Retinal detachment in a pediatric patient with enhanced S-cone syndrome.

Enhanced S-cone syndrome (ESCS), also known as Goldmann-Favre syndrome, is a retinal degeneration that presents in childhood and leads to progressive nyctalopia and visual field loss. In advanced cases, this degeneration can result in loss of central visual acuity. We describe the case of a 15-year-old boy with ESCS who presented with retinal detachment, a rare complication.

Cardiac anomalies in Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome is a rare multi-system disorder associated with cardiac anomalies. All patients with a diagnosis of Axenfeld-Rieger syndrome were identified from our electronic medical record. Chart review was performed to document the presence and types of CHD. Out of 58 patients, 14 (24.1%) had CHD and a wide variety of cardiac lesions were identified.

Whole exome sequencing revealed novel pathogenic variants in Vietnamese patients with FEVR.

Background: Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder marked by incomplete retinal vascularization associated with exudation, neovascularization, and tractional retinal detachment. FEVR is genetically heterogeneous and is caused by variants in six genes: FZD4, LRP5, NDP, TSPAN12, ZNF408, and CTNNB1. In addition, the phenotypic overlap between FEVR and other disorders has been reported in patients harboring variants in other genes, such as KIF11, ATOH7, and RCBTB1. Purpose: To identify pathogenic variants in Vietnamese pediatric patients diagnosed with FEVR and to investigate the clinical findings in correlation with each causative gene. Methods: A total of 20 probands underwent ocular examinations with fundoscopy (ophthalmoscopy) or fluorescein angiography. Genomic DNA was extracted from the peripheral blood of the probands and their family members. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect copy number variants of FEVR-causing genes. Short variants were screened by whole-exome sequencing (WES) and then validated by Sanger sequencing. Results: Fluorescein angiography showed retinal vascular anomalies in all patients. Other ocular abnormalities commonly found were strabismus, nystagmus, exudation, and retinal detachment. Genetic analysis identified 12 different variants in the FZD4, NDP, KIF11, and ATOH7 genes among 20 probands. Four variants were novel, including FZD4 c.169G>C, p.(G57R); NDP c.175-3A>G, splicing; KIF11 c.2146C>T, p.(Q716*) and c.2511_2515del, p.(N838Kfs*17). All patients with the KIF11 variant showed signs of microcephaly and intellectual disability. The patient with Norrie syndrome and their family members were found to have a deletion of exon 2 in the NDP gene. Conclusions: This study sheds light on the genetic causes of ocular disorders with the clinical expression of FEVR in Vietnamese patients. WES was applied as a comprehensive tool to identify pathogenic variants in complex diseases, such as FEVR, and the detection rate of pathogenic mutations was up to 60%.

Laser Prophylaxis in Patients with Stickler Syndrome.

PURPOSE: To evaluate the association among laser prophylaxis treatment, retinal detachment (RD), and visual acuity (VA) in patients with Stickler syndrome (SS). DESIGN: Retrospective comparative case series. PARTICIPANTS: Patients with SS. METHODS: Patients received extended vitreous base laser (EVBL), nonprotocol laser (NPL), or no laser prophylaxis treatment of any kind. MAIN OUTCOME MEASURES: The 2 main outcome measures that were examined in these patients were rates of RD and VA. RESULTS: In this study, 230 eyes of 115 patients were included. Fifty-nine patients were women (51%). The median age at the time of laser prophylaxis treatment was 9.5 years (interquartile range [IQR], 6-13 years), and the median age of patients with RD was 11 years (IQR, 7-18 years). Of the 230 eyes, 92 did not undergo any laser treatment, 9 received NPL treatment, and 129 received EVBL treatment. Of the 129 eyes that underwent EVBL treatment, 4 (3%) had RD, compared with 74 eyes (73%) that had RD and did not receive laser or NPL treatment (P < 0.001). Eyes that received EVBL treatment had approximately 8 lines better vision, on average, compared with those that did not receive laser or NPL treatment (-0.86 logarithm of the minimum angle of resolution; 95% confidence interval,-1.1 to -0.64; P < 0.001). CONCLUSIONS: Treatment with EVBL seems to reduce the rate of subsequent RD and is associated with better VA in patients with SS.

Congenital alacrima.

The congenital absence of tear production or alacrima is a distinctively unusual clinical sign that harbors a wide variety of etiologies. While alacrima can be only isolated to the lacrimal system, it is more often associated with progressive multisystem involvement from underlying genetic disorders. Recognizing the subtle ocular signs in these diseases will promote a timely diagnosis and management before potential life-threatening consequences occur. Hence, the current article will review the ophthalmological findings, systemic manifestations, genetic associations, and differential diagnosis of congenital alacrima.

Extraocular muscle hypoplasia associated with Axenfeld-Rieger syndrome.

