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Prcis: Gonioscopy-assisted transluminal trabeculotomy yielded a 45% reduction in intraocular pressure in primary congenital glaucoma, with a success rate of 86.6%. Hyphema was the most common complication. We did not encounter any vision-threatening complications., Background: To assess the outcome of gonioscopy-assisted transluminal trabeculotomy (GATT) in primary congenital glaucoma (PCG) and identify the potential prognostic factors for adverse outcomes., Methods: This prospective study included patients aged <14 years, presenting with PCG from November 2019 till November 2021. We excluded eyes with hazy cornea, secondary glaucoma, peripheral anterior synechiae ≥90 degrees, and eyes in which the extent of GATT was <270 degrees. Success was defined as a final intraocular pressure (IOP) <18 mm Hg with IOP reduction >20%. Primary outcomes were reduction in IOP and medications, secondary outcomes were complications and correlation of IOP reduction and surgical success with possible risk factors., Results: We included 60 eyes of 50 patients aged 1-156 months (mean: 25.5±36.5). A 353±21 degrees incision was created, with 85% achieving a 360-degree incision. There was a significant reduction in IOP and medications at all follow-up intervals up to 2 years, with a mean of 45% IOP reduction. The final success rate was 86.6%, with 76.7% being controlled without medications. There was a significant positive correlation between the preoperative cup-to-disc ratio (CDR) and failure rates ( P =0.03) and between the incision extent and the IOP reduction (r=0.4, P =0.001). Hyphema was the most common complication, affecting 33%, and resolved spontaneously in all cases. No vision-threatening complications occurred., Conclusions: GATT is a safe and effective procedure in eyes with PCG and clear cornea, including eyes that had previous failed glaucoma surgery. Circumferential GATT is associated with more favorable outcomes, while eyes with a larger CDR are at a higher risk for failure., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Brittle cornea syndrome type 2 is associated with corneal thinning, joint hypermobility, dental and skeletal issues, osteal fragility, and deafness. We present a rare association of congenital glaucoma with brittle cornea syndrome type 2 and keratoglobus in a patient with a novel PRDM5 gene mutation. Our case underscores the importance of genetic testing for early clinical diagnosis and tailored surgical approaches., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Primary congenital glaucoma (PCG) is one of the leading causes of visual damage and blindness, severely affecting the quality of life of affected children. It is characterized by cupping of the optic disc and loss of ganglion cells due to elevated intraocular pressure. While most PCG patients exhibit epiphora, photophobia, and buphthalmos with corneal opacity, variability in phenotypic manifestations is not uncommon. Prompt diagnosis and treatment of PCG affected individuals becomes relevant to preserve visual function throughout their lives. Most PCG cases are sporadic or autosomal recessive; however, an incompletely dominant autosomal dominant form arising from mutations in the TEK gene has recently been demonstrated. Here, we describe the clinical and mutational features of a cohort of Mexican patients with TEK-related PCG. Our results support the involvement of the TEK gene as an important cause of the disease in our ethnic group and expand the mutational spectrum causing PCG by reporting 10 novel disease-causing variants., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in CYP1B1 , LTBP2 , and TEK and their interactions with MYOC , FOXC1 , and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes ( MYOC ) and perform ciliary functions ( TEK ), we explored the involvement of a core centrosomal protein, CEP164 , which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E , which synergistically interacts with CEP164 , and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis.

Purpose: To assess the effectiveness of switching from the concomitant use of brinzolamide 1% (BZM) and brimonidine 0.1% (BMD) to a BZM/BMD fixed-dose combination (BBFC) for the reduction of corneal epithelial damage., Study Design: Retrospective cohort study., Methods: This study involved 52 eyes of 52 glaucoma patients (26 women, 26 men; mean age: 67.0 ± 14.0 years) followed for more than 3 months after being switched from concomitant BZM and BMD to BBFC. Superficial punctate keratitis (SPK) was assessed by fluorescein staining according to the National Eye Institute classification, with the cornea divided into 5 areas: center, superior, nasal, temporal, and inferior. SPK density was graded as 0 (no SPK), 1 (separate SPK), 2 (moderately dense SPK), and 3 (high SPK with overlapping lesions). SPK scores and intraocular pressure (IOP) at pre switching to BBFC (pre-BBFC) and at 3-months post switching to BBFC (post-BBFC) were then compared using the Wilcoxon signed-rank test., Results: At pre-BBFC and post-BBFC, respectively, mean IOP was 12.4 ± 2.5 and 12.4 ± 2.7 mmHg, thus illustrating no significant difference in IOP between pre and post switch (p = 0.924), and the mean SPK score for center, superior, nasal, temporal, and inferior was 0.06 ± 0.24, 0.04 ± 0.19, 0.52 ± 0.67, 0.15 ± 0.36, and 0.92 ± 0.74, and 0.04 ± 0.19, 0.02 ± 0.14, 0.37 ± 0.56, 0.04 ± 0.19, and 0.75 ± 0.62, thus clearly showing a significant reduction in SPK scores for the nasal, temporal, and inferior areas at post-BBFC compared to those at pre-BBFC (p < 0.05)., Conclusion: Our findings reveal that compared with the concomitant use of BZM and BMD, BBFC is effective in reducing corneal epithelial damage., (© 2024. Japanese Ophthalmological Society.)

Purpose: To evaluate the safety and efficacy of the PAUL Glaucoma Implant (PGI) for managing refractory primary congenital glaucoma (PCG) over a one-year period., Study Design: Retrospective., Methods: A study was conducted using the medical records of thirty eyes of 17 patients who underwent PGI surgery for the treatment of refractory PCG. Primary outcome measures included failure criteria such as intraocular pressure (IOP) > 21 mm Hg, < 20% IOP reduction, necessity for further glaucoma intervention, implant removal, or loss of vision. Secondary outcomes focused on mean IOP, average number of glaucoma medications, best corrected visual acuity (logMAR), and incidence of complications., Results: The mean preoperative IOP of 38.8 ± 9.2 mmHg significantly decreased to 16.1 ± 3.3 mmHg at 12 months postoperatively (p < 0.001). The average number of glaucoma medications reduced from 3.6 ± 0.5 preoperatively to 0.9 ± 1.2 at 12 months post-op. Visual acuity remained stable in 24 eyes, decreased in 4, and increased in 2. Early postoperative complications occurred in 13.3% of patients, but no late complications were reported. The cumulative success rate was 86.6%., Conclusion: The PGI appears to be a safe and effective option for managing refractory primary congenital glaucoma, demonstrating significant IOP reduction and decreased dependence on glaucoma medications over a one-year period, with a high success rate and manageable complication profile., (© 2024. The Author(s).)

