Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to a T494M mutation in the PRPF3 gene

PURPOSE: To characterize the clinical, psychophysical, and electrophysiological phenotypes in a five-generation Swiss family with dominantly inherited retinitis pigmentosa caused by a T494M mutation in the Precursor mRNA-Processing factor 3 (PRPF3) gene, and to relate the phenotype to the underlying genetic mutation. METHODS: Eleven affected patients were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldmann perimetry, and digital fundus photography. Some patients had autofluorescence imaging, Optical Coherence Tomography, and ISCEV-standard full-field electroretinography. All affected patients had genetic testing. RESULTS: The age of onset of night blindness and the severity of the progression of the disease varied between members of the family. Some patients reported early onset of night blindness at age three, with subsequent severe deterioration of visual acuity, which was 0.4 in the best eye after their fifties. The second group of patients had a later onset of night blindness, in the mid-twenties, with a milder disease progression and a visual acuity of 0.8 at age 70. Fundus autofluorescence imaging and electrophysiological and visual field abnormalities also showed some degree of varying phenotypes. The autofluorescence imaging showed a large high-density ring bilaterally. Myopia (range: -0.75 to -8) was found in 10/11 affected subjects. Fundus findings showed areas of atrophy along the arcades. A T494M change was found in exon 11 of the PRPF3 gene. The change segregates with the disease in the family. CONCLUSIONS: A mutation in the PRPF3 gene is rare compared to other genes causing autosomal dominant retinitis pigmentosa (ADRP). Although a T494M change has been reported, the family in our study is the first with variable expressivity. Mutations in the PRPF3 gene can cause a variable ADRP phenotype, unlike in the previously described Danish, English, and Japanese families. Our report, based on one of the largest affected pedigree, provides a better understanding as to the phenotype/genotype description of ADRP caused by a PRPF3 mutation

Longitudinal case study and phenotypic multimodal characterization of McArdle disease-linked retinopathy: insight into pathomechanisms.

Background: We present a longitudinal clinical characterization of PYGM-linked pattern dystrophy in an adult male patient.Materials and Methods: A patient affected by McArdle disease (glycogen storage disease type V) and homozygous for the nonsense variant PYGM c.148C>T p.(Arg50*) underwent ophthalmic examinations over a 9-year-interval, including fundus photography, fundus autofluorescence, optical coherence tomography (OCT), OCT-angiography and electroretinography (ERG).Results: At age 52, the patient was asymptomatic but yellow flecks were first observed in the macula of both eyes. This yellow flecks at the posterior pole progressed towards a pattern-like dystrophy over a 5-year-period. By fundus autofluorescence imaging the appearance of new hyperautofluorescent flecks and the extension of existing ones was observed over time. Concomitantly, a slow progression of the size of atrophic areas was seen at the posterior pole. Scotopic ERGs were within normal limits, but photopic Flicker responses were decreased, indicating reduced cone function.Conclusions: This additional case of PYGM-linked pattern dystrophy further confirms retinopathy as a clinical phenotype associated with McArdle disease. PYGM expression pattern suggests a disease mechanism involving impaired glycogen metabolism both in the retinal pigment epithelium and in cone photoreceptors

Acute bilateral blindness due to diffuse outer retinopathy following clear lens exchange: a case report

Abstract Background As the trend of refractive lens exchange for presbyopia continues to grow, our case report shows the first occurrence of an acute bilateral outer retinopathy following uncomplicated sequential clear lens extraction in an otherwise healthy individual. Case presentation A 54-year-old male without significant medical history benefited from a sequential bilateral lens exchange for presbyopia. He then experienced a rapid vision loss in both eyes, accompanied by photopsias and myodesopsias, with symptoms appearing respectively 4 and 3 weeks after the surgeries. Multimodal imaging revealed a fulminant outer retinopathy, leading to a total loss of light perception within a few days. Immediate intravenous corticosteroid therapy was administered, permitting to recover a small area of central visual function in both eyes, enabling shape and color distinction. The primary diagnostic hypothesis is a presumed autoimmune retinopathy, triggered by the cataract extraction, while an alternative diagnosis could be a toxic reaction secondary to the use of intracameral cefuroxime and lidocaine during the surgery. Conclusion In this report, the authors describe the first recorded instance of outer retinopathy following cataract surgery. This occurrence raises the possibility of auto-immunization leading to retinal atrophy and vision loss as a potential outcome after undergoing cataract surgery

