Profile of a large cohort of children with persistent fetal vasculature and their predictors of poor visual outcome in a tertiary eye hospital in Saudi Arabia.

PURPOSE: To present the profile of a large cohort of children with persistent fetal vasculature (PFV) and identify their predictors of poor visual outcome in a tertiary eye hospital in Saudi Arabia. METHODS: This was a single-center study. Medical records of children diagnosed with persistent fetal vasculature between January 1990 and January 2020 at King Khaled Eye Specialist Hospital (KKESH), Riyadh, were reviewed. Data were collected on PFV type, presenting features, management, and visual acuity. Poisson regression with robust error variance was used to identify the predictors of poor visual outcome. RESULTS: Data of 175 eyes of 170 children with PFV were analyzed. Most had unilateral disease (n = 165, 96.2%), and over half of them (57.1%) were males. The main presenting complaints were leukocoria (n = 126, 72.0%), followed by smaller eye (n = 36, 20.6%), poor vision (n = 15, 8.6%), and strabismus (n = 13, 7.4%). Anterior, posterior, and combined PFV were present in 30.9%, 10.9%, and 58.3% eyes, respectively. In eyes with measurable visual acuity (n = 124), BCVA at the last follow-up was ≥20/100, <20/100-20/400, CF/HM and LP/NLP in 11 (8.9%), 32 (25.8%), 43 (34.7%), and 38 (30.6%) eyes, respectively. In the multivariable poisson regression analysis, eyes with posterior PFV were approximately two times more likely to have a BCVA of CF or worse than those with anterior PFV (Adjusted incidence ratio: 1.82 (95%: 1.23, 2.70; P = 0.003). Compared with eyes with primary or secondary IOL implantation, aphakic eyes or those with no cataract surgery were significantly more likely to have BCVA of CF or worse (adjusted incidence ratio: 1.84 [95%: 1.18, 2.86], p = 0.007 and adjusted incidence ratio: 1.64 [95%: 1.08, 2.50], p = 0.020, respectively). CONCLUSIONS: The prognosis of PFV varies depending on the severity of the disease. Patients with posterior PFV had worse visual outcome than anterior or combined type. Whether primary or secondary, IOL implantation increases the probability of having BCVA better than CF.

Novel CRB1 pathogenic variant in Chuuk families with Leber congenital amaurosis.

The purpose of this article is to determine the cause of Leber congenital amaurosis (LCA) in Chuuk state, Federated States of Micronesia (FSM). In this prospective observational case series, five patients with early-onset vision loss were examined in Chuuk state, FSM, during an ocular genetics visit to study the elevated incidence of microphthalmia. Because of their low vision these patients were incorrectly assumed to have microphthalmia. A complete ophthalmological exam established a clinical diagnosis of LCA. Candidate gene exons were sequenced with a targeted retinal dystrophy panel. Five subjects in three related families were diagnosed with LCA. All five were from Tonoas Island, within the Chuuk Lagoon, with ages ranging from 6 months to 16 years. DNA sequencing of affected individuals revealed a homozygous CRB1 NM_201253.3:c.3134del pathogenic variant, which was heterozygous in their parents. CRB1 genotypes were confirmed by a PCR restriction assay. We report identification of a founder pathogenic variant in CRB1 responsible for autosomal recessive LCA in this isolated community. This discovery will lead to appropriate recurrence risk counseling.

A Novel PGAP3 Gene Mutation-Related Megalocornea Can Be Misdiagnosed as Primary Congenital Glaucoma.

Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) is a rare autosomal recessive disorder caused by glycosylphosphatidylinositol (GPI) deficiency. GPI deficiency results from a mutation in one of six known genes. Mutation in post-GPI attachment to protein phospholipase 3 gene (PGAP3) is linked to HPMRS4. Patients usually present with dysmorphic features, developmental delay, central hypotonia, and seizure. However, in our case, we report a novel homozygous missense mutation of PGAP3 gene in a female child who presented with megalocornea, which is an unusual clinical presentation for HPMRS4. Megalocornea, in her first days of life, led to a misdiagnosis of primary congenital glaucoma. Later, other common clinical features of HPMRS4 became apparent.

