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Development of the anterior segment of the eye requires reciprocal sequential interactions between the arising tissues, facilitated by numerous genetic factors. Disruption of any of these processes results in congenital anomalies in the affected tissue(s) leading to anterior segment disorders (ASD) including aniridia, Axenfeld-Rieger anomaly, congenital corneal opacities (Peters anomaly, cornea plana, congenital primary aphakia), and primary congenital glaucoma. Current understanding of the genetic factors involved in ASD remains incomplete, with approximately 50% overall receiving a genetic diagnosis. While some genes are strongly associated with a specific clinical diagnosis, the majority of known factors are linked with highly variable phenotypic presentations, with pathogenic variants in FOXC1, CYP1B1, and PITX2 associated with the broadest spectrum of ASD conditions. This review discusses typical clinical presentations including associated systemic features of various forms of ASD; the latest functional data and genotype-phenotype correlations related to 25 ASD factors including newly identified genes; promising novel candidates; and current and emerging treatments for these complex conditions. Recent developments of interest in the genetics of ASD include identification of phenotypic expansions for several factors, discovery of multiple modes of inheritance for some genes, and novel mechanisms including a growing number of non-coding variants and alleles affecting specific domains/residues and requiring further studies. [ABSTRACT FROM AUTHOR]

Background. Primary congenital glaucoma (PCG) is the most common subtype of glaucoma caused by defects in the cytochrome P450 1B1 (CYP1B1) gene. It is developing among infants in more than 80% of cases who exhibit impairments in the anterior chamber angle and the trabecular meshwork. Thus, a comprehensive in silico approach was performed to evaluate the effect of high-risk deleterious missense variations in the CYP1B1 gene. Material and methods. All the information for CYP1B1 missense variants was retrieved from the dbSNP database. Seven different tools, namely: SIFT, PolyPhen-2, PROVEAN, SNAP2, PANTHER, PhD-SNP, and Predict-SNP, were used for functional annotation, and two packages, which were I-Mutant 2.0 and MUpro, were used to predict the effect of the variants on protein stability. A phylogenetic conservation analysis using deleterious variants was performed by the ConSurf server. The 3D structures of the wild-type and mutants were generated using the I-TASSER tool, and a 50 ns molecular dynamic simulation (MDS) was executed using the GROMACS webserver to determine the stability of mutants compared to the native protein. Co-expression, proteinprotein interaction (PPI), gene ontology (GO), and pathway analyses were additionally performed for the CYP1B1 in-depth study. Results. All the retrieved data from the dbSNP database was subjected to functional, structural, and phylogenetic analysis. From the conducted analyses, a total of 19 highrisk variants (P52L, G61E, G90R, P118L, E173K, D291G, Y349D, G365W, G365R, R368H, R368C, D374N, N423Y, D430E, P442A, R444Q, F445L, R469W, and C470Y) were screened out that were considered to be deleterious to the CYP1B1 gene. The phylogenetic analysis revealed that the majority of the variants occurred in highly conserved regions. TheMDsimulation analysis exhibited that all mutants' average root mean square deviation (RMSD) values were higher compared to the wild-type protein, which could potentially cause CYP1B1 protein dysfunction, leading to the severity of the disease. Moreover, it has been discovered that CYP1A1, VCAN, HSD17B1, HSD17B2, and AKR1C3 are highly co-expressed and interact with CYP1B1. Besides, the CYP1B1 protein is primarily involved in the metabolism of xenobiotics, chemical carcinogenesis, the retinal metabolic process, and steroid hormone biosynthesis pathways, demonstrating its multifaceted and important roles. Discussion. This is the first comprehensive study that adds essential information to the ongoing efforts to understand the crucial role of genetic signatures in the development of PCG and will be useful for more targeted gene-disease association studies. [ABSTRACT FROM AUTHOR]

Purpose: Primary congenital glaucoma (PCG) is a form of childhood glaucoma caused by maldevelopment of the anterior chamber. Disease severity differs greatly amongst patients. Ultrasound biomicroscopy (UBM) is a non‐invasive technique that can visualize the anterior segment in infants in vivo. The purpose of this narrative review is to make an overview of the UBM data in PCG and study the applicability of UBM in characterizing the disease. Methods: An online search was performed on PubMed in December 2020. After a critical appraisal of the included articles, study and patient characteristics were summarized. The UBM measurements of the anterior segment in PCG of the different studies were analysed. Results: Six studies were included in this review. All were cross‐sectional prospective studies. A total of 221 PCG eyes were examined. PCG eyes showed a larger trabecular iris angle, decreased iris thickness, narrower or absent Schlemm's canal and an increased zonular length compared to controls. Abnormal tissue membrane covering the trabecular meshwork and abnormal insertion of the iris and ciliary process were frequently found. The success rate of glaucoma surgery depended on the severity of anterior segment malformations found with UBM. Conclusion: Malformations of the anterior segment in PCG can be demonstrated by UBM in vivo. This imaging can help to characterize disease severity and might support surgical treatment decisions. [ABSTRACT FROM AUTHOR]