Adams-Oliver syndrome (AOS) is a rare inherited disorder characterized by aplasia cutis congenita, cutis marmorata telangiectatica congenita, and terminal limb defects. Ocular associations have been rarely reported. We report a 6-month-old boy with AOS associated with refractory glaucoma, megalocornea, and anterior polar cataract. To our knowledge, this is the first case of glaucoma to be reported in association with AOS., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the incidence of rise in intraocular pressure (IOP) in fellow eyes of patients with unilateral primary congenital glaucoma (PCG) and to identify risk factors for IOP increase over long-term follow-up., Methods: The medical records of unilateral PCG patients who had completed at least 5 years of follow-up were reviewed retrospectively. The incidence of developing ocular hypertension / glaucoma in fellow eyes was analyzed. Fellow eye progressors were those which showed an increase in optic nerve cupping by at least 0.2 since the first presentation or had IOP of >21 mm Hg on two occasions. The risk factors for progression that were analyzed included IOP, visual acuity, axial length, central corneal thickness (CCT), corneal diameters (CD), presence or absence of angle dysgenesis on high-resolution anterior segment optical coherence tomography (AS-OCT), and morphology of aqueous outflow pathways., Results: After a median follow-up of 8.2 years (range, 5-25.5) progression to bilateral disease was found in 17 of 54 patients (32%), of whom 8 (15%) developed ocular hypertension and 9 (17%) developed glaucoma in the fellow eye. Among the unaffected fellow eyes, those with a larger CD (>12 mm), measured after at least 5 years' follow-up, were ten times more likely to progress (P = 0.01; OR = 9.5 [95% CI, 1.7-54.3]). The presence of a patent supraciliary channel was significantly more frequently associated in fellow eyes compared with affected eyes on AS-OCT (OR = 1.4 [95% CI, 0.46-4.68])., Conclusions: One-third of unaffected fellow eyes of unilateral PCG eventually progress over time, most often after 5 years. Larger CD at follow-up in the fellow eye is strongly predictive for progression., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the inheritance pattern and clinical variability of primary congenital glaucoma (PCG) in a family with two affected siblings., Materials and Methods: Two sisters diagnosed at birth with bilateral PCG, whose father had bilateral PCG and mother had bilateral microphthalmus, were subjected to a familial genetic study and ophthalmologic follow-up including intraocular pressure (IOP) measurement, and collection of biometric and cup-to-disc ratio data., Results: The inheritance pattern was autosomal recessive in compound heterozygosis. The sisters were found to be carriers of three pathogenic allele variants of the CYP1B1 gene: c.317C>A (p.Ala106Asp) and c.1345delG (p.Asp449MetfsTer8) in one patient (10 years) and c.1345delG (p.Asp449MetfsTer8) and c.202&#95;209delCAGGCGGC (p.Gln68Serfs153Ter) in her older sister (12 years). Surgical histories included: three goniotomies and two Ahmed valves in each eye, and two trabeculectomies and a pupilloplasty in the right eye in the 10-year old; and one goniotomy, trabeculectomy and three Ahmed valves in each eye in the older sister. Currently, both sisters have a controlled intraocular pressure of 18-20 mmHg in both eyes. The father is blind in both eyes and carries two variants c.317C>A (p.Ala106Asp) and c.202&#95;209delCAGGCGGC (p.Gln68Serfs153Ter) . The mother with a single variant c.1345delG (p.Asp440MetfsTer8) has a prosthetic right eye and microphthalmus left eye., Conclusions: The sisters were found to show two different allelic CYP1B1 variants (compound heterozygosis) with different repercussions on the clinical severity of PCG. These findings highlight the importance of genetic screening of affected families.

Purpose: To investigate the long-term outcomes of congenital cataract surgery performed within the first 6 months of life., Setting: 11 ophthalmic surgical sites in Japan., Design: Retrospective chart review., Methods: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia., Results: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this time frame. The incidence of secondary glaucoma was similar between groups while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes., Conclusions: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of IOL with sophisticated surgical techniques shows promise even in congenital cataract surgery., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants., Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI., Results: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2)., Conclusion: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG., (© 2024 Wiley Periodicals LLC.)

Objective: The aim of this study was to report on the long-term (>5 years) results of surgery for glaucoma after congenital cataract surgery., Design: Retrospective., Methods: A chart review was conducted of all children operated on for glaucoma after congenital cataract surgery in the Pediatric Ophthalmology Service of the Ophthalmology Department of Alexandria main University Hospital in Alexandria, Egypt, between 2005 and 2014 who completed 5 years of follow-up. Demographic, clinical, and operative data were retrieved from the medical records. Success was defined by stability and (or) reversal of optic nerve cupping in relation to presentation and, if this information was not available, by an intraocular pressure (IOP) less than the presenting IOP and less than 16 mm Hg with (true) or without (qualified) IOP-lowering therapy., Results: The records of 48 children were reviewed. Thirty-two eyes of 24 children had completed at least 5 years of follow-up and were included in the study. The mean age (±SD) of the study children was 11.6 ± 11.3 months (range, 3.2-52.0 months) at presentation, and the mean (±SD) follow-up was 105.5 ± 31.4 months (range, 60-156 months). Of 47 glaucoma surgical procedures in total, combined angle and filtering surgery with antimetabolite was the most common procedure performed (n = 30;63.8%). Annual success percentages from the fifth year onward to the thirteenth year were 69.6%, 68.8%, 77.8%, 50.0%, 71.4%, 60.0%, 50.0%, 83.3%, and 50.0%, respectively., Conclusions: Surgery for glaucoma after congenital cataract surgery remains safe and successful for 13 years after surgery., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Congenital glaucoma is a disease that involves increased intraocular pressure and can result in irreversible visual deterioration. The study of epidemiology allows the delineation of the characteristics associated with patients and specific risk factors., Objective: The objective of this study was to examine epidemiological trends, place of residence, duration of gestation, sex, and race of the newborn diagnosed with congenital glaucoma in Brazil., Methods: Data from SINASC (National Live Birth System) were used to analyze the period from 2017 to 2021 in Brazil. Linear regression and analysis of variance tests were employed to assess significance. The statistical significance was determined by p<0.05., Results: A total of 47 cases of congenital glaucoma were identified in Brazil during the study period, with the highest incidence between the years of 2018 and 2021. The analysis of the distribution indicated that the states with the highest incidence were São Paulo, followed by Rio Grande do Sul and Pernambuco. Approximately 60% of cases occurred in male individuals, compared with 19 female cases. The ethnic analysis showed the highest incidence among whites and mixed. Regarding the length of pregnancy, statistical differences were observed between newborns of different periods of gestation. Infants born from pregnancies lasting between 28 and 31 weeks and 32 and 36 weeks were significant when analyzed with the group between 37 and 41 weeks., Conclusion: Studies on the mechanisms of congenital glaucoma seek to improve knowledge about the disease. Epidemiological evaluation is essential for identifying demographic and clinical patterns of the disease.

