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Bardet-Biedl syndrome (BBS), one of the most common forms of syndromic inherited retinal diseases (IRDs), is characterized by the combination of retinal degeneration with additional extra-ocular manifestations, including obesity, intellectual disability, kidney disease, polydactyly and other skeletal abnormalities. We observed an Israeli patient with autosomal recessive apparently non-syndromic rod-cone dystrophy (RCD). Extra-ocular findings were limited to epilepsy and dental problems. Genetic analysis with a single molecule molecular inversion probes-based panel that targets the exons and splice sites of 113 genes associated with retinitis pigmentosa and Leber congenital amaurosis revealed a homozygous rare missense variant in the BBS9 gene (c.263C>T;p.(Ser88Leu)). This variant, which affects a highly conserved amino acid, is also located in the last base of Exon 3, and predicted to be splice-altering. An in vitro minigene splice assay demonstrated that this variant leads to the partial aberrant splicing of Exon 3. Therefore, we suggest that this variant is likely hypomorphic. This is in agreement with the relatively mild phenotype observed in the patient. Hence, the findings in our study expand the phenotypic spectrum associated with BBS9 variants and indicate that variants in this gene should be considered not only in BBS patients but also in individuals with non-syndromic IRD or IRD with very mild extra-ocular manifestations.
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PURPOSE: The purpose of this study is to describe a case series of infants with isolated congenital sixth nerve palsy (ICSNP) and suggest a management algorithm based on our experience and a review of the literature. METHODS: A retrospective cohort design was used. The clinical database of a single tertiary medical center was reviewed to identify all patients diagnosed with ICSNP from January 2020 to November 2022. Data were collected as follows: demographic parameters, age at initial presentation, presenting symptoms and signs, findings on ophthalmic and neurologic examinations, findings on follow-up, and outcome. RESULTS: Six patients were included. All were born at term. The average gestational weight was 3675.7 ± 262.7 g. Three mothers had gestational diabetes. Five deliveries necessitated labor induction either by oxytocin (n = 4) or by membrane stripping followed by oxytocin (n = 1). One had also gone a forceps assisted delivery. Symptoms were noticed in all newborns by their parents within the first week of life. Ophthalmological and neurological examinations were otherwise unremarkable apart of one patient with a head turn to the side of the involved eye. Four patients underwent brain imaging that were unremarkable. All abduction deficits resolved by 1 to 3 months of age. Follow up examinations were unremarkable (mean follow up 14.3 ± 5.0 months, range 4-23). CONCLUSIONS: This case series, together with previous reports, support ICSNP's benign nature. We suggest an initial basic work-up that solely includes ophthalmological and neurological examinations which will be elaborated in case of any additional pathologic findings or if ICSNP does not fully resolve by 3 months.
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Enfermedades del Nervio Abducens , Oxitocina , Recién Nacido , Lactante , Humanos , Estudios Retrospectivos , Enfermedades del Nervio Abducens/diagnóstico , Ojo , AlgoritmosRESUMEN
BACKGROUND: Patients with genetic optic atrophies must navigate all stages of life with their visual impairment, including the important milestone of family planning. Advances in genetic testing now allows physicians and affected families to consider medical help with the aim of preventing blindness through preconception, preimplantation, and perinatal methods. METHODS: This case series presents 4 patients with different genetic optic atrophies (Leber hereditary optic neuropathy [LHON], autosomal dominant optic atrophy, Wolfram syndrome, and papillorenal syndrome) who were followed by the Neuro-Ophthalmology Unit at a tertiary medical center between 2010 and 2023 and were of child-bearing age. The aim of this study was to increase understanding in family planning options for patients with optic atrophies, raise awareness of the solutions available, and provide guidance for clinicians to support their patients. RESULTS: Advances in medicine, genetics, and medical technology allow multidisciplinary teams to assist patients in fulfilling their desire for a genetically healthy offspring. Customized solutions can be designed to meet the specific challenges posed by each type of genetic optic atrophy. The solutions proposed in this series are based on genetic testing done in the parents, which then allows to plan medical and genetic intervention individually. The solutions opted for in this series range from the decision to not have another child until PGD (Preimplantation genetic diagnosis). CONCLUSION: We describe how genetic advancements have made it possible for patients with the 4 most common hereditary optic atrophies to fulfill their wish to have children without visually threatening genetic mutations. We also review the recent literature on the penetrance of optic atrophy in OA-mutation carriers and raise 2 significant ethical considerations: the reduction of a future life to a non-life-threatening impairment and that of public expenditure for non-life-threatening conditions.
