Retinitis Pigmentosa Cases Research Articles

Clinical and Electrophysiological Report of a Unilateral Retinitis Pigmentosa Case

Introduction: To describe clinical and electrophysiological features of a patient with unilateral Retinitis Pigmentosa (RP). Case: A 29-year-old female with a long history of progressive visual disturbance in the right eye has undergone multiple eye examinations during the past eight years. There was nothing noticeable in her past medical and ocular history. Comprehensive eye examinations were done in the first visit. All data was suggestive of right eye RP. Posterior segment fundal examination findings were: a pallor waxy disc, vessel attenuation, and extended pigmentary degeneration of the mid-peripheral retina. The left eye examination was normal. Comparing the automated 60 degree and 30 degree visual fields of both eyes obviously showed significant defects in the right eye visual field but normal in the left eye. All of the probable infectious agents, which can cause similar ocular manifestations, were ruled out by serological tests. The standard photopic and scotopic electroretinographies were significantly reduced in amplitude in the right eye; however, they were normal in the left eye. Also, the standard Electro-Oculography (EOG) results were the same as the Electro-Retinography (ERG) ones in both eyes. Eye examinations were normal in other family members. Over an eight-year follow-up period, progressive deteriorating vision has gradually become more noticeable in the right eye. The left eye has been completely normal since. This data was compatible with the Francois and Verriesr unilateral RP diagnostic criteria. Conclusion: Clinical signs and symptoms, a minimum of a five-year follow-up period, and confirmatory ERG and EOG are very helpful to diagnose andaffirm the case of unilateral RP.

Molecular Genetics of FAM161A in North American Patients with Early-Onset Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent investigations have revealed that defects in FAM161A represent a rather prevalent cause of hereditary blindness in Israel and the Palestinian territories, whereas they seem to be rarely present within patients from Germany. Genetic or clinical data are currently not available for other countries. In this work, we screened a cohort of patients with recessive RP from North America to determine the frequency of FAM161A mutations in this ethnically-mixed population and to assess the phenotype of positive cases. Out of 273 unrelated patients, only 3 subjects had defects in FAM161A. A fourth positive patient, the sister of one of these index cases, was also identified following pedigree analysis. They were all homozygous for the p.T452Sfx3 mutation, which was previously reported as a founder DNA variant in the Israeli and Palestinian populations. Analysis of cultured lymphoblasts from patients revealed that mutant FAM161A transcripts were actively degraded by nonsense-mediated mRNA decay. Electroretinographic testing showed 30 Hz cone flicker responses in the range of 0.10 to 0.60 microvolts in all cases at their first visit (age 12 to 23) (lower norm = 50 μV) and of 0.06 to 0.32 microvolts at their most recent examination (age 27 to 43), revealing an early-onset of this progressive disease. Our data indicate that mutations in FAM161A are responsible for 1% of recessive RP cases in North America, similar to the prevalence detected in Germany and unlike the data from Israel and the Palestinian territories. We also show that, at the molecular level, the disease is likely caused by FAM161A protein deficiency.

Genetic high throughput screening in Retinitis Pigmentosa based on high resolution melting (HRM) analysis

Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n = 96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4% of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for medium sized (<4 kb transcript) RP genes, which constitute over 80% of the total of known RP genes.

Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements

Retinitis pigmentosa (RP) is a devastating form of retinal degeneration, with significant social and professional consequences. Molecular genetic information is invaluable for an accurate clinical diagnosis of RP due to its high genetic and clinical heterogeneity. Using a gene capture panel that covers 163 of the currently known retinal disease genes, including 48 RP genes, we performed a comprehensive molecular screening in a collection of 123 RP unsettled probands from a wide variety of ethnic backgrounds, including 113 unrelated simplex and 10 autosomal recessive RP (arRP) cases. As a result, 61 mutations were identified in 45 probands, including 38 novel pathogenic alleles. Interestingly, we observed that phenotype and genotype were not in full agreement in 21 probands. Among them, eight probands were clinically reassessed, resulting in refinement of clinical diagnoses for six of these patients. Finally, recessive mutations in CLN3 were identified in five retinal degeneration patients, including four RP probands and one cone-rod dystrophy patient, suggesting that CLN3 is a novel non-syndromic retinal disease gene. Collectively, our results underscore that, due to the high molecular and clinical heterogeneity of RP, comprehensive screening of all retinal disease genes is effective in identifying novel pathogenic mutations and provides an opportunity to discover new genotype-phenotype correlations. Information gained from this genetic screening will directly aid in patient diagnosis, prognosis, and treatment, as well as allowing appropriate family planning and counseling.

