scholarly journals Retinal Degeneration Associated With RPGRIP1: A Review of Natural History, Mutation Spectrum, and Genotype–Phenotype Correlation in 228 Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Avigail Beryozkin ◽  
Hamzah Aweidah ◽  
Roque Daniel Carrero Valenzuela ◽  
Myriam Berman ◽  
Oscar Iguzquiza ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Degeneration ◽  
Clinical Data ◽  
Age Of Onset ◽  
Outer Nuclear Layer ◽  
Visual Fields ◽  
Severe Form ◽  
Posterior Pole ◽  
Missense Mutations ◽  
Full Field

Purpose:RPGRIP1 encodes a ciliary protein expressed in the photoreceptor connecting cilium. Mutations in this gene cause ∼5% of Leber congenital amaurosis (LCA) worldwide, but are also associated with cone–rod dystrophy (CRD) and retinitis pigmentosa (RP) phenotypes. Our purpose was to clinically characterize RPGRIP1 patients from our cohort, collect clinical data of additional RPGRIP1 patients reported previously in the literature, identify common clinical features, and seek genotype–phenotype correlations.Methods: Clinical data were collected from 16 patients of our cohort and 212 previously reported RPGRIP1 patients and included (when available) family history, best corrected visual acuity (BCVA), refraction, comprehensive ocular examination, optical coherence tomography (OCT) imaging, visual fields (VF), and full-field electroretinography (ffERG).Results: Out of 228 patients, the majority (197, 86%) were diagnosed with LCA, 18 (7%) with RP, and 13 (5%) with CRD. Age of onset was during early childhood (n = 133, average of 1.7 years). All patients but 6 had moderate hyperopia (n = 59, mean of 4.8D), and average BCVA was 0.06 Snellen (n = 124; only 10 patients had visual acuity [VA] > 0.10 Snellen). On funduscopy, narrowing of blood vessels was noted early in life. Most patients had mild bone spicule-like pigmentation starting in the midperiphery and later encroaching upon the posterior pole. OCT showed thinning of the outer nuclear layer (ONL), while cystoid changes and edema were relatively rare. VF were usually very constricted from early on. ffERG responses were non-detectable in the vast majority of cases. Most of the mutations are predicted to be null (363 alleles), and 93 alleles harbored missense mutations. Missense mutations were identified only in two regions: the RPGR-interacting domain and the C2 domains. Biallelic null mutations are mostly associated with a severe form of the disease, whereas biallelic missense mutations usually cause a milder disease (mostly CRD).Conclusion: Our results indicate that RPGRIP1 biallelic mutations usually cause severe retinal degeneration at an early age with a cone–rod pattern. However, most of the patients exhibit preservation of some (usually low) BCVA for a long period and can potentially benefit from gene therapy. Missense changes appear only in the conserved domains and are associated with a milder phenotype.

Progressive Retinal Degeneration in Ranch Mink

1984 ◽  
Vol 21 (1) ◽  
pp. 18-27 ◽  
Author(s):  
W. J. Hadlow
Keyword(s):  
Visual Acuity ◽  
Retinal Degeneration ◽  
Structural Integrity ◽  
Pigment Epithelium ◽  
Outer Nuclear Layer ◽  
Viral Diseases ◽  
Rods And Cones ◽  
Progressive Degeneration ◽  
Ranch Mink ◽  
Growth And Reproduction

Retinal degeneration was prevalent in a large group of sapphire and pastel mink (Mustela vison) kept for studies on slow viral diseases. Nearly 78% of those two to eight years old were affected. The retinopathy was equally common in both sexes but more frequent in sapphires (85%) than in pastels (63%), and it was severe more often in sapphires than in pastels. By light microscopy, the primary change appeared to be progressive degeneration of fully developed photoreceptors, beginning in their outer segments. In many mink, including some younger ones, the rods and cones and outer nuclear layer had disappeared from all but the far periphery of the fundus. The inner retinal layers were spared until late in the disease, and the pigment epithelium remained essentially unchanged. The cause of the retinopathy was not established. It may represent an abiotrophy in which the structural integrity of the photoreceptors began to wane in many mink after they reached two years of age. Apart from reducing visual acuity, the retinopathy has implications for the photoperiodic control of fur growth and reproduction in this highly light-sensitive carnivore.