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Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry. Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing). Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4-c.6077delT, is likely a founder mutation among the studied population. Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.
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Enfermedades de la Retina , Retinitis Pigmentosa , Femenino , Humanos , Masculino , Judíos/genética , Israel/epidemiología , Linaje , Retina , Retinitis Pigmentosa/epidemiología , Retinitis Pigmentosa/genética , Mutación/genética , Análisis Mutacional de ADN , Transportadoras de Casetes de Unión a ATP/genéticaRESUMEN
Most childhood acute lymphoblastic leukaemia (ALL) protocols include high-dose steroid therapy. However, the known potential of high-dose steroids to significantly elevate intraocular pressure (IOP) and lead to glaucomatous optic neuropathy has not been intensively investigated in children with ALL. Moreover, as children with ALL do not routinely undergo IOP measurements, the need for IOP monitoring and therapy is unknown. We prospectively measured IOP in 90 children with newly diagnosed ALL attending a tertiary paediatric haematology/oncology centre, at diagnosis and at the middle and end of induction therapy. Ocular hypertension (IOP > 21 mm Hg) at any time point was documented in 64 children (71%), and the prevalence increased during induction. Thirty-six children (40%) had elevated IOP at ALL diagnosis before therapy initiation, and stratification to non-standard ALL was a risk factor. IOP reduction therapy was administered to 13 children (14%); none required surgery. Values normalised in all cases. On multivariate logistic regression analysis, dexamethasone therapy was a significant risk factor for ocular hypertension. High body mass index was an additional risk factor in children with elevated IOP at ALL diagnosis. Routine evaluation of IOP during steroid therapy is very important in children with ALL to ensure early intervention which may prevent permanent ocular damage.
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Antineoplásicos Hormonales/efectos adversos , Dexametasona/efectos adversos , Presión Intraocular , Hipertensión Ocular/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Antineoplásicos Hormonales/uso terapéutico , Índice de Masa Corporal , Niño , Preescolar , Dexametasona/uso terapéutico , Femenino , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Lactante , Presión Intraocular/efectos de los fármacos , Masculino , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Estudios Prospectivos , Factores de RiesgoRESUMEN
PURPOSE: Retinol dehydrogenase 5 (RDH5)-related fundus albipunctatus can present with phenotypic variability. Our purpose was to investigate new clinical characteristics and multimodal imaging findings in patients from different ethnic origins, carrying different mutations. METHODS: Multicenter international retrospective case series of 18 patients with genetically confirmed RDH5-related fundus albipunctatus. Patients' files were reviewed for fundus images, visual acuity, macular optical coherence tomography scans, near-infrared images, fundus autofluorescence, electroretinogram, and genetic mutations. Imaging and electroretinogram findings. RESULTS: All eyes (n = 36, 100%) showed small circular findings seen on near-infrared images, termed as the "target sign," correlating to the yellowish dots seen clinically and to the distinct hyperreflective linear lesions on optical coherence tomography at the level between external limiting membrane and retinal pigment epithelium. Perifoveal atrophy with foveal sparing was seen in 4 eyes of 2 patients (both RDH5-c.160C>T, p.R54X mutation). Fundus autofluorescence revealed small hyperautofluorescent dots (n = 16, 44.4%). Scotopic electroretinograms were significantly reduced in all cases with an electronegative pattern, 66.7% displayed cone dysfunction. CONCLUSION: Our results show distinct imaging findings present in all patients with fundus albipunctatus independent of ethnicity or genetic mutation. Our results can facilitate the current algorithm to diagnose RDH5-related fundus albipunctatus and allow for targeted genetic testing.
