Congenital Corneal Staphyloma: A Comprehensive Histopathologic Assessment Including Associated Anterior Segment Abnormalities.

Congenital corneal staphyloma is a rare congenital malformation with guarded visual potential. The cornea is opaque, markedly ectatic, and lined by uveal tissue with a variety of associated anterior segment abnormalities. In this case report, the detailed histopathology of this condition is highlighted with an unusual finding of the malformed lens. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e28-e32.].

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

A bird's eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases.

Phenotypic and genotypic heterogeneity in congenital ocular diseases, especially in anterior segment dysgenesis (ASD), have created challenges for proper diagnosis and classification of diseases. Over the last decade, genomic research has indeed boosted our understanding in the molecular basis of ASD and genes associated with both autosomal dominant and recessive patterns of inheritance have been described with a wide range of expressivity. Here we describe the molecular characterization of a cohort of 162 patients displaying isolated or syndromic congenital ocular dysgenesis. Samples were analyzed with diverse techniques, such as direct sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing (WES), over 20 years. Our data reiterate the notion that PAX6 alterations are primarily associated with ASD, mostly aniridia, since the majority of the cohort (66.7%) has a pathogenic or likely pathogenic variant in the PAX6 locus. Unexpectedly, a high fraction of positive samples (20.3%) displayed deletions involving the 11p13 locus, either partially/totally involving PAX6 coding region or abolishing its critical regulatory region, underlying its significance. Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome). Our data clearly suggest that WES allows expanding the analytical portfolio of ocular dysgenesis, both isolated and syndromic, and that is pivotal for the differential diagnosis of those conditions in which there may be phenotypic overlaps and in general in ASD.

Surgical management of a case of double optic disc pits with maculopathy.

BACKGROUND: Double optic disc pit maculopathy is a rare entity. It can be difficult to manage because of excessive leakage and chronic maculopathy. PURPOSE: To describe surgical management in a case of double optic disc pits with maculopathy. SYNOPSIS: A 42-year-old male presented with double optic disc pits with macular detachment in the left eye. The best-corrected visual acuity (BCVA) was 20/60, N12. Preoperative OCT showed the presence of two disc pits. The macular region had large retinoschisis and subretinal fluid (SRF) with a central foveal thickness of 879 microns and loss of the ellipsoid zone. A shallow communication from the temporal aspect of the disc to the submacular area was also noted. Among the options of observation, laser photocoagulation, and surgery, the patient opted for surgical management. SURGICAL TECHNIQUE: A standard-3 port 23-gauge pars plana vitrectomy was done. After staining the ILM with brilliant blue, ILM peeling was done with the help of forceps and Finesse loop. ILM flaps were inverted over to cover the optic disc pits and sealed with a drop of fibrin glue. Next, 20% SF6 gas was used for tamponade. Pre- and post-surgery parameters such as visual acuity and OCT were evaluated. POSTOPERATIVE EVALUATION: After 6 weeks, left eye BCVA was 20/40 with OCT showing reduced SRF and reduced intraretinal schisis with a foveal thickness of 546 microns. At 3 months of follow-up, the vision in the left eye had improved to 20/30 with further reduction in the retinoschisis and foveal thickness of 482 microns. HIGHLIGHTS: In this interesting case, we demonstrate a unique way of sealing the defect surgically by vitrectomy and inverted ILM flap with fibrin glue over the disc pits. Despite sealing the maculopathy is slow to resolve. VIDEO LINK: https://youtu.be/s9nY5UPe1s4.

Double temporal retinochoroidal coloboma with posterior embyotoxon and persistent pupillary membrane: a case report.

Ocular colobomas are typically located in the inferonasal quadrant and attributable to defective fetal fissure closure. Colobomas can, however, affect any part of the eye, from the eyelid to the optic nerve. We present the case of a 7-year-old girl with two retinochoroidal colobomas in an atypical temporal location, with associated other ocular defects.

Genetic Characteristics and Clinical Manifestations of Foveal Hypoplasia in Familial Exudative Vitreoretinopathy.

