Bilateral keratouveitis associated with COVID-19 multisystem inflammatory syndrome in children.

We report the case of a 16-year-old girl admitted to hospital with multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19. Conjunctivitis-like symptoms prompted ocular examination, which demonstrated peripheral confluent corneal opacities and anterior uveitis. Uveitis laboratory investigations were negative, and with topical steroid treatment her signs and symptoms resolved completely. These features may be overlooked in the setting of MIS-C, where patients are systemically unwell and are typically examined at the bedside.

Multiple giant retinal tears due to inflicted injury in a neonate.

Purpose: This case represents the longest follow-up period and youngest patient treated for multiple GRTs in the same eye associated with physical abuse. Observations: A 4-week-old otherwise healthy male presented with a constellation of unexplained injuries. Examination of the left eye revealed a mild lens opacity and a shallow retinal detachment with two giant retinal tears (GRTs) and no retinal hemorrhages. Examination of the right eye was unremarkable. Extensive investigations were negative for any underlying medical conditions. The constellation of injuries was felt to be due to physical abuse. The giant retinal tears were treated successfully with lens sparing pars plana vitrectomy. After long-term follow-up of 5 years, there was no cataract progression or development of glaucoma. Conclusions and importance: Clinicians should suspect child abuse in any pediatric patient with GRTs, with or without retinal hemorrhages, to ensure they are connected with the appropriate children's safeguarding society as soon as possible.

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.

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.

Utility of spectral domain OCT in differentiating optic disc drusen from papilledema in children.

OBJECTIVE: The purpose of this study was to test the diagnostic accuracy of optical coherence tomography (OCT) in differentiating optic disc drusen (ODD) from papilledema in children. DESIGN: Retrospective cross-sectional study at a tertiary-care pediatric hospital. PARTICIPANTS: Children with high-quality OCT imaging of ODD or papilledema. METHODS: Quantitative OCT parameters and qualitative OCT features were compared for diagnostic accuracy. RESULTS: There were 41 eyes with ODD and 21 eyes with papilledema. Both the quantitative and qualitative OCT parameters showed highly statistically significant differences between ODD and papilledema (p ≤ 0.01 for all). For quantitative parameters (Bruch's membrane opening and retinal nerve fiber layer thicknesses), the area under the curve from the receiver operator curves ranged from 0.81 to 0.90. For qualitative parameters, the sensitivity for ODD ranged from 27% to 100% and specificity ranged from 67% to 100%. The presence of at least 1 of 3 qualitative OCT parameters (hyporeflective boot-shaped area, isolated/clustered hyperreflective bands, or signal-poor regions in the core) had a sensitivity of 90% and a specificity of 100% for ODD. CONCLUSIONS: Both quantitative and qualitative OCT parameters differed significantly between ODD and papilledema in this cohort of children. A combination of several qualitative OCT features had high sensitivity for ODD while effectively ruling out papilledema.

Retinal ultra-wide-field colour imaging versus dilated fundus examination to screen for sickle cell retinopathy.

PURPOSE: To compare ultra-wide-field colour fundus imaging (UWFI) to dilated fundus examination (DFE) for the screening of sickle cell retinopathy (SCR). DESIGN: This study is a prospective, blinded, multicentre case series. PARTICIPANTS: This study included two groups: an adult group (n=268 eyes) and a paediatric group (n=168 eyes). Sickle cell disease (SCD) types included haemoglobin S homozygous (HbSS), haemoglobin S and C (HbSC) and Hb S with ß-thalassaemia (HbSß-Thal). METHODS: Participants underwent DFE and UWFI. Each eye received three independent grades (1-4), documented by three graders: clinical grader, image grader 1 and image grader 2. Three clinically relevant diagnostic thresholds were determined. Based on these thresholds, the sensitivity, specificity, positive predictive value and negative predictive value for all three graders were calculated relative to each other as reference tests. RESULTS: HbSC was associated with the most advanced SCR grades. When compared to the clinical grader, image grader 1 and image grader 2 consistently detected more SCR and higher SCR grades in both adult and paediatric groups. In both groups, image grader 1 and image grader 2 identified twice as many cases of capillary occlusion/anastomosis than clinical grader. To detect the presence of any proliferative SCR, image grader 1 and image grader 2 had a sensitivity of 82%, 71% in the paediatrics group and 90% and 72% in the adult group. The clinical grader sensitivity was 52% in the paediatrics group and 53% in the adult group. CONCLUSION: The UWFI is a sensitive tool to screen for SCR. It is superior to DFE in detecting capillary occlusion or anastomosis.