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Ceguera Nocturna , Distrofias Retinianas , Oxidorreductasas de Alcohol , Electrorretinografía , Etnicidad , Angiografía con Fluoresceína , Humanos , Imagen Multimodal , Ceguera Nocturna/diagnóstico , Ceguera Nocturna/genética , Enfermedades de la Retina , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of Israeli IRD patients. To date, we recruited 2,420 families including 3,413 individuals with IRDs. On the basis of our estimation, these patients represent approximately 40% of Israeli IRD patients. To the best of our knowledge, this is, by far, the largest reported IRD cohort, and one of the first studies addressing the genetic analysis of IRD patients on a nationwide scale. The most common inheritance pattern in our cohort is autosomal recessive (60% of families). The most common retinal phenotype is retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone-rod dystrophy. We identified the cause of disease in 56% of the families. Overall, 605 distinct mutations were identified, of which 12% represent prevalent founder mutations. The most frequently mutated genes were ABCA4, USH2A, FAM161A, CNGA3, and EYS. The results of this study have important implications for molecular diagnosis, genetic screening, and counseling, as well as for the development of new therapeutic strategies for retinal diseases.
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Enfermedades Genéticas Congénitas/epidemiología , Enfermedades Genéticas Congénitas/genética , Predisposición Genética a la Enfermedad , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/genética , Alelos , Sustitución de Aminoácidos , Análisis Mutacional de ADN , Electrorretinografía , Efecto Fundador , Estudios de Asociación Genética , Enfermedades Genéticas Congénitas/diagnóstico , Pruebas Genéticas , Geografía Médica , Humanos , Patrón de Herencia , Israel/epidemiología , Mutación , Vigilancia de la Población , Enfermedades de la Retina/diagnóstico , Secuenciación Completa del GenomaRESUMEN
Purpose: To describe the coexistence of additional non-ocular genetic diseases in patients diagnosed with inherited retinal degenerations (IRDs). Methods: The study was based on a retrospective chart review of patients diagnosed with IRD and additional rare systemic diseases. The chart review included the ophthalmic and genetic aspects of each patient. The ophthalmic examination included best-corrected visual acuity, biomicroscopic examination, cycloplegic refraction, retinal imaging (fundus photos, optical coherence tomography, and fundus autofluorescence), and electroretinography. Genetic testing included homozygosity mapping, whole exome sequencing, and Sanger sequencing. Results: Fifteen index cases diagnosed with IRDs and one or more rare systemic diseases were identified. Six of the families were consanguineous. Of six patients with complete molecular diagnosis, four (66%) had pathogenic variants in two autosomal recessive (AR) disease genes, and of the total pathogenic variants identified, AR mutations were the most common (16/22, 72%). One patient was diagnosed with mutations in three different genes, underlying three distinct genetic conditions. Nine patients could have had an incorrect clinical diagnosis based on the clinical evaluation only (e.g., retinitis pigmentosa and hearing loss could have been diagnosed as Usher syndrome). Conclusions: The common working paradigm for the ophthalmologist is combining the different symptoms observed in a patient into one unifying diagnosis. However, IRD is a strikingly heterogeneous condition, and may coincide with other genetic (and non-genetic) rare conditions. Establishing a correct diagnosis is important for the patients and their family members, as it enables prediction of disease prognosis, aids in tailoring the correct follow-up and treatment, and allows patients to pursue prenatal counseling and reproductive planning.