Keratoconus eyes develop corneal decompensation more often compared to eyes with primary congenital glaucoma (PCG) following Descemet's membrane (DM) tear. This study was conducted to compare the posterior corneal morphology in areas with DM breaks with regards to DM and pre-Descemet's layer (PDL) between the two. In this cross-sectional comparative study, anterior segment optical coherence tomography (AS-OCT) scans of the posterior cornea of advanced keratoconus eyes with hydrops ( n = 12), PCG eyes with Haab's striae ( n = 15), and healthy control eyes ( n = 14) were compared for DM-PDL morphology. These were further corroborated by the histopathology of corneal buttons from keratoconus ( n = 14) and PCG ( n = 13) cases obtained following penetrating keratoplasty and compared with controls (enucleated retinoblastoma globes, n = 6) on light microscopy and collagen IV immunostaining. AS-OCT showed a thicker median DM/PDL complex in PCG (80 µm) versus keratoconus eyes (36 µm, P = 0.01; Kruskal-Wallis test). The median height and length of detached DM-PDL were significantly more in keratoconus versus PCG (145 μm, 1766.1 ± 1320.6 μm vs. 26.5 μm, 453.3 ± 303.2 μm, respectively, P = 0.012; Kruskal-Wallis test). Type-1 DM/PDL detachment (seen as a characteristic taut chord) in keratoconus (90%) was the most common morphological pattern versus intracameral twin protuberance (92%) following DM breaks in PCG. Histopathology confirmed thicker DM in PCG (median: 63.4 μm) versus keratoconus eyes (median: 33.2 µm) or controls (27.1 μm) ( P = 0.001; Kruskal-Wallis test). Greater height/length of DM/PDL detachment compounded by poor healing response (lower DM/PDL thickness) probably causes more frequent corneal decompensation in keratoconus eyes when compared to PCG eyes following DM tears., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Primary congenital glaucoma is a rare disease that occurs in early birth and can lead to low vision. Evaluating affected children is challenging and there is a lack of studies regarding color vision in pediatric glaucoma patients. This cross-sectional study included 21 eyes of 13 children with primary congenital glaucoma who were assessed using the Farnsworth D-15 test to evaluate color vision discrimination and by spectral domain optical coherence tomography to measure retinal fiber layer thickness. Age, visual acuity, cup-to-disc ratio and spherical equivalent data were also collected. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were measured and compared based on color vision test performance. Four eyes (19%) failed the color vision test with diffuse dyschromatopsia patterns. Only age showed statistical significance in color vision test performance. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were similar between the color test outcomes dyschromatopsia and normal. While the color vision test could play a role in assessing children with primary congenital glaucoma, further studies are needed to correlate it with damage to retinal fiber layer thickness., (© 2024. The Author(s).)

Purpose: To evaluate the anterior segment structures using ultrasound biomicroscopy (UBM) in primary congenital glaucoma (PCG) and explore their correlation with disease severity and surgical outcomes., Methods: Clinical information of PCG patients who underwent UBM prior to their first glaucoma surgeries from September 2014 to March 2021 were reviewed. The study included 214 UBM images of 154 PCG eyes and 60 fellow unaffected eyes. Anterior segment characteristics were analyzed. UBM parameters, including the iris thickness (IT) at variant distances from the pupil edge and iris root, anterior chamber depth (ACD), and pupil diameter (PD), were compared between two groups and their relationship with clinical factors and surgical outcomes were analyzed in PCG eyes., Results: PCG eyes had unclear scleral spur, thin iris, wide anterior chamber angle, deep anterior chamber, rarefied ciliary body, elongated ciliary processes, and abnormal anterior iris insertion. ITs were thinner, ACD was deeper, and PD was larger in PCG eyes than fellow unaffected eyes (all P < 0.001). In PCG eyes, thinner ITs correlated with bilateral involvement and earlier age at presentation, and larger PD correlated with earlier age at presentation (P = 0.030) and higher intraocular pressure (P < 0.001). Thinner IT2 (P = 0.046) and larger PD (P = 0.049) were identified as risk factors for surgical failure., Conclusion: UBM is a powerful technique to exam anterior segment structures in PCG. The anatomical features are associated with disease severity and surgical outcomes, providing essential clinical insights., (© 2023. The Author(s).)

Background: There have been studies on the use of cognitive behavioral nursing intervention (CBNI) but the main subjects were patients with secondary glaucoma and there are fewer studies on the care of congenital glaucoma., Objective: To explore the clinical value of cognitive behavioral nursing model in patients with congenital glaucoma., Methods: One hundred and fifty-three postoperative patients with congenital glaucoma treated in our hospital between January 2021 and December 2022 were prospectively selected for the study and randomly divided into a control group (n= 77) and an observation group (n= 76). The control group was given routine nursing, and the observation group was given cognitive behavioral nursing mode on the basis of the control group. Anxiety self-assessment scale (SAS), depression self-assessment scale (SDS), Connor-Davidson toughness scale, and treatment adherence evaluation scale were used to evaluate the psychological state, mental toughness, treatment adherence, treatment effect and nursing care satisfaction in the two groups before and after 2 weeks of intervention. The efficacy of the treatment was also assessed by determining the visual acuity (VA), intraocular pressure (IOP), and mean defective (MD) value of the visual field of the two groups of patients., Results: After nursing, the SDS score (46.33 ± 6.16 versus 53.21 ± 5.94) and SAS score (44.41 ± 5.6 versus 52.82 ± 6.31) in the observation group were lower than those in the control group (P< 0.05). The scores of optimism (11.55 ± 1.90 versus 8.20 ± 1.95), self-improvement (22.05 ± 3.60 versus 17.60 ± 4.30), tenacity (37.45 ± 3.10 versus 28.90 ± 4.55) and total score (71.35 ± 8.00 versus 56.85 ± 8.50) in the observation group were higher than those in the control group (P< 0.05). After care, the VA of the observation group (0.95 ± 0.22) was greater than that of the control group (0.84 ± 0.16), and the IOP (14.25 ± 0.58 versus 15.89 ± 0.67) and the MD (5.42 ± 0.46 versus 6.68 ± 0.49) of the observation group were less than that of the control group. The difference between the two groups was statistically significant (P< 0.05). The compliance (96.05% versus 85.71%) and nursing satisfaction (96.10% versus 85.71%) of the observation group were higher than those of the control group (P< 0.05)., Conclusion: Cognitive-behavioural nursing care for glaucoma patients can improve patients' mental toughness, improve visual acuity, reduce intraocular pressure and mean visual field defect values, and have a positive effect on enhancing patients' treatment adherence and nursing satisfaction.

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., (Copyright © 2023 Molecular Vision.)

