Macular corneal dystrophy with iridofundal coloboma in the same patient: a unique combination.

A young a presented with painless, progressive diminution of vision in both eyes (BE). Slit lamp examination revealed the presence of a single central corneal opacity in the right eye and multiple corneal opacities of varying sizes in the left eye (LE), limited to the anterior-mid corneal stroma. Microcornea with reduced central corneal thickness and complete inferonasal iris coloboma along with inferior fundal coloboma, sparing both the disc and macula, were noted in BE. A diagnosis of BE macular corneal dystrophy (MCD) and iridofundal coloboma (IFC) was made. The patient underwent LE sutureless anterior lamellar therapeutic keratoplasty. On histopathological examination, the excised corneal tissue revealed stromal lamellar disarray with positive colloidal iron staining, strongly suggestive of MCD. Whole-exome sequencing revealed the presence of a likely pathogenic carbohydrate sulfotransferase 6 (CHST6) mutation, confirming the diagnosis of MCD. This concurrent presence of IFC with a corneal stromal dystrophy is previously unreported in the literature, to the best of our knowledge.

Measuring Visual Fields in Children With Glaucoma Using a Portable Tablet.

Purpose: To compare perimetric outcomes of an iPad perimetry app (Melbourne Rapid Fields [MRF]) with those of the Humphrey Field Analyser (HFA) testing children with glaucoma. Methods: Sixteen children diagnosed and treated for glaucoma were recruited to evaluate their perimetric performance over two visits. At each visit, they undertook visual field assessment using the MRF application as well as the HFA. The HFA test was part of their usual clinical work up and a clinical assistant judged which test format (24-2 SITA standard or SITA fast) might be suited to the testing of that child. The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests, by way of regression, intraclass correlation coefficient and Bland-Altman analysis. Secondary measures were comparisons of pattern deviation indices, test times as well as an indication of participant test preference. Summary data show means ± standard deviation. Results: The age for our cohort was 7 to 15 years of age (mean, 10.0 ± 2.4 years of age). The MRF MD was in close concordance to HFA MD with an intraclass correlation coefficient of 0.91 (95% confidence interval, 0.82-0.95). Bland-Altman analysis found little bias (-0.6 dB) and a 95% coefficient of repeatability of 2.1 dB in eyes having a normal HFA MD. In eyes with glaucomatous visual field defects the 95% coefficient of repeatability at retest was much larger for both the MRF (10.5 dB) as well as for the HFA (10.0 dB). Average MRF test times (5.6 ± 1.2 minutes) were similar to SITA Fast (5.4 ± 1.9 minutes) with both being significantly faster than SITA standard (8.6 ± 1.4 minutes; P < 0.001). All children chose testing with the MRF as their preference. Conclusions: MRF correlated strongly with HFA and was preferred by the children over the HFA. MRF is suitable for perimetric evaluation of children with glaucoma. Translational Relevance: This study finds that an iPad based visual field test can be used with children having glaucoma to yield outcomes similar to SITA-fast. Children indicate a preference for such testing.

Reduced Aqueous Humor Outflow Pathway Arborization in Childhood Glaucoma Eyes.