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Patrón de Herencia/genética , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Linaje , FenotipoRESUMEN
PURPOSE: This work examined the antibacterial and physical effects of a novel Zn-CuO nanocoating applied on a silicone hydrogel contact lens. METHODS: Zn-CuO coating of PureVision balafilcon-A soft contact lenses (Bausch&Lomb, Rochester, NY) was performed by sonochemical deposition using a high-intensity ultrasonic horn. Non-coated PureVision lenses served as a control in all experiments. Adhesion assays for P. aerueginosa and S. epidermidis to the coated lenses were performed to identify the minimal coating concentration which still possessed antibacterial activity. Lens water content, oxygen transfer light transfer, leaching, and electron microscopy studies were performed using this concentration. RESULTS: Coated lenses showed 3-5 log reductions in adhesion of both species. The lowest tested coating concentration of 0.02 wt% led to a log reduction of 3.25 ± 1.25 of P. aeruginosa CFU/lens (P = 0.007) and a log reduction of 4.37 ± 0.75 of S. epidermidis (p = 0.0007). Using this coating concentration, water content (36%, 33.6%), oxygen transfer (87.22 ± 10.96, 92.18 ± 2.38, × 10-11(cm2/s)(mlO2)/(ml × mmHg)), p = 0.12), and light transfer properties did not differ significantly between the coated and the control contact lenses. In the range of 380-780 nm wavelength, the coated lenses transmitted 96.47 ± 1.52% while the control lenses transmitted 97.36 ± 1.35%. The corresponding values for the range of 300-380 nm wavelength were 79.343 ± 8.754 and 80.169 ± 1.35. Leaching studies for 0.5 mM coated lenses have demonstrated the excellent stability of the coating with the release of only 0.005% of the coating after 1 week of exposure to the test solution. CONCLUSION: Sonochemical-assisted nanocoating of contact lenses showed significant and consistent antibacterial activity while preserving the basic properties of a silicone hydrogel contact lens.
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Lentes de Contacto de Uso Prolongado/microbiología , Cobre , Ensayo de Materiales/métodos , Pseudomonas aeruginosa/fisiología , Staphylococcus epidermidis/fisiología , Zinc , Humanos , Hidrogeles , Nanoestructuras , SiliconasRESUMEN
INTRODUCTION: The sense of vision is highly important for humans and its loss markedly affects function and quality of life. Many inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptor cells. These diseases show clinical and genetic heterogeneity. AIMS: The Israeli IRD consortium (IIRDC) was established with the goal of performing clinical and genetic mapping of IRDs in the Israeli population. METHODS: Clinical evaluation is carried out at electroretinography (ERG) centers and ophthalmology departments, where the patients undergo a comprehensive eye exam, including testing of visual acuity, refractive error, imaging techniques and ERG tests. Genetic analysis is performed using Sanger sequencing, analysis of founder mutations, and whole exome sequencing. RESULTS: We recruited over 2,000 families including more than 3,000 individuals with IRDs. The most common inheritance pattern is autosomal recessive (65% of families). The most common retinal phenotype is retinitis pigmentosa (RP- 45% of families), followed by cone/cone-rod dystrophy, Stargardt Disease and Usher syndrome. We identified the cause of disease in 51% of families, mainly due to mutations in ABCA4, USH2A, FAM161A, CNGA3, and EYS. IIRDC researchers were involved in the identification of 16 novel IRD genes. In parallel, IIRDC members are involved in the development of therapeutic modalities for these currently incurable diseases. CONCLUSIONS: IIRDC works in close collaborative efforts aiming to continue and recruit for the genotype - phenotype study from the vast majority of Israeli IRD families, to identify all disease-causing mutations, and to tailor therapeutic interventions to each IRD patient.