Autofluorescence Imaging in Age-Related Macular Degeneration Complicated by Choroidal Neovascularization. A Prospective Study

PURPOSE: To determine if integrity of the retinal pigment epithelium (RPE)/photoreceptor complex as assessed by autofluorescence imaging can be predicted on the basis of visual acuity (VA), size, or fluorescein angiographic characteristics of the lesion in the early stage of choroidal neovascularization in age-related macular degeneration (AMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Seventy-nine eyes of 78 patients with untreated early-stage subfoveal neovascular AMD. METHODS: Digital color fundus photography and fluorescein angiography were carried out by certified photographers using the same camera throughout the study. Confocal scanning laser ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence images were compared with digital fluorescein angiography and fundus color photographs using IMAGEnet. MAIN OUTCOME MEASURES: Autofluorescence at the macula was correlated with VA, angiographic lesion characteristics, lesion size, and length of symptoms. RESULTS: Of the 79 eyes studied, 40 had classic and predominantly classic choroidal neovascularization, 10 had minimally classic, 29 had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes, autofluorescence was continuous at the central macula, and this correlated significantly with VA, lesion size, and symptom length but not choroidal neovascularization type. However, there was considerable overlap between the 2 groups such that the integrity of RPE autofluorescence could not be predicted on the basis of these criteria. CONCLUSION: Intact autofluorescence at the macula in early choroidal neovascularization correlates with VA, lesion size, and symptom length but not lesion type. None predict with any certainty the integrity of the outer retina. Our data suggest that the RPE/photoreceptor complex may be intact at the macula for several months in the presence of choroidal neovascularization, suggesting that VA might be rescued if treatment were effective in suppressing neovascular growth without damaging the RPE/retina complex, although this remains to be tested. It would be sensible to assess autofluorescence in treatment protocols to test this concept because it may be a marker for earlier disease and predict outcomes of treatment

Morphological Reconstitution and Persistent Changes After Intravitreal Ocriplasmin for Vitreomacular Traction and Macular Hole

Abstract Purpose: To assess the long-term anatomical and functional findings in patients with symptomatic vitreomacular traction (VMT), with or without full thickness macular hole (FTMH), after eye treatment with intravitreal ocriplasmin injection (IOI). Methods: This longitudinal case series includes 51 eyes from 51 symptomatic patients with VMT (<800 μm) who received a single IOI (Jetrea® 0.125 mg); 21 cases with an FTMH (<400 μm) were included. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were recorded before IOI, and 1 day to 24 months thereafter. Data are presented as mean ± standard deviation. Results: Mean adhesion size before injection was 345 ± 146 μm. In 34 eyes (67%), complete release of VMT was observed; whereas VMT persisted in 17 eyes (33%). The latter included 15 of the 21 eyes (71%) with FTMH, 15 of which underwent pars plana vitrectomy and inner limiting membrane peeling. BCVA improved from (logarithm of the minimal angle of resolution [logMAR]) 0.41 ± 0.03 before injection to 0.32 ± 0.03 after 1 month and 0.23 ± 0.05 after 6 months and remained stable thereafter (0.24 ± 0.06 after 24 months of follow-up). Forty-five percent of the eyes presented submacular deposits soon after IOI that were not functionally relevant; 61% completely resolved by 12 months. Except floaters that disappeared within 48 h, no other adverse events were reported during follow-up. Conclusions: Treatment with ocriplasmin in a real-life setting showed an overall efficacy of 67% in patients with symptomatic VMT, with better results evident in the absence of an FTMH (70% vs. 62% VMT release) and a visual gain for over 2 years