Gene Therapy for Retinal Degeneration.

Biallelic mutations in the RPE65 gene are associated with inherited retinal degenerations/dystrophies (IRD) and disrupt the visual cycle, leading to loss of vision. A new adenoviral vector-based gene therapy surgically delivered to retinal cells provides normal human RPE65 protein that can restore the visual cycle and some vision. To view this Bench to Bedside, open or download the PDF.

Optical coherence tomography and molecular analysis of sudden acquired retinal degeneration syndrome (SARDS) eyes suggests the immune-mediated nature of retinal damage.

OBJECTIVE: To perform detailed analysis of retinal changes in dogs with SARDS using optical coherence tomography (OCT), funduscopy, and molecular analysis. ANIMALS: Subjects were 29 dogs from 12 US states and Canada diagnosed with SARDS by 8 ophthalmologists. An additional 7 eyes from 5 deceased SARDS dogs were used for molecular and histological analysis. PROCEDURES: Dogs were evaluated using chromatic pupil light reflex testing (cPLR), and electroretinography (ERG); subjects underwent complete ophthalmic examination, including funduscopy, retinal photography, and OCT, in addition to complete laboratory analysis, blood pressure evaluation, abdominal and thoracic radiographs, and computerized tomography (CT) imaging to assess possible systemic abnormalities. Histology and immunohistochemistry analysis was performed in 2 SARDS eyes. Microarray analysis was performed in 5 SARDS retinas. RESULTS: Thirty-eight percent of patients had <1-mm wide retinal detachments (RD) on OCT analysis, which could not be detected by funduscopy or retinal photographs. Systemic hypertension did not seem to be a contributing factor (RD 22.2%; ND 20%, Odds ratio = 1.1). No dogs showed neoplastic changes by thoracic or abdominal radiography, or CT imaging. There was no statistically significant difference in age (RD 7.9 ± 1.9 years (mean ± SD); ND 7.6 ± 1.7 years, p = 0.69) or duration of blindness prior to presentation (RD 18 ± 7 days (mean±SD); ND 21 ± 12 days, p = 0.28). Microarray and histology analysis of SARDS eyes revealed molecular changes suggestive of immune-mediated damage. CONCLUSIONS: Observed histological, molecular, and OCT changes are highly suggestive of immune-mediated damage in SARDS eyes.

X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers.

X-linked retinitis pigmentosa (XLRP) is a type of severe retinal dystrophy, and female carriers of XLRP demonstrate markedly variable clinical severity. In this study, we aimed to elucidate the clinical findings of male patients with and female carriers of XLRP in a Japanese cohort and demonstrate the genetic contribution. Twelve unrelated families (13 male patients, 15 female carriers) harboring pathogenic mutations in RPGR or RP2 were included, and comprehensive ophthalmic examinations were performed. To identify potential pathogenic mutations, targeted next-generation sequencing was employed. Consequently, we identified 11 pathogenic mutations, of which five were novel. Six and five mutations were detected in RPGR and RP2, respectively. Only one mutation was detected in ORF15. Affected male patients with RP2 mutations tended to have lower visual function than those with RPGR mutations. Female carriers demonstrated varying visual acuities and visual fields. Among the female carriers, 92% had electroretinographical abnormalities and 63% had a radial autofluorescent pattern, and the carriers who had higher myopia showed worse visual acuity and more severe retinal degeneration. Our results expand the knowledge of the clinical phenotypes of male patients with and female carriers of XLRP and suggest the possibility that RP2 mutations are relatively highly prevalent in Japan.

The assessment of retina in pregnant women with myopia.