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Calidad de Vida , Retinitis Pigmentosa , Análisis Mutacional de ADN , Electrorretinografía , Proteínas del Ojo/genética , Humanos , Mutación , Linaje , Retinitis Pigmentosa/complicaciones , Retinitis Pigmentosa/genéticaRESUMEN
Importance: Data regarding the prevalence of various inherited retinal diseases (IRDs) are limited and vary across populations; moreover, nationwide prevalence studies may be limited to a specific IRD phenotype, potentially leading to inaccurate prevalence estimations. Therefore, nationwide prevalence data are needed. Objective: To determine the prevalence of 67 IRD phenotypes in the Israeli population. Design, Setting, and Participants: This cohort study collected nationwide data regarding the number of individuals affected with IRD phenotypes assessed in 10 clinical and academic centers in Israel as part of the research activity of the Israeli inherited retinal disease consortium. Data were collected in May 2023 on 9396 individuals residing in Israel who were diagnosed by an ophthalmologist with an IRD using either electroretinography or retinal imaging where included. Individuals with retinal diseases known to have a nonmendelian basis or without a clear genetic basis and those who were reported as deceased at the time of data collection were excluded from this study. Main Outcomes and Measures: Prevalence of 67 IRD phenotypes. Results: Among the 9396 participants in our cohort, the most common IRD in Israel was retinitis pigmentosa with a disease prevalence of approximately 1:2400 individuals, followed by cone-rod dystrophy (approximately 1:14â¯000), Stargardt disease (approximately 1:16â¯000), Usher syndrome (approximately 1:16,000), and congenital stationary night blindness (approximately 1:18â¯000). The prevalence of all IRDs combined was 1:1043 individuals. Conclusions and Relevance: The current study provides large prevalence dataset of 67 IRD phenotypes, some of which are extremely rare, with only a single identified case. This analysis highlights the potential importance of performing additional nationwide prevalence studies to potentially assist with determining the prevalence of IRDs worldwide.
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Electrorretinografía , Enfermedades de la Retina , Humanos , Israel/epidemiología , Prevalencia , Masculino , Femenino , Adulto , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/genética , Enfermedades de la Retina/diagnóstico , Persona de Mediana Edad , Fenotipo , Adolescente , Adulto Joven , Anciano , Niño , Enfermedades Hereditarias del Ojo/epidemiología , Enfermedades Hereditarias del Ojo/genética , PreescolarRESUMEN
Purpose: To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population. Methods: Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources. Results: A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein. Conclusions: This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.
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Distrofia Macular Viteliforme , Humanos , Israel/epidemiología , Prevalencia , Mutación , Estudios de Asociación Genética , BestrofinasRESUMEN
BACKGROUND: This study aims to examine the rare entity of unilateral macular lesions in the pediatric population and describe the distinct diagnoses and characterizations related to these findings. METHODS: A retrospective cohort design. The database of the ophthalmology clinic in a tertiary medical center was reviewed to identify all children with incidental unilateral macular findings, examined during 2016 through 2021. RESULTS: Twenty children were included. Mean age was 7.8 ± 3.4 years, 50% were girls. The most common macular lesion was torpedo maculopathy (50%), followed by pigmentary changes (25%), discoid maculopathy (15%), macular scar and combined hamartoma of the retina and retinal pigment epithelium (RPE) (5% each). None of the lesions changed after a mean follow-up duration of 2.3 ± 1.5 years. Visual acuity in the involved eye was equal to that in the contralateral eye in 90% of patients and did not change from initial to final visit. CONCLUSION: Incidental unilateral macular lesions in the pediatric population are usually benign, stable, and do not affect vision. Long-term follow-up is advised, as vision-threatening alterations may appear. [Ophthalmic Surg Lasers Imaging Retina 2023;54:346-352.].
