Iris Concavity, Corneal Biomechanics, and Their Correlations With Ocular Biometry in a Cohort of 10-to 12- Year-Old UK School Boys: Baseline Data

PURPOSE. Pigment dispersion syndrome is associated with iris concavity. This study investigated the prevalence of iris concavity, defined as a measurement of À0.1 mm, in a cohort of 10-to 12-year-old boys, and explored the relationship between iris curvature and anterior segment biometry. Associations with corneal biomechanical parameters also were explored. METHODS. A cohort of school boys (n ¼ 96) was recruited from a local school. Anterior segment optical coherence tomography (AS-OCT) was performed under accommodative and nonaccommodative conditions, and iris curvature quantified. Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured with the ocular response analyzer (ORA). Noncontact axial biometry was performed using laser interferometry. RESULTS. The prevalence of iris concavity was 24% on distance fixation, increasing to 65% on accommodation. Variables significantly associated with nonaccommodating iris curvature were lens vault (P ¼ 0.02) and mean keratometry (P ¼ 0.02). For both variables acting jointly, R 2 ¼ 0.30. Variables associated significantly with accommodating iris curvature were anterior chamber depth (P ¼ 0.009), lens vault (P ¼ 0.049), and mean scleral spur angle (P < 0.0001). For these three variables acting jointly, R 2 ¼ 0.33. Significant association was found between CH and spur-to-spur distance (R 2 ¼ 0.07, P ¼ 0.025). CONCLUSIONS. Iris concavity was a common finding in this cohort and related to anterior segment biometric parameters. Further work is required to clarify whether anatomical differences exist between iris concavity seen in the adolescent eye and that found in adults with pigment dispersion syndrome

A synonymous codon variant in two patients with autosomal recessive bestrophinopathy alters in vitro splicing of BEST1

Purpose: Autosomal recessive bestrophinopathy (ARB) is a newly defined retinal dystrophy caused by biallelic mutations in bestrophin-1 (BEST1) and is hypothesized to represent the null bestrophin-1 phenotype in humans. The aim was to determine whether a synonymous BEST1 variant, c.102C>T, identified in two unrelated ARB patients, alters pre-mRNA splicing of the gene. Additionally a detailed phenotypic characterization of this distinctive condition is presented for both patients.Methods: BEST1 was analyzed by direct sequencing. Patients underwent standard ophthalmic assessment. In silico and in vitro analysis using a minigene system was performed to assess whether a synonymous variant identified, c.102C>T p.Gly34Gly, alters pre-mRNA splicing of BEST1.Results: Both ARB patients harbored either proven (patient 1; c.102C>T p.Gly34Gly and c.572T>C p.Leu191Pro) or presumed (patient 2; c.102C>T p.Gly34Gly and c.1470_1471delCA, p.His490GlnfsX24) biallelic mutations in BEST1 and were found to have phenotypes consistent with ARB. In vitro analysis of the synonymous variant, c.102C>T p.Gly34Gly, demonstrated it to introduce a cryptic splice donor site 52 nucleotides upstream of the actual splice donor site.Conclusions: The novel BEST1 variant identified, c.102C>T p.Gly34Gly, alters pre-mRNA splicing in vitro and is potentially pathogenic. In vivo this splicing variant is predicted to lead to the production of an mRNA transcript with a premature termination codon (p.Glu35TrpfsX11) that is predicted to be degraded by NMD

The treatment of refractory angle-closure glaucoma in a patient with X-linked juvenile retinoschisis

<p>X-Linked Retinoschisis (XLRS) is a common genetically determined form of macular degeneration affecting young males. XLRS is due to mutations in the RS1 gene located on chromosome Xp22 which codes for retinoschisin and is estimated to affect between 1:5000 to 1:20000 individuals worldwide.</p> <p>We report a case of refractory angle-closure glaucoma in a thirty-nine-year-old Caucasian man with atypical XLRS. The patient presented with a two-day history of left eye pain, acutely reduced vision and a nine-month history of hemicranial pain. Examination identified left intraocular pressure (IOP) of 52mmHg. Gonioscopy confirmed complete angle closure.</p> <p>Following failure of medical management and persistently raised left IOP (43-46mmHg), the patient underwent left phacoemulsification and intraocular lens insertion without complication. After surgery, his IOP reduced to 10-14mmHg on all follow up examinations without the need for glaucoma drops. His iridocorneal angle remained open and vision improved to 20/100.</p> <p>Our case demonstrates the additional role of lens surgery in the treatment of secondary angle-closure glaucoma in the presence of an inherited retinal dystrophy. All patients with inherited retinopathy presenting with a headache or eye pain should undergo gonioscopic examination to exclude angle-closure glaucoma.</p

A new paradigm for delivering personalised care:integrating genetics with surgical interventions in BEST1 mutations

BACKGROUND: The availability and reduced cost of genotyping has improved gene susceptibility testing and our scientific understanding of disease pathophysiology. Whilst several personalised translational models exist within medical frameworks, genetic-based surgical therapy is a translational application not widely used in surgical specialties. METHOD: We present a clinical series of five patients with genetically confirmed bestrophinopathy and malignant glaucoma (MG). Patients were followed up for 12 months or more after receiving surgical intervention to manage refractory intraocular pressure (IOP) resistant to medical treatment. FINDINGS: Patients with BEST1 gene mutations are at higher risk of MG after filtration surgery. A multi-disciplinary approach after four patients experienced poor outcomes concluded that traditional first-line glaucoma surgery was not sufficient to prevent visual loss. A fifth patient presenting with the identified at-risk phenotype underwent primary pars plana vitrectomy, with pars plana Baerveldt tube insertion, successfully preventing MG and had no glaucoma progression after 5 years. INTERPRETATION: We provide proof-of-principle that genetic analysis can be used to inform the selection of surgical therapy to improve outcomes. In this case, a refinement of current surgical methods to avoid MG. Although challenges remain, personalised surgery has the potential to improve clinical outcomes beyond the scope of current surgical practice