The purpose of this research study was to investigate the prevalence of the p.G61E variant of the CYP1B1 gene among primary congenital and open angle glaucoma (PCG and POAG) patients in the province of Punjab, Pakistan. A total of 112 POAG and 50 PCG patients were enrolled in this study. Detailed clinical examination was carried out on all patients. Screening of G61E was done by direct Sanger sequencing. Different in silico tools, e.g., Clustal Omega, PSIPRED, and Franklin tools were used to check the conservation, secondary structure, and pathogenicity, respectively, of this variant. Sanger sequencing of the whole CYP1B1 gene revealed a homozygous missense transition, c.182G>A, p.G61E in 25/50 (50%) of PCG and in 42/112 (37.5%) of POAG cases, which co-segregated with the disease phenotype. This study revealed that p.G61E is the relatively major contributor of PCG. However, 42 POAG patients harbouring the G61E mutation showed moderate to severe phenotype, suggesting the genetic heterogeneity of this variant in Pakistani population. [ABSTRACT FROM AUTHOR]

Abstract Purpose: To estimate carrier frequencies of CYP1B1 mutations p.Gly61Glu and p.Arg368His, respectively, in Talesh and the east of Guilan province in Iran with a maximum error of 2%. Previously, it was shown that these CYP1B1 mutations may be relatively prevalent in these regions. Methods: Population-based screenings were performed. DNA was extracted from saliva samples of 1036 individuals from Talesh and 3029 individuals from the east of Guilan. P.Gly61Glu and p.Arg368His screenings were performed, respectively, by RFLP and ARMS-based PCR protocols. For confirmation, the DNA of individuals with mutations was sequenced using the Sanger protocol. Results: Nine individuals from Talesh (0.86%; 95%CI: 0.45–1.64%) carried the p.Gly61Glu mutation, and 73 from the east of Guilan (2.41%; 95%CI: 1.91–3.04%) carried p.Arg368His. There was no significant difference in frequencies between urban and rural regions of the various cities, nor among four cities within the east of Guilan. Conclusion: The frequencies of p.Gly61Glu carriers in Talesh and of p.Arg368His carriers in the east of Guilan were within the 95% confidence interval of a previous study based on screenings of fewer individuals. The reliability of the recent estimates is higher, as the confidence interval for p.Gly61Glu decreased from 6.5% to 1.19% and the interval for p.Arg368His decreased from 4% to 1.13%. Based on the new findings, the maximum expected frequency of p.Gly61Glu carriers in Talesh is 1.64%, and of p.Arg368His carriers in the east of Guilan is 3%. The need for performing premarital screenings in the respective cities can be evaluated.

Background Primary congenital glaucoma (PCG) is the most common subtype of glaucoma caused by defects in the cytochrome P450 1B1 (CYP1B1) gene. It is developing among infants in more than 80% of cases who exhibit impairments in the anterior chamber angle and the trabecular meshwork. Thus, a comprehensive in silico approach was performed to evaluate the effect of high-risk deleterious missense variations in the CYP1B1 gene. Material and methods All the information for CYP1B1 missense variants was retrieved from the dbSNP database. Seven different tools, namely: SIFT, PolyPhen-2, PROVEAN, SNAP2, PANTHER, PhD-SNP, and Predict-SNP, were used for functional annotation, and two packages, which were I-Mutant 2.0 and MUpro, were used to predict the effect of the variants on protein stability. A phylogenetic conservation analysis using deleterious variants was performed by the ConSurf server. The 3D structures of the wild-type and mutants were generated using the I-TASSER tool, and a 50 ns molecular dynamic simulation (MDS) was executed using the GROMACS webserver to determine the stability of mutants compared to the native protein. Co-expression, protein-protein interaction (PPI), gene ontology (GO), and pathway analyses were additionally performed for the CYP1B1 in-depth study. Results All the retrieved data from the dbSNP database was subjected to functional, structural, and phylogenetic analysis. From the conducted analyses, a total of 19 high-risk variants (P52L, G61E, G90R, P118L, E173K, D291G, Y349D, G365W, G365R, R368H, R368C, D374N, N423Y, D430E, P442A, R444Q, F445L, R469W, and C470Y) were screened out that were considered to be deleterious to the CYP1B1 gene. The phylogenetic analysis revealed that the majority of the variants occurred in highly conserved regions. The MD simulation analysis exhibited that all mutants’ average root mean square deviation (RMSD) values were higher compared to the wild-type protein, which could potentially cause CYP1B1 protein dysfunction, leading to the severity of the disease. Moreover, it has been discovered that CYP1A1, VCAN, HSD17B1, HSD17B2, and AKR1C3 are highly co-expressed and interact with CYP1B1. Besides, the CYP1B1 protein is primarily involved in the metabolism of xenobiotics, chemical carcinogenesis, the retinal metabolic process, and steroid hormone biosynthesis pathways, demonstrating its multifaceted and important roles. Discussion This is the first comprehensive study that adds essential information to the ongoing efforts to understand the crucial role of genetic signatures in the development of PCG and will be useful for more targeted gene-disease association studies.