Purpose: To compare aqueous humor outflow (AHO) pathway patterns between eyes of childhood glaucoma patients and non-glaucomatous patients receiving cataract surgery. Methods: Aqueous angiography was performed in childhood glaucoma eyes (n = 5) receiving glaucoma surgery and in pediatric (n = 1) and healthy adult (n = 5) eyes receiving cataract surgery. Indocyanine green (0.4%) was introduced into the anterior chamber, and AHO was imaged using an angiographic camera (SPECTRALIS HRA+OCT with Flex Module). Images were acquired and analyzed (ImageJ with Analyze Skeleton 2D/3D plugin) from the nasal sides of the eyes, the usual site of glaucoma angle procedures. Image analysis endpoints included AHO vessel length, maximum vessel length, number of branches, number of branch junctions, and vessel density. Results: Qualitatively, childhood glaucoma eyes demonstrated lesser AHO pathway arborization compared to pediatric and adult eyes without glaucoma. Quantitatively, childhood glaucoma and healthy adult cataract eyes showed similar AHO pathway average branch lengths and maximum branch lengths (P = 0.49-0.99). However, childhood glaucoma eyes demonstrated fewer branches (childhood glaucoma, 198.2 ± 35.3; adult cataract, 506 ± 59.5; P = 0.002), fewer branch junctions (childhood glaucoma, 74.6 ± 13.9; adult cataract, 202 ± 41.2; P = 0.019), and lower vessel densities (childhood glaucoma, 8% ± 1.4%; adult cataract, 17% ± 2.5%; P = 0.01). Conclusions: Childhood glaucoma patients demonstrated fewer distal AHO pathways and lesser AHO pathway arborization. These anatomical alternations may result in a new source of trabecular meshwork-independent AHO resistance in this disease cohort. Translational Relevance: Elevated distal outflow pathway resistance due to decreased AHO pathway arborization may explain some cases of failed trabecular bypass surgery in childhood glaucoma.

Machine learning-assisted prediction of trabeculectomy outcomes among patients of juvenile glaucoma by using 5-year follow-up data.

OBJECTIVE: To develop machine learning (ML) models, using pre and intraoperative surgical parameters, for predicting trabeculectomy outcomes in the eyes of patients with juvenile-onset primary open-angle glaucoma (JOAG) undergoing primary surgery. SUBJECTS: The study included 207 JOAG patients from a single center who met the following criteria: diagnosed between 10 and 40 years of age, with an IOP of >22 mmHg in the eyes on two or more occasions, open angle on gonioscopy in both eyes, with glaucomatous optic neuropathy, and requiring a trabeculectomy for IOP control. Only the patients with a minimum 5-year follow-up after surgery were included in the study. METHODS: A successful surgical outcome was defined as IOP ≤18 mmHg (criterion A) or 50% reduction in IOP from baseline (criterion B) 5 years after trabeculectomy. Feature selection techniques were used to select the most important contributory parameters, and tenfold cross-validation was used to evaluate model performance. The ML models were evaluated, compared, and prioritized based on their accuracy, sensitivity, specificity, Matthew correlation coefficient (MCC) index, and mean area under the receiver operating characteristic curve (AUROC). The prioritized models were further optimized by tuning the hyperparameters, and feature contributions were evaluated. In addition, an unbiased relationship analysis among the parameters was performed for clinical utility. RESULTS: Age at diagnosis, preoperative baseline IOP, duration of preoperative medical treatment, Tenon's thickness, scleral fistulation technique, and intraoperative mitomycin C (MMC) use, were identified as the main contributing parameters for developing efficient models. The three models developed for a consensus-based outcome to predict trabeculectomy success showed an accuracy of >86%, sensitivity of >90%, and specificity of >74%, using tenfold cross-validation. The use of intraoperative MMC and a punch for scleral fistulation compared to the traditional excision with scissors were significantly associated with long-term success of trabeculectomy. CONCLUSION: Optimizing surgical parameters by using these ML models might reduce surgical failures associated with trabeculectomy and provide more realistic expectations regarding surgical outcomes in young patients.

Indocyanine green-assisted goniotomy in eyes with hazy cornea.

Corneal haze, due to edema or opacity, is a major contraindication for performing ab interno angle surgeries such as goniotomy in children with primary congenital glaucoma (PCG), despite otherwise favorable surgical outcomes expected in these patients. In this case series involving patients of PCG with moderate corneal haze, the authors describe a technique for performing goniotomy in cases with compromised visibility by using indocyanine green (ICG) to aid in the visualization of angle structures. The authors used 0.2% ICG intracamerally, which stained the anterior and posterior trabecular meshwork (TM) with different intensities, before proceeding with goniotomy. The junction between the two zones was discernible due to the contrast imparted by ICG staining, despite poor visibility, allowing the surgeon to incise the TM at the correct site. The possibility of performing goniotomy in such patients with the help of ICG can revolutionize our surgical approach to patients with PCG and corneal edema.