Incidence and outcomes of microbial keratitis after cyclophotocoagulation to treat childhood refractory glaucoma.

PURPOSE: To report the incidence and outcomes of microbial keratitis (MK) following cyclophotocoagulation (CPC) for treatment of refractory childhood glaucoma (CG) at a single center over a period of 6 years. METHODS: In this cohort study, the medical records of children with CG who underwent CPC and subsequently presented with MK from 2014 to 2020 were reviewed retrospectively. Data were collected on age, type of glaucoma, surgeries before MK, CPC parameters, interval between CPC and MK, presenting symptoms of MK, infiltrate location, bacterial isolates, MK treatment, and outcomes. RESULTS: Among the 312 children who underwent CPC during the study period, 37 eyes of 33 children had MK, with an incidence of 1.8% (95% CI, 0.3-3.2). The median interval between CPC and MK was 4 years (IQR, 2.7-7.4). CPC was repeated once in 20 eyes (54%) and twice in 4 (11%). In 20 eyes, there was no pain at MK onset. The primary isolates were Streptococcus pneumoniae (12/27 [22%]) and Staphylococcus epidermis (8/27 [30%]). MK resolved in 17 eyes (46%) after treatment; 8 eyes (22%) underwent evisceration or had phthisis, and keratoplasty failed in 6 eyes (16%). The absence of pain at presentation with MK was negatively associated with resolution (OR = 5.0 [95% CI, 1.1-23.8]; P = 0.04). CONCLUSIONS: The absence of pain at MK onset may be a proxy for neurotrophic keratitis after CPC and is linked to poor response to management.

Pediatric Retinal Detachment in Homozygous Protein C Deficiency: Genetic and Phenotypic Description of a Single Family.

Homozygous protein C deficiency is a rare hypercoagulability disorder. This study describes the ocular manifestations and the genetic background in a family with two affected children. This is a retrospective review of ophthalmic examinations, investigations, genetic testing, and blood work-up of two children with homozygous protein C deficiency from a single family. A family with a positive history of consanguineous marriage was found to have two affected children with homozygous protein C deficiency. Abnormal visual behavior was the presenting symptom. Both children had bilateral total tractional retinal detachments at presentation. Skin manifestations included episodes of discoloration and bruising. Laboratory work-up revealed absent protein C activity. Genetic testing confirmed the presence of a homozygous pathogenic mutation in protein C gene (NM_000312.3: c.1297G>A: p.Gly433Ser). Homozygous protein C deficiency should be considered in the differential diagnosis of early-onset tractional retinal detachment in infancy. Although rare, the ophthalmologist may be the first to encounter the condition, and treatment with protein C replacement or anticoagulants may be life-saving. Examination under anesthesia with fluorescein angiography and laser treatment early in life may be warranted to preserve vision. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:293-296.].

Retinal arterial macroaneurysms with supravalvular pulmonic stenosis syndrome can be associated with coronary and major systemic arterial disease.