Background: Primary prevention of primary congenital glaucoma (PCG) includes improving families of children with PGC. We evaluated the level of knowledge and attitudes of parents of children on PCG in Saudi Arabia. Methodology: This was a personal interview-based survey of parents of children with PCG at a tertiary eye hospital in Saudi Arabia. The study was conducted in 2018. A close-ended questionnaire in Arabic was used. Demographic data were collected on the children and parents. Clinical data on PCG were collected from electronic case records. Five questions each on knowledge and attitudes toward genetic counseling were queried. A Likert-type scale was used to collect the responses. Rasch analysis was carried out for knowledge and attitudes. The score was correlated with demographics and clinical determinants. p < 0.05 was considered statistically significant. Results: The study sample comprised 60 participants. The median Rasch score for knowledge on genetic counseling for PCG was -4.57 [interquartile range (IQR) -7.28; -1.0]. The median Rasch score for attitudes toward genetic counseling for PCG was -8.9 (IQR -11.6: -5.9). Parents with more than one family member with PCG had a significantly higher knowledge than those with one family member with PCG (p = 0.007). Knowledge of etiology and genetic counseling was significantly better if the child had residual vision amenable to low vision care (p < 0.001). The Rasch scores for knowledge and attitude were positively correlated (p < 0.001). Conclusion: Knowledge of the cause of PCG and genetic counseling was high among parents. The positive attitude toward genetic counseling could be useful for the primary prevention of CG in Saudi Arabia. [JBCGenetics 2021; 4(1.000): 22-26]

Mohamed F Farid, Mohamed Anany, Mohamed A Awwad Ophthalmology Department, Benha University, Benha, EgyptCorrespondence: Mohamed A AwwadOphthalmology Department, Benha University, PO Box: 13511, 1 Fareed Nada Street, Benha, EgyptEmail mohdzahir82.ma@gmail.comPurpose: To present outcomes of surgical management of primary congenital glaucoma (PCG) in children less than one year of age in a population based at the Nile Delta.Methods: A retrospective review of medical records of patients with PCG less than one year of age at presentation who underwent surgical intervention in a tertiary care facility based at the Nile Delta. All patients underwent measurement of intraocular pressure (IOP), horizontal corneal diameter (HCD), cup-to-disc ratio (CDR) before and after surgery and a minimum of 6 months follow up was required. Surgical success was defined as IOP less than 22mmHg without medications and without progression of main disease parameters.Results: The review revealed 44 eyes of 26 consecutive patients who underwent surgical treatment for PCG. Average age at surgery was 5.2 months and mean follow up was 18.5 months. Preoperative IOP was 28.5± 4 mmHg, HCD was 13.7± 0.7mm, and CDR (when visible) was 0.65± 0.18. A total of 69 surgical procedures were performed with an average of 1.56 procedures per eye. Postoperative IOP was 13.3± 4.8 mmHg, HCD was 12.8± 0.9mm, and CDR was 0.3± 0.2 (P< 0.0001). Surgical success was achieved in 32 eyes (72.7%) while sight-threatening postoperative complications were reported in 3 eyes.Conclusion: Surgical management of PCG younger than one year of age achieved good success rate in the region of the Nile Delta with low rate of visually significant postoperative complications. However, larger studies with longer follow up are needed to fully reveal the overall characteristics of PCG in the region.Keywords: primary congenital glaucoma, intraocular pressure, trabeculotomy, trabeculectomy, Ahmed glaucoma valve, the Nile Delta