Reliability of Handheld Optical Coherence Tomography in Children Younger Than Three Years of Age Undergoing Vigabatrin Treatment for Childhood Epilepsy.

Purpose: Vigabatrin-associated retinal toxicity manifests as reduction in the clinical electroretinogram and retinal nerve fiber layer (RNFL) thinning. This observational investigation of RNFL thickness in young vigabatrin-treated children was to identify intravisit and intervisit reliabilities of peripapillary RNFL thickness measurements performed with Envisu (optical coherence tomography) OCT. Secondarily, a longitudinal assessment investigated the presence and extent of RNFL thinning. Methods: We measured the handheld OCT in sedated children to evaluate the RNFL thickness using segmentation software. Intraclass correlation coefficient (ICC) statistics identified intravisit and intervisit reliabilities for RNFL thickness. Results: Twenty-nine children (10.1 ± 6.0 months old) underwent handheld optical coherence tomography (OCT). Fourteen of these completed follow-up assessments. Intravisit reliability was good for the right eye (ICCs = 0.82-0.98) and the left eye (ICCs = 0.75-0.89) for each of the 4 retinal quadrants. Inter-visit ICCs for each of the 4 retinal quadrants were good (ICC = 0.82-0.98). There was no consistent change in RNFL thickness longitudinally. Conclusions: In this pediatric cohort, RNFL thickness measures using handheld OCT provided good reliability within a single visit and between consecutive visits supporting its use as an adjunctive tool in the clinical setting. Further long-term follow-up is required to understand RNFL thickness changes in this specific population and its association with vigabatrin toxicity. Translational Relevance: The findings of good reliability and clinical feasibility would provide an opportunity for the handheld OCT to monitor reliably for vigabatrin-associated retinal toxicity in children who often show noncompliance to traditional testing approaches.

Secondary Prevention of Retinoblastoma Revisited: Laser Photocoagulation of Invisible New Retinoblastoma.

PURPOSE: Invisible retinoblastoma tumors are now detected with screening for retinal tumors in at-risk neonates (those inheriting RB1 pathogenic alleles from affected parents) using handheld OCT. Laser photocoagulation is challenging, requiring exact localization of a tumor invisible to indirect ophthalmoscopy and standard imaging. We describe OCT-guided localization and photocoagulation of these invisible tumors with 1-year follow-up. DESIGN: Retrospective, noncomparative, single-institutional, observational case series. PARTICIPANTS: Children with any clinically invisible retinoblastoma tumor that was detected on OCT posterior pole screening. METHODS: OCT revealed round homogeneous invisible tumors within the inner nuclear layer. Software calipers placed beside anatomic retinal landmarks (branched/curved vessels, fovea, or optic disc) mapped the tumor location and extent. A single laser (532 nm) burn flagged the location, and OCT evaluated the tumor-laser burn relationship; laser treatment was then continued in the correct location. Post-laser OCT ensured complete treatment. MAIN OUTCOME MEASURES: Accuracy (frequency of geographic miss and skip areas), effectiveness (recurrence rate), and burden (scar size and characteristics at final follow-up) of laser treatment. RESULTS: Eleven new invisible posterior pole tumors in 7 eyes of 5 children were treated by this technique. Localization and tumor-laser burn relationships were accurate in 11 of 11 tumors (100%, 95% confidence interval [CI], 49.9-100), and all showed swelling and hyper-reflectiveness of the tumor in post-laser OCT. Two photocoagulation sessions (2 weeks apart) were sufficient to successfully manage 9 of 11 tumors (82%, 95% CI, 37.4-100) with resulting permanent flat scars. One tumor (9%, 95% CI, 0.2-50.6) developed OCT-detected subclinical recurrences within 3 months, treated by 1 laser session. No treatment scar showed gliosis, foveal involvement, or retinal traction at 1-year follow-up. Scar expansion occurred in 1 tumor (9%, 95% CI, 0.2-50.6), and all scars (100%, 95% CI, 49.9-100) showed pigmentary changes. CONCLUSIONS: The OCT-guided localization and photocoagulation technique is valuable in achieving precision results in managing invisible new retinoblastoma tumors. This technique shows a potential to improve outcomes of secondary prevention screening for retinoblastoma.