scholarly journals Prediction of Function in ABCA4-Related Retinopathy Using Ensemble Machine Learning

2020 ◽  
Vol 9 (8) ◽  
pp. 2428 ◽  
Author(s):  
Philipp L. Müller ◽  
Tim Treis ◽  
Alexandru Odainic ◽  
Maximilian Pfau ◽  
Philipp Herrmann ◽  
...  
Keyword(s):  
Machine Learning ◽  
Visual Impairment ◽  
Age Of Onset ◽  
Outer Nuclear Layer ◽  
Stargardt Disease ◽  
Full Field ◽  
Corrected Visual Acuity ◽  
Ensemble Machine Learning ◽  
Prediction Of Function ◽  
Patient Burden

Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility is limited by variability and patient burden. To address these limitations, an ensemble machine-learning-based approach was evaluated to differentiate patients from controls, and predict disease categories depending on ERG (‘inferred ERG’) and visual impairment (‘inferred visual impairment’) as well as BCVA values (‘inferred BCVA’) based on microstructural imaging (utilizing spectral-domain optical coherence tomography) and patient data. The accuracy for ‘inferred ERG’ and ‘inferred visual impairment’ was up to 99.53 ± 1.02%. Prediction of BCVA values (‘inferred BCVA’) achieved a precision of ±0.3LogMAR in up to 85.31% of eyes. Analysis of the permutation importance revealed that foveal status was the most important feature for BCVA prediction, while the thickness of outer nuclear layer and photoreceptor inner and outer segments as well as age of onset highly ranked for all predictions. ‘Inferred ERG’, ‘inferred visual impairment’, and ‘inferred BCVA’, herein, represent accurate estimates of differential functional effects of retinal microstructure, and offer quasi-functional parameters with the potential for a refined patient assessment, and investigation of potential future treatment effects or disease progression.

scholarly journals Double Hyperautofluorescent Rings in Patients with USH2A-Retinopathy

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 956
Author(s):  
Ana Fakin ◽  
Maja Šuštar ◽  
Jelka Brecelj ◽  
Crystel Bonnet ◽  
Christine Petit ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Fundus Autofluorescence ◽  
Visual Fields ◽  
Cone Dystrophy ◽  
Missense Mutations ◽  
Autofluorescence Imaging ◽  
Single Ring ◽  
Auditory Performance ◽  
Moderate Hearing Loss

USH2A mutation is the most common cause of retinitis pigmentosa, with or without hearing impairment. Patients most commonly exhibit hyperautofluorescent ring on fundus autofluorescence imaging (FAF) and rod-cone dystrophy on electrophysiology. A detailed study of three USH2A patients with a rare pattern of double hyperautofluorescent rings was performed. Twenty-four patients with typical single hyperautofluorescent rings were used for comparison of the ages of onset, visual fields, optical coherence tomography, electrophysiology, and audiograms. Double rings delineated the area of pericentral retinal degeneration in all cases. Two patients exhibited rod-cone dystrophy, whereas the third had a cone-rod dystrophy type of dysfunction on electrophysiology. There was minimal progression on follow-up in all three. Patients with double rings had significantly better visual acuity, cone function, and auditory performance than the single ring group. Double rings were associated with combinations of null and missense mutations, none of the latter found in the single ring patients. According to these findings, the double hyperautofluorescent rings indicate a mild subtype of USH2A disease, characterized by pericentral retinal degeneration, mild to moderate hearing loss, and either a rod-cone or cone-rod pattern on electrophysiology, the latter expanding the known clinical spectrum of USH2A-retinopathy.

Full-field electroretinography, visual acuity and visual fields in Usher syndrome: a multicentre European study

2019 ◽  
Vol 139 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Katarina Stingl ◽  
Anne Kurtenbach ◽  
Gesa Hahn ◽  
Christoph Kernstock ◽  
Stephanie Hipp ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Usher Syndrome ◽  
Visual Fields ◽  
European Study ◽  
Full Field

scholarly journals An experimental pig model with outer retinal degeneration induced by temporary intravitreal loading of N-methyl-N-nitrosourea during vitrectomy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kwang-Eon Choi ◽  
Vu Thi Que Anh ◽  
Jee Taek Kim ◽  
Cheolmin Yun ◽  
Seongkwang Cha ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Wave Amplitude ◽  
Outer Nuclear Layer ◽  
Pig Model ◽  
Full Field ◽  
Eye Model ◽  
Amplitude Noise ◽  
Hematoxylin And Eosin ◽  
The Mean ◽  
Hematoxylin And Eosin Staining