Purpose: To compare the efficacy and safety of viscocanalostomy plus near‐360‐degree suture trabeculotomy (VST) with viscocanalostomy plus rigid probe trabeculotomy (VT) in treating primary congenital glaucoma (PCG) over a one‐year follow‐up. Methods: This consecutive retrospective study included patients with PCG confirmed within 3 years of age from March 2017 to October 2019. Efficacy was evaluated by comparing the postoperative intraocular pressure (IOP) curve and the success rate at one year after surgery. Safety was assessed by comparing the postoperative complications. The number of anti‐glaucoma agents, horizontal corneal diameter (HCD) and cup‐to‐disc ratio (C/D) of the two surgical methods were also compared. Results: Data of 90 eyes from 61 patients were analysed. The baseline parameters of the two groups were similar. The IOP at 12 months after surgery in the VST group was 12.7 ± 4.8 mmHg, while that in the VT group was 15.8 ± 6.5 mmHg. The IOP at 6, 9 and 12 months postoperatively in the VST group was significantly lower than in the VT group (p < 0.05). Viscocanalostomy plus near‐360‐degree suture trabeculotomy (VST) remained a significant favourable factor for complete one‐year success (93.6% versus 74.4%, p = 0.005) but not qualified one‐year success (97.9% versus 88.4%, p = 0.06). The number of anti‐glaucoma agents, HCD and C/D were reduced in both groups. Postoperative complications were not significantly different between the two groups. Conclusions: In children with PCG, VST provides a more durable IOP control than VT over the one‐year follow‐up, with a similar safety profile. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the long-term visual outcomes and factors associated with vision loss in Chinese patients with primary congenital glaucoma (PCG) after successful intraocular pressure (IOP) control (IOP ≤21 mm Hg). Methods: PCG patients with IOP control who were examined in the glaucoma clinic at Zhongshan Ophthalmic Center from 2019 to 2020 were enrolled. The final visual outcome was evaluated by the best corrected visual acuity (VA). Univariate and multivariate analyses were used to investigate the associations of visual impairment with potential risk factors. The causes for decreased VA (<20/50) were also analyzed. Results: Fifty-nine patients (95 eyes) were included in the cohort, with a mean age of 8.7 years. The mean logMAR VA was 0.62 ± 0.64. The VAs of eyes treated for PCG were good (≥20/50) in 56%, fair (20/60–20/200) in 30%, and poor (<20/200) in 14%. The most common cause of decreased VA was amblyopia (64.3%). Multivariate logistic regression analysis showed that undergoing multiple surgeries (OR: 4.86, 95% CI: 1.11–21.16, p = 0.035) was significantly associated with visual impairment. Conclusion: The results showed that good VA was attainable in approximately half of PCG eyes under IOP control. Prompt and effective treatment of PCG, management of amblyopia and ocular comorbidities may be potential steps toward achieving good visual outcomes in PCG patients. [ABSTRACT FROM AUTHOR]

Primary congenital glaucoma (PCG) is a rare type of glaucoma that is inherited in an autosomal recessive manner. PCG can lead to blindness if not detected early in children aged 3 or younger. PCG varies in presentation among various populations, where disease presentation and disease severity vary by mutation. The most common gene implicated in PCG is cytochrome p450 1B1 (CYP1B1). Here, we sought to review the literature for mutations in CYP1B1 and their presentation among different populations. Areas of interest include recent findings on disease presentation and potential implications on our understanding of PCG pathophysiology. [ABSTRACT FROM AUTHOR]

Purpose: To determine the success of combined trabeculotomy and trabeculectomy with application of Mitomycin C in primary congenital glaucoma. Study Design: Interventional case series. Place and Duration of Study: Mughal eye hospital Lahore from January 2018 to December 2019. Methods: Twenty-four patients of primary congenital glaucoma were included. Secondary glaucoma and patients with corneal haze were excluded. Corneal diameter above 11.5, 12.5 and 13 mm (when combined with raised IOP) were considered indications for the surgery in neonates, at 1 year of age and at any age respectively. I-Care tonometer was used to measure IOP in all the cases. Trabeculotomy combined with Trabeculectomy plus MMC was performed in all cases. Procedure was successful if post-operative IOP was between 5 and 21 mm of Hg and stable optic nerve head at 3 months after surgery. Results: Mean age of the patients was 9.7 ± 7.6 months. Mean preoperative intraocular pressure (IOP) was 27.8 ± 4.4 mm of Hg. Mean post operative IOP was 13.5 ± 6.5, 17.8 ± 5 and 16.9 ± 4.8 mm of Hg on first day, at the end of one month and after 3 months respectively.Twenty-one (88 %) cases were successful based on the set criteria.Complications included non-identification of Canal of Schlemn, full thickness superficial flap with uveal show due to very thin sclera, hyphema, collapse of anterior chamber and choroidal detachment. Conclusion: Combined Trabeculotomy and Trabeculectomy with application of Mitomycin C is effective in decreasing IOP significantly. [ABSTRACT FROM AUTHOR]

