SLC16A8 is a causal contributor to age-related macular degeneration risk.

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter.

Venous Tortuosity in -Associated Gould Syndrome.

Mutations in collagen-encoding genes have been linked to numerous systemic diseases. Specifically, pathologic alterations in have been linked to Gould syndrome, a hereditary angiopathy affecting the brain, kidneys, and eyes. However, the ocular phenotype associated with -associated disease has yet to be fully characterized.

Insights Into PROM1-Macular Disease Using Multimodal Imaging.

Purpose: To describe the features of genetically confirmed PROM1-macular dystrophy in multimodal images.

Methods: Thirty-six (36) eyes of 18 patients (5-66 years; mean age, 42.4 years) were prospectively studied by clinical examination and multimodal imaging.

Chorioretinal atrophy following voretigene neparvovec despite the presence of fundus autofluorescence.

Introduction: Leber congenital amaurosis (LCA) type 2, due to disease-causing variants in RPE65, is characterized by severe visual loss in early infancy. Current treatments include voretigene neparvovec-rzyl (VN) for RPE65-associated LCA. Herein, we present the long-term follow-up of a patient treated with VN using quantitative autofluorescence (488 nm excitation).

Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series.

Background: Inherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5.

Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease.

Allgrove syndrome with amyotrophy.

Allgrove syndrome is an autosomal recessive disease mostly caused by mutations in the gene. It has variable clinical features but its cardinal features comprise the triad of achalasia, alacrimia and adrenal insufficiency. It typically develops during the first decade of life, but some cases have second and third decades onset.

Central Serous Chorioretinopathy Analyzed by Multimodal Imaging.

Purpose: We correlated quantitative fundus autofluorescence (qAF) with other fundus features in patients exhibiting central serous chorioretinopathy (CSC).

Methods: Short wavelength fundus autofluorescence (SW-AF, 488 nm excitation) was measured by qAF. Using nonnormalized images qAF values were calculated within eight concentric segments (qAF) located at an eccentricity of 7° to 9°.

Compound heterozygous inheritance of two novel COQ2 variants results in familial coenzyme Q deficiency.

Background: Primary coenzyme Q10 deficiency is a rare disease that results in diverse and variable clinical manifestations. Nephropathy, myopathy and neurologic involvement are commonly associated, however retinopathy has also been observed with certain pathogenic variants of genes in the coenzyme Q biosynthesis pathway. In this report, we describe a novel presentation of the disease that includes nephropathy and retinopathy without neurological involvement, and which is the result of a compound heterozygous state arising from the inheritance of two recessive potentially pathogenic variants, previously not described.

Retinal Manifestations of Mitochondrial Oxidative Phosphorylation Disorders.

Purpose: The purpose of this paper was to discuss manifestations of primary mitochondrial dysfunctions and whether the retinal pigment epithelium or the photoreceptors are preferentially affected.

Methods: A retrospective analysis was performed of patients with clinically and laboratory confirmed diagnoses of maternally inherited diabetes and deafness (MIDD) or Kearns-Sayre syndrome (KSS). Patients underwent full ophthalmic examination, full-field electroretinogram, and multimodal imaging studies, including short-wavelength autofluorescence, spectral domain-optical coherence tomography, and color fundus photography.

Quantitative Fundus Autofluorescence in HCQ Retinopathy.

Purpose: To increase our understanding of the mechanisms underlying hydroxychloroquine (HCQ) retinopathy, analyses by quantitative fundus autofluorescence (qAF) and near-infrared fundus autofluorescence (NIR-AF) were compared to results obtained by recommended screening tests.

Methods: Thirty-one patients (28 females, 3 males) were evaluated with standard automated perimetry and spectral domain optical coherence tomography (SD-OCT); 28 also had multifocal electroretinography (mfERG). Measurement of short-wavelength fundus autofluorescence (SW-AF) by qAF involved the use of an internal fluorescent reference and intensity measurements in eight concentric segments at 7° to 9° eccentricity.

A mutation in causing pigmented paravenous retinochoroidal atrophy.

