Mala Subash’s research while affiliated with UCL Eastman Dental Institute and other places

Objective To evaluate the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON). Design Multicenter cohort study Methods The study involved 37 patients with WON carrying pathogenic or candidate pathogenic WFS1 variants. Genetic and clinical data were retrieved from the medical records. Thirteen patients underwent additional comprehensive ophthalmological assessment. Deep phenotyping involved visual electrophysiology and advanced psychophysical testing with a complementary metabolomic study. Main Outcome Measures WFS1 variants, functional and structural optic nerve and retinal parameters, and metabolomic profile. Results Twenty-two recessive and five dominant WFS1 variants were identified. Four variants were novel. All WFS1 variants caused loss of macular retinal ganglion cells (RGCs) as assessed by optical coherence tomography (OCT) and visual electrophysiology. Advanced psychophysical testing indicated involvement of the major RGC subpopulations. Modeling of vision loss showed an accelerated rate of deterioration with increasing age. Dominant WFS1 variants were associated with abnormal reflectivity of the outer plexiform layer (OPL) on OCT imaging. The dominant variants tended to cause less severe vision loss compared with recessive WFS1 variants, which resulted in more variable phenotypes ranging from isolated WON to severe multisystem disease depending on the WFS1 alleles. The metabolomic profile included markers seen in other neurodegenerative diseases and type 1 diabetes mellitus. Conclusions WFS1 variants result in heterogenous phenotypes influenced by the mode of inheritance and the disease-causing alleles. Biallelic WFS1 variants cause more variable, but generally more severe vision and RGC loss compared with heterozygous variants. Abnormal cleft-like lamination of the OPL is a distinctive OCT feature that strongly points towards dominant WON.

This study assessed the barriers to sight impairment certification in the East London Borough of Tower Hamlets amongst patients attending the Diabetic Retinopathy Screening Service (DRSS). All patients who attended DRSS between 1stApril 2009 and 31st of March 2010 and whose recorded best corrected visual acuity (BCVA) at DRSS fulfilled the requirements for sight impairment in the UK were included. An additional 24 patients whose general practitioners (GPs) reported them to be certified blind due to no perception of light (NPL) vision were re-examined to ascertain the reason for certification, and their potential social and visual aids needs. 78 patients were identified with certifiable vision and were reviewed: 10 deceased in the preceding 12 months; 60 were not known to be certified. Of these, 57 attended further assessment, 27 were found to have non-certifiable vision, 9 were referred for further interventions, 9 were certified and 9 were found to be eligible, but declined certification. Five patients were registered due to diabetic eye disease. Of those 24 reported by the GP of NPL vision, only 4 had true NPL, the rest had usable vision. Only two of them were certified blind due to diabetes. Our data shows that sight certification in patients with diabetes might be underestimated and these patients often have non-diabetes related visual loss. We propose that data on certifiable visual impairment could serve, along with existing certification databases, as a resource for quality of care standards assessment and service provision for patients with diabetes.

To describe the clinical features of a case series of patients with unilateral vitelliform maculopathy and the results of screening BEST1 and PRPH2 for disease-causing mutations. This was a retrospective case series study of six patients ascertained over a 2-year period. Ophthalmological examination, fundus photography, autofluorescence imaging, optical coherence tomography and detailed electrophysiological assessment were undertaken. Blood samples were taken for DNA extraction and mutation screening of BEST1 and PRPH2 was performed. Six patients (3 men and 3 women) with unilateral vitelliform maculopathy were identified, ranging in age from 30 to 68 years. Vision in the affected eye ranged from 20/10 to 20/100. There was no clinical, retinal imaging or electrophysiological evidence of fellow eye involvement. Direct sequencing of BEST1 and PRPH2 did not reveal any disease-causing variants. A case series of patients is reported with an unusual unilateral vitelliform phenotype, often associated with good visual function. The patients do not have the typical characteristics associated with age-related maculopathy or any inherited macular disorders, such as Best vitelliform macular dystrophy. Molecular screening of the candidate genes BEST1 and PRPH2 revealed no mutations.