Childhood glaucoma represents a heterogenous group of rare ocular conditions that may result in significant sight threatening complications related to elevated intraocular pressure (IOP). It can be classified as either primary or secondary and the latter may have systemic associations. This review will be based on the work of the childhood glaucoma research network (CGRN) and will focus on the diagnosis and management of the most common types of childhood glaucoma. These include primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG) as well as secondary causes of glaucoma associated with non‐acquired ocular anomalies (Axenfeld‐Rieger anomaly; Peters anomaly and Aniridia), glaucoma associated with systemic disease (Sturge Weber syndrome and Neurofibromatosis), those due to acquired conditions (Uveitic glaucoma, trauma and tumours) and importantly glaucoma following cataract surgery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Primary congenital glaucoma is potentially blinding condition characterized by elevated intraocular pressure and optic disc cupping. It is typically bilateral and usually manifest in the first year of life. Spontaneously arrested primary congenital glaucoma can occur, but it is very rare. CASE REPORT: A 32-year-old male patient from North Shewa presented to the department of ophthalmology, Menelik II Hospital with deterioration of vision. On examination he had large corneas with horizontal diameter of 14 mm, increased axial length, faint corneal stromal opacity and Haab's striae of both eyes. Anterior chamber angles were wide open. His intraocular pressure, optic nerve head appearance and visual field in both eyes were normal. He had subluxated dense cataract of the right eye. CONCLUSION: Late presentation with sequelae of primary congenital glaucoma without optic neuropathy is possible. Regular follow-up of spontaneously arrested congenital glaucoma and scleral fixation of intraocular lens is recommended. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long‐term visual and surgical outcomes, and associated risk factors for poor outcomes in patients with primary congenital glaucoma (PCG). Methods: Retrospective review of medical records of children who underwent combined trabeculotomy−trabeculectomy (CTT) without mitomycin‐C as the first surgical procedure by a single surgeon between January 1990 and December 2010. Success was defined as intraocular pressure (IOP) <16 mmHg without (complete) or with (qualified) one glaucoma medication. We used the WHO criteria of vision loss to categorize the levels of vision impairment (VI). For purposes of statistical analysis, we randomly chose one eye of patients for bilateral PCG and affected eye in unilateral PCG. Results: The cohort included 653 consecutive PCG patients (1128 eyes; mean age, 26 months), of whom 475 (73%) underwent simultaneous bilateral CTT. Kaplan‐Meier survival analysis revealed 1‐, 5‐, 10‐, 15‐, and 19‐year complete success rates of 92.6% (n = 372), 75.5% (n = 173), 55.9% (n = 72), 44.7% (n = 19), and 21.6% (n = 3), respectively. Multivariate analysis revealed independent associations between failure, preoperative corneal clarity, and prior glaucoma surgery. Mean follow‐up was 41 ± 51 months (range, 6 months to 19 years; median, 1 year). Of the visual acuity (VA) data in the affected eyes obtained at last follow‐up (n = 333, 51%), seventy‐four patients (22%) had VA of ≥6/12. Of the remaining 259 patients, 18 (7%) had mild VI, 87 (34%) had moderate VI, 58 (22%) had severe VI, and 96 (37%) were blind. No serious complications were noted. Conclusions: Primary CTT may be safely employed to control IOP and may provide long‐term benefits in PCG patients. [ABSTRACT FROM AUTHOR]

Hazem Helmy Glaucoma Unit, Glaucoma and Optic Nerve Disease Department, Research Institute of Ophthalmology; RIO, Giza, EgyptCorrespondence: Hazem Helmy 48, Palm City Katameya, EgyptTel +20 201288882616Email hazem.helmy@yahoo.comIntroduction: Primary congenital glaucoma (PCG) is a challenging disease that needs to be surgically managed with more innovative methods. Conventional incisional surgery, such as goniotomy and trabeculotomy, has a primary high success rate, but does not seem to be a very effective treatment in advanced stages.Design: A prospective clinical case study.Purpose: To qualify the outcome, in terms of success rate, of goniotomy combined with trabeculotomy as a surgical option to treat eyes affected by PCG with a corneal diameter larger than 14 mm.Patients and Methods: This study included 50 eyes of 50 patients diagnosed with PCG with corneal diameter larger than 14 mm who underwent ab interno goniotomy combined with ab externo trabeculotomy. Intraocular pressure (IOP) was measured preoperatively and 24 months postoperatively. A statistical analysis was performed to detect correlations between the success rate and corneal diameter, preoperative IOP, age of onset, axial length, and consanguinity. The main outcome was reduction in IOP; secondary outcomes were factors affecting the success rate, complications, and the need for additional surgical intervention to control IOP.Results: The mean age of the patients was 18.86± 9.94 months. Males made up 52% of cases and females 48% of cases. Positive consanguinity was present in 38% of cases. Axial length ranged between 20 and 22 mm, with a mean of 20.98± 0.8 mm. Mean preoperative IOP was 29.56± 3.36 mmHg, which decreased postoperatively to 12.6± 2.5, 14.1± 3.2, 16.8± 5.5, 14.4± 2.3, 14.3± 1.6, 14.3± 1.6, 14.3± 1.6, 14.3± 1.7, and 14.3± 1.7 mmHg at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months respectively (p˂0.001). Use of medical treatment was decreased from 2.7± 0.4 preoperatively to 1.4± 0.7 postoperatively (p˂0.001). Hyphema was the only complication that appeared, occurring in 47% of cases. The success rate was 94%. Complete success (IOP < 21 mmHg without treatment) was achieved in 70% of cases, 24% were considered a qualified success (IOP < 21 mmHg with treatment), while failure was documented in 6% of cases (IOP > 21 mmHg with treatment). The success rate was significantly related to preoperative IOP, corneal diameter, axial length, consanguinity, and age of onset (p˂0.001). All cases were followed for 24 months.Conclusion: Ab interno goniotomy combined with ab externo trabeculotomy improves the success rate of buphthalmos surgery. A significant correlation was detected between success rate and preoperative IOP, corneal diameter, axial length, consanguinity, and age of onset.Keywords: primary congenital glaucoma, intraocular pressure, corneal diameter, trabeculotomy, goniotomy

