Analysis of imaging biomarkers and retinal nerve fiber layer thickness in RPGR-associated retinitis pigmentosa.

Purpose: To investigate multimodal retinal imaging characteristics including the retinal nerve fiber layer (RNFL) thickness in patients with RPGR-associated retinitis pigmentosa (RP).

Methods: This cross-sectional case-control study included 17 consecutive patients (median age, 21 years) with RPGR-associated RP who underwent retinal imaging including optical coherence tomography (OCT), short-wavelength fundus autofluorescence (AF) imaging, and RNFL scans centered on the optic disc. RNFL thickness was manually segmented and compared to clinical and imaging parameters including the transfoveal ellipsoid zone (EZ) width, the horizontal diameter of the macular hyperautofluorescent ring.

Safe and Effective Treatment of Intracranial Infantile Hemangiomas with Beta-Blockers.

Infantile hemangiomas are common benign vascular tumors but are rarely found in an intracranial location. Our literature review identified 41 reported cases. There is no general consensus on management of these rare lesions and until recently, treatment was limited to surgery or pharmacological management with steroids or interferon.

Papillorenal syndrome: a systemic diagnosis not to be missed on funduscopy.

A 45-year-old man presented to the ophthalmology department with visual symptoms in his left eye. Almost two decades ago, he required a renal transplant for focal segmental glomerular sclerosis and a detailed enquiry revealed a strong family history of renal and ocular disease. Fundus examination demonstrated significant optic disc dysplasia in his left eye and optical coherence tomography showed intraretinal fluid bilaterally.

Expression of Rab Prenylation Pathway Genes and Relation to Disease Progression in Choroideremia.

Purpose: Choroideremia results from the deficiency of Rab Escort Protein 1 (REP1), encoded by CHM, involved in the prenylation of Rab GTPases. Here, we investigate whether the transcription and expression of other genes involved in the prenylation of Rab proteins correlates with disease progression in a cohort of patients with choroideremia.

Methods: Rates of retinal pigment epithelial area loss in 41 patients with choroideremia were measured using fundus autofluorescence imaging for up to 4 years.

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a multifactorial retinal disorder that is a major global cause of severe visual impairment. The development of an effective therapy to treat geographic atrophy, the predominant form of AMD, remains elusive due to the incomplete understanding of its pathogenesis. Central to AMD diagnosis and pathology are the hallmark lipid and proteinaceous deposits, drusen and reticular pseudodrusen, that accumulate in the subretinal pigment epithelium and subretinal spaces, respectively.

CRISPR genome engineering for retinal diseases.

Novel gene therapy treatments for inherited retinal diseases have been at the forefront of translational medicine over the past couple of decades. Since the discovery of CRISPR mechanisms and their potential application for the treatment of inherited human conditions, it seemed inevitable that advances would soon be made using retinal models of disease. The development of CRISPR technology for gene therapy and its increasing potential to selectively target disease-causing nucleotide changes has been rapid.

NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy.

Biallelic deletions in the NPHP1 gene are the most frequent molecular defect of nephronophthisis, a kidney ciliopathy and leading cause of hereditary end-stage kidney disease. Nephrocystin 1, the gene product of NPHP1, is also expressed in photoreceptors where it plays an important role in intra-flagellar transport between the inner and outer segments. However, the human retinal phenotype has never been investigated in detail.

Prevalence and phenotype associations of complement factor I mutations in geographic atrophy.

Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age-related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease-causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross-sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels.

Chimeric human opsins as optogenetic light sensitisers.

Human opsin-based photopigments have great potential as light-sensitisers, but their requirement for phototransduction cascade-specific second messenger proteins may restrict their functionality in non-native cell types. In this study, eight chimeric human opsins were generated consisting of a backbone of either a rhodopsin (RHO) or long-wavelength-sensitive (LWS) opsin and intracellular domains from Gq/11-coupled human melanopsin. Rhodopsin/melanopsin chimeric opsins coupled to both Gi and Gq/11 pathways.

Longitudinal Evaluation of Hyper-Reflective Foci in the Retina Following Subretinal Delivery of Adeno-Associated Virus in Non-Human Primates.

Purpose: The purpose of this study was to evaluate whether clinical grade recombinant adeno-associated virus serotype 8 (rAAV8) leads to increased appearance of hyper-reflective foci (HRF) in the retina of non-human primates (NHPs) following subretinal gene therapy injection.