Purpose: To report novel life-threatening coronary and systemic arterial disease associated with Retinal Arterial Macroaneurysms with Supravalvular Pulmonic Stenosis (RAMSVPS) syndrome, previously known as Familial Retinal Arterial Macroaneurysms (FRAM). Observations: A 29-years old woman with longstanding poor vision in her right eye presented with acute myocardial infarction and subclavian bruit. Her polyangiogram showed peculiar ostial coronary aneurysms, left anterior descending coronary artery stenosis, occlusion of the left subclavian artery, stenosis of both renal arteries, irregularities in the mesenteric artery and tapering of the aorta. Takayasu arteritis was initially presumed, however fundus examination revealed beading and macroaneurysms along major retinal arteries, intraretinal exudation and hemorrhages, retinal arterial sheathing and stenosis, Coats'-like features and submacular gliosis in the right eye, vitreous hemorrhage in the left eye, and persistent hyaloid artery remnant in both eyes. These features evoked RAMSVPS syndrome. Genetic testing identified the same homozygous IGFBP7 c.830-1G > A mutation reported with RAMSVPS syndrome, rectifying the systemic diagnosis. Conclusion and importance: RAMSVPS syndrome can be associated with more life-threatening coronary and widespread major arterial disease than previously recognized. It is crucial for ophthalmologists to recognize RAMSVPS syndrome and refer patients for a thorough cardiovascular evaluation. Likewise, a careful retinal examination and the possibility of an IGFBP7 mutation should be considered in the setting of systemic arterial or cardiac disease.

Clinical features of LONP1-related infantile cataract.

Biallelic mutations in the nuclear gene LONP1 (LON peptidase 1, mitochondrial) cause CODAS syndrome (cerebral, ocular, dental, auricular, and skeletal anomalies), a systemic disease that can include infantile cataract. However, we have found that biallelic mutations in the gene can also underlie infantile cataract in the setting of minimal or no apparent extraocular findings. This report highlights our clinical experience with children referred for the management of infantile cataract who were found to harbor biallelic LONP1 gene mutations. Ptosis, external ear abnormalities, and joint abnormalities were accompanying findings and thus should raise suspicion for mutations in the gene when one or more are present in children with infantile cataract.

Biometry, optical coherence tomography, and further clinical observations in Knobloch syndrome.

PURPOSE: Knobloch syndrome is a pathognomonic vitreo-retinopathy that includes zonular weakness, high myopia, and a distinct fundus appearance with tessellation out of proportion to the degree of myopia. Whether myopia in Knobloch syndrome is axial or lenticular is unclear. Also not known are the optical coherence tomography (OCT) correlates to the distinct fundus appearance. In this study we assess cycloplegic refraction, biometry, and macular spectral domain (SD) OCT in children with Knobloch syndrome. METHODS: A retrospective case series of seven children (12 eyes) with Knobloch syndrome. RESULTS: Twelve eyes with attached retinas (seven patients, aged 6-17 years old, mean 11 years) were identified, seven of which had OCT. Best-corrected vision was typically 20/300 or worse. Axial length divided by corneal radius was >3 for all eyes (3.23-3.77, mean 3.52), consistent with axial myopia, and axial lengths (26.58-30.27 mm, mean 28.16) were consistent with spherical equivalent degree of myopia (-10.00 to -18.50, mean -12) when compared to historical controls. OCT revealed lack of choriocapillaries, outer retinal disorganization, and lack of or only rudimentary foveal pit. CONCLUSIONS: Refractions and biometry in Knobloch syndrome are consistent with the myopia being axial. In addition to vitreo-retinopathy, choroidopathy is part of the phenotype and is an anatomical correlate to the distinctive fundus appearance.

Elevation deficiency in children with recessive RDH12-related retinopathy.

Children with retinal dystrophies often have nonspecific strabismus, but vertical incomitant deviations are uncommon. We report 4 children from 3 consanguineous families with bilateral elevation deficiency in the context of retinal dystrophy. All were found to harbor recessive mutations in retinal dehydrogenase 12 (RDH12).

Congenital ptosis, scoliosis, and malignant hyperthermia susceptibility in siblings with recessive RYR1 mutations.

Malignant hyperthermia susceptibility is a rare pharmacogenic disorder of skeletal muscle calcium regulation caused by mutations in the skeletal muscle ryanodine receptor 1 gene (RYR1). It is important to identify children who are candidates for ophthalmic surgery who might harbor RYR1 mutations because intraoperative malignant hyperthermia is potentially lethal. We report 2 siblings with congenital ptosis and scoliosis who were considered for ptosis surgery but were found to harbor underlying recessive RYR1 mutations.