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PURPOSE: To demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis. METHODS: A case series was constructed by reviewing medical records. RESULTS: Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis. CONCLUSION: Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered.

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Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease.

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BACKGROUND: To describe the phenotype and genotype of 10 Brazilian patients with variants in MFRP, posterior microphthalmos and retinal findings. METHODS: Complete ophthalmological evaluation was done at 4 different Brazilian centers. Genetic analysis was performed using commercial next generation sequencing panels for inherited retinal disorders. RESULTS: Ages of the patients ranged from 10 to 65 years and visual acuities from 0,05 to no perception of light. All were hyperopes (+4,25 to + 17,50) with a short axial length (14,4 mm to 18 mm). Common posterior segment features, though not present in all, were optic disc drusen (5/10), foveoschisis (5/10) and retinal pigmentary changes (8/10). Isolated patients presented with macular atrophy, serous retinal detachment, and chorioretinal folds. The most common variant in MFRP found in our patients was a deletion in exon 5 (c.498delC; p.Asn267Thrfs *25), present in all except 2 patients. Other variants found were c.523C>T (p.Gln175*), c.298delG (p.Ala100Argfs *37), c.666del (p.Thr223Argfs *83) and the novel variant c.257C>A (p.Ala86Asp). CONCLUSIONS: This is the first report of Brazilian patients with posterior microphthalmos and pathogenic variants in MFRP and the first describe of the variant p.Ala86Asp in literature. Our cases confirm the previously reported phenotype of high hyperopia, optic disc drusen, alterations in foveal architecture, retinal pigmentary changes with loss of photoreceptor function and visual field constriction. Report of such a rare condition is important to increase awareness to the phenotype of posterior microphthalmia with associated retinal conditions.

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Retinitis pigmentosa is a group of genetically determined retinal dystrophies characterized by primary photoreceptor apoptosis and can occur in isolated or syndromic conditions. This study reviewed the clinical data of 15 patients with syndromic retinitis pigmentosa from a Rare Disease Reference Center in Brazil and the results of their next-generation sequencing tests. Five males and ten females participated, with the mean ages for ocular disease onset, fundoscopic diagnosis, and molecular evaluation being 9, 19, and 29 years, respectively. Bardet-Biedl syndrome (n = 5) and Usher syndrome (n = 3) were the most frequent diagnoses, followed by other rare conditions. Among the patients, fourteen completed molecular studies, with three negative results and eleven revealing findings in known genes, including novel variants in MKKS (c.432_435del, p.Phe144Leufs*14), USH2A (c.(7301+1_7302-1)_(9369+1_9370-1)del), and CEP250 (c.5383dup, p.Glu1795Glyfs*13, and c.5050del, p.Asp1684Thrfs*9). Except for Kearn-Sayre, all presented an autosomal recessive inheritance pattern with 64% homozygosity results. The long gap between symptom onset and diagnosis highlights the diagnostic challenges faced by the patients. This study reaffirms the clinical heterogeneity of syndromic retinitis pigmentosa and underscores the pivotal role of molecular analysis in advancing our understanding of these diseases.

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Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression.

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ABSTRACT Retinitis pigmentosa is one of the leading causes of hereditary blindness in developed countries and unfortunately there is currently no cure. Photobiomodulation therapy can penetrate the retina and optic nerve and restore the function of damaged mitochondria as an intracellular target. This study is proposed to review and analyze photobiomodulation as a strategy that has the potential to be a new hope therapy and non-invasive treatment for retinitis pigmentosa in the long term. PubMed® and Google Scholar were used to perform a systematic review of photobiomodulation as a therapy for retinitis pigmentosa. Using PRISMA 2020 Guidelines, we include seven studies in this review. The inclusion criteria for each study were as follows: the study documented the use of photobiomodulation therapy for retinitis pigmentosa, was conducted in human eyes or animals' eye, its full text was in English, and it published in the last 10 years. We anticipated that most studies would be experimental design, we evaluated the quality of eligible studies using relevant items from the ROBINS-I, which is the recommended tool to evaluate experimental study. There is a clinical improvement in visual acuity and visual fields. Further eye examination showed functional and outer nuclear layer preservation, decline waveforms of electroretinogram slower than control, disruption of retinal pigment epithelium, and preserved photoreceptor nuclei twice thicker than control (p < 0.05). Photobiomodulation also increases retinal mitochondrial function and maintains mitochondrial redox state, revealing significant recovery of photoreceptors' cell function. Photobiomodulation showed significant change in clinical improvement, mitochondrial repair, and retinal layer thickening; thus, photobiomodulation can be a new hope for therapeutic strategies for retinitis pigmentosa. Several studies only have a few participants, so it does not provide a long-term outcome in retinitis pigmentosa.

