Association of Speckle-Based Blood Flow Measurements and Fluorescein Angiography in Infants with Retinopathy of Prematurity.

Purpose: To determine the correlation between blood flow metrics measured by intravenous fluorescein angiography (IVFA) and the blood flow velocity index (BFVi) obtained by laser speckle contrast imaging (LSCI) in infants with retinopathy of prematurity (ROP). Design: Prospective comparative pilot study. Subjects: Seven eyes from 7 subjects with ROP. Methods: Unilateral LSCI and IVFA data were obtained from each subject in the neonatal intensive care unit. Five LSCI-based metrics and 5 IVFA-based metrics were extracted from images to quantify blood flow patterns in the same region of interest. Correlation between LSCI-based and IVFA-based blood flow metrics was compared between 2 subgroups of ROP severity: moderate ROP (defined as stage ≤ 2 without Plus disease) and severe ROP (defined as stage ≥3 or Plus disease). Main Outcome Measures: Pearson and Kendall rank correlation coefficients between IVFA and LSCI metrics; Student t test P values comparing LSCI metrics between "severe" and "moderate" ROP groups. Results: Pearson correlations between IVFA and LSCI included arterial-venous transit time (AVTT) and peak BFVi (pBFVi; r = -0.917; P = 0.004), AVTT and dip BFVi (dBFVi; r = -0.920; P = 0.003), AVTT and mean BFVi (r = -0.927- P = 0.003), and AVTT and volumetric rise index (r = -0.779; P = 0.039). Kendall rank correlation between AVTT and dBFVi was r = -0.619 (P = 0.051). pBFVi was higher in severe ROP than in moderate ROP (8.4 ± 0.6 and 4.4 ± 1.8, respectively; P = 0.0045 using the 2-sample t test with pooled variance and P = 0.0952 using the Wilcoxon rank-sum test). Conclusions: Correlation was found between blood flow metrics obtained by IVFA and noninvasive LSCI techniques. We demonstrate the feasibility of obtaining quantitative metrics using LSCI in infants with ROP in this pilot study; however, further investigation is needed to evaluate its potential use in clinical assessment of ROP severity. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Repeatability and reliability of semi-automated anterior segment-optical coherence tomography imaging compared to manual analysis in normal and keratoconus eyes.

PURPOSE: To assess the repeatability and reliability of semi-automated EyeMark Python program measurements compared to manual ImageJ image processing of anterior segment-optical coherence tomography (AS-OCT) structures in healthy and keratoconus eyes. METHODS: Heidelberg AS-OCT was used to image 25 eyes from 14 healthy subjects and 25 eyes from 15 subjects with keratoconus between the ages of 20 and 80 years, collected prospectively, in this observational case-control study. Visual axis scan containing vertical fixation light beam was selected from the 15-line AS-OCT scan raster. Central corneal thickness (CCT), anterior corneal radius of curvature (ACRC), posterior corneal radius of curvature (PCRC), and truncated anterior vault (TAV) were measured using ImageJ software and the EyeMark Python program. MedCalc and R were used to calculate the intraclass correlation coefficient (ICC) and generate Bland-Altman plots (BAP). RESULTS: When comparing the measurements of CCT, ACRC, PCRC, and TAV between manual ImageJ analysis and the EyeMark Python program, ICC values were consistently greater than 0.9, indicating excellent agreement. BAPs comparing the ImageJ and Python measurements of anterior segment structures show no systematic proportional bias and the average differences were near zero and within 95% of the limits of agreement. CONCLUSIONS: Semi-automated tools may provide the necessary efficiency for point-of-care quantitative corneal analysis of raw AS-OCT images. The semi-automated EyeMark Python program offers a repeatable and reliable tool compared to manual ImageJ analysis for measuring anterior segment structures from AS-OCT images among individuals with keratoconus.

Multimodal prenatal and postnatal imaging of microphthalmia with cyst.