The Severe Autosomal Dominant Retinitis Pigmentosa Rhodopsin Mutant Ter349Glu Mislocalizes and Induces Rapid Rod Cell Death

Mutations in the rhodopsin gene cause approximately one-tenth of retinitis pigmentosa cases worldwide, and most result in endoplasmic reticulum retention and apoptosis. Other rhodopsin mutations cause receptor mislocalization, diminished/constitutive activity, or faulty protein-protein interactions. The purpose of this study was to test for mechanisms by which the autosomal dominant rhodopsin mutation Ter349Glu causes an early, rapid retinal degeneration in patients. The mutation adds an additional 51 amino acids to the C terminus of the protein. Folding and ligand interaction of Ter349Glu rhodopsin were tested by ultraviolet-visible (UV-visible) spectrophotometry. The ability of the mutant to initiate phototransduction was tested using a radioactive filter binding assay. Photoreceptor localization was assessed both in vitro and in vivo utilizing fluorescent immunochemistry on transfected cells, transgenic Xenopus laevis, and knock-in mice. Photoreceptor ultrastructure was observed by transmission electron microscopy. Spectrally, Ter349Glu rhodopsin behaves similarly to wild-type rhodopsin, absorbing maximally at 500 nm. The mutant protein also displays in vitro G protein activation similar to that of WT. In cultured cells, mislocalization was observed at high expression levels whereas ciliary localization occurred at low expression levels. Similarly, transgenic X. laevis expressing Ter349Glu rhodopsin exhibited partial mislocalization. Analysis of the Ter349Glu rhodopsin knock-in mouse showed a rapid, early onset degeneration in homozygotes with a loss of proper rod outer segment development and improper disc formation. Together, the data show that both mislocalization and rod outer segment morphogenesis are likely associated with the human phenotype.

High resolution retinal image analysis of unilateral retinitis pigmentosa using adptive optics

AbstractPurpose To report the findings of en face adaptive optics (AO) fundus imaging in eyes with unilateral retinitis pigmentosa(RP) patient.Methods The both eyes from a unilateral RP patient, 52 y.o. female, was imaged using both an infrared AO camera (rtx1™, Imagine Eyes, France) and spectral‐domain optical coherence tomography (SD‐OCT – Cirrus™, Carl Zeiss Meditec, Germany). Full field scotopic and phototic electroretinograms(ERGs) were recorded according to the ISCEV standard. Normal funduscopic examination, Goldmann visual field and fluorescence angiography(FA) were also examined. The AO images acquired from the unilateral RP patient were analyzed on cone density and then compared to the AO data from the eyes of 21 healthy volunteers with a mean age of 36 years (range 20‐57).Results The unilateral RP patient showed boney spicule changes, vascular attenuation and decreased peripheral visual field in the right eye. FA showed granular hyperfluorescence in the post pole, mottling of RPE and atrophy of choroid capillary in the peripheral retina in the right eye. Her ERGs of the right eye showed non‐recordable in all responses tested. OCT findings in the right eye showed preservation of the photoreceptor layer only in the foveal and parafoveal regions with loss in the more peripheral macula. All these results in her left eye were normal. AO data showed severe reduction of cone density in the right eye and the left eye showed normal cone density and regular cone mosaic.Conclusion In unilateral RP patient, AO showed only one eye was affected even in the cellular level examination. The examinations using AO may be useful in diagnosis and better understanding of pathology and management of unilateral RP cases.

Intravitreal and subtenon depot triamcinolone as treatment of retinitis pigmentosa associated cystoid macular edema.