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Degeneración Macular , Enfermedades de la Retina , Femenino , Humanos , Niño , Preescolar , Masculino , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/patología , Epitelio Pigmentado de la Retina/patología , Degeneración Macular/patología , Angiografía con Fluoresceína/métodosRESUMEN
Background: TCC21B is a ciliary protein. The most common phenotypic features associated with TCC21B biallelic mutations are nephronophthisis and skeletal abnormalities. To date, retinal dystrophy has been reported in only one patient.Materials and Methods: Clinical evaluation included best-corrected visual acuity, cycloplegic refraction, fundus examination, fundus photography, retinal imaging by optical coherence tomography, full-field electroretinography, multifocal electroretinography, and visual evoked potentials. Genetic analysis included Whole Exome Sequencing and confirmation of the identified mutations in the patient and his parents by PCR amplification and direct sequencing.Results: A ten-year-old Caucasian male presented with nephronophthisis, high myopia and nycatalopia. Best-corrected visual acuity was preserved to 20/20 in each eye with significant myopic correction. Visual fields were constricted. Optical coherence tomography confirmed the lack of outer retinal layers in the perifoveal area on both eyes. Electroretinography confirmed significant retinal dystrophy. Whole Exome Sequencing revealed compound heterozygous mutations in the TTC21B gene.Conclusions: TTC21B is associated with ciliopathy, but retinal dystrophy is a rare finding in these patients. We report retinal dystrophy secondary to TTC21B mutations, and provide for the first time detailed clinical information of the ophthalmic phenotype.
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Ciliopatías/genética , Proteínas Asociadas a Microtúbulos/genética , Mutación , Distrofias Retinianas/genética , Niño , Análisis Mutacional de ADN , Electrorretinografía , Potenciales Evocados Visuales , Humanos , Enfermedades Renales Quísticas/congénito , Enfermedades Renales Quísticas/diagnóstico , Enfermedades Renales Quísticas/genética , Masculino , Reacción en Cadena de la Polimerasa , Refracción Ocular/fisiología , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/fisiopatología , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Secuenciación del ExomaRESUMEN
Background: To describe genetic molecular findings in individuals with congenital nystagmus, foveal hypoplasia, and subnormal vision, with normal ocular pigmentation (absence of diffuse transillumination or transparent retinal pigment typical for albinism).Methods: This is a retrospective, multicenter study of ophthalmic, systemic, and genetic features, as collected from medical records of patients diagnosed with infantile nystagmus and foveal hypoplasia. Ophthalmic findings include best-corrected visual acuity (BCVA), biomicroscopic examination, cycloplegic refraction, retinal examination, macular optical coherence tomography, and electroretinography. Genetic information was retrieved from the participating genetic clinics and included ethnicity and molecular diagnosis.Results: Thirty-one individuals met the inclusion criteria and had a secure molecular diagnosis. Mutations in two genes predominated, constituting 77.4% of all the represented genes: SLC38A8 (45.1%) and PAX6 (32.3%). Seventy-eight percent of the subjects who had a measurable BCVA had moderate and severe visual impairment (range 20/80 to 20/270). Most patients with a mutation in SLC38A8 had mild to moderate astigmatism, while most patients with PAX6 mutation had moderate and severe myopia. Patients in the PAX6 group had variable degrees of anterior segment manifestations.Conclusion: In our cohort, the main causative genes for congenital nystagmus and foveal hypoplasia in normally pigmented eyes were SLC38A8 and PAX6. A mild phenotype in PAX6 mutations may be an under-diagnosed cause of nystagmus and foveal hypoplasia. Reaching an accurate genetic diagnosis is essential for both the patients and their family members. This enables predicting disease prognosis, tailoring correct follow-up, and providing genetic counseling and family planning to affected families.
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Sistemas de Transporte de Aminoácidos Neutros/genética , Anomalías del Ojo/genética , Fóvea Central/anomalías , Nistagmo Congénito/genética , Factor de Transcripción PAX6/genética , Baja Visión/genética , Agudeza Visual/fisiología , Adolescente , Adulto , Anciano , Albinismo/genética , Astigmatismo/genética , Niño , Preescolar , Proteínas del Citoesqueleto/genética , Anomalías del Ojo/diagnóstico , Femenino , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Miopía/genética , Nistagmo Congénito/diagnóstico , Estudios Retrospectivos , Microscopía con Lámpara de Hendidura , Baja Visión/diagnóstico , Baja Visión/fisiopatología , Adulto JovenRESUMEN
Lymphatic-venous malformations (LVMs) are development defects that result in abnormal connections between the lymphatic and venous systems. The authors describe a 7-weeks-old female infant who presented with a right orbital LVM extending to the ipsilateral cheek and subconjunctiva of the right eye, intracranial developmental venous anomalies in the right cerebellum, and a significant right eye intraocular retinal vascular malformation. Since orbital LVM is usually diagnosed in infancy or childhood, pediatric ophthalmologists should actively look for intraocular vascular malformations as such findings can poorly affect a patient's vision.