PurposeWe aimed to describe the characteristics, epidemiology, management, and outcomes of glaucoma in pediatric patients in central China.MethodsThis study retrospectively analyzed inpatients with pediatric glaucoma at Henan Provincial People's Hospital, Henan Eye Institute, and Henan Eye Hospital between 2017 and 2020.ResultsOverall, 239 cases (276 eyes) of pediatric glaucoma in patients, comprising 87 girls (36.40%) and 152 boys (63.60%) were analyzed. The mean age was 6.65 ± 4.46, and 2.93% of the patients had a family history of glaucoma. Primary congenital glaucoma (PCG) was the most common type of glaucoma, followed by traumatic glaucoma in 8.33% of the patients, which was considered secondary glaucoma. The most common signs and symptoms were elevated intraocular pressure (IOP) and eye pain. Trabeculotomy (Trab) and microcatheter-assisted 360° trabeculotomy (MAT) combined with Trab were the most commonly performed surgeries. The IOP of patients with PCG, juvenile open-angle glaucoma (JOAG), and secondary glaucoma were 15.27 ± 7.48 mmHg, 17.16 ± 10.05, and 18.65 ± 8.55, respectively, at the final follow up. The rate of re-operations in patients with PCG, JOAG, and secondary glaucoma were 9.15%, 6.78%, and 4.69%, respectively. The mean visual acuity of the eyes with PCG, JOAG, and secondary glaucoma was 0.79 ± 0.68, 0.51 ± 0.48, and 0.53 ± 0.50, respectively.ConclusionPCG, JOAG, and traumatic glaucoma were the most prevalent subtypes in patients with pediatric glaucoma in central China. Trab and MAT combined with Trab were the most common interventions used in this study. Pediatric amblyopia might require full attention during the entire treatment, especially after glaucoma surgery. Effective preventive measures and more public education on glaucoma prevention and the importance of early diagnosis and treatment is necessary.

Purpose: To report a case of gonioscopy-assisted transluminal trabeculotomy (GATT) in a patient with primary congenital glaucoma. Observations: A three-year-old boy who presented with buphthalmos and elevated intraocular pressure. Despite the presence of iris and iris processes extending to Schwalbe's line, GATT was performed successfully. Conclusions: GATT may be successful with primary congenital glaucoma even when angle structures are not initially visible.

Purposes: Recent studies have suggested that loss-of-function mutations of the tunica intima endothelial receptor tyrosine kinase (TEK) are responsible for approximately 5% of primary congenital glaucoma (PCG) cases in diverse populations. However, the causative role of TEK mutations has not been studied in Chinese PCG patients. Here, we report the mutation spectrum of TEK after screening a large cohort of PCG patients of Chinese Han origin and analyze the identified variants in functional assays. Methods: TEK-targeted next-generation sequencing (NGS) was performed in 200 PCG patients. Candidate variants were prioritized by mutation type and allele frequency in public datasets. Plasmids containing wild type and identified variants of TEK were constructed and used to assess protein expression, solubility, receptor auto-phosphorylation, and response to ligand stimulation in cell-based assays. Results: Ten missense and one nonsense heterozygous variants were detected by NGS in 11 families. The clinical features of TEK variants carriers were comparable to that of TEK-mutated patients identified in other populations and CYP1B1-mutated individuals from in-house database. Functional analysis confirmed four variants involving evolutionarily conserved residues to be loss-of-function, while one variant (p.R1003H) located in tyrosine kinase domain seemed to be an activating mutation. However, our results did not support the pathogenicity of the other five variants (p.H52R, p.M131I, p.M228V, p.H494Y, and p.L888P). Conclusion: We provide evidence for TEK variants to be causative in Chinese PCG patients for the first time. Attention needs to be paid to TEK mutations in future genetic testing. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long‐term efficacy and safety of circumferential trabeculotomy (CT) in the treatment of primary congenital glaucoma (PCG). Methods: Retrospective, single‐institutional case series of CT performed for PCG in years 1997–2016. The surgery could be completed in 42 out of 65 eyes (65%) intended for CT, and 39 of them were included in the study. A follow‐up examination was performed in 2017. Success was defined as intraocular pressure ≤ 16 mmHg without (complete) or with (qualified) glaucoma medication. Results: Complete success was obtained in 33/39 eyes (85%), qualified success in 34/39 eyes (87%). Of the 39 eyes with CT, 4 eyes (10%) needed additional surgery. Median follow‐up time was 120 months (range, 19–245 months). Median pre‐ and postoperative IOP were 26.0 mmHg (range, 10–41 mmHg) and 11.0 mmHg (range, 8–19 mmHg), respectively (p < 0.001). Cup‐disc ratio was ≥0.5 in 82% at baseline, at follow‐up in 9%. The median distance corrected visual acuity at follow‐up was logMAR 0.06 (range, −0.2 to 1.1). Median number of glaucoma medication at follow‐up was 0 (range, 0–2), at baseline 1.0 (range, 0–2). No serious complications were noted. Conclusion: Circumferential trabeculotomy is an efficacious, safe and medication saving surgical treatment for PCG in the long term. After a median follow‐up of 10 years (120 months), the morphological status of the optic nerve was either normalized or stabilized, and the visual acuity overall well preserved. [ABSTRACT FROM AUTHOR]

