Reliability and Repeatability of Cone Density Measurements in Patients With Stargardt Disease and RPGR-Associated Retinopathy.

Purpose: To assess reliability and repeatability of cone density measurements by using confocal and (nonconfocal) split-detector adaptive optics scanning light ophthalmoscopy (AOSLO) imaging. It will be determined whether cone density values are significantly different between modalities in Stargardt disease (STGD) and retinitis pigmentosa GTPase regulator (RPGR)-associated retinopathy.

Methods: Twelve patients with STGD (aged 9-52 years) and eight with RPGR-associated retinopathy (aged 11-31 years) were imaged using both confocal and split-detector AOSLO simultaneously.

A Quantitative and Qualitative Exploration of Photoaversion in Achromatopsia.

Purpose: Photoaversion (PA) is a disabling and ubiquitous feature of achromatopsia (ACHM). We aimed to help define the characteristics of this important symptom, and present the first published assessment of its impact on patients' lives, as well as quantitative and qualitative PA assessments.

Methods: Molecularly confirmed ACHM subjects were assessed for PA using four tasks: structured survey of patient experience, novel quantitative subjective measurement of PA, visual acuities in differing ambient lighting, and objective palpebral aperture-related PA testing.

The Pattern of Retinal Ganglion Cell Loss in OPA1-Related Autosomal Dominant Optic Atrophy Inferred From Temporal, Spatial, and Chromatic Sensitivity Losses.

Purpose: Progressive retinal ganglion cell (RGC) loss is the pathological hallmark of autosomal dominant optic atrophy (DOA) caused by pathogenic OPA1 mutations. The aim of this study was to conduct an in-depth psychophysical study of the visual losses in DOA and to infer any selective vulnerability of visual pathways subserved by different RGC subtypes.

Methods: We recruited 25 patients carrying pathogenic OPA1 mutations and age-matched healthy individuals.

The Effect on Retinal Structure and Function of 15 Specific ABCA4 Mutations: A Detailed Examination of 82 Hemizygous Patients.

Purpose: To determine the effect of 15 individual ABCA4 mutations on disease severity.

Methods: Eighty-two patients harboring 15 distinct ABCA4 mutations in trans with null (hemizygous), 10 homozygous, and 20 nullizygous patients were recruited. Age of onset was determined from medical histories.

Genotype-Phenotype Correlation for TGFBI Corneal Dystrophies Identifies p.(G623D) as a Novel Cause of Epithelial Basement Membrane Dystrophy.

Purpose: The majority of anterior corneal dystrophies are caused by dominant mutations in TGFBI (transforming growth factor β-induced) collectively known as the epithelial-stromal TGFBI dystrophies. Most cases of epithelial basement membrane dystrophy (EBMD) are thought to result from a degenerative (nongenetic) process; however, a minority of cases are associated with specific TGFBI mutations. We evaluated the spectrum of TGFBI mutations and associated phenotypes in a United Kingdom cohort with typical epithelial-stromal TGFBI dystrophies and an EBMD cohort.

Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1.

Purpose: Mutation of RGR, encoding retinal G-protein coupled receptor was originally reported in association with retinal dystrophy in 1999. A single convincing recessive variant segregated perfectly in one family of five affected and two unaffected siblings. At least one further individual, homozygous for the same variant has since been reported.

Phenotype and Progression of Retinal Degeneration Associated With Nullizigosity of ABCA4.

Purpose: We describe the phenotypes associated with nullizigosity and nine splicing mutations in the ABCA4 gene.

Methods: The study included 19 patients with biallelic null mutations (Group A, nullizygous), 27 with splicing mutations in the homozygous state or in trans with a null mutation (Group B), and 20 with p.G1961E in trans with a null mutation (Group C, control).

Nonsyndromic Retinal Dystrophy due to Bi-Allelic Mutations in the Ciliary Transport Gene IFT140.

Purpose: Mutations in the ciliary transporter gene IFT140, usually associated with a severe syndromic ciliopathy, may also cause isolated retinal dystrophy. A series of patients with nonsyndromic retinitis pigmentosa (RP) due to IFT140 was investigated in this study.

Methods: Five probands and available affected family members underwent detailed phenotyping including retinal imaging and electrophysiology.

Investigation of Aberrant Splicing Induced by AIPL1 Variations as a Cause of Leber Congenital Amaurosis.

Purpose: Biallelic mutations in AIPL1 cause Leber congenital amaurosis (LCA), a devastating retinal degeneration characterized by the loss or severe impairment of vision within the first few years of life. AIPL1 is highly polymorphic with more than 50 mutations and many more polymorphisms of uncertain pathogenicity identified. As such, it can be difficult to assign disease association of AIPL1 variations.

Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation of RBP3 Is Associated With High Myopia and Retinal Dystrophy.

Purpose: We present a detailed clinical and molecular study of four patients from two consanguineous families with a similar childhood-onset retinal dystrophy resulting from novel homozygous nonsense mutations in RBP3.

Methods: Four children with mutations in RBP3 encoding interphotoreceptor binding protein (IRBP) were ascertained by whole exome sequencing and subsequent direct Sanger sequencing. Detailed phenotyping was performed, including full clinical evaluation, electroretinography, fundus photography, fundus autofluorescence (FAF) imaging, and spectral-domain optical coherence tomography (OCT).