Purpose: To evaluate the outcomes of microcatheter-assisted trabeculotomy (MAT) in childhood glaucoma (primary congenital glaucoma [PCG], juvenile open-angle glaucoma [JOAG], and secondary childhood glaucoma [SCG]) after failed glaucoma surgery., Design: Retrospective interventional case series., Methods: Patients with childhood glaucoma who underwent MAT after failed glaucoma surgery with at least 12 months of follow-up were evaluated. Pre- and postoperative intraocular pressure (IOP) and the number of glaucoma medications were recorded and compared. Success was defined as an IOP ≤21 mm Hg with or without glaucoma medication. Analysis of variance was used to compare the glaucoma subgroups., Results: Forty-five eyes (42 patients) with a median follow-up period of 19 months were included. The median age at the time of MAT was 10 (range, 0.8-33) years. The mean number of previous surgeries was 1.3 ± 0.5. The IOP had significantly reduced from baseline in all PCG, JOAG, and SCG patients (27.9 ± 4.5 vs 16.3 ± 8.0 mm Hg, P = .001; and 30.8 ± 9.4 vs 13.5 ± 3.0 mm Hg, P < .001; and 31.5 ± 7.1 vs 16.5 ± 5.3 mm Hg, P = .001, respectively). Fewer glaucoma medications were needed after MAT in all 3 groups (each P < .001). At the last visit, the total success rates in PCG, JOAG, and SCG were 93.8%, 100%, and 88.9%, respectively. No severe complications were observed., Conclusion: MAT can effectively manage PCG, JOAG, and SCG after failed surgeries, providing successful outcomes and no serious complications. Following failed glaucoma surgeries, MAT may offer these patients with childhood glaucoma an excellent opportunity to achieve IOP control., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mutations in the thrombospondin 1 ( THBS1 ) gene have been previously reported in primary congenital glaucoma (PCG) pedigrees that exhibit autosomal dominant inheritance with low penetrance. We sought to determine the role of THBS1 mutations in a cohort of 20 patients with PCG and 362 normal controls from Iowa using a combination of Sanger sequencing and whole exome sequencing. We detected 16 different THBS1 variants, including 4 rare, nonsynonymous variants (p.Thr611Met, p.Asn708Lys, p.Gln1089His, and p.Glu1166Lys). However, none of these variants were judged to be disease-causing mutations based on: 1) prevalence in cases and controls from Iowa, 2) prevalence in the public database gnomAD, 3) mutation analysis algorithms, and 4) THBS1 DNA sequence conservation. These results indicate THBS1 mutations are not a common cause of PCG in patients from Iowa and may be a rare cause of PCG overall., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely associated with congenital glaucoma. To obtain a better surgical view, palatoplasty requires neck extension during surgery. The intraocular pressure (IOP) of patients with Patau syndrome can increase owing to the neck extension position while undergoing palatoplasty, particularly in those with congenital glaucoma. Here, we describe a case with increased IOP measured using a rebound tonometer during palatoplasty in a pediatric patient with Patau syndrome and congenital glaucoma. This case shows that it may be important to reduce the degree of neck extension and shorten the operation time to minimize any increase in the IOP during palatoplasty in pediatric patients with Patau syndrome accompanied by congenital glaucoma.

Prcis: Angle procedures are safe and relatively effective for neonatal onset PCG. Watchful delay in intervention to close to the second month of life is helpful in ensuring diagnosis and making surgery more successful and easier., Purpose: The purpose of this study was to compare the surgical outcomes of visco-circumferential-suture-trabeculotomy (VCST) to rigid-probe double-entry viscotrabeculotomy (DEVT) and rigid-probe single-entry viscotrabeculotomy (SEVT) in infants with neonatal-onset primary congenital glaucoma (PCG)., Design: This was a retrospective chart review., Patients and Methods: Retrospective chart review of 64 eyes of 64 infants with neonatal-onset PCG referred to Mansoura Ophthalmic Center in Mansoura, Egypt between February 2008 and November 2018. Study groups included VCST, DEVT, and SEVT, and follow-up covered 4 postoperative years. Complete (qualified) success was defined as intraocular pressure (IOP) ≤18 mm Hg and with 35% IOP reduction from baseline without (with) IOP-lowering medications or further surgical interventions, and without any sign of progression in corneal diameter, axial length, or optic disc cupping and without visual devastating complications., Results: The mean±SD age at presentation and at the surgery of the study children was 3.63±1.74 and 55.23±1.60 days, respectively. The mean±SD IOP and cup/disc ratio of all study eyes at presentation and at final follow-up were 34.91±0.82 mm Hg and 0.70±0.09 and 17.04±0.74 mm Hg and 0.63±0.08, respectively. Complete success was achieved in 54.5%, 43.5%, and 31.6% in the VCST, DEVT, and SEVT groups, respectively. A self-limited hyphema was the commonest complication in all groups., Conclusions: Angle procedures are safe and marginally effective for the surgical treatment of neonatal-onset PCG, bringing IOP under control for at least 4 years of follow-up. Circumferential trabeculotomy as a first-line treatment has more favorable outcomes than rigid-probe SEVT. Rigid-probe viscotrabeculotomy offers an alternative to the noncompleted circumferential procedure., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objectives: to establish the incidence, prevalence and long-term outcomes of primary congenital glaucoma (PCG) in Northern Ireland's general and Irish Traveller (IT) populations over a 59-year period., Subjects/methods: chart review of all PCG cases in Northern Ireland between 1962 and 2020. Incidence and prevalence were calculated with the aid of national population statistics. Long-term outcomes were analysed for eyes with at least 5 years follow up. Visual outcomes were stratified into groups: good-VA ≥ 6/12; moderate-VA 6/12 to 6/60, poor-VA < 6/60. Kaplan-Meier analysis was constructed to determine the probability of eyes retaining a good visual outcome over time. Outcomes of different surgeries were compared with regard to final vision, re-operations and complications., Results: 57 PCG cases were identified between 1962 and 2020. Overall incidence was 3.4 per 100,000 live births. PCG prevalence in general and IT populations in 2019 was 4.3 per 100,000 and 238 per 100,000, respectively. Sixty eyes had sufficient data for long-term outcome analysis with a mean of 20.5 years follow up, 58% of which had good final visual outcome. Fifty-seven percent of eyes required multiple surgeries. Visual outcomes between trabeculectomies and tubes were comparable; however, there were more serious complications and reoperations associated with tubes., Conclusions: Incidence of PCG in NI is similar to Great-Britain and Ireland; however, PCG appears to be particularly prevalent within IT community. Although a good visual outcome can be achieved in the majority of patients, a subset of cases remain challenging to manage despite surgical advances., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: In patients with primary congenital glaucoma (PCG), elevated intraocular pressure (IOP) causes abnormal eye growth. This study compared the outcomes of children with PCG who underwent ab externo trabeculotomy (TROC) at age ≤ 6 months (early TROC) and of those who underwent TROC at age > 6 months (delayed TROC)., Methods: Intraocular pressure, horizontal corneal diameter (HCD), central corneal thickness (CCT) and axial length (AL) were compared before TROC and at 1-, 3-, 6- and 12-month follow-up visits between the groups of children who underwent TROC until or after 6 months of age. The ALs of these groups were also compared with the ALs of healthy age-matched eyes examined under the same conditions., Results: Trabeculotomy was performed in 43 children: 18 (33 eyes) aged 6 months (group 1) and 25 (37 eyes) aged >6 months (group 2); the mean ages were 86.56 ± 53.64 and 504.48 ± 448.14 days, respectively. The mean pre- and 12-month postoperative IOP values were 15.97 ± 4.78/16.62 ± 4.85 and 9.77 ± 2.88/10.93 ± 4.83 mmHg, respectively. Delayed TROC was associated with abnormal AL in 31 (88.6%) out of 37 eyes, while after early TROC, only 13 (41.9%) out of 33 eyes had abnormal AL (chi-square, 8.00; p = 0.03). In multivariable analysis, each 1-mmHg increase in preoperative IOP was associated with a 0.25-mmHg increase at 12 months (p = 0.04). On average, the mean IOP of the delayed TROC group was higher than that of the early TROC group by 3.72 mmHg at postoperative month 12 (95% CI = 0.44-6.99; p = 0.02)., Conclusion: Compared with delayed TROC, early TROC is associated with reduced IOP and substantially reduced incidence of abnormal AL at postoperative month 12., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To assess long-time results of primary surgical treatment in children with glaucoma after congenital cataract surgery., Methods: A retrospective study of 37 eyes from 35 children with glaucoma after congenital cataract surgery, who underwent surgery between 2011 and 2021 at the Childhood Glaucoma Center, University Medical Center Mainz, Germany. Only children, who received a primary glaucoma surgery in our clinic within the given time (n = 25) and had at least one-year follow-up (n = 21), were included in the further analysis. The mean follow-up time was 40.4±35.1 months. The primary outcome was the mean reduction in IOP (in mmHg) from baseline to follow-up visits after the surgery, measured with Perkins tonometry., Results: 8 patients (38%) were treated with probe trabeculotomy (probe TO), 6 (29%) with 360° catheter-assisted trabeculotomy (360° TO) and 7 (33%) with cyclodestructive procedures. IOP was significantly reduced after probe TO and 360° TO after 2 years, from 26.9 mmHg to 17.4 mmHg (p<0.01) and 25.2 mmHg to 14.1 mmHg (p<0.02), respectively. There was no significant IOP reduction after cyclodestructive procedures after 2 years. Both, probe TO and 360° TO led descriptively to eye drops reduction after 2 years, from 2.0 to 0.7 and 3.2 to 1.1. The reduction was not significant., Conclusions: In glaucoma after congenital cataract surgery, both trabeculotomy techniques, lead to good reduction of IOP after 2 years. There is a need for a prospective study with comparison to the use of glaucoma drainage implants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Strzalkowska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To compare the corneal endothelial cell morphology using specular microscopy imaging between primary congenital glaucoma (PCG) and age-matched healthy controls, and to determine if the endothelial cell parameters vary among different subtypes of PCG., Design: Retrospective case-control study., Participants: One hundred forty-five eyes of 145 patients operated for PCG between 1991 and 2018 and who returned for a follow-up visit between June 2021 and May 2022. Three hundred and nineteen age-matched healthy individuals constituted the control group., Methods: Corneal endothelial cell layer analysis was performed with EM-3000 (Tomey) noncontact specular microscope. Patients were categorized according to the clinical subtypes of PCG (neonatal, infantile, and late-onset) based on the Childhood Glaucoma Research Network classification., Main Outcome Measures: Specular microscopic parameters, including endothelial cell density (ECD), average cell size, coefficient of variation (CV), and maximum and minimum cell size, were compared with that of the control group., Results: Mean ± standard deviation (SD) age of patients at endothelial imaging was 13.5 ± 6.54 years, and there was a male preponderance (n = 88, 61%). The majority of the patients had infantile-onset PCG (n = 67, 46%). Eyes with PCG demonstrated a significantly lower ECD compared with controls (2158.7 ± 636.5 vs. 2840.9 ± 232.5 cells/mm 2 ; P < 0.0001). Other endothelial cell parameters were also significantly worse in PCG compared with controls. The mean ± SD ECD was 2344.3 ± 544.3, 2131.9 ± 626.4, and 2054.2 ± 714.0 cells/mm 2 in neonatal onset, infantile, and late-onset PCG groups, respectively. Although the ECD was lowest in the late-onset PCG group, there was no significant difference in the ECD between the 3 subgroups. Except for CV, all the endothelial cell parameters were significantly worse in eyes with Haab striae than in eyes without., Conclusions: Patients with PCG have significantly lower ECD compared with healthy controls. Furthermore, other endothelial cell parameters were also significantly worse in the PCG group. These changes in the corneal endothelium in patients with PCG should be considered in long-term medical and surgical management., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Mutations were previously identified in the CYP1B1 gene in six out of 18 Lebanese families (33%) with primary congenital glaucoma (PCG). The purpose of this study is to determine the frequency and type of pathogenic mutations in other genes and compare to other populations using whole-exome sequencing and perform genotype-phenotype correlations., Methods: Twelve PCG patients previously negative for CYP1B1/MYOC mutations were subjected to whole-exome sequencing. Targeted screening for glaucoma-associated genes was performed. Candidate variants were verified by Sanger sequencing and evaluated in family members for segregation analysis and in 100 normal controls. Clinical correlations were established as to severity of disease presentation, course, and visual outcomes., Results: Six mutations in known PCG-causing genes were identified in five patients: homozygous mutations in CYP1B1 (p.R368G), LTBP2 (p.E1013G), and TEK (p.T693I), and heterozygous mutations in FOXC1 (p.Q92*), TEK (c.3201-1 G>A), ANGPT1 (p.K186N), and CYP1B1 (p.R368G). Two patients, negative for CYP1B1 in the previous study, were revealed positive in the current study, due to different sets of primers and PCR conditions. Potentially damaging variants were noted in several candidate genes. Except for FOXC1 mutations, all genetic variants described here are novel. Intra-ocular pressure and final optic nerve cup-to-disc ratio were highest in the patient with three mutations in LTBP2/TEK/ANGPT1 genes., Conclusion: This study provides new data on the spectrum of mutations of PCG in Lebanon. This highlights the genetic heterogeneity of the Lebanese population, noted for high rates of consanguinity in 50% in this cohort. This study emphasizes the importance of whole-exome sequencing in elucidating new candidate genes for PCG in the Lebanese.