We present a case of retinitis pigmentosa (RP) related cystoid macular edema (CME) refractory to oral acetazolamide and topical ketorolac that was treated with intravitreal and subtenon depot triamcinolone. A 32-year-old male with RP presented with complaints of bilateral decrease in visual acuity. His best-corrected visual acuity (BCVA) was 20/50 in the right eye and 20/100 in the left eye. After being informed of the available treatment options, the patient received bilateral intravitreal injection triamcinolone. The patient's BCVA improved to 20/40 in the right eye and 20/50 in the left eye and the CME was resorbed. However, 5 months after the injection in the left eye and two months in the right eye, visual acuity decreased due to recurrence of CME. We performed a second intravitreal injection in the left eye with improvement of visual and anatomic results, but we observed a recurrence of CME. Afterwards, we treated the patient with subtenon depot triamcinolone in both eyes, with the result that there was no recurrence after 4 months in OD or after 3 months in OS. We conclude that intravitreal and subtenon depot triamcinolone appear to provide at least temporary benefit in refractory CME as regards the improvement of visual acuity.

Gene Therapy for X-Linked Retinitis Pigmentosa

Copyright: © 2013 Shu X. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Retinitis Pigmentosa (RP) is a group of heterogeneous genetic disorders with a worldwide prevalence of 1 in 4000 individuals [1]. RP can be inherited in autosomal, X-linked or mitochondrial format. X-linked RP (XLRP) is one of the most severe forms of retinopathies, accounting for about 10-20% of all RP cases. Mutations in the Retinitis Pigmentosa Gtpase Regulator (RPGR) gene are the major cause of XLRP, accounting for 70 to 80% of affected XLRP cases [2]. The initially identified RPGR (RPGRex1-19) contains 19 exons and encodes for a predicted 90 KDa protein [3]. A subsequent study identified a large C-terminal exon, called ORF15, in the major functional form (RPGRORF15). The exon ORF15 encodes a repetitive glycine and glutamic acid-rich domain with a evolutionary conserved basic C-terminal domain, and harbors a high frequency of reading-frameshift and premature stop mutations, producing truncated proteins of varying length [4]. More than 300 RPGR mutations have been reported, most causing XLRP, a few causing human cone-rod, cone, or macular dystrophies, or syndromal forms of XLRP with primary ciliary dyskinesia and hearing loss [5].

Tracing the progression of retinitis pigmentosa via photoreceptor interactions

Retinitis pigmentosa (RP) is a group of inherited degenerative eye diseases characterized by mutations in the genetic structure of the photoreceptors that leads to the premature death of both rod and cone photoreceptors. Defects in particular genes encoding proteins that are involved in either the photoreceptor structure, phototransduction cascades, or visual cycle are expressed in the rods but ultimately affect both types of cells. RP is “typically” manifested by a steady death of rods followed by a period of stability in which cones survive initially and then inevitably die too. In some RP cases, rods and cones die off simultaneously or even cone death precedes rod death (reverse RP). The mechanisms and factors involved in the development of the different types of RP are not well understood nor have researchers been able to provide more than a limited number of short-term therapies. In this work we trace the progression of RP to complete blindness through each subtype via bifurcation theory. We show that the evolution of RP from one stage to another often requires the failure of multiple components. Our results indicate that a delicate balance between the availability of nutrients and the rates of shedding and renewal of photoreceptors is needed at every stage of RP to halt its progression. This work provides a framework for future physiological investigations potentially leading to long-term targeted multi-facet interventions and therapies dependent on the particular stage and subtype of RP under consideration. The results of this mathematical model may also give insight into the progression of many other degenerative eye diseases involving genetic mutations or secondary photoreceptor death and potential ways to circumvent these diseases.

Current mutation discovery approaches in Retinitis Pigmentosa

With a worldwide prevalence of about 1 in 3500–5000 individuals, Retinitis Pigmentosa (RP) is the most common form of hereditary retinal degeneration. It is an extremely heterogeneous group of genetically determined retinal diseases leading to progressive loss of vision due to impairment of rod and cone photoreceptors. RP can be inherited as an autosomal-recessive, autosomal-dominant, or X-linked trait. Non-Mendelian inheritance patterns such as digenic, maternal (mitochondrial) or compound heterozygosity have also been reported. To date, more than 65 genes have been implicated in syndromic and non-syndromic forms of RP, which account for only about 60% of all RP cases. Due to this high heterogeneity and diversity of inheritance patterns, the molecular diagnosis of syndromic and non-syndromic RP is very challenging, and the heritability of 40% of total RP cases worldwide remains unknown. However new sequencing methodologies, boosted by the human genome project, have contributed to exponential plummeting in sequencing costs, thereby making it feasible to include molecular testing for RP patients in routine clinical practice within the coming years. Here, we summarize the most widely used state-of-the-art technologies currently applied for the molecular diagnosis of RP, and address their strengths and weaknesses for the molecular diagnosis of such a complex genetic disease.

