Chromatic vision and structural assessment in primary congenital glaucoma.

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.

Comparative posterior corneal profile of keratoconus hydrops versus Haab's striae in congenital glaucoma.

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.

Microcatheter-Assisted Circumferential Trabeculotomy After Failed Glaucoma Surgeries in Childhood Glaucoma.

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.

Influence of different primary surgical techniques on long-term intraocular pressure and medication in glaucoma after congenital cataract surgery.

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.

Thrombospondin Mutations and Patients With Primary Congenital Glaucoma in a United States Population.

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.

Congenital glaucoma in a tiger (Panthera tigris).

OBJECTIVE: To describe a case of congenital glaucoma in atiger (Panthera tigris). ANIMAL STUDIED: An 8-month-old intact female tiger wasreferred for suspected glaucoma of the right eye. The right eye was buphthalmicwith moderate episcleral injection, circumferential superficial cornealneovascularization, moderate corneal edema, and a fixed dilated pupil. Tapetalreflection was absent due to a mature cataract. Rebound tonometry under generalanesthesia revealed 70 mmHg and 21 mmHg in the right and left eye, respectively. PROCEDURE: A trans-conjunctival enucleation was performedand the globe was submitted for histopathology. RESULTS: Histopathology revealed a thin sclera, amorphousmaterial contouring an imperforate and hypoplastic iridocorneal angle, ahypoplastic lens with severe anterior-posterior compression, subcapsularepithelial hyperplasia, and Morganian globules, and segmental moderate retinalatrophy. Periodic acid-Schiff stain highlighted segmental dilations of theDescemet's membrane. Masson trichrome stain highlighted a pre-irido collagenmembrane. CONCLUSION: The tiger's age and histopathologic findingsare consistent with congenital goniodysgenesis. This is the first known reportof congenital glaucoma in a tiger.

Visco-Circumferential-Suture-Trabeculotomy Versus Rigid-Probe Viscotrabeculotomy in Neonatal-Onset Primary 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.

Comparative efficacies of 13 surgical interventions for primary congenital glaucoma in children: a network meta-analysis of randomized clinical trials.

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.

Whole-exome screening for primary congenital glaucoma in Lebanon.

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.

[Glaucoma in infancy and childhood]. / Glaukom im Säuglings- und Kindesalter.

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.

Exome Sequencing Reveals SLC4A11 Variant Underlying Congenital Hereditary Endothelial Dystrophy (CHED2) Misdiagnosed as Congenital Glaucoma.

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.

Epidemiology and long-term outcomes of primary congenital glaucoma: a population-based study.

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.

Corneal Endothelial Features in Patients Operated for Primary Congenital Glaucoma.

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/mm2; 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/mm2 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.

Exome-based mutation screening in South African children with primary congenital glaucoma.

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.

Neck Extension and Intraocular Pressure Elevation During Palatoplasty in a Patient with Patau Syndrome and Congenital Glaucoma: A Case Report.

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.

CYP1B1 and MYOC variants in neonatal-onset versus infantile-onset primary congenital glaucoma.

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.

Outcomes of early versus delayed trabeculotomy for primary congenital glaucoma.

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.

Controversies in Pediatric Angle Surgery and Secondary Surgical Treatment.

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.

Screening of candidate genes at GLC3B and GLC3C loci in Chinese primary congenital glaucoma patients with targeted next generation sequencing.

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.