Background: Primary congenital glaucoma (PCG) is characterized by developmental abnormalities of the anterior chamber angle. Although several genes have been associated with PCG, pathogenic mutations could only be detected in about 20% of Chinese patients. GLC3B (1p36.2-36.1) and GLC3C (14q24.3) loci were previously identified in PCG pedigrees via linkage analysis. However, no causative genes were reported in these loci. This study was designed to search for novel PCG-related genes in these genetic regions., Materials and Methods: DNA samples from 100 PCG patients and 200 normal controls were pooled and sequenced using a customized panel of 133 positional candidate genes located around GLC3B and GLC3C loci (±1Mb). PCG-related genes were prioritized by the distribution of variants between patients and controls. Confirmation of selected variants and co-segregation analysis were performed using Sanger sequencing., Results: Patient and control group contained 116 and 147 rare variants respectively after screening. Three genes (ZC2HC1C, VPS13D, and PGF) were prioritized according to the distribution of variants between the two groups. Rare variants of PGF were only identified in PCG patients., Conclusions: To the best of our knowledge, this is the first study aiming at exploring novel PCG-related genes at GLC3B and GLC3C loci. Our preliminary results suggest that there are potential associations between ZC2HC1C, VPS13D, PGF, and PCG. However, larger cohort studies and functional assays are required to provide further evidence for the proposed genotype-phenotype association.

Pediatric glaucoma is a constellation of challenging ophthalmic conditions that, left untreated, can result in irreversible vision loss. The mainstay of treatment for primary congenital glaucoma and select secondary glaucoma subtypes is angle surgery, either trabeculotomy or goniotomy. More recently, MIGS devices have been utilized to enhance the efficacy of these procedures. Despite the high success rates of these primary surgical options, refractory cases are challenging to manage. There is no consensus on the next step of treatment following primary angle surgery. Glaucoma drainage devices and trabeculectomies have been the traditional options, with laser treatment reserved for more severe cases. The benefits and disadvantages of each of these options are discussed.

