ABSTRACT Background Ocular anomalies reported in FGFR2-related craniosynostosis include refractive errors, exophthalmos, and strabismus. Anterior segment anomalies have occasionally been reported in cases of FGFR2-related craniosynostosis. Methods We report a three-year-old boy with unilateral Peters anomaly, short stature, facial dysmorphism, posterior plagiocephaly, heart defects, and developmental delay. His maternal half-sister had bilateral posterior embryotoxon, dysmorphism, brittle teeth, umbilical hernia, developmental delay, heart defects, and microcephaly. Their mother had a normal slit lamp exam. Results A novel variant was found in FGFR2 (NM_000141.4: c.1376T>G p.(Met459Arg)) in the proband and maternal half-sister. No other variants of interest were identified in anterior segment genes. Incidentally, we identified a hemizygous variant in FGD1 (NM_004463.3: c.1292dupT p.(His432Profs*8)) in the proband; heterozygous in the mother. Conclusion FGD1 is associated with Aarskog-Scott syndrome (AAS) while FGFR2 is linked with 14 different phenotypes. The proband’s features suggest AAS except for Peters anomaly and heart defects, which have been reported with FGFR2 variants. The shared novel FGFR2 variant suggests a dual diagnosis for the proband. Our findings support a role for FGFR2 in anterior segment development and broaden the genotypic and phenotypic spectrum of FGFR2-related disorders.

ABSTRACT We describe a novel missense variant in IMPG2 in a patient with early-onset rod-cone dystrophy with central macular atrophy and evaluate the potential of adenine base editing (ABE) as a therapeutic strategy. Ophthalmic evaluation included ultra-widefield fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. Genetic testing was performed with a targeted next-generation sequencing panel and Sanger confirmation. Variant pathogenicity was assessed using in silico prediction tools, protein stability algorithms, and structural modeling. ABE feasibility was analyzed through PAM site identification and guide RNA design. Genetic testing revealed compound heterozygosity for a pathogenic nonsense variant (c.411G>A; p.Trp137*) and a novel missense variant (c.871C>A; p.Arg291Ser) within the SEA-1 domain. While in silico prediction tools classified p.Arg291Ser as benign or neutral, structural modeling and stability analyses supported a destabilizing effect. Base editing assessment indicated that c.411G>A is targetable with ABE. This case underscores the clinical relevance of domain-specific IMPG2 variants and the limitations of in silico predictions. ABE offers a promising therapeutic option for IMPG2-associated retinopathy.

ABSTRACT Introduction The aim was to uncover potential associations between the VEGF gene variants rs699947, rs833061, and rs3025039 and diabetic retinopathy (DR). Methods A total of 202 individuals with type 2 diabetes mellitus (T2DM) were divided into three groups: controls (T2DM without retinopathy), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Genotyping was performed using the PCR-RFLP assay. Results Allele and genotype frequencies did not show any significant difference among three groups (p > 0.05, all). Under recessive model in NPDR group CA genotype of rs699947 exhibited significantly lower HbA1c (%) and HbA1c (mmol) levels (p = 0.049, p = 0.048, respectively) compared to CC and AA genotypes. Under dominant model in NPDR group of rs699947, HbA1c (%) and HbA1c (mmol) levels were significantly higher in variant allele carriers compared to normal genotypes (p = 0.03, p = 0.031, respectively). Fasting plasma glucose (FPG) levels of normal rs699947 genotypes were significantly higher compared to variant genotypes in NPDR and PDR groups (p = 0.047, p = 0.023, respectively). Logistic regression analysis showed that the variations examined do not affect DR (p > 0.05, all). Conclusion In conclusion, as the first study in the studied ethnicity, we did not observe any association between DR an VEGF gene variations rs699947, rs833061, and rs3025039.