OBJECTIVES: Myopia is associated with increased frequency of retinal degenerative changes which are the risk factors of intra- and postpartal ophthalmological complications. Aim of this study was to analyze the degenerative lesions detected in opthalmological examination (including peripheral retinal lesions) as a potential risk factors for eyes' status in terms of delivery in myopic women. MATERIAL AND METHODS: 254 pregnant women affected with myopia underwent opthalmological examination as a screening method to examine retina. In case of any degenerative lesions, the qualification for laser photocoagulation treatment was performed. Furthermore, study group was divided into two subgroups due to presence or absence of the retinal lesions and opthalmological outcomes compared. Follow up examination was performed in every patient from the study group between 3 and 6 months after the delivery. RESULTS: Among 508 eyes, retinal lesions were revealed in 69 women (121 eyes) what constituted for 23.8%. In remaining 185 patients results of the opthalmological examination were normal. Average maternal age was higher in group affected with degenerative lesions (p<0.001). Myopia in women with retinal lesions ranged between -0.25 and -12 dioptries (D), while in 43 cases of degenerative lesions qualified for laser photocoagulation this value ranged between -0.5 and -12.0 D (p=ns). Postpartal follow-up examination did not reveal any abnormalities in this group, as well. CONCLUSION: Degenerative retinal lesions are present in one fourth of pregnant women. Both the severity and type of the lesions are not associated with severity of myopia. Among pregnant patients, retinal lesions occur in patients with more advanced maternal age. opthalmological examination remains an important prophylactic modality in retinal disorders, especially in primary retinal detachment due degenerative disorders.

Cofactors associated with Sudden Acquired Retinal Degeneration Syndrome: 151 dogs within a reference population.

OBJECTIVE: To determine factors associated with sudden acquired retinal degeneration syndrome (SARDS) diagnosed within one referral population. ANIMALS STUDIED: 151 dogs diagnosed with SARDS. PROCEDURES: Breed, age, sex, and body weight were compared between dogs with electroretinogram-confirmed SARDS and dogs presented to the UC Davis Veterinary Medical Teaching Hospital (UCD-VMTH) from 1991 to 2014. RESULTS: SARDS was diagnosed in 151 dogs, representing 1.3% of dogs presented to the UCD-VMTH for ophthalmic disease. Although dogs of 36 breeds were affected, the Dachshund (n = 31, 21%), Schnauzer (16, 11%), Pug (11, 7%), and Brittany (5, 3%) were significantly overrepresented, and the Labrador Retriever (3, 2%) was significantly underrepresented vs. the reference population (P < 0.001). Median (range) age and body weight of affected vs. reference dogs were 8.9 (3-20) vs. 6.8 (0.1-26) years and 12.4 (2.8-52.7) vs. 22.3 (0.1-60) kg, respectively. Dogs 6-10 years of age and between 10-20 kg in body weight were significantly overrepresented in the SARDS population, while dogs <6 years of age were significantly underrepresented (P < 0.01). Spayed females (59% of affected dogs) were significantly overrepresented compared to the reference population, whereas intact females (1% of affected dogs) were significantly underrepresented. CONCLUSIONS: Consistent with previous studies, smaller, middle-aged, spayed female dogs may be at increased risk of developing SARDS. Unlike previous studies, this is the first study comparing a variety of SARDS-affected breeds to a reference population. Potentially increased risk of SARDS in several breeds, particularly Dachshunds, suggests a familial factor that warrants further investigation using genetic techniques.

Sudden acquired retinal degeneration syndrome in western Canada: 93 cases.

This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) in western Canada. Medical records from the Western College of Veterinary Medicine from 2002 to 2016 showed that 93 cases of SARDS were diagnosed based on presentation for sudden blindness and a bilaterally extinguished electroretinogram. The most common pure breeds were the miniature schnauzer, dachshund, and pug. The mean age at diagnosis was 8.1 years and males and females were equally affected. Most of the dogs were presented with normal non-chromatic, but abnormal chromatic pupillary light reflexes. The incidence of retinal degeneration as detected via ophthalmoscopy increased over time after SARDS diagnosis. Polyuria, polydipsia, polyphagia, weight gain, elevated liver enzyme values, isosthenuria, and proteinuria were common clinical and laboratory findings. Chromatic pupillary light reflex testing may be more valuable than non-chromatic pupillary light testing in detecting pupil response abnormalities in dogs with SARDS, although electroretinography remains the definitive diagnostic test.