Background: Timely and proper intraocular pressure (IOP) management is vital to the prevention of visual impairment in children with primary congenital glaucoma (PCG). Although various surgical interventions have been proposed, no well-founded evidence exists on their comparative efficacies. We aimed to compare the efficacies of surgical interventions for PCG., Methods: We searched relevant sources up to 4 April 2022. Randomized controlled trials (RCTs) entailing surgical interventions for PCG in children were identified. A network meta-analysis (NMA) was performed, comparing 13 surgical interventions: Conventional partial trabeculotomy ([CPT] control), 240-degree trabeculotomy, Illuminated microcatheter-assisted circumferential trabeculotomy (IMCT), Viscocanalostomy, Visco-circumferential-suture-trabeculotomy, Goniotomy, Laser goniotomy, Kahook dual blade ab-interno trabeculectomy, Trabeculectomy with mitomycin C, Trabeculectomy with modified scleral bed, Deep sclerectomy, Combined trabeculectomy-trabeculotomy with mitomycin C, and Baerveldt implant. The main outcomes were mean IOP reduction and surgical success rate at postoperative 6 months. The mean differences (MDs) or odds ratios (ORs) were analyzed by a random-effects model, and the efficacies were ranked by P -score. We appraised the RCTs using the Cochrane risk-of-bias (ROB) tool (PROSPERO: CRD42022313954)., Results: Sixteen RCTs were eligible for NMA, including 710 eyes of 485 participants and 13 surgical interventions, which formed a network of 14 nodes comprising both single interventions and intervention combinations. IMCT was superior to CPT in both IOP reduction [MD (95% CI): -3.10 (-5.50 to -0.69)] and surgical success rate [OR (95% CI): 4.38 (1.61-11.96)]. The MD and OR comparing the other surgical interventions and intervention combinations with CPT were not statistically significant. The P -scores ranked IMCT as the most efficacious surgical intervention in terms of success rate ( P -score =0.777). Overall, the trials had a low-to-moderate ROB., Conclusion: This NMA indicated that IMCT is more effective than CPT and might be the most efficacious of the 13 surgical interventions for management of PCG., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Glaucoma in infancy and childhood is a rare disease. An immediate diagnosis and treatment are absolutely necessary to prevent blindness of affected children. Childhood glaucoma is characterized by a heterogeneous phenotype: besides primary congenital glaucoma, secondary types often exist and the individualized treatment requires an experienced interdisciplinary team. The pathogenesis is not always discernible and genetic alterations sometimes cause the disease. A surgical procedure is usually necessary to lower the intraocular pressure. Refractive and orthoptic care are equally important to avoid amblyopia. This article gives an overview of childhood glaucoma and outlines the most important diagnostic and therapeutic aspects., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: To identify pathogenic variants in a cohort of 23 black South African children with sporadic primary congenital glaucoma (PCG) using an exome-based approach., Methods: Children with PCG were recruited from two Paediatric Ophthalmology Clinics in Johannesburg, South Africa. Whole exome sequencing was performed on genomic DNA. Of the 23 children, 19 were male and 19 had bilateral PCG. A variant prioritization strategy was employed whereby variants in known PCG genes (CYP1B1, LTBP2 and TEK) were evaluated first, followed by the identification of putative disease-causing variants in other genes related to eye diseases and phenotypes., Results: Validated pathogenic variants in the CYP1B1 gene (c.1169 G>A; p.Arg390His) and TEK gene (c.922 G>A; p.Gly308Arg) were identified in one child each. No LTBP2 mutations were identified in this cohort. In silico predictions identified potentially damaging rare variants in genes previously associated with eye development phenotypes or glaucoma in a further 12 children., Conclusions: This study demonstrates the value of whole exome sequencing in identifying disease-causing variants in African children with PCG. It is the first report of a TEK disease-causing variant in an African PCG patient. Potential causative variants detected in PCG candidate genes warrant further investigation., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: To compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG)., Methods: This prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups., Results: Babies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls., Conclusions: Patients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Autosomal recessive congenital hereditary endothelial dystrophy (CHED2) may be misdiagnosed as primary congenital glaucoma (PCG) due to similar clinical phenotypes during early infancy. In this study, we identified a family with CHED2, which was previously misdiagnosed as having PCG, and followed up for 9 years. Linkage analysis was first completed in eight PCG-affected families, followed by whole-exome sequencing (WES) in family PKGM3. The following in silico tools were used to predict the pathogenic effects of identified variants: I-Mutant 2.0, SIFT, Polyphen-2, PROVEAN, mutation taster and PhD-SNP. After detecting an SLC4A11 variant in one family, detailed ophthalmic examinations were performed again to confirm the diagnosis. Six out of eight families had CYP1B1 gene variants responsible for PCG. However, in family PKGM3, no variants in the known PCG genes were identified. WES identified a homozygous missense variant c.2024A>C, p.(Glu675Ala) in SLC4A11 . Based on the WES findings, the affected individuals underwent detailed ophthalmic examinations and were re-diagnosed with CHED2 leading to secondary glaucoma. Our results expand the genetic spectrum of CHED2. This is the first report from Pakistan of a Glu675Ala variant with CHED2 leading to secondary glaucoma. The p.Glu675Ala variant is likely a founder mutation in the Pakistani population. Our findings suggest that genome-wide neonatal screening is worthwhile to avoid the misdiagnosis of phenotypically similar diseases such as CHED2 and PCG.

