Use of an Artificial Intelligence-Generated Vascular Severity Score Improved Plus Disease Diagnosis in Retinopathy of Prematurity.

PURPOSE: To evaluate whether providing clinicians with an artificial intelligence (AI)-based vascular severity score (VSS) improves consistency in the diagnosis of plus disease in retinopathy of prematurity (ROP). DESIGN: Multireader diagnostic accuracy imaging study. PARTICIPANTS: Eleven ROP experts, 9 of whom had been in practice for 10 years or more. METHODS: RetCam (Natus Medical Incorporated) fundus images were obtained from premature infants during routine ROP screening as part of the Imaging and Informatics in ROP study between January 2012 and July 2020. From all available examinations, a subset of 150 eye examinations from 110 infants were selected for grading. An AI-based VSS was assigned to each set of images using the i-ROP DL system (Siloam Vision). The clinicians were asked to diagnose plus disease for each examination and to assign an estimated VSS (range, 1-9) at baseline, and then again 1 month later with AI-based VSS assistance. A reference standard diagnosis (RSD) was assigned to each eye examination from the Imaging and Informatics in ROP study based on 3 masked expert labels and the ophthalmoscopic diagnosis. MAIN OUTCOME MEASURES: Mean linearly weighted κ value for plus disease diagnosis compared with RSD. Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPR) for labels 1 through 9 compared with RSD for plus disease. RESULTS: Expert agreement improved significantly, from substantial (κ value, 0.69 [0.59, 0.75]) to near perfect (κ value, 0.81 [0.71, 0.86]), when AI-based VSS was integrated. Additionally, a significant improvement in plus disease discrimination was achieved as measured by mean AUC (from 0.94 [95% confidence interval (CI), 0.92-0.96] to 0.98 [95% CI, 0.96-0.99]; difference, 0.04 [95% CI, 0.01-0.06]) and AUPR (from 0.86 [95% CI, 0.81-0.90] to 0.95 [95% CI, 0.91-0.97]; difference, 0.09 [95% CI, 0.03-0.14]). CONCLUSIONS: Providing ROP clinicians with an AI-based measurement of vascular severity in ROP was associated with both improved plus disease diagnosis and improved continuous severity labeling as compared with an RSD for plus disease. If implemented in practice, AI-based VSS could reduce interobserver variability and could standardize treatment for infants with ROP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Biallelic RP1-associated retinal dystrophies: Expanding the mutational and clinical spectrum.

Purpose: To evaluate the phenotypic spectrum of autosomal recessive RP1-associated retinal dystrophies and assess genotypic associations. Methods: A retrospective multicenter study was performed of patients with biallelic RP1-associated retinal dystrophies. Data including presenting symptoms and age, visual acuity, kinetic perimetry, full field electroretinogram, fundus examination, multimodal retinal imaging, and RP1 genotype were evaluated. Results: Nineteen eligible patients from 17 families were identified and ranged in age from 10 to 56 years at the most recent evaluation. Ten of the 21 unique RP1 variants identified were novel, and mutations within exon 2 accounted for nearly half of alleles across the cohort. Patients had clinical diagnoses of retinitis pigmentosa (13), cone-rod dystrophy (3), Leber congenital amaurosis (1), early-onset severe retinal dystrophy (1), and macular dystrophy (1). Macular atrophy was a common feature across the cohort. Symptom onset occurred between 4 and 30 years of age (mean 14.9 years, median 13 years), but there were clusters of onset age that correlated with the effects of RP1 mutations at a protein level. Patients with later-onset disease, including retinitis pigmentosa, had at least one missense variant in an exon 2 DCX domain. Conclusions: Biallelic RP1 mutations cause a broad spectrum of retinal disease. Exon 2 missense mutations are a significant contributor to disease and can be associated with a considerably later onset of retinitis pigmentosa than that typically associated with biallelic RP1 mutations.

Paediatric Cogan Syndrome masquerading as IgA vasculitis.