In vivo identification of angle dysgenesis and its relation to genetic markers associated with glaucoma using artificial intelligence.

PURPOSE: To predict the presence of angle dysgenesis on anterior-segment optical coherence tomography (ADoA) by using deep learning (DL) and to correlate ADoA with mutations in known glaucoma genes. PARTICIPANTS: In total, 800 high-definition anterior-segment optical coherence tomography (AS-OCT) images were included, of which 340 images were used to build the machine learning (ML) model. Images used to build the ML model included 170 scans of primary congenital glaucoma (16 patients), juvenile-onset open-angle glaucoma (62 patients), and adult-onset primary open-angle glaucoma eyes (37 patients); the rest were controls (n = 85). The genetic validation dataset consisted of another 393 images of patients with known mutations that were compared with 320 images of healthy controls. METHODS: ADoA was defined as the absence of Schlemm's canal, the presence of hyperreflectivity over the region of the trabecular meshwork, or a hyperreflective membrane. DL was used to classify a given AS-OCT image as either having angle dysgenesis or not. ADoA was then specifically looked for on AS-OCT images of patients with mutations in the known genes for glaucoma. RESULTS: The final prediction, which was a consensus-based outcome from the three optimized DL models, had an accuracy of >95%, a specificity of >97%, and a sensitivity of >96% in detecting ADoA in the internal test dataset. Among the patients with known gene mutations, ( MYOC, CYP1B1, FOXC1, and LTBP2 ) ADoA was observed among all the patients in the majority of the images, compared to only 5% of the healthy controls. CONCLUSION: ADoA can be objectively identified using models built with DL.

THE HAIRY PHOENIX.

PURPOSE: To report a case a patient of anterior uveitis, iris neovascularization, high IOP and vasculitis in a patient with subconjunctival and intra ocular caterpillar hair. METHOD: Case report. RESULTS: A 30-year-old man complaining of episodes of blurring of vision and colored haloes in his LE was referred for high IOP that was uncontrolled despite maximum tolerable medication in LE. He was diagnosed as a case of Posner Schlossman syndrome in view of signs of anterior uveitis. He was also noted to have retinal hemorrhages in the peripheral fundus with peripheral vasculitis and capillary non perfusion areas. He underwent an uneventful trabeculectomy. During surgery caterpillar hair were noted in his inferior conjunctiva that were removed. Later a seta was also found in the vitreous in supertemporal quadrant. CONCLUSION: The case is an unusual presentation of caterpillar hair masquerading as a Posner Sclhossman syndrome.

Distribution of TGFBI variants in patients with early onset glaucoma.

Purpose: To describe a novel association of TGFBI variants with congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome, as well as among other unrelated cases of juvenile onset open-angle glaucoma (JOAG) and primary congenital glaucoma (PCG). Methods: This study of one family of GAPO with congenital glaucoma and three unrelated patients with JOAG analyzed a common link to glaucoma pathogenesis. Three girls with GAPO syndrome born to consanguineous parents in a multi-generation consanguineous family were identified. Two of the girls had congenital glaucoma in both eyes, while the elder sibling (a 10-year-old female) had features of GAPO syndrome without glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a novel homozygous ANTXR1 mutation in all three affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense variant in the TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome. We found three other unrelated patients with JOAG and one patient with primary congenital glaucoma with no known glaucoma causing gene mutations, but having four different missense variants in the TGFBI gene. One of these patients with JOAG had familial granular corneal dystrophy. Molecular dynamic simulations of TGFBI and 3-D structural models of three of its variants showed significant alterations that could influence TGFBI protein function. Conclusions: The possibility that variations in the TGFBI gene could have a possible role in the pathogenesis of congenital and juvenile onset open-angle glaucomas needs further evaluation.