PURPOSE: This study aimed to ascertain the occurrence of foveal hypoplasia (FH) in individuals diagnosed with familial exudative vitreoretinopathy (FEVR). DESIGN: Retrospective cohort study. METHODS: In this study, FEVR families and sporadic cases were diagnosed at the Eye and ENT Hospital, Fudan University, between 2017 and 2023. All patients attended routine ophthalmologic examinations and genetic screenings. The classification of FH was determined using optical coherence tomography (OCT) scans. The FH condition was classified into 2 subgroups: group A (FH being limited to the inner layers) and group B (FH affecting the outer layers). A total of 102 eyes from 58 patients were suitable for analysis. RESULTS: Forty-nine mutations in LRP5, FZD4, NDP, TSPAN12, KIF11, CTNNB1, and ZNF408 were examined and detected, with 26 of them being novel. Forty-seven eyes (46.1%) revealed FH. The majority (53.2%) were due to the typical grade 1 FH. Patients with mutations in LRP5 and KIF11 were found to exhibit a higher prevalence of FH (P = .0088). Group B displayed the lowest visual acuity compared with group A (P = .048) and the group without FH (P < .001). The retinal arteriolar angle in group B was significantly smaller than in group A (P = .001) and those without FH (P < .001). CONCLUSIONS: This study offers a new diagnostic approach and expands the spectrum of FEVR mutations. LRP5 and KIF11 were found to be more susceptible to causing FH in patients with FEVR. FEVR eyes with FH exhibited both greater visual impairment and reduced retinal arteriolar angles. The assessment of foveal status in patients with FEVR should be valued.

Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome.

Axenfeld-Rieger Syndrome (ARS) type 1 is a rare autosomal dominant condition characterized by anterior chamber anomalies, umbilical defects, dental hypoplasia, and craniofacial anomalies, with Meckel's diverticulum in some individuals. Here, we describe a clinically ascertained female of childbearing age with ARS for whom clinical targeted sequencing and deletion/duplication analysis followed by clinical exome and genome sequencing resulted in no pathogenic variants or variants of unknown significance in PITX2 or FOXC1. Advanced bioinformatic analysis of the genome data identified a complex, balanced rearrangement disrupting PITX2. This case is the first reported intrachromosomal rearrangement leading to ARS, illustrating that for patients with compelling clinical phenotypes but negative genomic testing, additional bioinformatic analysis are essential to identify subtle genomic abnormalities in target genes.

Penetrating keratoplasty in brittle Cornea syndrome: Case series and review of the literature.

It concerns three siblings (two 28 year old twin boys and a 25 year old woman) who presented a previous history of rupture of eyeball in one eye and very poor vision in the other. At the first ophthalmoscopic and instrumental evaluation, three patients presented with bluish sclera and keratoglobus in the intact eye. A genetic analysis with whole exome sequencing was then performed on the three siblings, identifying a biallelic variant of the PRDM5 gene that led to the diagnosis of Brittle Cornea Syndrome (BCS), a rare autosomal recessive disorder characterized by corneal thinning and blue sclera. To preserve the only intact eye from possible breakage, the three siblings were trained in using protective measures (polycarbonate goggles etc.) to carry out close monitoring of symptoms and were asked to continue with follow-up visits for ocular and systemic diseases associated with BCS. Given the poor best corrected visual acuity achievable with glasses and contact lenses, penetrating keratoplasty was performed, achieving good visual acuity maintained in the 2-year follow-up in two of the three patients. Knowledge of this pathology and its clinical manifestations is essential for early diagnosis and correct management of this rare but very debilitating pathology. To our knowledge, this is the first case series of BCS reported in an Albanian population.

Bevacizumab as adjunctive therapy in anterior persistent fetal vasculature.

PURPOSE: Surgical removal of a vascularized pupillary membrane may be challenging with the risk of intraoperative bleeding and postoperative recurrence. We present a case of a 4-week-old who presented with anterior persistent fetal vasculature (PFV) and dense vascularized pupillary membrane in which the use of intracameral and intravitreal bevacizumab may have contributed to successful treatment. OBSERVATION: A 4-week-old-month-old otherwise healthy girl was referred to Boston Children's Hospital for evaluation of cataract. Ocular examination revealed right microcornea and vascularized pupillary membrane. The left eye exam was unremarkable. Only three weeks after surgical excision of the pupillary membrane and cataract extraction, recurrence of a vascular pupillary membrane was noted. Repeat membranectomy with pupilloplasty and use of intracameral bevacizumab was performed. The pupillary opening was further opened 5 months later, after repeat (intravitreal) bevacizumab, and the pupil has remained open and stable with >6 months' follow-up. CONCLUSION AND IMPORTANCE: This case suggests a role for bevacizumab in the management of PFV, however, a cause-and-effect relationship cannot be proven. Further prospective comparative studies are needed to confirm our findings.