Introduction: Mutations in the cone-rod homeobox () gene, a known cause of inherited retinal dystrophy, are characterized by extensive phenotypic heterogeneity. We describe a novel presentation of rod-cone dystrophy (RCD) phenocopying pigmented paravenous retinochoroidal atrophy associated with a mutation in .

Case Description: A 53-year-old man and his 48-year-old brother presented with a history of progressive vision loss and nyctalopia.

Optical coherence tomography in the evaluation of retinitis pigmentosa.

Background: Optical coherence tomography (OCT) is a non-invasive imaging test that provides easily obtainable and highly reproducible cross-sectional images of the retina. Improved modalities of the OCT that are capable of providing high quality images of not only the retina, but also the deeper structures and vasculature have been developed, including swept-source OCTs and OCT angiography.

Materials And Methods: Review.

Short-Wavelength and Near-Infrared Autofluorescence in Patients with Deficiencies of the Visual Cycle and Phototransduction.

Fundus autofluorescence is a valuable imaging tool in the diagnosis of inherited retinal dystrophies. With the advent of gene therapy and the numerous ongoing clinical trials for inherited retinal degenerations, quantifiable and reliable outcome measurements continually need to be identified. In this retrospective analysis, normalized and non-normalized short-wavelength (SW-AF) and near-infrared (NIR-AF) autofluorescence images of ten patients with mutations in visual cycle (VC) genes and nineteen patients with mutations in phototransduction (PT) genes were analyzed.

Optical Gap Biomarker in Cone-Dominant Retinal Dystrophy.

Purpose: To characterize the progression of optical gaps and expand the known etiologies of this phenotype.

Design: Retrospective cohort study.

Methods: Thirty-six patients were selected based on the identification of an optical gap on spectral-domain optical coherence tomography (OCT) from a large cohort of patients (N = 746) with confirmed diagnoses of inherited retinal dystrophy.

Differences in Intraretinal Pigment Migration Across Inherited Retinal Dystrophies.

Purpose: To determine whether there are differences in the prevalence of intraretinal pigment migration (IPM) across ages and genetic causes of inherited retinal dystrophies (IRDs).

Design: Retrospective cohort study.

Methods: Patients were evaluated at a single tertiary referral center.

Sequential multiple retinal vein occlusions and transient ischemic attack in MTHFR polymorphism and protein S deficiency.

Background: The C677T variant of the MTHFR (5,10-Methylenetetrahydrofolate reductase) gene is associated with increased susceptibility to homocystinuria (OMIM#236250), neural tube defects (OMIM#601634), schizophrenia (OMIM#181500), thromboembolism (OMIM#188050), and vascular diseases. Protein S deficiency is also associated with an increased risk of thromboembolism from reduced thrombin generation. In this report, we describe the case of a patient who presented with multiple retinal vein occlusions likely caused by an underlying combination of a homozygous MTHFR C677T variant and protein S deficiency.

Comparative Analysis of Functional and Structural Decline in Retinitis Pigmentosas.

Retinitis pigmentosa (RP) is a category of inherited retinal dystrophies that is best prognosticated using electroretinography (ERG). In this retrospective cohort study of 25 patients with RP, we evaluated the correlation between 30 Hz flicker ERG and structural parameters in the retina. Internationally standardized 30 Hz flicker ERG recordings, short-wavelength autofluorescence (SW-AF), and spectral domain-optical coherence tomography (SD-OCT) were acquired at two visits at least one year apart.

Effects of deficiency in the -encoded visual cycle protein CRALBP on visual dysfunction in humans and mice.

Mutations in (), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11--retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11--retinol oxidation to 11--retinal. CRALBP also maintains the 11- configuration and protects against unwanted retinaldehyde activity.

Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results.

Background: Whole exome sequencing (WES) allows for an unbiased search of the genetic cause of a disease. Employing it as a first-tier genetic testing can be favored due to the associated lower incremental cost per diagnosis compared to when using it later in the diagnostic pathway. However, there are technical limitations of WES that can lead to inaccurate negative variant callings.