Purpose: A central diagnostic tool in adult glaucoma is the peripapillary retinal nerve fibre layer (pRNFL) thickness. It can be assessed by scanning laser polarimetry (SLP) or optical coherence tomography (OCT). However, studies investigating the relevance of pRNFL measurements in children are rare. This study aims to compare the glaucoma diagnosing ability of SLP and OCT pRNFL thickness measurements in a paediatric population. Methods: This retrospective study included 105 children (glaucoma: 22 (21.0%); healthy glaucoma suspects: 83 (79.0%)) aged 4–18 years, examined with SLP (GDxPro/ECC, Carl Zeiss Meditec) and spectral-domain OCT (SPECTRALIS®, Heidelberg Engineering). The thickness of pRNFL sectors was compared between diseased and healthy participants. Areas under the receiver-operating characteristic curves (AUC) and logistic regression results were used to compare the glaucoma discriminative capacity between SLP and OCT measurements. Results: Using OCT, pRNFL thickness was decreased in the superior, nasal, and inferior quadrants of glaucoma patients compared to healthy controls (P < 0.001, each). With SLP, such a difference was only observed in the inferior quadrant (P = 0.011). A correlation between glaucoma diagnosis and OCT-measured pRNFL thickness was found in all quadrants (P < 0.001) other than the temporal. With SLP, a correlation was found for the total average thickness (P = 0.037) and inferior quadrant (P = 0.0019). Finally, the AUCs of OCT measurements were markedly higher than those of SLP (e.g., inferior quadrant: OCT 0.83, SLP 0.68). Conclusion: pRNFL thickness measurements using both OCT and SLP, correlate notably with the presence of glaucoma. In general, the diagnostic performance of pRNFL thickness measurements seems higher for OCT than for SLP. Thus, pRNFL thickness measurements could provide important information, complementing conventional clinical and functional parameters in the diagnostic process of paediatric glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To assess intraocular pressure (IOP) changes after the water drinking test (WDT) in patients with primary congenital glaucoma (PCG). Methods: In this prospective interventional study, 20 eyes of 20 patients with PCG were included. All patients had undergone trabeculotomy. Six out of twenty eyes had received a glaucoma drainage device (GDD) implantation. IOP was measured using an air-puff tonometer at baseline, and 15, 30, 45, and 60 min after WDT. The repeated-measures analysis of variance test was used to compare the mean IOPs at different time points. Results: The mean ( ± standard deviation) of participants' age was 9.9 ± 2.7 years (range, 6 to 16 years), and 8 (40%) participants were male. The mean IOPs at baseline and 15, 30, 45, and 60 minutes after the WDT were 15.8 ± 3.7, 18.6 ± 3.4, 19.0 ± 3.8, 17.9 ± 3.8, and 16.9 ± 3.5 mmHg, respectively (P < 0.001). Pairwise comparisons revealed that the mean IOPs after 15 and 30 min were significantly greater than the baseline IOP (P < 0.001 and P = 0.002, respectively); however, the difference in mean IOPs after 45 and 60 min were not statistically significant from the baseline IOP. The averages of IOP peak and IOP fluctuation after the WDT were 20.0 ± 3.5 and 4.2 ± 2.9 mmHg, respectively. IOP fluctuation in those who underwent trabeculotomy alone was twice that of those with GDDs, but the difference was not statistically significant (5.0 vs 2.5 mmHg; P = 0.08). Conclusions: In patients with PCG, WDT induced significant IOP elevation 15 and 30 min after the test, which returned to pre-test values after 45 min.