AbstractWe aimed to develop an outer retinal degeneration pig model induced by temporary intravitreal loading of N-methyl-N-nitrosourea (MNU) during vitrectomy. In a preliminary experiment involving 5 mini-pig cases to determine the appropriate concentration of MNU, the vitreous cavity of each eye was filled with 4, 8, 10, 12, or 16 mg/mL MNU for 10 min, which was then replaced with a balanced salt solution. Multimodal examinations including spectral-domain optical coherence tomography (OCT) images and full-field electroretinography (ffERG) were obtained at baseline and week 2, week 6, and week 12. The retinal degeneration was classified according to the amplitudes of a dark adaptive (DA) 10.0 a-wave amplitude. The degree of moderate retinal degeneration was defined as DA 10.0 a-wave amplitude ≥ 10% and < 60% of baseline amplitude. The degree of severe degeneration was defined as DA 10.0 a-wave amplitude < 10% of baseline amplitude, noise, or flat signal. Hematoxylin and eosin staining and immunohistochemistry were performed at week 12. The main experiments were conducted first with 10 cases of 5 mg/mL and later with 13 cases of 10 mg/mL. In the preliminary experiment, degree of outer retinal degeneration increased with MNU concentration. Use of 4, 8, 10, 12, and 16 mg/mL MNU showed no, moderate, severe, severe, and atrophic changes, respectively. In the main experiments, there were 9 cases of moderate retinal degeneration and 1 case of severe degeneration in 5 mg/mL MNU group. Two cases of moderate degeneration and 11 of severe degeneration were recorded in 10 mg/mL group. Mean thickness of total retina, inner nuclear layer, and outer nuclear layer decreased at week 2 in both groups. The mean amplitudes on ffERG decreased at week 2. The ffERG and OCT findings did not change from week 2 to week 6 or week 12. The results of staining supported those of ffERG and OCT. Temporal MNU loading in a vitrectomized pig-eye model induced customized outer retinal degeneration with changing the concentration of MNU.

Effect of autologous growth factors on apoptosis and thickness of the outer nuclear layer in an experimental retinal degeneration model

2021 ◽  
pp. 1-12
Author(s):  
Emin Ozmert ◽  
Sibel Demirel ◽  
Umut Arslan ◽  
Özlem Biçer ◽  
Ozan Ahlat ◽  
...  
Keyword(s):  
Growth Factors ◽  
Retinal Degeneration ◽  
Outer Nuclear Layer

scholarly journals Feasibility of peripheral OCT imaging using a novel integrated SLO ultra-widefield imaging swept-source OCT device

2021 ◽  
Author(s):  
Simrat K. Sodhi ◽  
John Golding ◽  
Carmelina Trimboli ◽  
Netan Choudhry
Keyword(s):  
Posterior Pole ◽  
Field Of View ◽  
Retinal Diseases ◽  
Swept Source ◽  
Full Field ◽  
Swept Source Oct ◽  
Oct Imaging ◽  
Field Device ◽  
Areas Of Interest ◽  
Retinal Pathologies

Abstract Purpose To describe the feasibility of peripheral OCT imaging in retinal diseases using a novel full-field device. Methods A total of 134 consecutive eyes were referred and imaged on the Optos Silverstone swept-source OCT (SS-OCT) (Optos PLC; Dunfermline, UK). Scanning laser ophthalmoscope (SLO) images and the associated SS-OCT images were obtained in the posterior pole, mid-periphery or far periphery based on the nature of the referral and on new areas of interest observed in the optomap images at the time of imaging. Results A total of 134 eyes (96 patients) were enrolled in the study. One hundred and twenty-five eyes (91 patients) with 38 retinal pathologies were prospectively assessed and 9 eyes (5 patients) were excluded due to incomplete image acquisition. The average age of the subjects was 54 years (range 21–92 years). Thirty-nine out of 125 eyes (31%) had macular pathologies. Eighty-six out of 125 eyes (69%) had peripheral only pathologies, an area which cannot be visualized by standard OCT devices with a 50 degree field-of-view. Conclusions The ability to capture peripheral pathologies using an integrated SLO-UWF imaging with full-field swept-source provided high-grade anatomical insight that confirmed the medical and surgical management in a majority of cases. Its use in the mid- and far periphery provides a holistic clinical picture, which can potentially aid in the understanding of various retinal pathologies.