Congenital ocular anomalies may be detected on prenatal imaging using fetal ultrasound and magnetic resonance imaging (MRI), although standard prenatal ultrasound for fetal physical development does not currently include ocular and orbital evaluation. We present the case of a male infant born at 39 weeks' gestation with microphthalmia with cyst that was characterized using serial multimodal imaging, including fetal ultrasound and MRI, B-scan ultrasonography, ultrasound biomicroscopy, and postnatal MRI. Multiple prenatal and postnatal imaging modalities yielded comparable evaluations of the ocular and orbital pathology, validating the prenatal assessments.

Surgical Management of Iris Bombe in Muscle-Eye-Brain Disease.

A 2-year-old girl with severe muscular dystrophy presented with unilateral eye pain and corneal clouding. She was found to have absent red reflex, hypotonia, cerebral hypoplasia, and iris bombe on ultrasound biomicroscopy, a feature not previously reported in this syndrome. She responded favorably to surgical management. Iris bombe can be a cause of glaucoma in muscle-eye-brain disease. This highlights the importance of incorporating ultrasound biomicroscopy into the diagnostic algorithm of muscle-eye-brain disease and other types of congenital syndromic glaucoma. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e35-e37.].

Congenital ankyloblepharon in a newborn with an IRF6 mutation.

We present the case of a boy born at 41 weeks' gestational age who was found to have multiple anatomic anomalies, including abnormalities of the oral cavity, eyelids, and digits. He had ankyloblepharon that was localized to the lateral portion of the palpebral fissure bilaterally. Genetic testing confirmed a mutation in the interferon regulatory factor 6 (IRF6) gene, a known etiology for a spectrum of rare disorders that includes eyelid abnormalities. We present a novel surgical technique for bedside ankyloblepharon repair and describe the relevant clinical features of this case.

Retinal hemorrhages in abusive head trauma with atraumatic neuroimaging.

We report 3 cases of suspected abusive head trauma with retinal hemorrhages on fundus examination and neuroimaging findings not necessarily suggestive of shaking injury. Previous studies have suggested that retinal hemorrhages are rare in patients without neuroimaging abnormalities. These cases demonstrate some common features (rib fractures, developmental delay, and history of abuse) that may increase suspicion for abusive head trauma. Our findings suggest a potential role for ophthalmic consultation in scenarios with high clinical suspicion for abusive head trauma without definitive neuroimaging evidence of head injury. The nonspecific neuroimaging features of these 3 cases highlight the importance of interpreting cases with global clinical context.

Baltimore pediatric ocular trauma study: Health disparities and outcomes in pediatric and adolescent open globe trauma.

Purpose Children represent approximately one-third of patients with serious ocular injuries. Our study evaluates associations between race and socioeconomic status in presentation and outcomes of pediatric and adolescent traumatic open globe injuries. Methods We conducted a retrospective chart review of traumatic open globe injuries in pediatric and adolescent patients presenting to Johns Hopkins Hospital and University of Maryland Medical Center between 2006 and 2020. Variables assessed included age, gender, parent-identified race, median household income, mechanism of injury, initial and final visual acuity (VA), and length of follow-up. Results Eighty patients ranging from 4 months to 17.7 years (mean 9.3 years) presented with traumatic open globe injury. Identifications were 28 White (35%), 38 Black (48%), and 5 Hispanic (6%). Initial presenting and final VA, pediatric ocular trauma score (POTS), and length of follow-up did not differ significantly among race, gender, or income. Black patients had higher rates of blunt trauma (odds ratio (OR) 3.81; 95% confidence interval (CI) 0.95-15.24, p = 0.07), uveal prolapse (OR 3.58; 95% CI 1.03-12.43; p = 0.049), and enucleation (OR 10.55; 95% CI 1.26-88.31). Hispanic patients presented at a younger age of 2.8 years mean age vs. 9.9 years (p = 0.004) for others. Conclusion Visual outcomes following traumatic open globe injury were independent of race, gender, or income. However, blunt trauma, uveal prolapse, and enucleation rates were higher in Black patients, and ocular trauma occurred at a younger age in Hispanic patients.