Syndrome de la rétine silencieuse dans l'Ouest canadien : 93 cas. Cette étude a examiné les données cliniques provenant de chiens diagnostiqués avec le syndrome de la rétine silencieuse (syndrome de cécité soudaine acquise) dans l'Ouest canadien. Les dossiers médicaux du Western College of Veterinary Medicine de 2002 à 2016 ont montré que 93 cas du syndrome de la rétine silencieuse ont été diagnostiqués en se basant sur la présentation pour une cécité soudaine et un électrorétinogramme bilatéral sans incandescence. Les races les plus communes étaient le Schnauzer miniature, le Dachshund et le Pug. L'âge moyen au diagnostic était de 8,1 ans et les mâles et les femelles étaient également affectés. La plupart des chiens présentaient des réflexes pupillaires normaux à la lumière non chromatique mais des réflexes anormaux à la lumière chromatique. L'incidence de la dégénération rétinienne détectée par l'ophtalmoscopie a augmenté au fil du temps après le diagnostic du syndrome de la rétine silencieuse. La polyurie, la polydipsie, la polyphagie, le gain de poids, des valeurs d'enzymes hépatiques élevées, l'isosthénurie et la protéinurie étaient des résultats cliniques et de laboratoire communs. Le réflexe à la lumière pupillaire chromatique peut être plus utile que le test de la lumière pupillaire non chromatique pour détecter les anomalies de la réponse pupillaire chez les chiens atteints du syndrome de la rétine silencieuse, quoique l'électrorétinographie demeure le test diagnostique définitif.(Traduit par Isabelle Vallières).

PERIPHERAL RETINAL DEGENERATIONS AND RHEGMATOGENOUS DETACHMENT IN PRIMARY CONGENITAL GLAUCOMA.

BACKGROUND: To determine the prevalence of peripheral retinal degenerations (PRD) and rhegmatogenous retinal detachment in patients with primary congenital glaucoma (PCG). METHODS: Records of all patients with PCG operated from year 2000 onwards were evaluated to look for the prevalence of rhegmatogenous retinal detachment. Of these, those children who were old enough to cooperate and had sufficient medial clarity were screened with an indirect ophthalmoscopy in a cross-sectional evaluation from 2010 to 2014. Peripheral retina was examined, and prevalence of PRD was estimated in this subset. For statistical purposes, only one eye of each patient was considered in this cross-sectional analysis. RESULTS: Of the 310 eyes (180 patients with PCG) operated from the year 2000 onwards, a rhegmatogenous retinal detachment was noted in 13 eyes (4%). Mean axial length of these eyes was 26.3 ± 3.2 mm (range, 19.8-34.7 mm). Among the eyes screened for PRD (n = 60), prevalence of pathologic PRD (lattices with/without atrophic holes and isolated holes/tears) was 15%. The average follow-up between glaucoma filtering surgery and the date of last examination was 8.55 ± 3.98 years (range, 5-20 years) in this subset. Mean axial length was significantly greater in eyes with pathologic PRD than in those without (28.1 ± 3.3 mm vs. 25.8 ± 2.6 mm; P = 0.01). For axial length ≥ 26 mm, the odds of having a pathologic PRD were 14.4 times more than those with axial length < 26 mm (P < 0.001; 95% confidence interval, 1.7-120.5). CONCLUSION: Prevalence of PRD among eyes with PCG is high. Peripheral retinal screening should be performed in eyes with PCG, especially those with axial lengths ≥ 26 mm.

Therapy strategies for Usher syndrome Type 1C in the retina.

The Usher syndrome (USH) is the most common form of inherited deaf-blindness with a prevalence of ~ 1/6,000. Three clinical subtypes (USH1-USH3) are defined according to the severity of the hearing impairment, the presence or absence of vestibular dysfunction and the age of onset of retinitis pigmentosa (RP). USH1 is the most severe subtype with congenital severe to profound hearing loss and onset of RP before puberty. Currently only the amelioration of the hearing deficiency is implemented, but no treatment of the senso-neuronal degeneration in the eye exists.In our studies we are focusing on the evaluation of gene-based therapies to cure the retinal degeneration of USH1C patients: (i) gene augmentation using recombinant adeno-associated virus, (ii) genome editing by homologous recombination mediated by zinc-finger nucleases and, (iii) read-through therapy using novel designer aminoglycosides and PTC124. Latter compounds target in-frame nonsense mutations which account for ~ 20 % of all USH cases.All analyzed gene-based therapy strategies lead to the restoration of USH protein expression. These adjustments may be sufficient to reduce the progression of retinal degeneration, which would greatly improve the life quality of USH patients.