Functional Characterization of the HumanRPGRProximal Promoter

Mutations in the retinitis pigmentosa (RP) GTPase regulator (RPGR) gene account for more than 70% of X-linked RP cases. This study aims to characterize the proximal promoter region of the human RPGR gene.The 5'-flanking region (5 kb) of human RPGR was cloned and sequenced. A potential transcription start site and transcription factor binding motifs were identified by bioinformatic analysis. Constructs containing the putative human RPGR promoter region upstream of a luciferase reporter gene were generated and analyzed by transient transfection and luciferase assays. Transgenic mouse lines carrying a 3-kb human RPGR promoter sequence fused to lacZ were generated and RPGR proximal promoter activity was analyzed by X-gal staining.Bioinformatic analyses of the human RPGR 5'-flanking region uncovered potential transcription factor binding sites and a CpG island. Transient transfection assays with RPGR promoter/luciferase reporter constructs revealed a 980-bp fragment (-952 to +28) that produced higher levels of luciferase activity. Mutagenesis identified a putative Sp1 binding site that was critical for regulating transcriptional activity. We generated transgenic mice in which a lacZ reporter gene was controlled by the 3-kb upstream region of RPGR. β-galactosidase expression was predominantly found in mouse retina, brain, and kidney. In the retina, the photoreceptor cell layer showed the strongest β-galactosidase staining.Our study defined the human RPGR proximal promoter region in which a 3-kb fragment contained sufficient regulatory elements to control RPGR expression in mouse retina and other tissues. Characterization of the RPGR promoter will facilitate understanding of the functional role of RPGR in the retina and gene therapy of X-linked RP.

Genetics and Diagnostics of Retinitis Pigmentosa

AbstractPurpose To utilize next generation sequencing (NGS) and identity‐by‐descent mapping to identify mutations in known and new genes in patients with autosomal recessive (ar) or isolated (i) retinitis pigmentosa (RP).Methods We employed Roche 454‐NGS to screen the exons of 111 inherited retinal disease (IRD) genes in 12 IRD patients with known compound heterozygous variants and 100 unsolved ar/i RP patients. We used identity‐by‐descent mapping and SOLiD‐NGS to identify novel genes for arRP. We carried out segration analysis in the relevant families using Sanger sequencing.Results The NGS approach enabled us to robustly identify 21/24 known IRD‐associated variants. Taking into consideration that a proportion of the RP patients was previously screened for mutations in selected genes, we could solve 55 ar/i RP cases. Mutations were identified in arRP genes (n=45), X‐linked RP genes (n=4), and autosomal dominant RP genes (n=6). In at least 4 families de novo mutations were found. Targeted NGS of exons in selected chromosomal regions based on homozygosity mapping enabled us to identify at least one novel arRP gene. The interpretation of sequence variants derived from whole genome exon (exome) sequencing heavily depends on positional information (linkage analysis, homozygosity mapping).Conclusion NGS can be used for comprehensive mutation scanning of known IRD genes and for the identification of novel IRD genes. The known RP genes contain 55% of the causative mutations. In a significant proportion of isolated patients, we identified X‐linked and de novo autosomal dominant mutations, which has important repercussions for genetic counselling.

Homozygosity mapping identifies the Crumbs homologue 1 (Crb1) gene as responsible for a recessive syndrome of retinitis pigmentosa and nanophthalmos

The association of retinitis pigmentosa (RP) and microphthalmia has been reported in a number of familial and isolated cases. Here, the results of genetic analysis in a familial case of early RP associated with nanophthalmos are described. Two affected sibs were ascertained from an endogamous population in Mexico. A genome-wide linkage analysis was performed by means of an Affymetrix 250K microarray. Five large regions of homozygosity were demonstrated. The largest interval comprised 15.08 Mb at chromosome 1q31-32.1 and contained the Crumbs homologue-1, CRB1, a gene responsible for a number of recessive retinal dystrophies. Nucleotide sequence analysis demonstrated a c.1125C>G transversion in CRB1 exon 5, predicting a novel p.Tyr375X variant. To our knowledge this is the first instance in which a CRB1 mutation has been associated with early RP and nanophthalmos. Our results suggest a role for CRB1 in promoting axial growth of the eye. Clinical analysis of additional subjects with retinal dystrophies due to CRB1 mutations will help to identify if the high hyperopia, a frequently observed trait in these subjects, could be related to decreased eye axial length (nanophthalmos).