We describe a four-year-old girl with bilateral severe iris hypoplasia and secondary ocular hypertension. Genetic testing revealed a de novo deletion in the FOXC1 gene, establishing the diagnosis of Axenfeld-Rieger syndrome (ARS). The girl developed a gradually increasing exotropia, up to 95 prism diopters by the age of 3 years wherefore strabismus surgery was performed. Intra-operatively, only very rudimentary developed medial and lateral rectus muscles were found. This is the first observation of pronounced hypoplasia of both medial and lateral rectus muscles associated with ARS.

Recognizable Patterns of Submacular Fibrosis in Enhanced S-Cone Syndrome.

PURPOSE: To highlight recognizable patterns of subretinal fibrosis in enhanced S-cone syndrome (ESCS). DESIGN: Retrospective case series. PARTICIPANTS: Forty-seven patients with subretinal fibrosis identified from 101 patients with clinically diagnosed ESCS, confirmed by full-field electroretinography (35/47), genetic testing (34/47), or both. METHODS: Multimodal retinal imaging, electroretinography, and genetic analysis. MAIN OUTCOME MEASURES: Patterns of subretinal fibrosis with angiographic, OCT, and genetic correlations. RESULTS: Eighty-five eyes of 47 patients (24 male patients; 36 unrelated consanguineous families) had subretinal fibrosis. Mean age at presentation was 14 years. Best-corrected visual acuity ranged from 20/20 to hand movements. All 34 genetically tested patients were homozygous for pathogenic NR2E3 variants. Subretinal fibrosis was always in the macular area, although it extended beyond in some patients. Six recurrent patterns of submacular fibrosis were noted: central unifocal nodular, circumferential unifocal nodular, multifocal nodular, arcuate, helicoid, and thick geographic. Some patients showed a combination of patterns. Previous misdiagnosis as inflammatory disease was common. Fibrosis was fairly symmetrical in a given patient but not always present or identical in other affected individuals with a given homozygous mutation from the same or other families. CONCLUSIONS: These recognizable patterns of submacular fibrosis are part of the ESCS phenotypic spectrum and strongly suggest the disease. In addition to facilitating diagnosis, recognition of these patterns can spare patients unnecessary workup for an inflammatory cause.

Incidence and Natural History of Retinochoroidal Neovascularization in Enhanced S-Cone Syndrome.

OBJECTIVE: We examined the incidence and natural history of macular retinochoroidal neovascularization (RCN) in enhanced S-cone syndrome (ESCS). DESIGN: Retrospective case series. METHODS: This single-center study included 14 of 93 patients with ESCS who had signs of active or inactive RCN in ≥1 eye. We conducted multimodal retinal imaging, full-field electroretinography, and molecular genetic analysis of NR2E3 gene. Our main outcome measures included the cumulative incidence of RCN in ESCS, type of RCN, and mode of evolution of RCN. RESULTS: Fourteen (15.1%) of 93 patients with ESCS had RCN in ≥1 eye at 2 to 27 years of age. All 22 RCNs (21 eyes of 14 patients) were macular. Twelve of the RCNs were active with exudates/hemorrhages. Of these, 5 appeared de novo in a subretinal location, with photographic evidence of no pre-existing lesions. The latter were compatible with type 3 neovascularization or retinal angiomatous proliferation and subsequently evolved into unifocal fibrotic nodules. The remaining active lesions all had some degree of pre-existing fibrosis and remained stable. Ten inactive fibrotic nodules, identical to end-stage de novo lesions, were found and were presumed to represent healed RCNs. CONCLUSIONS: RCN, a treatable condition, may occur as early as 2 years of age and may be much more common in patients with ESCS than previously estimated. It may be the primary cause of the unifocal submacular fibrosis that is commonly observed in this condition. Additional research is needed to establish the pathogenesis of RCN in patients with ESCS and its optimal management.

OPTICALLY EMPTY CHOROIDAL SPACES IN HIGH HYPEROPIA.

PURPOSE: To describe the progressive optical coherence tomography findings of atypical choroidal cavitation in the inner choroid. METHODS: Case report. RESULTS: A 29-year-old asymptomatic woman was noted to display two flat translucent whitish subretinal lesions along the superotemporal arcade of the right eye, during routine retinal examination. Cross-sectional spectral domain optical coherence tomography of the choroid illustrated two hyporeflective lesions consistent with atypical choroidal cavitation of the Sattler layer, associated with corresponding thickening and bulging of the underlying choroid. En face optical coherence tomography through the lesions illustrated hyporeflectivity at the level of the inner choroid, compatible with choroidal cavitation. Progressive enlargement of these two choroidal lesions was noted with cross-sectional and en face optical coherence tomography. CONCLUSION: Intrachoroidal cavitation has been described in association with inferior peripapillary conus in myopic eyes. Progressive enlargement of these lesions has not been noted. The lesions reported herein are atypical for choroidal cavitation because they affect a young hyperopic woman and display progression. A common pathogenesis with myopic choroidal cavitation may be possible. These lesions may be secondary to a localized bulge in the sclera, or may be a "cavernous" space secondary to a congested choroid, that is, leaking fluid.