Methods: Different doses of rAAV8 vector (rAAV8. human phosphodiesterase 6A subunit (hPDE6A) at low dose: 1 × 1011 vector genomes (vg), medium dose: 5 × 1011 vg, or high dose: 1 × 1012 vg) were injected subretinally into the left eyes of NHPs in a formal toxicology study in preparation of a clinical trial.

Microperimetry Hill of Vision and Volumetric Measures of Retinal Sensitivity.

Purpose: Mean retinal sensitivity is the main output measure used in microperimetry. It is, however, of limited use in patients with poor vision because averaging is weighted toward zero in those with significant scotomas creating an artificial floor effect. In contrast, volumetric measures avoid these issues and are displayed graphically as a hill of vision.

The Effect of Congenital and Acquired Bilateral Anophthalmia on Brain Structure.

The aim of this study was to compare the pattern of changes in brain structure resulting from congenital and acquired bilateral anophthalmia. Brain structure was investigated using 3T magnetic resonance imaging (MRI) in Oxford (congenital) or Manchester (acquired). T1-weighted structural and diffusion-weighted scans were acquired from people with anophthalmia and sighted control participants.

Risk factors for posterior capsule rupture in cataract surgery as reflected in the European Registry of Quality Outcomes for Cataract and Refractive Surgery.

Purpose: To analyze the incidence and risk factors for posterior capsule rupture (PCR) in cataract surgery.

Setting: European clinics affiliated with the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO).

Design: Retrospective cross-sectional register-based study.

Investigating the presence of peer bias against ptosis in young children.

Purpose: To investigate the presence of peer bias directed at young children aged 3-6 years of age and the age at which this bias emerges.

Methods: Children (3-6 years) completed an individual testing session involving two tasks: (1) a paired photograph task examined the effect of the appearance of ptosis on children's preferences in two different social situations (toy sharing and birthday party); (2) a ranking task investigated whether different grades of ptosis are evaluated differently by children of different ages.

Results: A total of 217 children were included.

Is subretinal AAV gene replacement still the only viable treatment option for choroideremia?

Introduction: Choroideremia is an X-linked inherited retinal degeneration resulting from mutations in the gene, encoding Rab escort protein-1 (REP1), a protein regulating intracellular vesicular transport. Loss-of-function mutations in lead to progressive loss of retinal pigment epithelium (RPE) with photoreceptor and choriocapillaris degeneration, leading to progressive visual field constriction and loss of visual acuity. Three hundred and fifty-four unique mutations have been reported in While gene augmentation remains an ideal therapeutic option for choroideremia, other potential future clinical strategies may exist.

Low Luminance Visual Acuity and Low Luminance Deficit in Choroideremia and RPGR-Associated Retinitis Pigmentosa.

Introduction: Choroideremia and RPGR-associated retinitis pigmentosa (RP) are two distinct inherited rod-cone degenerations, where good visual acuity (VA) is maintained until late disease stages, limiting its usefulness as a disease marker. Low luminance VA and low luminance deficit (standard VA minus low luminance VA) may be more sensitive visual function measures.

Methods: Standard VA was obtained using Early Treatment Diabetic Retinopathy Study letter charts (Precision Vision, Bloomington, IL, USA).

Deep phenotyping of the Cdhr1 mouse validates its use in pre-clinical studies for human CDHR1-associated retinal degeneration.

Purpose: To validate the Cdhr1 mouse as a model for human CDHR1-associated retinal degeneration, which may present as cone-rod dystrophy or geographic atrophy.

Methods: Deep phenotyping of Cdhr1(n = 56) and C57BL6J wildtype control mice (n = 45) was undertaken using in vivo multimodal retinal imaging and dark- and light-adapted electroretinography (ERG) over 15 months to evaluate rod- and cone-photoreceptor responses and retinal morphology.

Results: Cdhr1 retinas exhibited outer retinal thinning on optical coherence tomography (OCT) at 1-month versus C57BL6J (mean 14.

Accurate Quantification of AAV Vector Genomes by Quantitative PCR.

The ability to accurately determine the dose of an adeno-associated viral (AAV) therapeutic vector is critical to the gene therapy process. Quantitative PCR (qPCR) is one of the common methods to quantify the AAV vector titre, but different variables can lead to inconsistent results. The aim of this study was to analyze the influence of the conformation of the DNA used as the standard control, and the enzymatic digestion was performed to release the viral genome from the protein capsid on the physical genome titration of a clinically relevant AAV8.

Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy - a case report.

Background: We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.

Case Presentation: A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance.