Genetic Diagnosis for 64 Patients with Inherited Retinal Disease.

The overlapping genetic and clinical spectrum in inherited retinal degeneration (IRD) creates challenges for accurate diagnoses. The goal of this work was to determine the genetic diagnosis and clinical features for patients diagnosed with an IRD. After signing informed consent, peripheral blood or saliva was collected from 64 patients diagnosed with an IRD.

Delineating the Clinical Phenotype of Patients With the c.629C>G, p.Pro210Arg Mutation in Peripherin-2.

Purpose: More than 200 different mutations in peripherin-2 (PRPH2) are associated with multiple subtypes of inherited retinal diseases (IRDs), including retinitis pigmentosa and cone or macular diseases. Our goal was to understand how the poorly characterized PRPH2 mutation p.Pro210Arg (P210R) affects visual function and retinal structure as well as gain insight into the mechanism driving the clinical pathology.

Adherent but Not Suspension-Cultured Embryoid Bodies Develop into Laminated Retinal Organoids.

Human induced pluripotent stem cells (iPSCs) are differentiated into three-dimensional (3D) retinal organoids to study retinogenesis and diseases that would otherwise be impossible. The complexity and low yield in current protocols remain a technical challenge, particularly for inexperienced personnel. Differentiation protocols require labor-intensive and time-consuming dissection of optic vesicles (OVs).

Functional Evaluation of Splicing for Variants of Uncertain Significance in Patients with Inherited Retinal Diseases.

Inherited retinal diseases (IRD) comprise a heterogeneous set of clinical and genetic disorders that lead to blindness. Given the emerging opportunities in precision medicine and gene therapy, it has become increasingly important to determine whether DNA variants with uncertain significance (VUS) are responsible for patients' IRD. This research was performed to assess the functional consequence of six VUS identified in patients with IRD.

Variable expressivity in patients with autosomal recessive retinitis pigmentosa associated with the gene .

Purpose: In a cohort of eight families (11 patients) with autosomal recessive retinitis pigmentosa (arRP), we clinically characterized disease associated with mutations in .

Methods: Visual function was determined by measuring the patients' visual acuity, dark- and light-adapted perimetry, and by full-field electroretinography. Retinal structure was evaluated with spectral-domain optical coherence tomography, fundus imaging, and autofluorescence imaging.

Disease Progression in Patients with Autosomal Dominant Retinitis Pigmentosa due to a Mutation in Inosine Monophosphate Dehydrogenase 1 (IMPDH1).

Purpose: Mutations in the inosine monophosphate dehydrogenase 1 (IMPDH1) gene are a common cause of inherited retinal degeneration (IRD). Due to species- and tissue-dependent expression of IMPDH1, there are no appropriate models of human disease. Therefore, a limited understanding remains of disease expression and rates of progression for IMPDH1-related IRD.

Regional Variations and Intra-/Intersession Repeatability for Scotopic Sensitivity in Normal Controls and Patients With Inherited Retinal Degenerations.

Purpose: Dark-adapted visual fields were obtained from patients with inherited retinal degeneration (IRD) and controls to evaluate the effect that age, retinal region, and disease had on scotopic sensitivity. Intra- and intersession test-retest repeatabilities for patients and controls were measured to establish significant change for longitudinal studies.

Methods: A total of 41 patients with IRD and 30 controls had one eye dilated and dark-adapted for 40 minutes.

Prospective Evaluation of Patients With X-Linked Retinoschisis During 18 Months.

Purpose: Prospective evaluation of patients with X-linked retinoschisis (XLRS).

Methods: Fifty-six males XLRS patients, age ≥7 years, had retinal structure and function tests performed every 6 months during an 18-month period.

Results: Best corrected visual acuity (BCVA) was abnormal (mean ± SD logMAR 0.

Dark-Adapted Chromatic Perimetry for Measuring Rod Visual Fields in Patients with Retinitis Pigmentosa.

Purpose: Although rod photoreceptors are initially affected in retinitis pigmentosa (RP), the full-field of rod vision is not routinely characterized due to the unavailability of commercial devices detecting rod sensitivity. The purpose of this study was to quantify rod-mediated vision in the peripheral field from patients with RP using a new commercially available perimeter.

Methods: Participants had one eye dilated and dark-adapted for 45 minutes.

Long-term Follow-up of Patients With Retinitis Pigmentosa Receiving Intraocular Ciliary Neurotrophic Factor Implants.

Purpose: To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa.

Design: Long-term follow-up of a multicenter, sham-controlled study.

Methods: Thirty-six patients at 3 CNTF4 sites were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye.

TOWARDS A TREATMENT FOR DIABETIC RETINOPATHY: Intravitreal Toxicity and Preclinical Safety Evaluation of Inducible Nitric Oxide Synthase Inhibitors.

Background: The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease.

Methods: Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.

Structure/Psychophysical Relationships in X-Linked Retinoschisis.

Purpose: To compare structural properties from spectral-domain optical coherence tomography (SDOCT) and psychophysical measures from a subset of patients enrolled in a larger multicenter natural history study of X-linked retinoschisis (XLRS).

Methods: A subset of males (n = 24) participating in a larger natural history study of XLRS underwent high-resolution SDOCT. Total retina (TR) thickness and outer segment (OS) thickness were measured manually.

Current Progress in Deciphering Importance of VLC-PUFA in the Retina.

Stargardt-like macular dystrophy-3 (STGD3) is a juvenile-onset disease caused by mutations in ELOVL4 (elongation of very long fatty acids-4). This gene product catalyzes the elongation of long chain saturated and polyunsaturated fatty acids (LC-FAs and LC-PUFAs) into very long chain FAs and PUFAs (VLC-FAs and VLC-PUFAs). These mutations cause a frame shift in the ELOVL4 transcript, introducing a premature stop codon that results in the translation of a truncated protein that has lost a C-terminus endoplasmic reticulum (ER) retention/retrieval signal.

Examination of VLC-PUFA-deficient photoreceptor terminals.

Purpose: Juvenile-onset autosomal dominant Stargardt-like macular dystrophy (STGD3) is caused by mutations in ELOVL4 (elongation of very long fatty acids-4), an elongase necessary for the biosynthesis of very long chain fatty acids (VLC-FAs ≥ C26). Photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs), which are necessary for long-term survival of rod photoreceptors. The purpose of these studies was to determine the effect of deletion of VLC-PUFAs on rod synaptic function in retinas of mice conditionally depleted (KO) of Elovl4.

Effect of reduced retinal VLC-PUFA on rod and cone photoreceptors.

Purpose: Autosomal dominant Stargardt-like macular dystrophy (STGD3) is a juvenile-onset disease that is caused by mutations in Elovl4 (elongation of very long fatty acids-4). The Elovl4 catalyzes the first step in the conversion of C24 and longer fatty acids (FAs) to very long-chain FAs (VLC-FAs, ≥C26). Photoreceptors are particularly rich in VLC polyunsaturated FAs (VLC-PUFA).