probing was successful in 56%(95% CI, 33%-76%) of cases.

CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX.

BACKGROUND: To learn about the molecular etiology of strabismus, we are studying the genetic basis of 'congenital fibrosis of the extraocular muscles' (CFEOM). These syndromes are characterized by congenital restrictive ophthalmoplegia affecting muscles in the oculomotor and trochlear nerve distribution. Individuals with the classic form of CFEOM are born with bilateral ptosis and infraducted globes. When all affected members of a family have classic CFEOM, we classify the family as a CFEOM1 pedigree. We have previously determined that a CFEOM1 gene maps to the FEOM1 locus on chromosome 12cen. We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in ARIX, the CFEOM2 disease gene. RESULTS: Eleven new CFEOM1 pedigrees were identified. All demonstrated autosomal dominant inheritance, and nine were consistent with linkage to FEOM1. Two small CFEOM1 families were not linked to FEOM1, and both were consistent with linkage to FEOM3. We screened two CFEOM1 families consistent with linkage to FEOM2 and 5 sporadic individuals with classic CFEOM and did not detect ARIX mutations. CONCLUSIONS: The phenotype of two small CFEOM1 families does not map to FEOM1, establishing genetic heterogeneity for this disorder. These two families may harbor mutations in the FEOM3 gene, as their phenotype is consistent with linkage to this locus. Thus far, we have not identified ARIX mutations in any affected members of CFEOM1 pedigrees or in any sporadic cases of classic CFEOM.