Managing the apparently blind child presenting in the first year of life: A review.

Severe vision impairment and blindness in childhood have a significant health burden on the child, family and society. This review article seeks to provide a structured framework for managing the apparently blind child presenting in the first year of life, starting from a comprehensive history and examination. Different investigation modalities and the increasingly important role of genetics will also be described, in addition to common causes of severe vision impairment. Crucially, a systematic approach to the blind infant is key to correct diagnoses and timely management. Incorrect diagnoses can be costly to all involved, however it is important to note that diagnoses can change with ongoing follow-up and investigations. Furthermore, the modern age of ophthalmology requires a multi-disciplinary approach and close collaboration with specialists including paediatricians, neurologists and geneticists, in addition to rehabilitation and low vision services, to ensure the best care for these vulnerable infants.

Prevalence of Choroidal Abnormalities and Lisch Nodules in Children Meeting Clinical and Molecular Diagnosis of Neurofibromatosis Type 1.

PURPOSE: To determine the prevalence of choroidal abnormalities (CAs) and Lisch nodules (LNs) in children who met the clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis (MCD) of neurofibromatosis type 1 (NF1), and to ascertain any differences between the groups. METHODS: This was a cross-sectional observational study. All children who met the CDC and/or had MCD of NF1 and underwent eye examination were included. At least two CAs or LNs between the two eyes were set as a threshold to define the presence of either abnormality. Frequencies alongside 95% confidence intervals (CIs) were calculated. The relationship between patient age and the presence of LNs and/or CAs was estimated using logistic regression. RESULTS: The study cohort included 94 patients; CAs (64%) were more prevalent than LNs (41%) (0.22; 95% CI, 0.08-0.36; P = 0.0023). The probability of the presence of LNs was lower than that of CAs across all ages (odds ratio = 0.37; 95% CI, 0.20-0.69; P = 0.00173). CAs were exclusively found in 37% of patients and LNs in 16%; 80% had either CAs or LNs, or both. In the CDC group (n = 41), the difference in prevalence (CAs = 68%, LNs = 51%) did not attain statistical significance (0.17; 95% CI, -0.06 to 0.40; P = 0.18). In the MCD group (n = 53), the difference in prevalence (CAs = 60%, LNs = 34%) was significant (0.26; 95% CI, 0.006-0.47; P = 0.023). CONCLUSIONS: CAs were more frequent than LNs in pediatric NF1 patients regardless of age and MCD status. Combining ophthalmological exams with near-infrared imaging will increase the diagnostic reach in pediatric NF1. TRANSLATIONAL RELEVANCE: CAs detected on near-infrared imaging are objective biomarkers in NF1. They are more prevalent and detected earlier in the pediatric population compared with LNs. Hence, the presence of CAs should be routinely ascertained in children suspected with NF1.

IgG4-related disease of the orbit in an infant.

IgG4-related disease is a chronic fibroinflammatory disorder that is becoming increasingly recognized in the pediatric population. The orbit is one of the most commonly affected sites. We present the youngest case of IgG4-related ophthalmic disease in the literature, with an immunodeficiency phenotype associated with a homozygous IRAK-4 variant gene. We also review the clinical and histological features in children with IgG4-related ophthalmic disease. In addition to the young age of presentation, the case is unique for absence of lacrimal gland involvement, dural enhancement on magnetic resonance imaging, and an association with an IRAK-4 deficiency phenotype. Management required a multidisciplinary approach, with judicious use of immunosuppression. IgG4-related ophthalmic disease should be considered as a differential diagnosis in infants and children presenting with an orbital mass. Further, a particularly young age of onset may indicate an overarching immune dysregulation syndrome.

Optic Atrophy and Inner Retinal Thinning in CACNA1F-related Congenital Stationary Night Blindness.