Paediatric Cogan Syndrome is a rare and underrecognised autoimmune vasculitis characterised by ocular inflammation and sensorineural hearing loss. Its etiopathogenesis, diagnosis, and management are not well defined. We report a 12-year-old girl who initially presented with symptoms of IgA vasculitis formerly called Henoch Schoenlein Purpura (HSP) and eventually developed anterior uveitis and bilateral sensorineural hearing loss leading to the diagnosis of atypical Cogan Syndrome. The workup for infectious etiologies and other systemic rheumatologic disorders was negative. The management was multidisciplinary involving Rheumatology, Ophthalmology, Otorhinolaryngology, and Audiology. The anterior uveitis responded well to systemic glucocorticoids and Methotrexate, but the hearing loss was grossly progressive warranting a cochlear implant. We are not aware of Paediatric Cogan Syndrome being reported as a mimicker of IgA vasculitis previously in the literature. It is an important finding as IgA vasculitis is prevalent in the paediatric age group and new-onset ocular or vestibular symptoms after IgA vasculitis should alert the clinician to the possibility of Cogan Syndrome. In the absence of well-defined diagnostic criteria, it is crucial to recognise the clinical symptoms of Paediatric Cogan Syndrome for early diagnosis and treatment since the delay in diagnosis can lead to permanent disability.

Oral Fluorescein Angiography for the Diagnosis of Papilledema Versus Pseudopapilledema in Children.

PURPOSE: To evaluate the accuracy and safety of oral fluorescein angiography (OFA) in differentiating papilledema from pseudopapilledema in pediatric patients. DESIGN: Retrospective evaluation of a diagnostic test. METHODS: We retrospectively reviewed medical records of all children ≤18 years of age who presented to the Arkansas Children's Hospital between May 2018 and August 2021 with suspected optic disc (OD) swelling that had OFA and images >30 minutes after oral ingestion. Two masked specialists interpreted the images as either OD leakage, no leakage, or borderline leakage. Optic disc swelling was graded clinically according to the Frisen grading scale (0-5). We compared OFA images to the final clinical diagnosis and calculated the accuracy of the test as follows: (number of eyes correctly identified as papilledema [true positive] + number of eyes correctly identified as pseudopapilledema [true negative]) / (total number of eyes) × 100%. RESULTS: Forty-five patients (90 eyes) were included, 11 patients with papilledema and 34 with pseudopapilledema. The mean age was 14.1 ± 3.5 years; 66.7% were female. The accuracy of OFA was 62% for reviewer 1 and 69% for reviewer 2. No ocular or systemic side effects after OFA were observed. There was substantial agreement (k = 0.779) between both reviewers in grading the OFA images. CONCLUSION: OFA cannot definitively distinguish papilledema from pseudopapilledema in children and should be interpreted in conjunction with other clinical findings.

Adaptive optics ophthalmoscopy, multifocal ERG and OCTA in unique case of suspected torpedo maculopathy presenting with vitelliform lesion.

PURPOSE: To report the case of a ten-year old girl with torpedo maculopathy with a complete vitelliform lesion and describe associated optical coherence tomography (OCT), OCT angiography (OCTA), multifocal electroretinogram (ERG) and adaptive optics ophthalmoscopy (AOO) imaging of the lesion. OBSERVATIONS: An asymptomatic ten-year old girl with visual acuity of 20/15 OU was referred for evaluation of possible Best's disease of her left eye. The unilaterality, location, and shape of the lesion was consistent with torpedo maculopathy. OCT and autofluorescence (AF) revealed that the entire lesion was composed of subretinal hyperreflective material that was hyperautofluorescent, consistent with vitelliform material. Within the boundary of the lesion, OCTA showed reduced choriocapillaris density while adjacent to the lesion, the choriocapillaris density was slightly increased. Microperimetry demonstrated normal sensitivity in both eyes, electrooculograms (EOG) were normal and multifocal ERG showed symmetrical mildly supernormal amplitudes. Additionally, AOO demonstrated that nasal to the lesion there were clusters of hyper-reflective areas, and immediately adjacent to the lesion cones were poorly resolved. However, there was a return to more normal photoreceptor architecture outside of the lesion. CONCLUSIONS AND IMPORTANCE: Torpedo maculopathy lesions typically present with outer retinal attenuation and retinal pigmented epithelium (RPE) atrophy. Vitelliform material was recently observed for the first time in association with Torpedo maculopathy in a case report that described small vitelliform material at the periphery of the lesion. We report the second case of torpedo maculopathy associated with a vitelliform lesion and the first description of a torpedo lesion composed fully of presumed vitelliform material. We also describe findings of OCTA, multifocal ERG and AOO imaging in torpedo maculopathy with vitelliform lesion.

Genotype Phenotype Correlation and Variability in Microcephaly Associated With Chorioretinopathy or Familial Exudative Vitreoretinopathy.