Current management of inherited retinal degenerations in Portugal (IRD-PT survey).

Inherited retinal dystrophies/degenerations (IRDs) are the leading cause of visual impairment and incurable familial blindness in the Western world. Given the clinical and genetic heterogeneity, establishing a molecular diagnosis is especially relevant. The aim of this study was to perform the first nationwide survey to understand the prevalence and current management of IRDs in Portugal. A response was obtained from 26 healthcare providers (HCP) (76.5% response rate). Only 4 respondents reported not managing IRD patients. Most HCPs (68.1%) reported managing up to 100 patients, while three currently manage between 501 and 1000 patients. Based on the Portuguese population, an estimated IRD prevalence of 0.031%, i.e., about 1 in 3000 individuals, was calculated. In most HCPs (86.3%), most patients are adults, and non-syndromic retinitis pigmentosa is the most frequent diagnosis. Only 4 HCPs currently use the national, web-based IRD registry (IRD-PT). However, all but one respondent expressed interest in participating in such a registry. Genetic testing is available in 54.5%, with 58.3% HCPs reporting solved rates between 61-80%, but 4 to 9 months to get a genetic test result in 83.4% of cases. Based on this survey, the prevalence of biallelic RPE65-associated disease in Portugal is 0.00031%, i.e., approximately 1:300,000 individuals. Data from this study provide vital background information on national differences in the diagnosis and management of IRD patients. Nationwide implementation of the IRD-PT registry should be encouraged and supported to provide population-based reference data and to identify patients eligible for current and future therapies.

Phenotypic characterization of a Chinese family with autosomal dominant cone-rod dystrophy related to GUCY2D.

BACKGROUND: This study aimed to evaluate the clinical phenotype and investigate the molecular genetic defect in a Chinese family with autosomal dominant cone-rod dystrophy (ADCRD). METHODS: Family history was collected and patients underwent regular ophthalmologic examinations. Two affected individuals underwent three-year follow-ups to analyze the course of the disease. Venous blood was collected from family members and genomic DNA was extracted. A whole genome linkage analysis of 11 family members was performed using an Illumina Infinium Human Linkage-12 panel. All exons and exon-intron boundaries of guanylate cyclase 2D gene (GUCY2D) were sequenced for familial gene mutation. RESULTS: Decreased visual acuity and photophobia usually commenced in early childhood in these patients. The family demonstrated an age-dependent increase in macular abnormalities with progressive development of geographic atrophy. Electrophysiological testing revealed a marked loss of cone function. Initially, a genome-wide linkage analysis mapped the disease to chromosome 17 (1-36 cM), with a maximum LOD score of 1.505. Sequence analysis of the GUCY2D gene in the linkage interval detected a recurrent heterozygous mutation, c.2513G > C (p.R838P). This mutation appeared in all seven patients with ADCRD but did not appear in any of the four unaffected family members. CONCLUSIONS: A missense mutation in the GUCY2D gene caused ADCRD in this family. Clinical follow-up of this family with a typical CRD phenotype revealed disease progression during the time period.

The Michigan Retinal Degeneration Questionnaire: A Patient-Reported Outcome Instrument for Inherited Retinal Degenerations.

PURPOSE: To create a psychometrically validated patient-reported outcome measure for inherited retinal degenerations. DESIGN: Qualitative and quantitative patient-reported outcome (PROs) questionnaire development using item response theory validation. METHODS: One hundred twenty-eight patients with a diagnosis of an inherited retinal degeneration at the Kellogg Eye Center (University of Michigan) were recruited and administered a 166-item questionnaire comprising 7 expert-defined domains. The questionnaire was re-administered 4-16 days later to a subset of 25 participants to assess test-retest variability. Graded response models were fit by Cai's Metropolis-Hastings Robbins-Monro algorithm using the R (version 3.6.3) package mirt. Model data were fit to assess questionnaire dimensionality, to estimate item information, and to score participants. Poorly functioning items were removed, and the model was refit to create the final questionnaire. RESULTS: The psychometrically validated PROs measure was reduced to a 59-item questionnaire measuring 7 unidimesnional domains: central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity. A total of 39 items were removed because of poor factor loading, low item information, poor person-ability differentiation, or high item-level interdependence. This novel questionnaire produces a reliable domain score for person ability that does not show significant test-retest variability across repeated administration. CONCLUSIONS: The final PRO questionnaire, known as the Michigan Retinal Degeneration Questionnaire, is psychometrically validated and available for use in the evaluation of patients with inherited retinal degenerations.

[Causes of visual impairment in Mie Prefecture during a 5-year period].

PURPOSE: The purpose of this study was to determine the causes of visual impairment in Mie prefecture during a five-year period. SUBJECTS AND METHODS: The study was conducted between April 2004 and March 2009 in Mie Prefecture. 1,322 visually impaired people as defined by the Act on Welfare of Physically Disabled Persons were enrolled. We reviewed age, sex, causes of visual impairment, degree of disability and medical conditions according to their physical disability certificate. RESULTS: The four major causes of visual impairment were glaucoma (20.3%), diabetic retinopathy (18.9%), retinitis pigmentosa (12.2%), and macular degeneration (9.1%), followed by chorioretinal degeneration, stroke or brain tumor, optic atrophy, and cataract. The average ages of the four major causes were glaucoma (77.1 years), diabetic retinopathy (65.1 years), retinitis pigmentosa (62.5 years) and macular degeneration (77.7 years). CONCLUSIONS: The most common cause of visual impairment in Mie prefecture was glaucoma. The four major causes in Mie prefecture were the same as the results of the nation-wide investigation reported in 2006.

Age related macular degeneration and presence of posterior vitreous detachment.

PURPOSE: To find correlation between presence of PVD and incidence of different forms of AMD. MATERIAL AND METHODS: 210 eyes of patients with AMD were examined. Fluorescein angiography determined type of AMD and ultrasound examination evaluated presence of PVD. Control group included 164 eyes of patients routinely admitted to the hospital for cataract surgery. Inclusion criterium was lack of AMD and retinal medical history. RESULTS: In the control group prevalence of PVD was higher in women than in men--respectively 50.5% and 23.6%. PVD was more frequent in male patients with dry AMD (50%) than in male controls (23.6%). PVD was also more frequent in female patients with dry form of AMD (69.2%) than in controls (50.5%). In female group with AMD PVD was more frequent in patients with dry form of AMD than in patients with wet form of AMD (69.2% and 44.8%). In patients with dry AMD, PVD was statistically more frequent in women (69.2%) than in men (50%). Statistically significant was the difference between prevalence of PVD in dry and wet group (male and females together)--60.7% in dry AM and 42.6% ind wet AMD. CONCLUSION: Persistence of vitreal adhesion and traction with age might lead to a shift of the dry form into wet form of AMD. Detachment of the vitreous in dry AMD might secure the persistence of dry form. Women, due to early PVD are more prone to complications resulting from vitreoretinal traction.

Electronegative Electroretinograms in the United Arab Emirates.

PURPOSE: An electronegative electroretinogram (ERG), defined as having a b:a wave ratio ≤1 in the scotopic flash ERG response, indicates relative inner retinal dysfunction. Causes vary depending upon the study population. In the Arabian Gulf, where inherited retinal disease is relatively prevalent, common diagnoses associated with electronegative ERGs have not been described. In this study, we report the frequency and causes of electronegative ERGs in a cohort of Emirati patients with inherited retinal disease. METHODS: A retrospective review was performed of all full-field ERGs done for Emirati patients in the Ocular Genetics Service of Cleveland Clinic Abu Dhabi from January 2017 to December 2019. Those who had an electronegative ERG in at least one eye were included in the study. RESULTS: Out of 137 patients, 9 probands (6.6%) had an electronegative ERG. The mean age at presentation was 24 years (range 5-48 years), and five patients (55.6%) were male. The final clinical diagnoses were congenital stationary night blindness (CSNB) (two TRPM1-related and one Oguchi disease), X-linked retinoschisis (XLRS) (one genetically confirmed and two not genetically tested), cone-rod dystrophy (one CRX-related and one not genetically tested), and enhanced S-cone syndrome (ESCS) (one NRL-related). The one patient who did not have bilateral electronegative ERGs was a male with XLRS whose fellow eye had an unrecordable ERG. CONCLUSIONS: In this series of Emirati patients, an electronegative ERG was most commonly associated with the inherited retinal diseases recessive CSNB and XLRS. An electronegative ERG was noted in a case of NRL-related ESCS.