RESUMO A retinite pigmentosa é uma das principais causas de cegueira hereditária em países desenvolvidos e, infelizmente, não há cura atualmente. A terapia de fotobiomodulação pode penetrar na retina e no nervo óptico e restaurar a função das mitocôndrias danificadas como alvo intracelular. Este estudo propõe-se a rever e a analisar a fotobiomodulação como estratégia que tem potencial para ser uma nova esperança terapêutica e tratamento não invasivo para a retinite pigmentosa a longo prazo. PubMed® e Google Scholar foram usados para realizar uma revisão sistemática da fotobiomodulação como terapia para retinite pigmentosa. Usando as diretrizes PRISMA de 2020, incluímos sete estudos nesta revisão. Os critérios de inclusão para cada estudo foram os seguintes: que tivesse documentado o uso de terapia de fotobiomodulação para retinite pigmentosa; o procedimento tivesse sido realizado em olhos humanos ou olhos de animais, e o texto fosse completo, em inglês, e publicado no último 10 anos. Previmos que a maioria dos estudos seria de desenho experimental, avaliamos a qualidade dos estudos elegíveis usando itens relevantes do ROBINS-I, que é a ferramenta recomendada para avaliação de estudo experimental. Houve melhora clínica da acuidade visual e dos campos visuais. O exame oftalmológico adicional mostrou preservação funcional e da camada nuclear externa; declínio das formas de onda do eletrorretinograma mais lento que o controle; ruptura do epitélio pigmentar da retina e núcleos fotorreceptores preservados duas vezes mais espessos que o controle (p < 0,05). A fotobiomodulação também aumenta a função mitocondrial da retina e mantém o estado redox mitocondrial, revelando uma recuperação significativa da função celular dos fotorreceptores. A fotobiomodulação mostrou mudança significativa na melhora clínica, reparo mitocondrial e espessamento da camada retiniana. Assim, a fotobiomodulação pode ser uma nova esperança para estratégias terapêuticas para retinite pigmentosa. Vários estudos têm apenas alguns participantes e, por isso, não fornecem um resultado a longo prazo na retinite pigmentosa.

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Patients with adult Refsum Disease (ARD) have retinitis pigmentosa and thus nyctalopia, anosmia, sensorineural deafness, polyneuropathy, and ataxia. Upon physical examination, patients with ARD have congenital short metacarpals, metatarsals, and cardiac arrhythmias. Manifestations due to the lack of phytanoyl-CoA hydroxylase in peroxisomes needed for alpha-oxidation of phytanic acid lead patients to accumulate phytanic acid in their body tissues. To our knowledge, no consensus for clinical diagnostic criteria for patients with ARD has been published. Our patient had nyctalopia, retinal findings, and visual field results compatible with retinitis pigmentosa. Additionally, the patient had decreased macular thickness and volume in both eyes, the findings being worse in the left eye. The patient had undergone hand surgery due to chronic pain in both hands, as well as his fourth and fifth metatarsal bones were shortened. Interestingly, audiology evaluation showed mild hearing loss in the right ear and mild to moderate hearing loss in the left ear. Inheritance patterns in patients with ARD have been described. Physical examination, phytanic acid evaluation, and genetic studies may all help reach an ARD diagnosis. This is the first report of adult Refsum disease in Puerto Rico.