ABSTRACT Aim To report a case of Adams-Oliver Syndrome (AOS) presenting with retinopathy of prematurity (ROP)-like retinal findings and a novel homozygous mutation in the DOCK6 gene. Methods Single patient case report. Results A 6-week-old female infant with a premature birth at 35 weeks and birth weight of 1580 grams was referred to our clinic for presumed ROP stage 5 in the right eye and stage 4 in the left eye. Fluorescein angiography revealed peripheral avascular retina, abnormal vascular sprouts, and tractional retinal folds. Lens-sparing vitrectomy was performed, with subsequent surgical stabilization and ambulatory vision achieved during 60-month follow-up period. Genetic testing identified a novel homozygous mutation in the DOCK6 gene (c.4198_4199insATGG). The patient had mild systemic findings, including brachydactyly and nail hypoplasia, without significant dermatological, cerebral or cardiovascular anomalies. Family screening did not reveal any pathological findings, even on wide-field FA. Conclusion This case highlights the importance of genetic testing in atypical retinal vasculopathies resembling ROP. The findings expand the genotypic spectrum of DOCK6-related AOS and emphasize the need for multidisciplinary evaluation in similar presentations to guide accurate diagnosis and management.

ABSTRACT Introduction This study reports the ocular and systemic manifestations, genetic findings, and management approaches in 10 patients diagnosed with ligneous conjunctivitis (LC) and followed at a university hospital. Methods In this retrospective case series, medical records were retrospectively reviewed to collect demographic characteristics, age at diagnosis, family history, serum plasminogen (PLG) activity levels, ocular/systemic findings, and treatment modalities. Results Ten patients (7 females, 3 males; age range: 2–40 years) were followed for a mean duration of 9.4 ± 5.5 years. PLG activity was markedly reduced (18–25%) in six individuals. Systemic comorbidities included hydrocephalus (n = 3), gingivitis (n = 3), cervicitis/vaginitis (n = 4), menstrual irregularities (n = 2), infertility (n = 2), dacryocystitis (n = 2), epilepsy (n = 1), growth retardation (n = 1), deafness (n = 1), and brain tumor (n = 1). Whole-exome sequencing identified four distinct PLG variants, including homozygous pathogenic variants in five patients and a heterozygous variant in one. Treatment strategies involved pseudomembrane excision, topical heparin, corticosteroids, cyclosporine, and fresh frozen plasma (FFP). Systemic FFP was administered in selected cases. Additional procedures included amniotic membrane transplantation (n = 4) and cataract surgery (n = 3). Conclusion The diagnosis of LC is based on the integration of clinical and genetic findings, characterized by recurrent, firm pseudomembranes on the tarsal conjunctiva and often supported by a positive family history or parental consanguinity. Reduced PLG activity, histopathological confirmation of fibrin-rich membranes, and supportive genetic findings further substantiate the diagnosis.

ABSTRACT This report presents the clinical and genetic findings of a patient with a de novo splice-site variant in the retinitis pigmentosa 2 (RP2) gene. A 32-year-old Japanese woman was experiencing night blindness and reduced visual acuity since her twenties. Her parents were not consanguineous, and she had no family history of ocular disease. Fundus examination revealed irregular-shaped degeneration and fundus autofluorescence imaging showed abnormal hypofluorescence in the area of the retinal degeneration. As whole exome sequencing on her and her parents revealed unremarkable in RetNetTM genes, she was diagnosed as a sporadic case of retinitis pigmentosa (RP). However, subsequent whole genome sequencing revealed a heterozygous variant (c.102 + 2_102 + 5del) in the RP2 gene, but her parents did not carry the variant. Based on these clinical and genetic findings, we concluded that the patient was a symptomatic female carrier of RP2-associated RP. This report underscores the importance of comprehensive genomic analysis and family-based evaluation in uncovering hidden inheritance patterns, specifically in symptomatic female carriers of X-linked retinal dystrophies that initially appear sporadic. This study represents the first report to characterize the clinical phenotype associated with the splice-site variant c.102 + 2_102 + 5del in RP2.

