Emma Duignan

A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration

Background The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa. Methods A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies. Results Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function. Conclusion These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse.

Panel-Based Population Next-Generation Sequencing for Inherited Retinal Degenerations.

Inherited retinopathies affect approximately two and a half million people globally, yet the majority of affected patients lack clear genetic diagnoses given the diverse range of genes and mutations implicated in these conditions. We present results from a next-generation sequencing study of a large inherited retinal disease patient population, with the goal of providing clear and actionable genetic diagnoses. Targeted sequencing was performed on 539 individuals from 309 inherited retinal disease pedigrees. Causative mutations were identified in the majority (57%, 176/309) of pedigrees. We report the association of many previously unreported variants with retinal disease, as well as new disease phenotypes associated with known genes, including the first association of the SLC24A1 gene with retinitis pigmentosa. Population statistics reporting the genes most commonly implicated in retinal disease in the cohort are presented, as are some diagnostic conundrums that can arise during such studies. Inherited retinal diseases represent an exemplar group of disorders for the application of panel-based next-generation sequencing as an effective tool for detection of causative mutations.

Corneal inlay implantation complicated by infectious keratitis

Background/aims To report five cases of infectious keratitis following corneal inlay implantation for the surgical correction of presbyopia. Methods This was a retrospective, observational case series. Five eyes of five patients were identified consecutively in two emergency departments during a 1-year period, from November 2013 to November 2014. Patients’ demographics, clinical features, treatment and outcomes are described. Results There were four female patients and one male, aged 52–64 years. Three patients had the KAMRA inlay (AcuFocus) and two had the Flexivue Microlens inlay (Presbia Coöperatief U.A.) inserted for the treatment of presbyopia and they presented from 6 days to 4 months postoperatively. Presenting uncorrected vision ranged from 6/38 to counting fingers. One patients corneal scrapings were positive for a putatively causative organism, Corynebacterium pseudodiphtheriticum, and all patients responded to broad-spectrum fortified topical antibiotics. All patients lost vision with final uncorrected visual acuity ranging from 6/12 to 6/60 and best-corrected vision ranging from 6/7.5 to 6/12. Two patients’ corneal inlays were explanted and three remained in situ at last follow-up. Conclusions Infectious keratitis can occur at an early or late stage following corneal inlay implantation. Final visual acuity can be limited by stromal scarring; in the cases where the infiltrate was small and off the visual axis at the time of presentation, the final visual acuity was better than those patients who presented with larger lesions affecting the visual axis. Though infection may necessitate removal of the inlay, early positive response to treatment may enable the inlay to be left in situ.

Long-term visual acuity, retention and complications observed with the type-I and type-II Boston keratoprostheses in an Irish population

Aim To evaluate the outcomes of the type-I and type-II Boston keratoprostheses in a single Irish centre. Methods A retrospective chart review of keratoprosthesis implantations carried out in our institution from November 2002 to March 2014 was performed. All procedures were performed by a single surgeon (WP). Results Thirty-four keratoprosthesis implantations were carried out in 31 patients with a mean follow-up of 42±31 months (range 2–110 months). Seventeen patients were female (54.8%) and 14 were male (45.2%). The majority of keratoprostheses implanted were type-I (31/34, 91.2%), and three were type-II (3/34, 8.8%). Twenty-nine patients (85.3%) had an improvement in distance best-corrected visual acuity (BCVA) from baseline. Fifty per cent (17/34) of patients had a best-ever BCVA of at least 6/12. Eighteen patients (64.3%) retained a BCVA of at least 6/60 at 1 year. Over the course of follow-up, six keratoprostheses were explanted from six eyes of five patients, one of which was a type-II keratoprosthesis. Twenty-six patients (76.5%) developed postoperative complications. Complications included retroprosthetic membrane (18 patients, 52.9%), an exacerbation or new diagnosis of glaucoma (6 patients, 17.6%), endophthalmitis (5 patients, 14.7%) and retinal detachment (2 patients, 5.9%). Conclusions These data demonstrate excellent visual acuity and retention outcomes in a cohort with a long follow-up period in a single centre. Complications remain a considerable source of morbidity. These outcomes provide further evidence for the long-term stability of type-I and type-II Boston keratoprostheses in the management of patients in whom a traditional graft is likely to fail.

The early treatment in Diabetic Retinopathy Study Chart compared with the Tumbling-E and Landolt-C

Visual acuity (VA) is a measure of the visual system’s ability to resolve fine detail and is expressed using the logarithm of the minimal angle of resolution (logMAR), which depends on the angular size of critical detail in optotypes. Charts originally developed for the Early Treatment in Diabetic Retinopathy Study (ETDRS) and subsequently refined have become the gold standard in ophthalmology research and are based on the design principles of Bailey and Lovie; they have logarithmic scales, 5 optotypes per line, and geometric progression in letter size and spacing. The letter size on each line is 1.2589, or 0.1 log units, times bigger than those on the next line and optotypes are the 10 Sloan letters (C, D, H, K, N, O, R, S, V, and Z).