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Introduction: Inosine monophosphate dehydrogenase 1 (IMPDH1) is a critical enzyme in the retina, essential for the correct functioning of photoreceptor cells. Mutations in IMPDH1 have been linked to autosomal dominant retinitis pigmentosa subtype 10 (adRP-10), a genetic eye disorder. Some of these mutations such as the Asp226Asn (D226N) lead to the assembly of large filamentous structures termed cytoophidia. D226N also gives IMPDH1 resistance to feedback inhibition by GDP/GTP. This study aims to emulate the adRP-10 condition with a long-term expression of IMPDH1-D226N in vitro and explore cytoophidium assembly and cell survival. We also assessed whether the introduction of an additional mutation (Y12C) to disrupt the cytoophidium has an attenuating effect on the toxicity caused by the D226N mutation. Results: Expression of IMPDH1-D226N in HEp-2 cells resulted in cytoophidium assembly in ∼70% of the cells, but the presence of the Y12C mutation disrupted the filaments. Long-term cell survival was significantly affected by the presence of the D226N mutation, with a decrease of ∼40% in the cells expressing IMPDH1-D226N when compared to IMPDH1-WT; however, survival was significantly recovered in IMPDH1-Y12C/D226N, with only a ∼10% decrease when compared to IMPDH1-WT. On the other hand, the IMPDH1 expression level in the D226N-positive cells was <30% of that of the IMPDH1-WT-positive cells and only slightly higher in the Y12C/D226N, suggesting that although cell survival in Y12C/D226N was recovered, higher expression levels of the mutated IMPDH1 were not tolerated by the cells in the long term. Conclusion: The IMPDH1-D226N effect on photoreceptor cell survival may be the result of a sum of problems: nucleotide unbalance plus a toxic long-life cytoophidium, supported by the observation that by introducing Y12C in IMPDH1 the cytoophidium was disrupted and cell survival significantly recovered, but not the sensibility to GDP/GTP regulation since higher expression levels of IMPDH1-D226N were not tolerated.

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Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies.

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El síndrome de Bardet-Biedl (SBB) es una entidad poco frecuente, con gran heterogeneidad clínica y genética. Pertenece a las ciliopatías y tiene un modo de herencia autosómico recesivo. Hasta la fecha se han identificado más de 26 genes asociados. Afecta múltiples sistemas con compromiso oftalmológico, renal, cognitivo, esquelético, gonadal y ponderal. Su diagnóstico se basa en criterios clínicos y se confirma mediante estudios genéticos específicos. Presentamos el caso de un paciente de 2 años y 7 meses de edad, con polidactilia, obesidad, retraso del neurodesarrollo y afección renal en quien se arribó al diagnóstico clínico de SBB con posterior confirmación mediante estudio molecular. Se detectó una variante patogénica en homocigosis en el gen BBS2. La sospecha y confirmación diagnóstica permitieron el manejo adecuado del paciente, planificar el seguimiento apropiado y completar el asesoramiento genético familiar

Bardet-Biedl syndrome (BBS) is a rare entity that holds a great clinical and genetic heterogeneity. It is a ciliopathy and has an autosomal recessive inheritance. To this day more than 26 associated genes have been identified. It affects multiple aspects predominantly ophthalmological, renal, cognitive, skeletal, gonadal and weight. The diagnosis is based on clinical criteria and confirmed by specific genetic studies. We describe a case of a 2-year-and 7 month old patient with polydactyly, obe39 sity, neurodevelopmental delay and kidney dysplasia in which clinical diagnosis was suspected by criteria and subsequently has confirmation by molecular study. An homozygous pathogenic variant was detected in the BBS2 gene. The diagnostic suspicion and later confirmation allowed the proper management of this patient as well as an appropriate follow-up and complete genetic family counseling