Spontaneous absorption of congenital cataract in trisomy 21.

We report a case of spontaneous cataract absorption over a period of 19 weeks in a 5-week-old boy with trisomy 21. Ultrasound biomicroscopy images at 5 and 24 weeks of age showed that 71% of the initial lens thickness was absorbed during this period. At surgery, the lens thickness was 0.92 mm in the right eye and 0.91 mm in the left eye. Uncomplicated cataract extraction was performed. Trypan blue staining revealed an area of possible lens leakage through the anterior lens capsule in the left eye, suggesting a mechanism for cataract absorption.

Inter-rater Reliability and Repeatability of Manual Anterior Segment Optical Coherence Tomography Image Grading in Keratoconus.

OBJECTIVES: To determine the repeatability of corneal measurements from anterior segment optical coherence tomography (AS-OCT) images using ImageJ software in healthy eyes compared with eyes with keratoconus. METHODS: Anterior segment OCT images of 25 eyes from 14 healthy subjects and 25 eyes from 15 subjects with keratoconus between the ages of 20 and 80 years were evaluated. Two trained observers used ImageJ to measure the central corneal cross-sectional area and anterior and posterior corneal arc lengths. MedCalc statistical software was used to generate the intraclass correlation coefficient (ICC) and Bland-Altman plots (BAPs) for observer measurements. RESULTS: Observer measurements of the central corneal cross-sectional area and anterior and posterior corneal arc lengths yielded an ICC >0.7. The ICC comparing the 3 parameters ranged from 0.75 to 0.84 for the control and 0.96 to 0.98 for the keratoconus group. No systematic proportional bias was detected by the BAPs. There were minimal differences between the 2 observer's measurements, with a mean of the difference of 0.3 mm2, 0 mm, and 0 mm, for the 3 measurements, respectively. CONCLUSIONS: This study suggests that ImageJ software is a repeatable and reliable tool in the analysis of corneal parameters from AS-OCT images among patients with keratoconus and may be applicable to AS-OCT imaging protocol development, an area of active keratoconus research.

Semiautomated Assessment of Anterior Segment Structures in Pediatric Glaucoma Using Quantitative Ultrasound Biomicroscopy.

The study was a prospective observational study comparing semiautomated to manual quantitative ultrasound biomicroscopy image analysis among 82 images from 41 eyes of 32 subjects (21 controls and 11 glaucoma) enrolled in the Pediatric Anterior Segment Imaging Innovation Study. Intraclass correlation coefficients and correlation coefficients were >0.8 for all parameters, and comparison of respective analysis speed was 7 times faster for the semiautomated method compared with manual image quantification.

Novel Homozygous Missense Variant in GJA3 Connexin Domain Causing Congenital Nuclear and Cortical Cataracts.

Congenital cataracts (CC) are responsible for approximately one-tenth of childhood blindness cases globally. Here, we report an African American family with a recessively inherited form of CC. The proband demonstrated decreased visual acuity and bilateral cataracts, with nuclear and cortical cataracts in the right and left eye, respectively. Exome sequencing revealed a novel homozygous variant (c.563A > G; p.(Asn188Ser)) in GJA3, which was predicted to be pathogenic by structural analysis. Dominantly inherited variants in GJA3 are known to cause numerous types of cataracts in various populations. Our study represents the second case of recessive GJA3 allele, and the first report in African Americans. These results validate GJA3 as a bona fide gene for recessively inherited CC in humans.

A systematic review of ultrasound biomicroscopy use in pediatric ophthalmology.