Prcis: This study demonstrates that a baseline corneal diameter >12.25, initial age <4 months at diagnosis, higher baseline IOP than 24 mm Hg, bilaterality, or inability to perform circumferential trabeculotomy, increases the risk of surgical failure of trabeculotomy in patients with primary congenital glaucoma (PCG)., Purpose: The aim of this study was to identify clinical predictive factors for surgical failure and to evaluate potential prognostic factors affecting surgical success in patients with PCG who underwent trabeculotomy., Patients and Methods: The medical charts of 123 eyes of 75 patients who underwent trabeculotomy surgery for the treatment of PCG were retrospectively reviewed. At baseline and each visit, intraocular pressure (IOP), corneal diameter, cup to disc ratio, axial length, number of medications, and need for further glaucoma surgery were noted. Surgical success was defined as an IOP ≤18 mm Hg and 20% IOP reduction from baseline with (qualified) or without (complete) medication and without any further IOP-lowering surgery., Results: The mean age at surgery was 4.2±6.6 months and the mean follow-up time was 60.0±37.6 months. The receiver operating characteristic curve showed 4 following best cutoff values to predict surgical failure: the first for age at surgery was 4.5 months; the second baseline IOP was 24.0 mm Hg; the third for baseline cup to disc ratio was 0.4; and the fourth for baseline corneal diameter was 12.25 mm. Multivariate logistic regression analysis revealed that baseline IOP more than 24 mm Hg increased the risk of surgical failure by 2 times, baseline mean corneal diameter >12.25 mm did by 4.2 times, younger age than 4 months did by 2.5 times, bilaterality did by 1.5 times., Conclusions: A higher baseline IOP, younger age, larger corneal diameter, and bilaterality were identified as risk factors for trabeculotomy failure in congenital glaucoma. The presence of one or more of these should be considered in the decision-making process when considering surgical options to manage glaucoma in these patients., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To describe the presentation and treatment outcomes of a cohort of children with primary aphakia (PA)., Methods: Clinical photographs and ultrasound biomicroscopy (UBM) images of children presenting with sclerocornea and undetermined anterior segment dysgenesis between July 2017 and December 2020 were reviewed retrospectively. Children who had no crystalline lens visible on UBM were included., Results: A total of 124 UBM images were captured for 124 children with cloudy corneas. Twelve children were identified with congenital primary aphakia: 5 had bilateral buphthalmos, 2 had buphthalmos in one eye and microphthalmos in the other, and 5 had bilateral sclerocornea-microphthalmia complex. All patients had a peculiar silvery-blue corneal appearance, with fine vascularization on the corneal surface. The overall corneal thickness was 409.1 ± 8.7 μm. The intraocular pressure (IOP) in eyes with glaucoma was 24.5 ± 7.3 mm Hg; in microphthalmic eyes, 11.4 ± 3.4 mm Hg (P <0.001). The raised IOP was treated with limited trans-scleral cyclophotocoagulation under transillumination and topical antiglaucoma medications. Children with glaucoma gained ambulatory vision with spectacles., Conclusions: Congenital primary aphakia has a characteristic clinical appearance and may present as buphthalmos or microphthalmos, depending on the extent of dysgenesis. Incisional surgery may result in phthisis because of ciliary body dysgenesis and unpredictable aqueous production., (Copyright © 2022 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Purpose: To assess the safety and efficacy of combining nasal goniotomy with temporal trabeculotomy in the management of primary congenital glaucoma., Design: Case series., Methods: Fifteen eyes of eleven children (3-12 months old at presentation) were enrolled in this study after the establishment of PCG diagnosis based on the criteria placed by the World Glaucoma Association. Combined nasal goniotomy and temporal trabeculotomy were done on each eye in an attempt to perform almost 360 degrees circumferential angle surgery without disturbing the superior 180 degrees of conjunctiva to preserve it for future filtering glaucoma surgeries., Results: By first month, average IOP was 10.5 ± 4.3 mmHg with a 65.3% reduction from average pre-operative IOP. Almost the same percentage of reduction was maintained at 3 rd ,6 th and 12 th months postoperative visits with average IOP of 11.9 ± 4.65, 11.8 ± 2.77 and 13 ± 2.82 mmHg (60.7%, 61.1% and 57.2% reduction from pre-operative average). According to success rates, complete success has been achieved in all eyes but one (93.3%), with minor complications in 4 out of 15 eyes (26.6%) that did not affect IOP outcome. Nine out of fifteen eyes completed 18 months post-operative follow-up visits with a successfully, maintained target average IOP of 13.3 ± 3.0 mmHg (57.2% reduction). All of the mean IOP readings during post-operative follow-up period were significantly lower when compared to pre-operative IOP ( p  < 0.0001). Only one eye had persistently elevated IOP of 26 mmHg at 1 st and 3 rd months post-operatively that necessitated a subsequent subscleral trabeculectomy which succeeded in controlling the pressure bringing it down to 15 mmHg on topical medications., Conclusion: Nasal goniotomy - temporal trabeculotomy (NGTT) is the combination of two well established surgeries that exploits the advantages of circumferential angle surgery while sparing the superior conjunctiva completely for future surgeries if needed. This new procedure was safe and effective in lowering IOP by an average of 60% from pre-operative IOP with a sustained effect till 18 months post-operatively. We believe that this surgery might be added to the armentarium of the surgical management of infantile glaucomas with other circumferential angle surgeries.

To delineate the genetic bases of primary congenital glaucoma (PCG), we ascertained a large cohort consisting of 48 consanguineous families. Of these, we previously reported 26 families with mutations in CYP1B1 and six families with LTBP2, whereas the genetic bases responsible for PCG in 16 families remained elusive. We employed next-generation whole exome sequencing to delineate the genetic basis of PCG in four of these 16 familial cases. Exclusion of linkage to reported PCG loci was established followed by next-generation whole exome sequencing, which was performed on 10 affected individuals manifesting cardinal systems of PCG belonging to four unresolved families along with four control samples consisting of genomic DNAs of individuals harboring mutations in CYP1B1 and LTBP2. The analyses of sequencing datasets failed to identify potential causal alleles in the 10 exomes whereas c.1169G > A (p. Arg390His) in CYP1B1 and c.3427delC (p.Gln1143Argfs*35) in LTBP2 were identified in the control samples. Taken together, next-generation whole exome sequencing failed to delineate the genetic basis of PCG in familial cases excluded from mutations in CYP1B1 and LTBP2. These data strengthen the notion that compound heterozygous coding variants or non-coding variants might contribute to PCG., (© 2022. The Author(s).)

Introduction: PITX3 has been reported to be associated with congenital cataracts, anterior segment mesenchymal dysgenesis, Peters' anomaly, and microphthalmia. In this case, an infant with unilateral buphthalmos, corneal staphyloma and corneal fistula carrying a variant in PITX3 was reported., Case Description: We describe a 4-month-old female infant who was referred to our Eye Clinic because of gradual enlargement of the eyeball in the right eye and whitish opacity in both eyes. Buphthalmos with long axial length (22.04 mm), macrocornea with diffuse corneal oedema and opacity (14.50 mm*14.50 mm) and high intraocular pressure (23.78 mmHg) were detected in the right eye. Microphthalmia with short axial length (16.23 mm), microcornea with diffuse corneal oedema and opacity (7.50 mm*6.50 mm) were detected in the left eye. A 360° trabeculotomy was performed for the right eye. However, corneal staphyloma and corneal fistula in the right eye were detected 6 months after the surgery. A variant in exon 4 of PITX3 (c.640&#95;656dup (p. Gly220Profs*95)) was identified in the proband but was not detected in her healthy parents., Conclusion: A novel phenotype characterized by unilateral buphthalmos, corneal staphyloma and corneal fistula in an infant were reported to be associated with PITX3 in our study. Our study expands the scope of the clinical heterogeneity of PITX3 variants. It also improves our understanding and increases the attention given to patients with PITX3 variants., (© 2022. The Author(s).)

