In vivo quasi-elastic light scattering detects molecular changes in the lenses of adolescents with Down syndrome.

Down syndrome (DS) is the most common chromosomal disorder in humans. DS is associated with increased prevalence of several ocular sequelae, including characteristic blue-dot cerulean cataract. DS is accompanied by age-dependent accumulation of Alzheimer's disease (AD) amyloid-ß (Aß) peptides and amyloid pathology in the brain and comorbid early-onset Aß amyloidopathy and colocalizing cataracts in the lens. Quasi-elastic light scattering (QLS) is an established optical technique that noninvasively measures changes in protein size distributions in the human lens in vivo. In this cross-sectional study, lenticular QLS correlation time was decreased in adolescent subjects with DS compared to age-matched control subjects. Clinical QLS was consistent with alterations in relative particle hydrodynamic radius in lenses of adolescents with DS. These correlative results suggest that noninvasive QLS can be used to evaluate molecular changes in the lenses of individuals with DS.

Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder.

A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases σ and δ (PTP σ/δ) is indispensable for intramuscular motor innervation. Despite this, thus far, pathogenic recessive variants in the COL25A1 gene had only been detected in a few patients with isolated ocular congenital cranial dysinnervation disorders. Here we describe five patients from three unrelated families with recessive missense and splice site COL25A1 variants presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype. The clinical features of the older patients remained stable over time, without central nervous system involvement. This study extends the phenotypic and genotypic spectrum of COL25A1 related conditions, and further adds to our knowledge of the complex process of intramuscular motor innervation. Our observations indicate a role for collagen XXV in regulating the appropriate innervation not only of extraocular muscles, but also of bulbar, axial, and limb muscles in the human.

Down syndrome: a review of ocular manifestations.

Down syndrome is the most common genetically mediated intellectual disability. Although many physiologic and pathologic features of Down syndrome are discussed at length in the literature, the ocular manifestations of Down syndrome have seldom been discussed in a comprehensive fashion. Given that Down syndrome has ocular manifestations from the front to the back of the eye, it is important for physicians to become familiar with these manifestations, especially given the prevalence of Down syndrome. This review aims to discuss the varied ophthalmologic manifestations of Down syndrome - including strabismus, amblyopia, nystagmus, accommodation deficits, nasolacrimal duct obstruction, keratoconus, optic nerve pathology, neoplastic disease, and retinal pathology - to facilitate better care and visual outcomes in this important patient population.

In Vivo Quasi-Elastic Light Scattering Eye Scanner Detects Molecular Aging in Humans.

The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo. We used quasi-elastic light scattering (QLS) to measure age-dependent signals in lenses of healthy human subjects. Age-dependent QLS signal changes detected in vivo recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro. Our findings demonstrate that QLS analysis of human lens proteins provides a practical technique for noninvasive assessment of molecular aging in vivo.

Pediatric cataract extraction with intraocular lens implantation: visual acuity outcome when measured at age four years and older.

PURPOSE: Assessment of visual outcome of pediatric eyes that underwent cataract extraction with primary intraocular lens (IOL) implantation at a single center. METHODS: A retrospective review of charts of 510 consecutive pediatric patients that underwent cataract extraction was performed. Exclusion criteria were traumatic cataract, secondary IOL implantation, retinopathy of prematurity, severe developmental delay, age less than 4 years at last follow-up, and follow-up less than 6 months. In bilateral cases, only right eye data were included. RESULTS: One hundred thirty-nine eyes met inclusion criteria. Median age at surgery was 5.12 years (range, 0.03-16.92); median age at last follow-up was 9.05 years, and median follow-up was 3.65 years. Sixty-six of 139 (47.5%) patients had unilateral cataracts compared with 73/139 (52.5%) bilateral cases. The median visual acuity of all eyes was 20/30, with median visual acuity of unilateral and bilateral cases being 20/40 and 20/25, respectively. Older patients achieved better visual acuity (unilateral cases: p = 0.003; bilateral cases: p = 0.07). Eyes with a greater interocular axial length difference achieved poorer visual acuity. Forty-five patients had a final visual acuity worse than 20/40. Of these, 34 (76%) had a diagnosis of amblyopia as the sole cause. Nineteen of 139 (13.7%) eyes had final visual acuity worse than 20/200. Eighteen patients required strabismus surgery, and 22 required additional intraocular surgery. CONCLUSIONS: Better visual acuity was associated with bilateral cataract, older age at surgery, and normal interocular axial length difference. Amblyopia was the major cause of residual visual deficit.

Superior rectus transposition and medial rectus recession for Duane syndrome and sixth nerve palsy.

OBJECTIVE: To describe our results using augmented temporal superior rectus transposition (SRT) with adjustable medial rectus muscle recession (MRc) for treatment of Duane syndrome and sixth nerve palsy. METHODS: Retrospective surgical case review of patients undergoing SRT. Preoperative and postoperative orthoptic measurements were recorded. Minimum follow-up was 6 weeks. Main outcome measures included the angle of esotropia in the primary position and the angle of head turn. Secondary outcomes included duction limitation, stereopsis, and new vertical deviations. RESULTS: The review identified 17 patients: 10 with Duane syndrome and 7 with sixth nerve palsy. Combining SRT with MRc improved esotropia from 44 to 10 prism diopters (P < .001), reduced abduction limitation from -4.3 to -2.7 (P < .001), and improved compensatory head posture from 28° to 4° (P < .001). Stereopsis was recovered in 8 patients (P = .03). Three patients required a reoperation: 1 for overcorrection and 2 for undercorrection. A new primary position vertical deviation was observed in 2 patients with complex sixth nerve palsy and none with Duane syndrome. No patient described torsional diplopia. CONCLUSIONS: Superior rectus transposition allows for the option of simultaneous MRc in patients with severe abduction imitation who require transposition surgery. Combining SRT and MRc improved esotropia, head position, abduction limitation, and stereopsis without inducing torsional diplopia.