Hemizygous pathogenic variants in CACNA1F lead to defective signal transmission from retinal photoreceptors to bipolar cells and cause incomplete congenital stationary night blindness in humans. Although the primary defect is at the terminal end of first-order neurons (photoreceptors), there is limited knowledge of higher-order neuronal changes (inner retinal) in this disorder. This study aimed to investigate inner retinal changes in CACNA1F-retinopathy by analyzing macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness and optic disc pallor in 22 subjects with molecularly confirmed CACNA1F-retinopathy. Detailed ocular phenotypic data including distance and color vision, refraction and electroretinogram (ERG) were collected. Distance vision was universally reduced (mean: 0.42 LogMAR), six had abnormal color vision and myopia was common (n = 15; mean: -6.32 diopters). Mean GCL-IPL thickness was significantly lower in patients (55.00 µm) compared to age-matched controls (n = 87; 84.57 µm; p << 0.001). The GCL-IPL thickness correlated with scotopic standard (p = 0.04) and bright-flash (p = 0.014) ERG b/a ratios and photopic b-wave amplitudes (p = 0.05). Twenty-one patients had some degree of disc pallor (bilateral in 19). Fifteen putative disease-causing, including five novel variants were identified. This study establishes macular inner retinal thinning and optic atrophy as characteristic features of CACNA1F-retinopathy, which are independent of myopia and could impact potential future treatment strategies.

Investigation of corneal endothelial changes post selective laser trabeculoplasty.

IMPORTANCE: Transient corneal endothelial changes are routinely noted on slit-lamp examination immediately following selective laser trabeculoplasty (SLT). BACKGROUND: To determine the mechanism of transient corneal endothelial changes observed following SLT. DESIGN: University laboratory-based observational study. SAMPLES: Ten corneas from six human cadaveric donors. METHODS: Corneas were treated with SLT, direct laser or peroxide, or used as controls. Haematoxylin and eosin staining and immunolabelling for zonula occludens-1 (ZO-1) and beta-catenin were performed. MAIN OUTCOME MEASURES: Histological appearance; ZO-1 and beta-catenin immunostaining. RESULTS: There were no differences in histological features between SLT-treated and control corneas. Corneas treated with SLT or peroxide showed reduced and less regular ZO-1 immunofluorescence along cell membranes compared with ZO-1 expression in controls. These changes were generalized across the endothelium. There was no effect on the ZO-1 immunostaining after direct laser. There was no difference in beta-catenin immunostaining patterns between control, SLT and peroxide-treated corneas. CONCLUSIONS AND RELEVANCE: Altered ZO-1 immunostaining may represent disassembly of tight junctions between corneal endothelial cells. The similarity of our findings between SLT-treated and peroxide-treated corneas suggests that both conditions trigger changes at the level of endothelial tight junctions, perhaps triggered by liberation of free radicals as previously proposed.

Selective laser trabeculoplasty: current perspectives.

Selective laser trabeculoplasty (SLT) has been used in the treatment of glaucoma for just over a decade. Here, we review the current literature in terms of suggested mechanism, efficacy, method of treatment, predictors of success, adverse events, repeatability, and cost of SLT. The exact mechanism by which SLT lowers intraocular pressure (IOP) remains unknown although circumstantial evidence has come in many forms in relation to structural alteration; oxidative stress and inflammatory responses; tight junction integrity; proliferative responses; and microbubble formation. SLT is as effective as argon laser trabeculoplasty and medications in reducing IOP in glaucoma and ocular hypertension. The treatment is not uniformly effective in all eyes, and its IOP-lowering effect decreases over time. High pretreatment IOP is the strongest predictor of success; however, significant pressure reduction has also been shown in normal-tension glaucoma and in patients already taking multiple antiglaucoma drops. Mild, transient adverse effects are common. Transient IOP spikes usually resolve quickly with or without antiglaucoma treatment but may be problematic in pigmented angles. The limited available evidence suggests SLT is repeatable and cost-effective for the treatment of glaucoma and ocular hypertension.

Metastatic Small-Cell Neuroendocrine Carcinoma Simulating Circumscribed Choroidal Hemangioma.

AIM: To report a case of metastatic small-cell neuroendocrine carcinoma presenting as an isolated choroidal mass and initially misdiagnosed as a circumscribed choroidal hemangioma. METHODS: The clinical history, fundus findings, imaging, cytology and immunohistochemical features are described. RESULTS: An otherwise healthy 66-year-old man was referred for a left nasal scotoma and a diagnosis of circumscribed choroidal hemangioma. Cytology showed cohesive clusters of small-to-intermediate malignant cells. The atypical cells stained positively for chromogranin, thyroid transcription factor-1 and synaptophysin consistent with small-cell neuroendocrine carcinoma. CONCLUSION: Small-cell neuroendocrine carcinoma metastatic to the choroid is extremely rare; however, it is particularly aggressive and should be included in the differential diagnosis of isolated choroidal lesions, even in otherwise healthy patients.