Ocular hypertension in Axenfeld-Rieger Syndrome.

Purpose: to describe a clinical case of ocular hypertension (OHT) in Axenfeld-Rieger Syndrome (ARS). Method: Observational case report of a 43-year-old woman with background of OHT. The data was collected originally with a standardized electronic medical record. A complete ophthalmologic examination was performed. Results: In the biomicroscopy, a posterior embryotoxon, iris atrophy with absence of crypts and irregularity of pigmentation, and discoria in OU were observed. Gonioscopy revealed an open angle with a prominent and anterior displaced Schwalbe line. Ocular fundus (OF) demonstrated small and oblique papillae, with normal neurorretinal ring. Functional tests were normal. The patient did not present systemic pathologies, so the diagnosis of Rieger anomaly was made. The IOP control was achieved with aqueous humor suppressants. Conclusions: Glaucoma is the main cause of visual morbidity in patients with ARS, therefore a complete periodic ophthalmological exam is a priority. Abbreviations :ARS = Axenfeld-Rieger Syndrome, RP = retinitis pigmentosa, IOP = Intraocular Pressure, BCVA = Best Corrected Visual Acuity, OR = right eye, OS = left eye, OU = both eyes, OF = ocular fundus, OCT = optical coherence tomography, VF = visual field, TBC = trabeculectomy.

Intracranial Hypertension and Papilledema in a Large Cohort of Pediatric Patients With Alagille Syndrome.

AIMS AND BACKGROUND: Ophthalmic abnormalities are amongst the 5 major criteria required for a diagnosis of Alagille syndrome (ALGS), of which embryotoxon, pseudopapilledema, and hypopigmented retinopathy are the most common. Papilledema with or without intracranial hypertension (ICHT) is rarely described. We report 9 pediatric cases of ALGS with bilateral papilledema, 5 of which were diagnosed with ICHT. METHODS: The ophthalmic data from 85 patients with clinically and/or genetically (n = 37) proven ALGS were reviewed. The study inclusion criteria were a positive diagnosis of ALGS and availability of ophthalmic follow-up data. Ophthalmic data from 40 patients after liver transplantation (LT) for other indications were also analyzed. RESULTS: Nine (13.0%) of the 69 patients meeting the inclusion criteria had papilledema. The neurological and neuroimaging results in all 9 patients were normal. These 9 patients were categorized into 4 groups: a nontransplant group (n = 1), a group with pretransplant papilledema persistent after LT (n = 2), a group with papilledema occurring after LT with spontaneous resolution (n = 1), and a group with papilledema and signs of ICHT after LT (n = 5). The patients with ICHT were treated with steroids alone (n = 1) or with acetazolamide (n = 4). A ventriculoperitoneal shunt was placed in 2 of the 5 cases because of progressive visual loss. Pseudopapilledema was present in 10 additional patients (14.5%, 10/69). One (2.5%) of the 40 patients without ALGS developed papilledema after LT. CONCLUSIONS: True ICHT may be underdiagnosed in patients with ALGS. Our findings underscore the need for close ophthalmic follow-up before and after LT in these patients.

A novel MFRP gene variant in a family with posterior microphthalmos, retinitis pigmentosa, foveoschisis, and foveal hypoplasia.

BACKGROUND: To characterize the phenotype and genotype of a syndrome associating posterior microphthalmos (PM), retinitis pigmentosa (RP), foveoschisis, and foveal hypoplasia (FH) in a consanguineous Portuguese family. MATERIALS AND METHODS: Three siblings were studied and underwent comprehensive eye examinations for best-corrected visual acuity, axial length, refractive error, B-mode ultrasound, electroretinography, retinography, fluorescein angiography (FA), kinetic visual field (VF), and optical coherence tomography (OCT). Molecular analysis was performed by Sanger sequencing of the entire coding region of the MFRP gene. RESULTS: All members presented nyctalopia, decreased visual acuity, and constriction of the VF, as well as bilateral shortening of the posterior ocular segment and normal anterior segment dimensions. The fundoscopy and ERG results were compatible with RP. Macular OCT analysis revealed schisis of the outer retinal layer, FH, as well as retinal and choroidal folds. We identified a homozygous mutation in intron 9 of the membrane frizzled-related protein (MFRP) gene (c.1124 + 1 G > A). CONCLUSIONS: Our study shows a family with PM and RP due to a mutation in the MFRP gene. The relationship has previously been proven, but this specific mutation has never been described. These gene mutations show wide phenotypic variability, being evident in the presence of foveoschisis, retinal and choroidal folds, and FH, other than PM and RP.