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Proteínas Portadoras/genética , Proteínas del Ojo/genética , Terapia Genética , Amaurosis Congénita de Leber/genética , Células Fotorreceptoras de Vertebrados/citología , Epitelio Pigmentado de la Retina/citología , Proteínas Adaptadoras Transductoras de Señales , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Amaurosis Congénita de Leber/terapia , Masculino , Células Fotorreceptoras de Vertebrados/fisiología , Epitelio Pigmentado de la Retina/fisiología , Tomografía de Coherencia Óptica , Agudeza Visual , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: When corneal perforation develops in patients with severe ocular surface disease and limbal stem cell deficiency following childhood trachoma infection, penetrating keratoplasty is doomed to fail. To overcome this problem, the use of a fresh-tissue corneolimbal covering graft is described. PATIENTS AND METHODS: Retrospective interventional case series of four patients who presented to a tertiary center from 2003 to 2005 with a large corneal perforation due to ocular surface disease. Emergency surgery consisted of suturing a fresh-tissue corneolimbal covering graft to the patients' peripheral sclera. RESULTS: The corneolimbal graft became partially incorporated into the perforated cornea, which healed by scar tissue, after a few months. The ocular epithelial surface improved considerably. There was no recurrence of corneal perforation during the follow-up period of 1 to 3 years. CONCLUSION: Fresh-tissue corneolimbal covering graft was found to be a useful technique for saving the integrity of the eye in cases of a large corneal perforation in patients with severe ocular surface disease, such as in childhood trachoma.
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Enfermedades de la Córnea/cirugía , Trasplante de Córnea , Limbo de la Córnea , Tracoma/complicaciones , Anciano , Anciano de 80 o más Años , Enfermedades de la Córnea/etiología , Tratamiento de Urgencia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Rotura Espontánea , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
BACKGROUND: We describe the ophthalmologic, clinical, and genetic findings in a patient of Yemenite-Jewish origin diagnosed with Alstrom syndrome due to a novel splice-site mutation 10 years after a clinical misdiagnosis of Leber congenital amaurosis. METHODS: Ophthalmological evaluations included visual acuity, cycloplegic refraction, slit-lamp, and optical coherent tomography. Genetic analyses included whole exome sequencing followed by bioinformatics analysis and segregation analysis. An in vitro splicing assay was used to evaluate the effect of the identified mutation on splicing. Taqman assay was used to determine the need for population screening for the identified mutation. RESULTS: Ophthalmologic findings at age 6 were impaired vision, nystagmus, and hyperopia. At age 16 years, the patient presented with obesity, hypothyroidism, and elevated transaminase levels in addition to reduced vision, wandering nystagmus, disc pallor, and degenerative retinal changes. Targeted genetic analysis of ALMS1 revealed a homozygous transversion, c.11544 + 3A>T, suggesting a novel splicing mutation, with elimination of the donor splice site and insertion of 73 nucleotides at the end of exon 16. These changes were validated by Sanger sequencing and co-segregation on family members. CONCLUSIONS: Ophthalmologists should be alert to the differential diagnosis of inherited retinal degeneration in young patients who present with impaired vision, especially if systemic symptoms are mild and there is no known family history. In the present case, targeted genetic analysis of a child with a syndromic cone-rod dystrophy yielded a novel splicing mutation in ALMS1 causing Alstrom syndrome.