scholarly journals Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa

2021 ◽  
Vol 22 (5) ◽  
pp. 2374
Author(s):  
Laura Kuehlewein ◽  
Ditta Zobor ◽  
Katarina Stingl ◽  
Melanie Kempf ◽  
Fadi Nasser ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Genetic Testing ◽  
Retinitis Pigmentosa ◽  
Fundus Autofluorescence ◽  
Retinal Disease ◽  
New Drugs ◽  
Autofluorescence Imaging ◽  
Full Field ◽  
Tertiary Referral Center ◽  
The Right

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.

scholarly journals Genotypes Predispose Phenotypes—Clinical Features and Genetic Spectrum of ABCA4-Associated Retinal Dystrophies

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1421
Author(s):  
Yu-Chi Sung ◽  
Chang-Hao Yang ◽  
Chung-May Yang ◽  
Chao-Wen Lin ◽  
Ding-Siang Huang ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Degeneration ◽  
Medical Center ◽  
Fundus Autofluorescence ◽  
Genetic Diagnosis ◽  
Common Disease ◽  
Genetic Characteristics ◽  
Retinal Dystrophies ◽  
High Prevalence ◽  
Abca4 Gene

The ABCA4 gene is one of the most common disease-causing genes of inherited retinal degeneration. In this study, we report different phenotypes of ABCA4-associated retinal dystrophies in the Taiwanese population, its clinical progression, and its relationship with genetic characteristics. Thirty-seven subjects were recruited and all patients underwent serial ophthalmic examinations at a single medical center. Fundus autofluorescence (FAF) images were quantified for clinical evaluation, and panel-based next-generation sequencing testing was performed for genetic diagnosis. Visual preservation, disease progression, and genotype–phenotype correlation were analyzed. In this cohort, ABCA4-associated retinal degeneration presented as Stargardt disease 1 (STGD1, 62.16%), retinitis pigmentosa (32.43%), and cone-rod dystrophy (5.41%). STGD1 could be further divided into central and dispersed types. In each phenotype, the lesion areas quantified by FAF increased with age (p < 0.01) and correlated with poorer visual acuity. However, three patients had the foveal sparing phenotype and had relatively preserved visual acuity. Forty-two ABCA4 variants were identified as disease-causing, with c.1804C>T (p.Arg602Trp) the most frequent (37.84%). Patients with a combination of severe/null variants could have more extensive phenotypes, such as arRP and dispersed STGD1. This is the first cohort study of ABCA4-associated retinal degeneration in Taiwan with wide spectrums of both genotypic and phenotypic characteristics. An extremely high prevalence of c.1804C>T, which has not been reported in East Asia before, was noted. The extensiveness of retinal involvement might be regarded as a spectrum of ABCA4-associated retinal dystrophies. Different types of genetic variations could lead to distinctive phenotypes, according to the coding impact of variants.

Vision through Various Scuba Facemasks

1974 ◽  
Vol 16 (4) ◽  
pp. 395-405 ◽  
Author(s):  
S. M. Luria ◽  
Steven H. Ferris ◽  
Christine L. McKay ◽  
Jo Ann S. Kinney ◽  
Helen M. Paulson
Keyword(s):  
Visual Acuity ◽  
Optical Properties ◽  
Visual Fields ◽  
Differential Susceptibility ◽  
Visual Performance ◽  
Visual Process ◽  
Hand Eye Coordination ◽  
Size Estimates

The visual performance using five commercially avaible facemasks was compared. Measurements were made of visual fields, visual acuity, stereoacuity, hand-eye coordination, accuracy of distance estimates, and accuracy of size estimates at both near and far distances. In addition, the optical properties of the masks were measured and the susceptibility of each mask to fogging was tested. There were significant differences among the masks for every visual process tested. Some masks were superior for one purpose and inferior for another purpose. For example, the mask which had lenses designed to compensate for the optical distortions found under water improved size and distance estimates and hand-eye coordination, but degraded acuity and stereoacuity. The results were not expplained on the basis of differential susceptibility to fogging.

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