Introduction: Primary congenital glaucoma (PCG), a type of childhood glaucoma, is primarily treated surgically to lower intraocular pressure (IOP). Failure to intervene could result in partial, or even total, blindness. Various surgical intervention types have been proposed for PCG, though the evidence on comparative effectiveness remains limited. The current protocol is an ongoing network meta-analysis enabling comparative investigation of surgical interventions for which randomised controlled trials (RCTs) are available. Our aim is to systematically compare the efficacy of various types of surgical intervention for patients with PCG., Methods and Analysis: Studies of interest will assess the effects of those surgical interventions on surgery-naïve children (age <18 years) suffering PCG. RCTs regardless of language or publication date will be searched from three electronic databases (Cochrane Central Register of Controlled Trials, Embase and MEDLINE) from 4 April 2022. Two reviewers will screen, first, titles and abstracts, followed by full-text papers, for useful data that they will extract. The primary outcome measure will be the IOP-lowering effect of a given surgical intervention. The two reviewers also will assess the internal validity of studies using the relevant and domain-based risk-of-bias assessment tool. Overall evidence quality will be assessed according to the Confidence in Network Meta-Analysis approach and will be presented in summarised form with network diagrams. For enhanced visualisation of the included interventions' effects, forest plots will be constructed. Pairwise effect sizes also will be calculated based on the evidence that is available in the network., Ethics and Dissemination: This work will synthesise evidence obtained from published studies, and as such, no ethics review or approval will be required. A paper presenting the findings will be submitted to a peer-reviewed scientific journal for publication., Prospero Registration Number: CRD42022313954., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Primary congenital glaucoma (PCG) is a heterogeneous rare recessively inherited disorder prevalent in regions with high consanguinity. Disease phenotype is associated with increased intra ocular pressure and is a major cause of childhood blindness. Sequence variations in Cytochrome P450 1B1 (CYP1B1) gene are a major cause of PCG. Current study was conducted to screen CYP1B1 gene in highly consanguineous PCG affected families from Pakistani population consistent with the autosomal recessive pattern of PCG inheritance., Methods: For this study, patients and controls (clinically unaffected individuals of each family) from 25 consanguineous families belonging to Punjab, Baluchistan and Khyber Pakhtunkhwa, Pakistan were recruited through ophthalmologists. DNA was isolated from collected blood samples. Genetic screening of CYP1B1 gene was done for all enrolled families. In-silico analysis was performed to identify and predict the potential disease-causing variations., Results: Pathogenicity screening revealed sequence variants segregating with disease phenotype in homozygous or compound heterozygous form in eleven out of 25 analyzed families. We identified a total of sixteen disease causing variants among which five frameshift i.e., c.629dup (p.Gly211Argfs*13), c.287dup (p.Leu97Alafs*127), c.662dup (p.Arg222Profs*2), c.758&#95;759insA (p.Val254Glyfs*73) and c.789dup (p.Leu264Alafs*63), two silent c.1314G>A, c.771T>G and six missense variations c.457C>G (p.Arg153Gly), c.516C>A (p.Ser172Arg), c.722T>A (p.Val241Glu), c.740T>A (p.Leu247Gln), c.1263T>A (p.Phe421Leu), and c.724G>C (p.Asp242His) are previously un reported. However two frameshift c.868dup (p.Arg290Profs*37), c.247del (p.Asp83Thrfs*12) and one missense variant c.732G>A (p.Met244Ile), is previously reported. Furthermore, six polymorphisms c.1347T>C, c.2244&#95;2245insT, c.355G>T, c.1294G>C, c.1358A>G and c.142C>G were also identified. In the intronic region, a novel silent polymorphism i.e., g.35710&#95;35711insT was found in homozygous state. All the newly detected disease-causing variants were negative in 96 ethnically matched controls., Conclusion: Among twenty-five screened families, eight families (PCG50, 52-54, 58, 59, 63 and 67) were segregating disease causing variants in recessive manner. Two families (PCG049 and PCG062) had compound heterozygosity. Our data confirms genetic heterogeneity of PCG in Pakistani population however we did not find molecular variants segregating with PCG in fifteen families in coding exons and intron-exon boundaries of CYP1B1 gene. Genetic counseling was provided to families to refrain from practicing consanguinity and perform premarital screening as a PCG control measure in upcoming generations., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To determine the visual outcomes and effectiveness of glaucoma surgeries in congenital ectropion uvea., Design: Retrospective interventional case series., Methods: Surgeries and examination findings were collected on 11 eyes of 8 patients with congenital ectropion uvea at 2 academic sites from 2001 to 2021. Visual outcomes, surgical success (intraocular pressure [IOP]: 5-20 mm Hg, no additional IOP-lowering surgery, no visually devastating complications), and survival rates of glaucoma surgeries were assessed., Results: Glaucoma in bilateral congenital ectropion uvea was diagnosed at an earlier age (0.02 ± 0.01 years) than unilateral disease (8.9 ± 5.3 years, P = .002). All eyes required glaucoma surgery with 91% requiring multiple surgeries (3.5 ± 2.1, median 3 surgeries per eye). Trabeculotomy (8 eyes) showed 13% success rate. Although none of the 4 eyes that underwent trabeculectomy with mitomycin C needed repeat trabeculectomy, glaucoma drainage device placement, or cycloablation, 75% required bleb revision surgery. Glaucoma drainage devices (7 eyes) had a 57% success rate with 3 eyes requiring subsequent cycloablation (2) or trabeculectomy (1). At the final follow-up (8.5 ± 6.6 years, median: 7.9 years), all eyes achieved IOP control, and IOP was lower compared with presentation (13.2 ± 2.6 mm Hg vs 32.9 ± 9.9 mm Hg, P = .002). Best-corrected logarithm of the minimum angle of resolution visual acuity at the final follow-up was 0.2 ± 0.2., Conclusions: Bilateral congenital ectropion uvea presents with glaucoma earlier than unilateral cases. The majority of eyes required multiple glaucoma surgeries. Angle surgery was less effective than trabeculectomy or glaucoma drainage devices. IOP control was obtained in all eyes and affected individuals had good visual outcomes., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To report an improved surgical procedure for primary congenital glaucoma (PCG)., Case Report: An apparently healthy 4-month-old male child was referred by an ophthalmologist with the preliminary diagnosis of congenital glaucoma. Office examination followed by evaluation under anaesthesia confirmed the diagnosis of advanced PCG in both eyes. Horizontal corneal diameter was 13.5 mm in both eyes and intraocular pressure was 36 mmHg in both eyes. The child was operated on both eyes in the same session. An illuminated microcatheter passage assisted circumferential trabeculotomy and trabeculectomy (IMPACTT) was performed. Two months postoperatively, the IOPs were 12 and 10 mmHg in the right and left eye, respectively, and the cornea was clear except for the presence of Haab's striae in both eyes. The child's visual acuity (binocularly) was 4 cycles/degree as recorded with Teller acuity cards., Conclusions: Illuminated microcatheter passage assisted circumferential trabeculotomy and trabeculectomy (IMPACTT) is safe and effective and may represent an improved surgical procedure for the management of advanced PCG.

Purpose: To describe anterior chamber angle (ACA) structures and parameters in primary congenital glaucoma (PCG) and normal infant eyes, using Hand-held anterior segment optical coherence tomography (HH AS-OCT), as an in-office, non-contact technique., Methods: Normal and PCG-infants <24 months were examined, using HH AS-OCT (RTVue RT- 100, Optovue Inc., Fremont, CA). Sedation was not required. Corneal pachymetry map, ACA width and iris thickness (IT) were measured. Trabecular meshwork (TM), Schlemm's canal (SC), and scleral spur (SS) identification were assessed in both groups., Results: Forty-eight infants; (26 PCG-eyes and 22 normal-eyes) aged 9.12 ± 6.7 months, were included. Nasal and temporal ACA width in PCG infants was found significantly larger (39.3 ± 6.6° vs. 30.4 ± 5.6, and 40.1 ± 5.3° vs. 32.5 ± 6.2 respectively) (p < 0.001). IT was significantly reduced (121.7 ± 43.9 μm in PCG-infants, vs. 160.3 ± 38.6 μm in normal-eyes) (p < 0.01). TM was identified in all normal eyes (100%) and nine (34.6%) PCG- eyes. SC was identified in 16 (72.7%) normal eyes versus four (15.4%) PCG. In PCG-eyes, an abnormal structure occluding the angle was seen in seven (26.9%), and a hyper-reflective membrane in five (19.2%), the iris was anteriorly inserted in all PCG-eyes, and iridotrabeculodysgenesis was clearly identified (with constant iris anterior insertion). The abnormal tissue obscuring the angle was seen in younger PCG-infants and iris thinning appeared to be part of the pathology, not a result of IOP elevation., Conclusion: Using HH AS-OCT permits tomographic examination of the ACA in PCG infants and may help in the understanding of disease pathology. Hence, may assist in optimizing treatment., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)