Accuracy of scleral transillumination techniques to identify infant ciliary body for sclerostomy and intravitreal injections.

IMPORTANCE: There is variation in the literature for sclerotomy and intravitreal injection placement in young children, ranging from 0.5 to 3.0 mm from the limbus. We assess the accuracy of scleral transillumination to identify the ciliary body in infants for safe sclerotomy and intravitreal injections in young children. BACKGROUND: The study compares the perilimbal "dark band" seen on scleral transillumination (STI) with the ultrasound biomicroscopy (UBM), and compares these measurements with the current guidelines for sclerotomy in infants. DESIGN: Prospective case series in a tertiary paediatric hospital. PARTICIPANTS: Children aged ≤36 months undergoing general anaesthesia for eye procedures. METHODS: Scleral transillumination was performed to measure the perilimbal dark band. UBM of the ciliary body region was then performed, and correlated with transillumination findings. MAIN OUTCOME MEASURES: The midpoints of STI and UBM were compared to current cadaver-based guidelines to assess the safe point for sclerotomy. RESULTS: Twenty children were recruited, 36 STI and 35 UBM measurements were obtained. The posterior edge of the dark band had good correlation with the posterior border of the ciliary body. Transillumination and UBM correlated well for midpoint measurements. The midpoint of the dark band on transillumination was confirmed to be in the ciliary body by UBM in all cases. CONCLUSIONS AND RELEVANCE: The STI technique is a useful and fast technique to demonstrate the ciliary body. The midpoint of the dark band on STI correlates well with the UBM, and has a potential use for confirming safe-entry into the posterior segment if using current guidelines. The current cadaver-based paediatric guidelines safely avoid retinal injury.

Vision and visual potential for perifoveal retinoblastoma after optical coherence tomographic-guided sequential laser photocoagulation.

BACKGROUND/AIMS: To assess tumour control, vision and anatomical visual potential in eyes with perifoveal retinoblastoma treated by sequential photocoagulation from the antifoveal tumour edge inwards, avoiding treatment near the fovea. Patients were monitored for tumour control, foveal and perifoveal anatomy at each treatment session by optical coherence tomography (OCT) and treated for amblyopia when the other eye had better vision. METHODS: Eyes with perifoveal retinoblastoma treated between 1 January 2011 and 31 May 2017 with laser therapy after chemotherapy for juxtafoveal (fovea clear of tumour but <3000 µm from tumour edge) or foveolar retinoblastoma (tumour underlying fovea) were retrospectively reviewed for tumour control without recurrence, anatomical success (foveal pit preservation and/or restoration with ≥500 µm perifoveal retina free of tumour and scar) and functional success (acceptable (>0.1 decimal) or good (>0.3 decimal) visual acuity (VA)). RESULTS: Twenty-two eyes (14 juxtafoveal, 8 foveolar tumours) of 20 patients (19 bilateral, 1 familial and 11 females) were included. No juxtafoveal tumour had tumour recurrence, and 13/14 patients showed foveal pit preservation with ≥500 µm of perifoveal retina tumour free. Foveolar tumours had significant worse anatomical outcomes: failure to restore foveal pit or perifoveal retina (8/8, p=0.001) and tumour recurrences (5/8, p=0.001). Functional success with acceptable VA was achieved in 12/14 juxtafoveal and 5/8 foveal tumours eyes (p=0.01). Amblyopia therapy data were insufficient to evaluate impact on VA. CONCLUSIONS: Anatomical visual potential and functional vision were better in juxtafoveal than foveolar retinoblastoma treated with foveal-sparing laser photocoagulation guided by OCT. The role of amblyopia therapy requires a prospective study.

