OBJECTIVES

To determine the phenotypic and genotypic characterization of individuals with retinitis pigmentosa (RP), identify their genetic etiologies, and provide counseling to affected patients.

This non-interventional, observational study evaluated 18 patients with clinically-diagnosed RP from 15 different families. The patients underwent complete ophthalmological examination with retinal functional and morphologic assessment. Genetic testing was done using next-generation sequencing.

Ten gene mutations with 22 variants were identified. The inheritance pattern was predominantly autosomal recessive (70%). The most common mutation was EYS (27.8%). One possible novel gene, RGS7, and novel variants of CNGB1 were identified. Characteristic RP profiles were observed, with syndromic findings noted in USH2A and BBS5 mutations.

Phenotypic characteristics among different gene mutations have distinct features. This is the first study in the country to demonstrate the genotypic heterogeneity of RP, displaying 22 variants with 3 noted novel mutations.

Background and Objective: The Philippines does not have a national congenital rubella syndrome (CRS) surveillance or registry. Regular monitoring of CRS cases in hospitals, including in a Philippine tertiary hospital, helped in the past to provide clinico-epidemiologic data on CRS. This study aimed to continue providing clinico-epidemiologic data on CRS cases seen in the Philippine tertiary hospital from 2009-2012 and 2019-2022 and compare the cases seen from said timelines. Methods: A cross-sectional study was used, employing chart review of patients newly diagnosed with CRS from 2009-2012 and 2019-2022 in the Department of Ophthalmology and Visual Sciences at the Philippine tertiary hospital. Results: Forty-two patients newly diagnosed with CRS from 2009-2012 and 2019-2022 were included. Only 14 (33%) were serologically-confirmed cases (albeit qualitatively). Median age (first and third interquartile ranges) at consult was 1 year (0.4, 2.5). Twenty-four (57%) patients had maternal history of rashes and/or fever. Trimester of pregnancy when mother became symptomatic was not significantly correlated with chief complaint (p=0.20) and numbers of ophthalmic (p=0.68) and systemic manifestations (p=0.32). Cataract was the most common ophthalmic manifestation present in 40 (95%) patients. Twenty-six (62%) patients had other associated systemic findings of which hearing loss was the most common. Only 29 of 40 patients with cataract underwent lensectomy, with 23 patients having poor visual prognosis prior to surgery (5 with nystagmus alone, 10 with nystagmus and strabismus, and 8 with strabismus alone). Discussion: Using ophthalmic manifestations as primary indicator, this study provided an update on the CRS cases in the country. Laboratory confirmation remains a challenge in diagnosing CRS as the tests are costly and not widely available. There was increase from 2009-2012 compared to 2019-2022 in number of patients who underwent surgical treatment for cataract but visual outcomes were suboptimal due to delay in consultation. Although there was a decrease in number of CRS cases seen in the Philippine tertiary hospital, this cannot be attributed to increased rubella-containing vaccine (RCV) coverage alone. Conclusion Provision of data from individual hospital-based studies similar to this highlights the need for a national CRS surveillance system or registry. This can better gauge the burden of CRS and identify the gap in RCV coverage.
Rubella Syndrome, Congenital ; Retinitis Pigmentosa

OBJECTIVE: To explore the genetic basis for a patient with early-onset retinitis pigmentosa (RP). METHODS: A patient who had presented at the West China Hospital of Sichuan University on March 10, 2020 was selected as the study subject. The patient and his parents were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and in silico analysis. RESULTS: The patient has featured substantial loss of binocular vision field. Funduscopy revealed characteristic bone spicule-type pigment deposits, as well as attenuated retinal arterioles and pale-appearing optic discs. WES revealed that he has harbored compound missense variants of a RP-associated CRB1 gene, including c.2969T>C (p.Leu990Ser) and c.1816T>C (p.Cys606Arg), which were respectively inherited from his father and mother. Homozygous c.1816T>C (p.Cys606Arg) variant has been identified among RP patients, whilst the c.2969T>C (p.Leu990Ser) variant was unreported previously. Both variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The novel compound heterozygous variants of the CRB1 gene probably underlay the early-onset RP in this patient. Above finding has enriched the mutational spectrum of the CRB1 gene.
Male ; Female ; Humans ; China ; Genomics ; Homozygote ; Mothers ; Retinitis Pigmentosa/genetics* ; Eye Proteins/genetics* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese patient with retinitis pigmentosa (RP). METHODS: Whole exome sequencing (WES) was carried out to screen potential variant in the proband. Candidate variants were determined by taking consideration of clinical phenotype. Sanger sequencing was used to verify the variant in the proband and his parents. RESULTS: The proband was found to harbor compound heterozygous variants of c.8G>A (p.Cys3Tyr) and c.958_959insA (p.Arg320Glnfs*29) in the C2ORF71 gene, which has derived from his father and mother, respectively. Both variants were unreported previously. Based on the ACMG guidelines, they were predicted to be likely pathogenic and pathogenic, respectively. CONCLUSION The novel compound heterozygous variants of the C2ORF71 gene probably underlay the pathogenesis of RP in the proband. Above finding has enriched the spectrum of C2ORF71 gene mutations and facilitated genetic counseling for the family.
Asians/genetics* ; China ; Humans ; Mutation ; Pedigree ; Retinitis Pigmentosa/genetics* ; Whole Exome Sequencing