Identification of Disease-Causing Mutations in Autosomal Dominant Retinitis Pigmentosa (adRP) Using Next-Generation DNA Sequencing

To determine whether massively parallel next-generation DNA sequencing offers rapid and efficient detection of disease-causing mutations in patients with monogenic inherited diseases. Retinitis pigmentosa (RP) is a challenging application for this technology because it is a monogenic disease in individuals and families but is highly heterogeneous in patient populations. RP has multiple patterns of inheritance, with mutations in many genes for each inheritance pattern and numerous, distinct, disease-causing mutations at each locus; further, many RP genes have not been identified yet. Next-generation sequencing was used to identify mutations in pairs of affected individuals from 21 families with autosomal dominant RP, selected from a cohort of families without mutations in "common" RP genes. One thousand amplicons targeting 249,267 unique bases of 46 candidate genes were sequenced with the 454GS FLX Titanium (Roche Diagnostics, Indianapolis, IN) and GAIIx (Illumina/Solexa, San Diego, CA) platforms. An average sequence depth of 70× and 125× was obtained for the 454GS FLX and GAIIx platforms, respectively. More than 9000 sequence variants were identified and analyzed, to assess the likelihood of pathogenicity. One hundred twelve of these were selected as likely candidates and tested for segregation with traditional di-deoxy capillary electrophoresis sequencing of additional family members and control subjects. Five disease-causing mutations (24%) were identified in the 21 families. This project demonstrates that next-generation sequencing is an effective approach for detecting novel, rare mutations causing heterogeneous monogenic disorders such as RP. With the addition of this technology, disease-causing mutations can now be identified in 65% of autosomal dominant RP cases.

Principal components′ analysis of multifocal electroretinogram in retinitis pigmentosa

Aims:To determine waveforms of multifocal electroretinogram (mfERG) in patients with retinitis pigmentosa (RP) contributing significantly to the overall retinal response by using principal components’ analysis.Settings and Design:Prospective, non-randomized, single-visit, observational, case-control study from a single tertiary ophthalmic center.Materials and Methods:Patients with various forms of RP underwent mfERG testing for a period of one year. The first-order kernel responses of RP cases were compared with concurrently recruited healthy controls.Statistical Analysis Used:Parametric data was analyzed using the unpaired t test for differences between the implicit time and amplitudes of cases and controls. Principal components’ analysis was done for each implicit time and amplitude in cases with RP using the Varimax rotation method.Results:From March 2006 to March 2007, 24 cases with typical RP (56%, 47 eyes) were included in the final analysis. Their mean age was 33.7 years (19-69 ± 15.5 years). Comparison of latencies and amplitudes among RP cases with log MAR acuity ≤ 0.18 and those > 0.18, revealed significant difference in the implicit time (P1) in Ring 2 only (P=0.028). Two components (predominently from Ring 1 and 2) each contributing 66.8% and 88.8% of the total variance in the data for latencies and amplitudes respectively, were seen.Conclusions:The first two rings of the mfERG contributed to the variance of waveforms in RP, irrespective of the visual acuity and poor visual field results.

Screening genes of the visual cycle RGR, RBP1 and RBP3 identifies rare sequence variations

The visual cycle is essential for vision and several genes encoding proteins of the cycle have been found mutated in various forms of inherited retinal dystrophy. We screened 3 genes of the visual cycle. RGR, encoding the retinal pigment epithelium (RPE) G protein-coupled receptor acting in vitro as a photoisomerase; RBP1, encoding the ubiquitous cellular retinol binding protein carrying intracellular all-trans retinoids; RBP3, encoding the interphotoreceptor retinoid binding protein, a retinal-specific protein which shuttles all-trans retinol from photoreceptors to RPE and 11-cis retinal from RPE to photoreceptors. We used denaturing high performance liquid chromatography (D-HPLC) and direct sequencing to screen 216 patients (134 with autosomal recessive or sporadic retinitis pigmentosa (RP) and 82 with other retinal dystrophies) for RBP1 and RBP3, and 331 patients for RGR (79 cases with autosomal dominant RP and 36 RP cases with undetermined inheritance were added to the 216 previous patients). Several variants were found in the 3 genes, including unique amino acid changes, but none of them showed evidence of pathogenicity. It is likely that mutations in RGR, RBP3, and possibly RBP1 occur rarely in inherited retinal dystrophies.

Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa

BackgroundRetinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.MethodsLinkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EYS was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.ResultsA single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.ConclusionsThe EYS gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To date, there are only eight mutations in EYS that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of EYS in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in EYS cause arRP. Additionally, this is the first EYS mutation identified in the Chinese population.

Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa

To assess and correlate fundus autofluorescence (FAF) characteristics with photoreceptor morphology and functional features in eyes with retinitis pigmentosa (RP). Thirty-four eyes of 17 patients with RP were examined. We compared FAF images obtained by confocal scanning laser ophthalmoscopy with Spectral-domain optical coherence tomography (SD-OCT) and retinal function assessed by microperimetry. Normal FAF surrounded by a ring of increased FAF at the macular area was detected in 32 (94%) eyes. The diameter of the normal FAF was correlated significantly with the preserved area of the photoreceptor inner segment and outer segment (IS/OS) junction on SD-OCT (R=0.939, p<0.001). The area outside the ring was associated with loss of IS/OS junction and external limiting membrane (ELM). The ring of increased FAF demarcated the border between the central retina with preservation of the IS/OS junction and ELM, and the adjacent eccentric retina with loss of these bands. In two eyes of one patient, there was no preservation of normal FAF at the macula and the photoreceptor IS/OS junction was not detected on SD-OCT. The mean retinal sensitivity derived from microperimetry was correlated significantly with the area of normal FAF (R=0.929, p=0.007) and the preserved area of the IS/OS junction (R=0.851, p=0.032). Ten eyes had progressive reduction in size of the normal FAF inside the ring accompanied by decreased area of preserved IS/OS during 3.1 years. FAF appears to reflect the integrity of the photoreceptor layer. It may serve as a secondary outcome measure for novel therapeutic strategies for RP.

Usher syndrome associated with Fuchs’ heterochromic uveitis

The purpose of this study is to report two new cases of Usher syndrome associated with Fuchs' heterochromic uveitis (FHU), to confirm our previous observation of the association between FHU and retinitis pigmentosa (RP), and to evaluate if FHU is particularly associated with Usher syndrome. Retrospective medical record review of all new RP cases at Hadassah Medical Center between the years 2000 and 2007, review of our previously published data, and a meta-analysis of published relevant articles in peer reviewed journals. During the time frame of the study we diagnosed 58 new cases of RP, of whom one male and one female had the typical findings of FHU, and both had Usher syndrome type II. The difference in the occurrence of FHU between the 616 controls and the patients with RP was significant (p = 0.0073, Fisher's exact test). In our combined data, FHU occurred only in two types of RP; RP simplex with an incidence of 0.57%, and Usher syndrome with an incidence of 13.5%. This difference between the incidence of FHU in patients with Usher syndrome and other types of RP was significant (p < 0.0001, Fisher's exact test). Adding up these two cases with what is already published in the literature makes up a total of 17 RP patients with coexisting FHU. This study confirms the association between FHU and RP; and a particularly stronger association with Usher syndrome type II. Although infectious agents seem to play a role, the cause for this significant correlation is still unclear.

Blindness and visual impairment in retinitis pigmentosa: a Cameroonian hospital-based study

We performed a retrospective, analytical study in February 2010 on all retinitis pigmentosa cases seen during ophthalmologic consultation at the Gyneco-Obstetrics and Pediatric Hospital of Yaounde between March 2002 and December 2009 (82 months). The aim of this research was to determine the significance of blindness and visual impairment associated with retinitis pigmentosa in Cameroon. Forty cases were reported, corresponding to a hospital prevalence of 1.6/1000 (21 men and 19 women). The average age of the patients was 43.3 +/- 18 years, ranging between 6 and 74 years. Bilateral blindness and low vision was noted in 30% and 27.5% of patients, respectively. The average age of patients with low vision was 40.38 +/- 16.27 years and the average age of those with bilateral blindness was 51.08 +/- 15.79 years. Retinitis pigmentosa was bilateral in all cases and isolated (without any eye or general additional disease) in 67.5% of cases. Visual impairment is common and becomes even more severe with aging. Patients should be screened to enable them to benefit from management focusing on both appropriate treatment and genetic counseling.