Optical Coherence Tomography-Guided Decisions in Retinoblastoma Management.

PURPOSE: Assess the role of handheld optical coherence tomography (OCT) in guiding management decisions during diagnosis, treatment, and follow-up of eyes affected by retinoblastoma. DESIGN: Retrospective, noncomparative, single-institution case series. PARTICIPANTS: All children newly diagnosed with retinoblastoma from January 2011 to December 2015 who had an OCT session during their active treatment at The Hospital for Sick Children (SickKids) in Toronto, Canada. The OCT sessions for fellow eyes of unilateral retinoblastoma without any suspicious lesion and those performed more than 6 months after the last treatment were excluded. METHODS: Data collected included age at presentation, sex, family history, RB1 mutation status, 8th edition TNMH cancer staging and International Intraocular Retinoblastoma Classification (IIRC), and number of OCT sessions per eye. Details of each session were scored for indication-related details (informative or not) and assessed for guidance (directive or not), diagnosis (staging changed, new tumors found or excluded), treatment (modified, stopped, or modality shifted), or follow-up modified. MAIN OUTCOME MEASURES: Frequency of OCT-guided management decisions, stratified by indication and type of guidance (confirmatory vs. influential). RESULTS: Sixty-three eyes of 44 children had 339 OCT sessions over the course of clinical management (median number of OCT scans per eye, 5; range, 1-15). The age at presentation and presence of a heritable RB1 mutation significantly correlated with an increased number of OCT sessions. Indications included evaluation of post-treatment scar (55%) or fovea (16%), and posterior pole scanning for new tumors (11%). Of all sessions, 92% (312/339) were informative; 19 of 27 noninformative sessions had large, elevated lesions; of these, 14 of 19 were T2a or T2b (IIRC group C or D) eyes. In 94% (293/312) of the informative sessions, OCT directed treatment decisions (58%), diagnosis (16%), and follow-up (26%). Optical coherence tomography influenced and changed management from pre-OCT clinical plans in 15% of all OCT sessions and 17% of directive sessions. CONCLUSIONS: Optical coherence tomography improves the accuracy of clinical evaluation in retinoblastoma management.

Hand-held high-resolution spectral domain optical coherence tomography in retinoblastoma: clinical and morphologic considerations.

PURPOSE: Hand-held spectral domain optical coherence tomography (HHSD OCT) has greatly expanded the imaging/diagnostic capacity for clinicians managing children with intraocular retinoblastoma. We present our early experience with HHSD OCT and conventional spectral domain OCT imaging in these patients. METHODS: In this retrospective cross-sectional observational study, infants were imaged during examination under anaesthesia with HHSD OCT in the supine position. Older cooperative retinoblastoma patients were additionally imaged with upright conventional OCT. Clinical data were derived from patient charts and from a prospectively maintained interinstitutional retinoblastoma database. Complementary imaging techniques, including RetCam™, fluorescein angiography and B-scan ultrasound, were assessed. RESULTS: Twenty-two intraocular lesions in 16 patients were imaged. HHSD OCT was used exclusively in 19 lesions, while conventional OCT was also performed in three cases. Small lesions were imaged in five cases, all of which were localised to the middle retinal layers. Clinical uses for HHSD OCT imaging identified included: diagnosis of new lesions, monitoring response to laser therapy and the identification of edge recurrences. CONCLUSIONS: Although indirect ophthalmoscopy remains the gold standard for diagnosis and treatment of retinoblastoma, HHSD OCT is a valuable tool in better understanding and managing retinoblastoma.