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Fundamento: la retinosis pigmentaria, enfermedad ocular de origen genético y baja prevalencia, progresa lentamente en años hacia el deterioro visual severo y afecta el desempeño social. En el Servicio de Oftalmología del Hospital Docente Clínico Quirúrgico Dr. Salvador Allende, existe un protocolo asistencial institucional que incluye la atención sistemática e integral de los afectados. Objetivo: identificar las enfermedades crónicas no transmisibles en pacientes con retinosis pigmentaria y en sus familiares. Métodos: estudio descriptivo, prospectivo, realizado entre marzo 2016-marzo 2022, con muestreo no probabilístico e intencionado. Se seleccionaron pacientes y familias registradas en la base de datos del servicio, residentes en los municipios Cerro y Plaza, en La Habana. Resultados: de 145 personas estudiadas (74 enfermos de retinosis pigmentaria y 71 familiares), 138 (95,1 %) presentaban enfermedades crónicas no transmisibles, entre las que se destacan la hipertensión arterial (29,7 %), la diabetes mellitus (21,0 %) y la asociación de ambas (13,0 %). En la dispensarización comunitaria se incluyen en el Grupo 4 las personas con déficit visual y además en otros grupos de dispensarización para atender mejor los factores de riesgo y enfermedades crónicas no transmisibles halladas en ellos. Conclusiones: la identificación de las enfermedades crónicas no transmisibles fue útil, para desplegar una atención médica holística e interdisciplinaria que facilite la prevención de enfermedades y complicaciones, permita preservar la visión, optimizar la rehabilitación visual y la calidad de vida. Se recomienda aplicar atento cuidado y mejorar la educación sanitaria en pacientes con retinosis pigmentaria.

Background: retinitis pigmentosa, an ocular disease of genetic origin and low prevalence, slowly progresses over years towards severe visual impairment and affects social performance. In the Ophthalmology Service of the Dr. Salvador Allende Clinical Surgical Teaching Hospital, there is an institutional care protocol that includes systematic and comprehensive care for those affected. Objective: to identify chronic non-communicable diseases in patients with retinitis pigmentosa and their relatives. Methods: descriptive, prospective study carried out between March 2016-March 2022, with non-probabilistic and intentional sampling. Patients and families registered in the service's database, residing in the Cerro and Plaza municipalities, in Havana, were selected. Results: of 145 people studied (74 patients with retinitis pigmentosa and 71 relatives), 138 (95.1%) had non-communicable chronic diseases, among which arterial hypertension (29.7%), diabetes mellitus (21 0.0%) and the association of both (13.0%). In community dispensing, people with visual impairment are included in Group 4 and also in other dispensing groups to better attend to the risk factors and chronic non-communicable diseases found in them. Conclusions: the identification of chronic non-communicable diseases was useful to deploy holistic and interdisciplinary medical care that facilitates the prevention of diseases and complications, preserves vision, optimizes visual rehabilitation and quality of life. It is recommended to apply attentive care and improve health education in patients with retinitis pigmentosa.

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PURPOSE: To describe a case of retinitis pigmentosa and nanophthalmos in a patient with attenuated Hunter's syndrome. METHODS: Fundus photography, total field electroretinogram, ultrasound, computerized visual field examination, biochemical examination and genetic testing were obtained. RESULTS: The fundus exam showed diffuse arteriolar attenuation, optic disc with regular contours, and pigment agglomerates like "bone spicules" in the middle periphery. Ultrasound examination revealed scleral thickening and short axial diameter in both eyes. The total field electroretinogram exam showed a subnormal result with greater impairment of the scotopic phase of the exam. Computerized visual field examination demonstrated a diffuse reduction in retinal sensitivity in the periphery. Biochemical examination showed increased urine glycosaminoglycan excretion and iduronate-2-sulphatase activity (IDS) deficiency in leukocytes, confirming the type II mucopolysaccharidosis. Molecular analysis revealed a novel missense mutation (p.A77D) in the IDS gene. CONCLUSION: The case report is about a patient presented an attenuated form of the syndrome, with no cognitive impairment. Ophthalmologic follow-up is still an important part of multidisciplinary treatment for Hunter's syndrome.