ABSTRACT Objective This study aims to describe the diagnosis and management of a case with bilateral anterior lenticonus. Methods A comprehensive ophthalmological assessment was performed on the proband, including: ultrasound biomicroscopy (UBM), optical biometric measurement, fundus photography, optical coherence tomography (OCT), visual field testing, and pure-tone audiometry. The patient subsequently underwent phacoemulsification with intraocular lens (IOL) implantation. Immunofluorescence analysis was utilized to assess the expression of the α5 chain of type IV collagen in the lens capsule. Whole exome sequencing (WES) of the proband complemented by Sanger sequencing validation of the parents was conducted to identify potential pathogenic variants. Results The proband exhibited binocular high myopia, with no significant improvement in visual acuity despite correction. UBM demonstrated anterior protrusion of the central lens area in both eyes. OCT revealed temporal retinal thinning in both eyes compared to the nasal retina. The corresponding protein was absent in the lens capsule of the proband. WES identified a novel variant (c.4821+2T>C: p.?) in the COL4A5 gene, and Sanger sequencing confirmed that the proband’s mother was a carrier of this variant. The proband exhibited an absence of expression of the alpha 5 chain of type IV collagen (α5(IV)) in the lens capsule of the proband. Among various refractive calculation formulas, the aphakic formula demonstrated the smallest error. Conclusion A novel pathogenic COL4A5 splicing variant (c.4821+2T>C) was identified, which was associated with Alport syndrome. Furthermore, the aphakic formula may reduce refractive prediction error in cases of anterior lenticonus.

ABSTRACT Purpose Case report describing electroretinography findings in a child with a pathogenic mutation in ATP1A3 Methods Details of this case were retrospectively reviewed. History was significant for progressive high myopia and alternating hemiplegia of childhood with a confirmed genetic diagnosis. Results Electroretinography findings demonstrated evidence of both rod and cone dystrophy in a child with a pathogenic mutation in ATP1A3 causing alternating hemiplegia of childhood Conclusions This report details a previously under-reported associated between mutations in ATP1A3 and retinal dystrophy. We believe that wider dissemination of these findings will help counsel patients and family members about vision loss that may be attributed to retinal rather than optic nerve findings.

ABSTRACT Aim We describe the ophthalmologic findings in a patient with a disorder of sex development (DSD) and chromosome 2q22 duplication. Methods The patient underwent a comprehensive ophthalmologic examination including visual acuity testing, refraction, slit-lamp biomicroscopy, fundus examination, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence. Results Other than a large-angle left exotropia, the patient’s corrected-distance visual acuity (CDVA) was 20/25 in the right and 20/40 in the left eye. Fundoscopy revealed small optic nerves on both sides, and venous tortuosity in both eyes. SD-OCT displayed normal foveal contour and retinal nerve fiber layer thickness bilaterally. Conclusion This is, to the best of our knowledge, the first detailed ophthalmologic report of a patient with DSD with 2q22 duplication with a presentation of a novel phenotype.

ABSTRACT Introduction Short stature, optic atrophy, and Pelger-Huët anomaly (SOPH) syndrome is a rare autosomal recessive condition associated with variants in the NBAS gene. First described in 2010, SOPH syndrome is a relatively newly recognized condition and our understanding of the range of its manifestations and the variable expressivity of its features continues to evolve. A total of 110 cases of SOPH syndrome have been published in the literature to date, 93 of which were published in two case series reporting on the Yakut population. Methods Case report and review of literature. Results We present a case of a 25-year-old female with a prior clinical diagnosis of cone-rod dystrophy, who was found to have incomplete SOPH syndrome associated with a paternally inherited splice site variant and a maternally inherited complete NBAS gene deletion. This is the first report of SOPH syndrome without Pelger-Huët anomaly. Discussion Our case expands the phenotypic and genetic spectrum of SOPH syndrome. Similarly to many other syndromic conditions, SOPH can display variable expressivity of disease features. Furthermore, our patient’s complete deletion of one copy of the NBAS gene provides a unique opportunity to investigate in isolation the effects of the NBAS splice site variant found on the other allele.