Why Miss the Chance? Incidental Findings while Telescreening for Diabetic Retinopathy.

PURPOSE: To report on incidental pathological findings met while screening for Diabetic Retinopathy (DR) in Diabetes Clinics (DC) by ophthalmologist-graded digital fundus imaging. METHODS: At the DC of Pescara (central Italy), for 3,859 eyes of 1,930 consecutive patients having not undergone fundus examination in the last year, two mydriatic fundus digital images, taken with a CenterVue DRS Digital Retinal Camera, were sent along with Best Corrected Visual Acuity, on a "store-and-forward" basis, to an ophthalmologist trained in DR screening, and graded according to the UK Diabetic Eye Screening Programme. Incidental fundus abnormalities other than DR were reported. RESULTS: No adverse event to mydriasis was reported. One hundred and eighty eyes (4.66%) were ungradable. Among the 3,679 gradable ones, 1,105 (30.04%) showed different degrees of DR (R1 to R3), and 126 (3.42%) maculopathy (M1). Any Age-Related Macular Degeneration was present in 387 eyes (10.52%), any optic disc and parapapillary area features suspect for glaucoma in 562 eyes (15.27%), any hypertensive retinopathy in 1,263 eyes (34.33%), vitreoretinal interface disease in 252 eyes (6.84%), myopic choroidopathy in 92 eyes (2.50%), disc pallor in 31 eyes (0.84%). Mean time was 5 min for screening, 2 min for grading. CONCLUSION: Teleretinography is a well-established, cost-effective procedure in DR screening. Along with increased attendance, locating a digital camera in a DC with a retina-specialist grader results in finding fundus pathologies also beyond DR, very similarly to fundus examination in an outpatient ophthalmic setting.

An epidemiological approach for the estimation of disease onset in Central Europe in central and peripheral monogenic retinal dystrophies.

PURPOSE: To study clinical patterns of disease onset in monogenic retinal dystrophies (MRD), using an epidemiological approach. METHODS: Records of patients with MRD, seen at the University Eye Hospital Tuebingen from 1994 to 1999, were selected from a database and retrospectively reviewed. For analysis, patients were divided into 2 groups by predominant part of visual field (VF) involvement: group 1 (predominantly central involvement) included Stargardt disease (ST), macular dystrophy (MD), and central areolar choroidal dystrophy (CACD), and group 2 (predominantly peripheral involvement) included Bardet-Biedl syndrome (BBD), Usher syndrome (USH) I and II, and choroideremia (CHD). Age, sex, age of first diagnosis, age of visual acuity (VA) decrease and VF emergence, night blindness and photophobia onset, types of VF defects and age of its onset, color discrimination defects and best corrected VA were analyzed. RESULTS: Records of 259 patients were studied. Men were more prevalent than women. Mean age of the patients was 47.2 (SD = 15.6) years old. Forty-five patients in the first group and 40 in the second were first diagnosed between 21 and 30 years of age. Ninety-four patients in the first group had VA decrease before 30 years of age; in the second group, 68 patients had VA decrease onset between 21 and 40 years of age. Forty-four patients in the first group noticed VF at an age between 21 and 30 years, and 74 patients between 11 and 30 years in the second group. Central scotoma was typical for the first group, and was detected in 115 patients. Concentric constriction was typical for the second group, and was found in 81 patients. Half of patients in both groups preserved best-corrected VA in the better eye at a level of 20/40 or better; 7% in the first group and 6% in the second group were registered as legally blind according to WHO criteria, having VA <1/50 or VF <5 degrees . Diagnosis frequency was USH I and II-34%, ST-31%, MD-18%, CHD-14%, BBD-5%. CONCLUSIONS: An epidemiological approach to the estimation of the disease onset of various subtypes of monogenic retinal degenerations will be useful for detection of disease duration, its prognosis, rehabilitation and the researching of future treatment possibilities.