Purpose: The purpose of this study was to analyze the natural history and phenotypic overlap of patients with microcephaly and a chorioretinopathy or familial exudative vitreoretinopathy (FEVR) ocular phenotype caused by mutations in KIF11, TUBGCP4, or TUBGCP6. Methods: Patients diagnosed with congenital microcephaly and chorioretinopathy or FEVR were included. Molecular investigations consisted of targeted genetic sequencing. Data from medical records, ophthalmologic examination and imaging, electroretinography, and visual fields were analyzed for systemic and ophthalmic features and evidence of posterior segment disease progression. Results: Twelve patients from 9 families were included and had a median of 8 years of follow-up. Nine patients had KIF11 variants, two had heterozygous TUBGCP6 variants, and one had heterozygous variants in TUBGCP4. All patients had reduced visual function and multiple individuals and families showed features of both chorioretinopathy and FEVR. Progression of posterior segment disease was highly variable, with some degree of increased atrophy of the macula or peripheral retina or increased vitreoretinal traction observed in 9 of 12 patients. Conclusions: Microcephaly due to mutations in KIF11, TUBGCP4, or TUBGCP6 can be associated with retinal disease on a spectrum from chorioretinal atrophy to FEVR-like posterior segment changes. Visually significant disease progression can occur and patients should be monitored closely by a team experienced in ophthalmic genetics.

Asymptomatic Leukemic Optic Nerve Infiltration as Presentation of Acute Lymphoblastic Leukemia Relapse.

The authors report a case of asymptomatic leukemic optic neuropathy as the first sign of acute lymphoblastic leukemia relapse in a 4-year-old boy. Routine ophthalmologic examination showed normal visual acuity and pupillary function in the presence of a tumoral mass covering the left optic disc. The mass resolved with preservation of vision after intrathecal chemotherapy. A routine ophthalmological examination is recommended for all patients with a history of acute lymphoblastic leukemia to exclude optic nerve involvement without systemic symptoms or signs. Vision can be preserved and radiation avoided by using targeted chemotherapy. [J Pediatr Ophthalmol Strabismus. 2017;54:e60-e62.].

Comparison of the Icare rebound tonometry with the Goldmann applanation tonometry in a pediatric population.

We report the results of a comparative study at a single center on 214 eyes of 109 pediatric patients in whom IOP was measured using the Icare rebound tonometer and Goldmann applanation tonometry. Measurements from the two modalities demonstrated a correlation coefficient of 0.83 (P < 0.001), with Icare measuring on average 1.38 mm Hg higher. Compared to Goldmann, the Icare was more easily tolerated in the children studied. In 37 eyes that tolerated pachymetry, central corneal thickness was positively correlated with Icare measurements.

The use of the iCare tonometer reduced the need for anesthesia to measure intraocular pressure in children.

PURPOSE: To determine whether the introduction of iCare rebound tonometry in a pediatric ophthalmology clinic resulted in fewer examinations under anesthesia to evaluate children with glaucoma. METHODS: The medical records of consecutive glaucoma patients were retrospectively reviewed. The numbers of examinations under anesthesia (EUAs) and office visits that included measurement of intraocular pressure (IOP) were compared for three periods relative to introduction of the Icare (Icare Finland Oy, Helsinki, Finland) rebound tonometer into our clinical practice: before device introduction, learning/transition period, and routine use. RESULTS: A total of 87 subjects were included: 48 subjects met inclusion criteria for the first period; 58 patients met inclusion criteria for the third period (some subjects straddled all three periods). The average patient age for the first period was 4.2 years and 4.9 years (P = 0.3) for the third period. The number of EUAs performed before the introduction of the Icare was 55 and after the introduction of the Icare was 18 (P < 0.001). The number of office visits at which IOP was measured increased from 34 to 151 (P < 0.001). Data from the transition period suggest a trend and a short learning period. CONCLUSIONS: The use of Icare tonometry decreased the need for EUAs to evaluate children with glaucoma and significantly increased successful IOP measurement in clinic.

Hyperacute infectious keratitis with Plesiomonas shigelloides following traumatic lamellar corneal laceration.

Plesiomonas shigelloides rarely causes extraintestinal human disease, and infection of ocular tissues is even rarer, never having been reported as the sole pathogen of posttraumatic ocular infection. We report the first case of infectious keratitis due solely to P. shigelloides following traumatic corneal laceration and a literature review with regard to P. shigelloides ocular disease.