Ultrasound biomicroscopy (UBM) is the only available option for noninvasive, high-resolution imaging of the intricate iridociliary complex, and for anterior segment imaging with corneal haze or opacity. While these unique features render UBM essential for specific types of trauma, congenital anomalies, and anterior segment tumors, UBM imaging has found clinical utility in a broad spectrum of diseases for structural assessments not limited to the anterior intraocular anatomy, but also for eyelid and orbit anatomy. This imaging tool has a very specific niche in the pediatric population where anterior segment disease can be accompanied by corneal opacity or clouding, and anomalies posterior to the iris may be present. Pediatric patients present additional diagnostic challenges. They are often unable to offer detailed histories or fully cooperate with examination, thus amplifying the need for high-resolution imaging. This purpose of this systematic review is to identify and synthesize the body of literature involving use of UBM to describe, evaluate, diagnose, or optimize treatment of pediatric ocular disease. The collated peer-reviewed research details the utility of this imaging modality, clarifies the structures and diseases most relevant for this tool, and describes quantitative and qualitative features of UBM imaging among pediatric subjects. This summary will include information about the specific applications available to enhance clinical care for pediatric eye disease.

Deep Learning Model for Accurate Automatic Determination of Phakic Status in Pediatric and Adult Ultrasound Biomicroscopy Images.

Purpose: Ultrasound biomicroscopy (UBM) is a noninvasive method for assessing anterior segment anatomy. Previous studies were prone to intergrader variability, lacked assessment of the lens-iris diaphragm, and excluded pediatric subjects. Lens status classification is an objective task applicable in pediatric and adult populations. We developed and validated a neural network to classify lens status from UBM images. Methods: Two hundred eighty-five UBM images were collected in the Pediatric Anterior Segment Imaging Innovation Study (PASIIS) from 80 eyes of 51 pediatric and adult subjects (median age = 4.6 years, range = 3 weeks to 90 years) with lens status phakic, aphakic, or pseudophakic (n = 33, 7, and 21 subjects, respectively). Following transfer learning, a pretrained Densenet-121 model was fine-tuned on these images. Metrics were calculated for testing dataset results aggregated from fivefold cross-validation. For each fold, 20% of total subjects were partitioned for testing and the remaining subjects were used for training and validation (80:20 split). Results: Our neural network trained across 60 epochs achieved recall 96.15%, precision 96.14%, F1-score 96.14%, false positive rate 3.74%, and area under the curve (AUC) 0.992. Feature saliency heatmaps consistently involved the lens. Algorithm performance was compared using 2 image sets, 1 from subjects of all ages, and the second from only subjects under age 10 years, with similar performance under both circumstances. Conclusions: A neural network trained on a relatively small UBM image set classified lens status with satisfactory recall and precision. Adult and pediatric image sets offered roughly equivalent performance. Future studies will explore automated UBM image classification for complex anterior segment pathology. Translational Relevance: Deep learning models can evaluate lens status from UBM images in adult and pediatric subjects using a limited image set.

Acute direct traumatic optic neuropathy treated with steroids, minocycline and hyperbaric oxygen: a case report.

We describe the emergency management of a man who experienced acute vision loss diagnosed as direct traumatic optic neuropathy (TON) in his right eye (no light perception) after falling from a height. TON is caused by a high-impact mechanism of injury. Clinical findings include acute vision loss, which is typically immediate, afferent pupillary defect, decreased color vision, and visual field defects. Treatment is controversial because of the lack of strong evidence supporting intervention over observation. In this case report, our treatment strategy comprised immediate hyperbaric oxygen (HBO2) and daily high doses of a steroid. On the second day, minocycline was added to the treatment regimen for its neuroprotective effects. The patient was discharged after receiving six HBO2 treatments and six days of intravenous solumedrol transitioned to oral prednisone. After the third HBO2 treatment, his vision improved to 20/100; after the fourth treatment, it was 20/40 and plateaued. At the time of discharge, it was 20/40. At two-month follow-up, his corrected visual acuity was 20/60+2 in the affected eye. Immediate HBO2 for ischemic and mechanical injury to the optic nerve following trauma is a therapeutic option.

Anterior segment ultrasound biomicroscopy image analysis using ImageJ software: Intra-observer repeatability and inter-observer agreement.