Non-vascular intracranial lesions in three children with PHACE association.

PHACE (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac anomalies, eye anomalies) association has many recognized clinical features. A link between PHACE and non-vascular intracranial lesions has not been well-described. We report three pediatric patients with PHACE and non-vascular intracranial lesions.

Magnetic Resonance Imaging Findings and Genetic Testing Results in Children With Congenital Corneal Opacities.

PURPOSE: This study investigates brain and globe abnormalities identified on magnetic resonance imaging (MRI) in children with congenital corneal opacities (CCO). DESIGN: Retrospective cohort study. METHODS: Clinical notes, radiology records, and genetic testing results were reviewed for patients diagnosed with corneal opacification within the first 6 months of life at a tertiary referral academic center between August 2008 and January 2018. Ocular findings, systemic anomalies, neuroimaging, and genetic testing results were summarized. RESULTS: A total of 135 patients presenting at age 1 day to 12 years (mean age, 1 year) were identified. Children with bilateral CCO were more likely to have systemic disease (P = 0.018). Of the entire cohort, 43 (31.8%) patients received MRI, of whom 27 (62.8%) had abnormal brain findings and 30 (69.7%) had abnormal orbital findings. The most common abnormal brain findings were ventriculomegaly (n = 16, 59.2%) and corpus callosum abnormalities (n = 10, 37.0%) followed by brainstem/pons anomalies (n = 5, 18.5%), and cerebellar anomalies (n = 2, 7.4%). Abnormal brain MRI findings were associated with the presence of neurologic (P = .003) and craniofacial (P = .034) disease. A total of 44 (32.1%) patients underwent genetic testing, of whom 29 (65.9%) had pathogenic results. CONCLUSIONS: More than 60% of the children with CCO who underwent MRI had abnormal brain and orbit findings that were correlated with significant neurologic disease. Furthermore, almost two-thirds of patients with CCO who underwent genetic testing had pathogenic results. These data demonstrate the value of systemic workup in children with CCO, and highlight the role of ophthalmologists in facilitating the diagnosis of systemic comorbidities associated with CCO.

Cleft Lip With Ankyloblepharon Filiforme Adnatum: A Case Report.

Ankyloblepharon filiforme adnatum (AFA) is a rare, benign congenital anomaly. Notably, it is characterized by the adhesion of the ciliary edges of the upper and lower eyelids at the trabecular line. AFA is usually a solitary malformation of sporadic occurrence; however, it can occur in conjunction with other congenital diseases. Herein, we report a case of cleft lip with AFA. A patient was referred to the ophthalmology department of our hospital. The ophthalmic diagnosis was AFA in both the eyes. The left eye was observed to have a fibrous adhesion in the center, and she underwent surgery to excise the fibrous adhesion of tissue with scissors. The right eye was observed to have a fibrous adhesion in the external canthus and was excised during lip plasty. After surgery, her eyes were able to fully open, and no other apparent disease was diagnosed. AFA is thought to be caused by an ectodermal-derived developmental abnormality. Notably, cases of AFA with a cleft lip are rare. Diagnosis and surgery should be performed promptly to minimize any risk of amblyopia and for the early detection of congenital diseases, including glaucoma.

A case of Joubert syndrome caused by novel compound heterozygous variants in the TMEM67 gene.

Joubert syndrome (JS) is a recessive disorder that is characterized by midbrain-hindbrain malformation and shows the "molar tooth sign" on magnetic resonance imaging. Mutations in 40 genes, including Abelson helper integration site 1 (AHI1), inositol polyphosphate-5-phosphatase (INPP5E), coiled-coil and c2 domain-containing protein 2A (CC2D2A), and ARL2-like protein 1 (ARL13B), can cause JS. Classic JS is a part of a group of diseases associated with JS, and its manifestations include various neurological signs such as skeletal abnormalities, ocular coloboma, renal disease, and hepatic fibrosis. Here, we present a proband with the molar tooth sign, ataxia, and developmental and psychomotor delays in a Dagestan family from Russia. Molecular genetic testing revealed two novel heterozygous variants, c.2924G>A (p.Arg975His) in exon 28 and c.1241C>G (p.Pro414Arg) in exon 12 of the transmembrane protein 67 (TMEM67) gene. These TMEM67 gene variants significantly affected the development of JS type 6. This case highlights the importance of whole exome sequencing for a proper clinical diagnosis of children with complex motor and psycho-language delays. This case also expands the clinical phenotype and genotype of TMEM67-associated diseases.