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ABSTRACT We describe the case of a 15-year-old girl with decreased visual acuity associated with elevated intraocular pressure in both eyes and angle closure on gonioscopy. She also presented attenuation of retinal vessels and optic disc pallor with large excavation in the left eye. Ultrasound biomicroscopy revealed an anteriorly positioned ciliary body and absence of ciliary sulcus, confirming the plateau iris configuration. Spectral-domain optical coherence tomography revealed a bilateral cystoid macular edema. Genetic screening revealed heterozygous variants of the Crumbs homolog 1 (CRB1) gene (c.2843G>A and c.2506C>A). The patient underwent trabeculectomy for intraocular pressure control and topical treatment for macular edema. This case highlights the importance of performing gonioscopy and evaluating intraocular pressure in patients with a shallow anterior chamber despite young age. In addition, it also shows the importance of genetic screening, when available, in elucidating the diagnosis and providing patients and their families' information on the patient's prognosis and possible therapeutic options.

RESUMO Nós descrevemos um caso de uma paciente de 15 anos com queda de acuidade visual e aumento da pressão intraocular em ambos os olhos, juntamente com fechamento angular no exame de gonioscopia. Na fundoscopia a paciente apresentava atenuação dos vasos retinianos, palidez de disco e aumento de escavação em olho esquerdo. Ao exame da biomicroscopia ultrassônica, foi evidenciado corpo ciliar anteriorizado e ausência de sulco ciliar em ambos os olhos, relevando presença de íris em plateau. Ao exame de tomografia de coerência óptica, visualizamos presença de edema macular cistoide bilateral. O screening genético revelou heterozigose no gene CRB1 (c.2843G>A and c.2506C>A), confirmando o diagnóstico de retinose pigmentar. Este caso reforça a importância do exame de gonioscopia e da avaliação da pressão intraocular em pacientes em câmara rasa, mesmo em pacientes jovens. Além disso, mostra a importância do screening genético como ferramenta útil para elucidação diagnóstica.

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Pre-mRNA splicing factors are crucial in regulating transcript diversity, by removing introns from eukaryotic transcripts, an essential step in gene expression. Splicing of pre-mRNA is catalyzed by spliceosomes. CWC27 is a cyclophilin associated with spliceosome, in which genetic defects of its components have been linked to spliceosomopathies with clinical phenotypes including skeletal developmental defects, retinitis pigmentosa (RP), short stature, skeletal anomalies, and neurological disorders. We report two siblings (male and female) of Mexican descent with a novel homozygous frameshift variant in CWC27 and aim to highlight the cardinal features among the previously described 12 cases as well as expand the currently recognized phenotypic spectrum. Both siblings presented with a range of ocular and extraocular manifestations including novel features such as solitary kidney and tarsal coalition in the male sibling, together with gait abnormalities, and Hashimoto's thyroiditis in the female sibling. Finally, we highlight ectodermal involvement including sparse scalp hair, eyebrows and lashes, pigmentary differences, nail dysplasia, and dental anomalies as a core phenotype associated with the CWC27 spliceosomopathy.

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Human-induced pluripotent stem cells (hiPSCs) have provided new methods to study neurodegenerative diseases. In addition to their wide application in neuronal disorders, hiPSCs technology can also encompass specific conditions, such as inherited retinal dystrophies. The possibility of evaluating alterations related to retinal disorders in 3D organoids increases the truthfulness of in vitro models. Moreover, both Alzheimer's (AD) and Parkinson's disease (PD) have been described as causing early retinal alterations, generating beta-amyloid protein accumulation, or affecting dopaminergic amacrine cells. This review addresses recent advances and future perspectives obtained from in vitro modeling of retinal diseases, focusing on retinitis pigmentosa (RP). Additionally, we depicted the possibility of evaluating changes related to AD and PD in retinal organoids obtained from potential patients long before the onset of the disease, constituting a valuable tool in early diagnosis. With this, we pointed out prospects in the study of retinal dystrophies and early diagnosis of AD and PD.