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a Chinese couple whom had conceived two fetuses featuring multiple malformations including polycystic kidney, polydactyly and encephalocele. METHODS: Following elective abortion, the fetus from the second pregnancy was subjected to whole exome sequencing. Suspected pathogenic variants were verified by Sanger sequencing of the fetus and its parents. RESULTS: The fetus was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2743G>T (p.E915X) and c.2587-2A>T, which were respectively inherited from its father and mother. The same variants were not detected among 100 healthy controls nor reported previously. Bioinformatic analysis suggested both variants to be deleterious. The fetus was diagnosed with Meckel-Gruber syndrome. Prenatal diagnosis for the couple during their next pregnancy suggested that the fetus did not carry the above pathogenic variants. CONCLUSION The compound heterozygous variants of the CEP290 gene probably underlay the pathogenesis of Meckel-Gruber syndrome in the second fetus. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the couple, and also enriched the mutational spectrum of the CEP290 gene.
China ; Ciliary Motility Disorders ; Encephalocele/genetics* ; Female ; Genetic Testing ; Humans ; Pedigree ; Polycystic Kidney Diseases/genetics* ; Pregnancy ; Prenatal Diagnosis ; Retinitis Pigmentosa

PURPOSE: To report a case of retinal toxicity after an intravitreal ganciclovir injection to treat acute retinal necrosis in an eye filled with silicone oil.CASE SUMMARY: A 56-year-old male presented with ocular pain and visual loss in his right eye. His best-corrected visual acuity was 20/25, inflammatory cells in the anterior chamber, multiple retinitis lesions and retinal vessel occlusions in the peripheral retina and vitreous opacity were showed. Acute retinal necrosis was suspected, anterior chamber polymerase chain reaction (PCR) test was done. Aciclovir 2,400 mg/day intravenously and ganciclovir 2.0 mg were administered by intravitreal injection. After 4 days, retinitis was worsened and PCR test was positive for varicella zoster virus. Ganciclovir intravitreal injections were increased twice a week. After 16 days, retinal detachment occurred, so scleral encircling, vitrectomy, laser photocoagulation, and silicone oil tamponade were conducted. Ganciclovir 1.0 mg was injected at the end of surgery. The patient's visual acuity decreased to hand motion, and multiple crystal deposits with multiple retinal hemorrhages were observed in the right eye the next day. Visual acuity did not recover and optical coherent tomography showed that the macula was thinned.CONCLUSIONS: Visual loss seemed to be related with the retinal toxicity of ganciclovir. The increased local concentration due to the silicone oil tamponade is thought to have caused the toxicity.
Acyclovir ; Anterior Chamber ; Ganciclovir ; Hand ; Herpesvirus 3, Human ; Humans ; Intravitreal Injections ; Light Coagulation ; Male ; Middle Aged ; Polymerase Chain Reaction ; Retina ; Retinal Detachment ; Retinal Hemorrhage ; Retinal Necrosis Syndrome, Acute ; Retinal Vessels ; Retinaldehyde ; Retinitis ; Silicon ; Silicones ; Visual Acuity ; Vitrectomy

No abstract available.
Bardet-Biedl Syndrome ; Humans ; Retinitis Pigmentosa ; Retinitis