PURPOSE: In this novel study, we demonstrate a standardized imaging and measurement protocol of anterior segment (AS) structures with reliability analysis using ultrasound biomicroscopy (UBM) and ImageJ software. METHODS: Ten pediatric and young adult patients undergoing examination under anesthesia for AS pathology were imaged using UBM. Four trained observers analyzed 20 images using ImageJ. Forty-five structural parameters were measured. Those that relied on the trabecular-iris angle (TIA) as a reference landmark were labeled TIA-dependent (TD) and all others were labeled non-TIA dependent (NTD). Intra-observer repeatability (IOR) and inter-observer agreement (IOA) of measurements were determined using coefficient of variation (CV) and intra-class correlation (ICC) followed by assessment of Bland-Altman plots (BAP) for each pair of observers, respectively. RESULTS: For NTD parameters, non-ciliary body (CB) related measurements showed CV range 0.60-16.22% and ICC range 0.84-0.89, whereas CB-related parameters showed CV range 2.86-23.40% and ICC range 0.29-0.92. For TD parameters, parameters < 2 degrees removed from reference showed CV range 0.02-5.40% and ICC range 0.89-1.00, whereas parameters > 1 degree removed showed CV range 0.63-27.44% and ICC range 0.22-1.00. No systematic proportional bias was detected by BAPs. CONCLUSIONS: Preplaced landmarks yielded good IOR and IOA in quantitative assessment of AS structures that were NTD and non-CB-related or less removed from the reference. CB-related NTD measurements varied greatly in IOR and IOA, indicating protocol modifications or CB qualitative assessments needed to improve accuracy. Variability in TD measurements increased the further removed from the reference, which supports implementation of a reliable reference landmark to minimize variation.

Effect of oral niacin on central retinal vein occlusion.

PURPOSE: Niacin, a treatment for dyslipidemia, is known to induce vasodilation as a secondary effect. Previous instances of patients with chronic central retinal vein occlusion (CRVO) and cystoid macular edema (CME) have been observed to spontaneously improve when placed on systemic niacin for hypercholesterolemia. The purpose of this study was to evaluate the effects of niacin on CRVO and associated ocular complications. METHODS: A prospective, single-center, non-randomized, interventional case series of niacin for CRVO was conducted. Best-correct visual acuity (BCVA), central macular thickness (CMT), and ocular complications were analyzed in 50 patients over 1 year. Eight patients were controls. RESULTS: The mean initial logMAR BCVA was 0.915, and improved with niacin to 0.745 (P = 0.12), 0.665 (P = 0.02) and 0.658 (P = 0.03) after 3, 6, and 12 months of follow-up, respectively. At baseline, mean CMT was 678.9 µm, and improved to 478.1 µm (P = 0.001), 388.6 µm (P < 0.001), and 317.4 µm (P < 0.001) for the same time points. The control group had a mean initial logMAR BCVA of 1.023, which gradually deteriorated to 1.162 (P = 0.36) after 12 months, and baseline CMT of 700.0 µm at baseline, which gradually improved to 490.9 µm (P = 0.06) after 12 months. Panretinal photocoagulation for neovascularization was required in 5 patients (13.2%) receiving niacin and 3 (37.5%) controls. CONCLUSIONS: These data suggest that niacin may be associated with functional and anatomic improvements in eyes with CRVO. Future investigations will help ascertain whether there is a role for niacin as an adjunct therapy to intravitreal injections in the management of CRVO.

Persistent Corneal Edema Associated With Subconjunctival 5-fluorouracil in an Infant With Primary Congenital Glaucoma.

A 3-month-old boy with primary congenital glaucoma developed a transient corneal endothelial opacity after needle bleb revision with adjunctive 5-fluorouracil. This case presents a rare toxicity that, although transient, is concerning due to the potential of amblyopia. The authors review prior cases of corneal opacity associated with 5-fluorouracil. [J Pediatr Ophthalmol Strabismus. 2016;53:e54-e57.].