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BACKGROUND: There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. METHODS: This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/µL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. RESULTS: Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. CONCLUSIONS: These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

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MOTIVATION: Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. RESULTS: We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.

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SUMMARY OBJECTIVE: Retinitis pigmentosa is an inherited degenerative disorder causing severe retinal dystrophy and visual impairment, mainly with onset in the first or second decades. The next-generation sequencing has become an efficient tool to identify disease-causing mutations in retinitis pigmentosa. The aim of this retrospective study was to investigate novel gene variants and evaluate the utility of whole-exome sequencing in patients with retinitis pigmentosa. METHODS: The medical records of 20 patients with retinitis pigmentosa at Eskişehir City Hospital between September 2019 and February 2022 were analyzed retrospectively. Peripheral venous blood was obtained, followed by the extraction of genomic DNAs. The medical and ophthalmic histories were collected, and ophthalmological examinations were performed. Whole-exome sequencing was performed to determine the genetic etiology of the patients. RESULTS: The proportion of genetically solved cases was 75% (15/20) in the patients with retinitis pigmentosa. Molecular genetic testing identified 13 biallelic and 4 monoallelic mutations in known retinitis pigmentosa genes, including 11 novel variants. According to in silico prediction tools, nine variants were predicted as pathogenic or possibly pathogenic. We identified six previously reported mutations to be associated with retinitis pigmentosa. The age of onset of the patients ranged from 3 to 19, with a mean age of onset of 11.6. All patients had a loss of central vision. CONCLUSION: As the first study of the application of whole-exome sequencing among patients with retinitis pigmentosa in a Turkish cohort, our results may contribute to the characterization of the spectrum of variants related to retinitis pigmentosa in the Turkish population. Future population-based studies will enable us to reveal the detailed genetic epidemiology of retinitis pigmentosa.

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Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies.

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Introduction Patients with Usher syndrome (USH) have retinitis pigmentosa (RP) and hearing loss inherited as an autosomal recessive (ar) trait. Mutations in the USH2A gene are the most common cause of Usher syndrome. We report the genotype-phenotype correlation in 10 patients with Usher syndrome from Puerto Rico (PR). This is the first genotype-phenotype analysis of patients with the syndrome in PR. Methods We conducted a chart review of patients who carried an Usher syndrome diagnosis. They underwent a comprehensive ophthalmic evaluation by at least one of the authors. This included best corrected visual acuity (BCVA), visual field mean deviation (VF MD), pattern standard deviation (PSD), and macular optical coherence tomography (mOCT) average volume and thickness. Genotyping was done using the Invitae Inherited Retinal Disease (IRD) Panel. Results Three patients had a logMAR BCVA of 1.0 or worse. The median VF MD was -29.7 dB and -29.2 dB in the OD and OS, respectively. The median PSD was 5.5 dB and 5.7 dB in the OD and OS, respectively. Upon macular OCT, patients had a median volume of 8.4 µm3 and 8 µm3 in the OD and OS, respectively. The median thickness was 235 µm and 223 µm in the OD and OS, respectively. All patients had pathogenic USH2A variants, and eight of these were compound heterozygotes. The most common variants were p.Cys575Tyr and p.Glu767Serfs*21, each present in four patients. Patients with the p.Cys759Phe variant had the worst phenotype with the worst BCVA, largest VF MD, and slimmer macular thickness. Conclusion Our findings are compatible with previously reported pathogenic mutations in the USH2A gene. However, the p.Cys759Phe variant has previously been correlated with a mild phenotype. In our study, the p.Cys759Phe variant correlated with the most severe phenotype. This variant has a high prevalence in the Spanish population, and PR was a Spanish colony for 400 years. The presence of this variant could be traced back to Spain. Genotyping patients with Usher syndrome is of utmost importance. Further studies to evaluate the common founder effect of patients with the syndrome in PR are warranted.