OBJECTIVE: To identify the pathogenic mutation underlying retinitis pigmentosa in a large pedigree. METHODS: The pedigree has included three generations showing an autosomal dominant transmission of retinitis pigmentosa. Potential mutations were screened using a retinitis pigmentosa gene panel and an Ion PGM platform. Suspected mutation was verified by Sanger sequencing. RESULTS: A novel heterozygous missense mutation, c.251T>C(p.Leu84Pro), was identified in the RHO gene. The mutation has co-segregated with the retinitis pigmentosa phenotype among all family members and was not found in public databases ExAC, 1000G and dbSNP or 831 healthy controls. The mutation was predicted to be damaging by three major protein-predicting software. CONCLUSION The c.251T>C (p.Leu84Pro) mutation of the RHO gene is a novel pathogenic mutation underlying the retinitis pigmentosa phenotype in this pedigree. Above findings have enabled prenatal diagnosis for the pedigree.
DNA Mutational Analysis ; Eye Proteins ; Humans ; Mutation ; Mutation, Missense ; Pedigree ; Phenotype ; Retinitis Pigmentosa ; genetics

PURPOSE: We report a case of cytomegalovirus (CMV) retinitis following placement of an intravitreal dexamethasone implant in an immunocompetent patient diagnosed with non-infectious uveitis. CASE SUMMARY: A 60-year-old woman was referred to our hospital for recurrent anterior uveitis. Fundus examination and fluorescein angiography showed dense vitritis, but no definite retinal infiltration. After laboratory examinations, the patient was diagnosed with non-infectious panuveitis. Uveitis was much improved after the patient started taking oral steroid medication. However, the patient complained of systemic side effects from the oral steroids. Medication was stopped, and an intravitreal dexamethasone implant was fitted to address worsening inflammation. Two months later, perivascular retinal infiltration developed and vitritis recurred. Viral retinitis was suspected, and the patient underwent diagnostic vitrectomy adjunctive with intravitreal ganciclovir injection. Polymerase chain reaction of vitreous fluid confirmed the diagnosis of CMV retinitis. The patient has remained inflammation-free for more than 20 months after vitrectomy, single ganciclovir injection, and 2 months of oral valganciclovir medication. CONCLUSIONS: This is a case report of CMV retinitis following placement of an intravitreal dexamethasone implant in an immunocompetent patient without any risk factors or previous history of immunosuppression. Potential risk factors for CMV retinitis should be evaluated and careful follow-up should be performed when intravitreal dexamethasone injections are unavoidable for the treatment of non-infectious uveitis.
Cytomegalovirus Retinitis ; Cytomegalovirus ; Dexamethasone ; Diagnosis ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Ganciclovir ; Humans ; Immunosuppression ; Inflammation ; Middle Aged ; Panuveitis ; Polymerase Chain Reaction ; Retinaldehyde ; Retinitis ; Risk Factors ; Steroids ; Uveitis ; Uveitis, Anterior ; Vitrectomy

PURPOSE: To report the long-term outcome after surgical repair of a full-thickness macular hole (FTMH) in a patient with retinitis pigmentosa (RP). CASE SUMMARY: A 55-year-old male who had been diagnosed with retinitis pigmentosa in both eyes 5 years earlier presented with decreased visual acuity in his left eye over the last 6 months. On examination, his Snellen best-corrected visual acuity (BCVA) was 1.0 in the right eye and 0.3 in the left eye. Slit-lamp examination of the anterior segment was remarkable only for posterior chamber intraocular lenses in each eye. Fundus examination demonstrated extensive bony spicule-like pigmentation in the mid-peripheral region in both eyes and a FTMH with approximately one-third disc diameter in the left eye. The optical coherence tomography (OCT) findings confirmed a FTMH with a surrounding cuff of intraretinal fluid and vitreomacular traction in the left eye. The patient underwent 23-gauge pars plana vitrectomy (PPV) with indocyanine green-assisted internal limiting membrane peeling and gas tamponade. One week postoperatively, an anatomically well-sealed macular hole was confirmed by OCT. At the 3-month postoperative follow-up, the BCVA improved to 0.63 and the hole remained closed until his last follow-up (postoperative 6 years). CONCLUSIONS: Although macular hole is a rare occurrence in RP patients, it should be considered as a cause of significant visual loss in patients with this disorder. Our case suggested that over the long-term, PPV may be tolerable in the management for FTMH in RP.
Follow-Up Studies ; Humans ; Lenses, Intraocular ; Male ; Membranes ; Middle Aged ; Pigmentation ; Retinal Perforations ; Retinitis Pigmentosa ; Retinitis ; Tomography, Optical Coherence ; Traction ; Visual Acuity ; Vitrectomy