Rhegmatogenous retinal detachment in Scotland: research design and methodology.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition and a common cause of ocular morbidity. Establishing an accurate estimate of disease incidence and distribution is an important first step in assessing the healthcare burden related to this condition and in subsequent planning and provision of treatment strategies. The aim of this study is to obtain a first estimate incidence of RRD in Scotland, to estimate the incidence of familial RRD and to describe the known associations of RRD within the study population. METHODS/DESIGN: We have established a national prospective observational study seeking to identify and recruit all incident cases of RRD in the Scottish population over a 2 year period. After fully informed consent, all participants will have a blood sample taken and a full medical history and clinical examination performed including visual acuity, refraction, slit-lamp examination, intra-ocular pressure measurement and detailed fundal examination. We describe the study design and protocol. CONCLUSION: This study will provide the first estimate of the annual incidence of RRD in Scotland. The findings of this study will be important in estimating the burden of disease and in the planning of future health care policy related to this condition. This study will also establish a genetic resource for a genome wide association study to investigate if certain genetic variants predispose to RRD.

[Effects of mobile phones and radar radiofrequencies on the eye]. / Effets des ondes hyperfréquences des téléphones mobiles et des radars sur l'oeil.

The increasing applications of microwaves, mainly in mobile phones and radar, induce a higher rate of exposed people, sometimes cause of worry. Eyeballs are hotspots of radiofrequency field radiation because of their anatomy and composition. We propose a review of the various effects on the eye. The studies are hardly comparable because the exposure systems, power densities and dosimetries are different. While the thermal effects on the eye are well known including cataracts, corneal edema, endothelial cell loss and retinal degeneration, the non-thermal effects are still controversial. Cell cycle abnormalities, early apoptosis were reported in experimental conditions likely due to oxidative stress, but the studies could not show any significant effect on human eyes when exposed to long-term and low-dose radiation. Next studies need to be closer to human exposure.

The genetic aetiology of retinal degeneration in children in Finland - new founder mutations identified.

PURPOSE: To study the genetic aetiology and phenotypes of retinal degeneration (RD) in Finnish children born during 1993-2009. METHODS: Children with retinal degeneration (N = 68) were investigated during 2012-2014 with a targeted gene analysis or a next-generation sequencing (NGS) based gene panel. Also, a full clinical ophthalmological examination was performed. RESULTS: The cohort covered 44% (68/153) of the Finnish children with inherited RD born 1993-2009. X-linked retinoschisis, retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophy were the most common clinical diagnoses in the study group. Pathogenic mutations were found in 17 retinal genes. The molecular genetic aetiology was identified in 77% of the patients (in 77% of the families) analysed by NGS method. Several founder mutations were detected including three novel founder mutations c.148delG in TULP1, c.2314C>R (p.Gln772Ter) in RPGRIP1 and c.533G>A (Trp178Ter) in TYR. We also confirmed the previous tentative finding of c.2944 + 1delG in GYCU2D being the most frequent cause of Leber congenital amaurosis (LCA) in Finland. CONCLUSIONS: Globally, RD is genetically heterogeneous with over 260 disease genes reported so far. This was shown not to be the case in Finland, where the genetic aetiology of RD is caused by a small group of genes, due to several founder mutations that are enriched in the population. We found that X-chromosomal retinoschisis constitutes the major group in Finnish paediatric RD population and is almost exclusively caused by two founder mutations. Several other founder mutations were detected including three novel founder mutations. All in all, the genetic aetiology of 77% of families was identified which is higher than previously reported from other populations, likely due to the specific genomic constitution of the Finns.