The characterization of retinal phenotype in a family with C1QTNF5-related late-onset retinal degeneration.

PURPOSE: To describe the clinical, spectral-domain optical coherence tomography and electrophysiological features of C1QTNF5-associated late-onset retinal degeneration in a molecularly confirmed pedigree. METHODS: Five members of a family participated, and affected individuals (n = 4) underwent detailed ophthalmologic evaluation including fundus autofluorescence and spectral-domain optical coherence tomography imaging and electroretinography. Electrooculography was performed in three individuals. RESULTS: The visual acuity was initially normal and worsened with time. Anterior segment abnormalities included peripupillary iris atrophy and long anterior insertion of zonules. Peripapillary atrophy, drusenoid deposition, and scalloped sectorial chorioretinal atrophy were observed in all older individuals (n = 3). Fundus autofluorescence demonstrated hypofluorescent areas corresponding to regions of chorioretinal atrophy. The spectral-domain optical coherence tomography demonstrated multiple areas of retinal pigment epithelium-Bruch membrane separation with intervening homogeneous deposition that corresponded to the drusenoid lesions and areas of chorioretinal atrophy. Electrooculography was normal in one individual and showed abnormally low dark trough measures in older individuals (n = 2). Electroretinography was normal in early stages (n = 1), but showed marked abnormalities in the rod system (n = 3), which was predominantly inner retinal (n = 2) in late stages. CONCLUSION: Late-onset retinal degeneration is a progressive degeneration, and anterior segment abnormalities present early. The widespread sub-retinal pigment epithelium deposition seen on spectral-domain optical coherence tomography in older individuals appears to be a characteristic in late stages. Electrooculography demonstrates abnormalities only in late stages of the disease.

Anterior segment imaging in pediatric ophthalmology.

Anterior segment imaging in the pediatric population using commercially available equipment is rewarding but can be challenging. Successful imaging requires familiarity with the imaging modality used, a positive attitude, and the ability to quickly develop rapport with children. In this review, we demonstrate how external and slitlamp photography, Scheimpflug imaging, handheld digital fundus camera, ultrasound biomicroscopy, and anterior segment optical coherence tomography can be valuable in the documentation, diagnosis, and management of pediatric anterior segment disease. Families understand their child's disease process when it is demonstrated photographically and feel more motivated and involved in their care. Compliance with treatment is often enhanced through this process.

Ocular motility changes after subtenon carboplatin chemotherapy for retinoblastoma.

BACKGROUND: Focal subtenon carboplatin injections have recently been used as a presumably toxicity-free adjunct to systemic chemotherapy for intraocular retinoblastoma. OBJECTIVE: To report our clinical experience with abnormal ocular motility in patients treated with subtenon carboplatin chemotherapy. METHODS: We noted abnormal ocular motility in 10 consecutive patients with retinoblastoma who had received subtenon carboplatin. During ocular manipulation under general anesthesia, we assessed their eyes by forced duction testing, comparing ocular motility after tumor control with ocular motility at diagnosis. Eyes subsequently enucleated because of treatment failure (n = 4) were examined histologically. RESULTS: Limitation of ocular motility was detected in all 12 eyes of 10 patients treated for intraocular retinoblastoma with 1 to 6 injections of subtenon carboplatin as part of multimodality therapy. Histopathological examination revealed many lipophages in the periorbital fat surrounding the optic nerve in 1 eye, indicative of phagocytosis of previously existing fat cells and suggesting prior fat necrosis. The enucleations were technically difficult and hazardous for globe rupture because of extensive orbital soft tissue adhesions. CONCLUSIONS: Subtenon carboplatin chemotherapy is associated with significant fibrosis of orbital soft tissues, leading to mechanical restriction of eye movements and making subsequent enucleation difficult. Subtenon carboplatin is not free of toxicity, and its use is best restricted to specific indications.