Purpose: To evaluate the long-term visual outcomes of ab externo trabeculotomy for primary congenital glaucoma (PCG) at a single pediatric ophthalmology center. Methods: In this retrospective single-center case series, data from 63 eyes of 40 patients who underwent ab externo trabeculotomy between September 2006 and June 2018 were included. The data were analyzed for best corrected visual acuity (BCVA), stereopsis, and surgical success. Kaplan–Meier analysis was performed using the surgical success criteria defined as intraocular pressure (IOP) ≤ 21 mmHg and ≥ 20% below baseline without the need for additional glaucoma surgery. Results: BCVA at the time of diagnosis was 0.37 ± 0.48 logMAR, which changed to 0.51 ± 0.56 logMAR at the final follow-up (P = 0.08). Twenty-five percent of patients had BCVA equal to or better than 20/40 at the final visit. The mean refraction at baseline was –4.78 ± 5.87 diopters, which changed to less myopic refraction of –2.90 ± 3.83 diopters at the final visit. Optical correction was prescribed in 66% of eyes at the final visit. The average final stereopsis was 395.33 sec of arc. The linear regression model showed a significant association between the surgery success rate and final BCVA as well as stereoacuity (P-values: 0.04 and 0.03, respectively). Intraocular pressure (IOP) decreased significantly from 29.79 ± 7.67 mmHg at baseline to 16.13 ± 3.41 mmHg at the final follow-up (P = 0.001). Conclusion: Patients with PCG can achieve an acceptable visual acuity and stereoacuity, particularly in cases of timely intervention and close follow-up.

Abdelhamid Elhofi, Hany Ahmed Helaly Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Hany Ahmed Helaly 30 Roshdy Street, Roshdy, Alexandria, EgyptTel +20 1225466733Email hany209209@yahoo.comPurpose: To evaluate the safety and efficacy of non-penetrating deep sclerectomy with a collagen implant versus trabeculectomy in primary congenital glaucoma.Subjects and Methods: This was a retrospective interventional comparative non-randomized clinical study that included 80 eyes of 80 children presenting with primary congenital glaucoma under the age of 3 years. Forty eyes have undergone non-penetrating deep sclerectomy (NPDS) and the other 40 eyes have undergone penetrating trabeculectomy. The main outcome measure was the reduction in intraocular pressure (IOP). Secondary outcomes included percentage of patients with complete and qualified success, need for topical antiglaucoma medications, rate of complications, and need for further interventions. Complete success of the surgical outcome was considered an IOP ≤ 16 mmHg with no antiglaucoma medications. Qualified success was considered an IOP ≤ 16 mmHg using antiglaucoma medications.Results: The mean preoperative IOP was 27.4 ± 6.9 and 28.5 ± 6.6 mmHg in NPDS and trabeculectomy groups, respectively (p = 0.175). At the end of the follow-up period, the mean IOP was 11.2 ± 4.5 and 11.1 ± 3.4 mmHg with a mean reduction of 16.2 and 17.4 mmHg in NPDS and trabeculectomy groups, respectively. At the end of the follow-up period, ie at 36 months postoperative, the complete success rate was 60% (24 eyes) versus 57.5% (23 eyes), the qualified success rate was 25% (10 eyes) versus 25% (10 eyes), the overall success rate was 85% (34 eyes) versus 82.5% (33 eyes), and the rate of failure was 15% (6 eyes) versus 17.5% (7 eyes) in NPDS and trabeculectomy groups, respectively (p = 0.952). Eight cases (20%) of the trabeculectomy group had shallow anterior chamber. None of the NPDS group cases suffered from shallow anterior chamber.Conclusion: Non-penetrating deep sclerectomy appears to be an efficient and safe surgical alternative to penetrating trabeculectomy in treatment of primary congenital glaucoma. Non-penetrating deep sclerectomy has fewer postoperative complications in comparison to penetrating trabeculectomy with a comparative postoperative reduction in the intraocular pressure and overall success rates.Trial Registration: The trial was registered on 11/01/2020 with number PACTR202002874953456 (https://pactr.samrc.ac.za).Keywords: deep sclerectomy, primary congenital glaucoma, non-penetrating, childhood glaucoma, non-penetrating deep sclerectomy, trabeculectomy

Glaucoma is a progressive optic neuropathy; increased intraocular pressure (IOP) is a modifiable risk factor for primary congenital glaucoma (PCG). Increase IOP causes retinal and optic nerve compression and leads to gradual and irreversible loss of eyesight if left untreated. It is the second most leading cause of blindness. PCG mainly affects children up to the age of three years, and symptoms include epiphora, photalgia, swollen eyes, opaque corneas, blepharospasm, rupture in the retina and ocular nerve damage due to IOP. Early detection, management, and treatment are the keys to preventing vision loss from glaucoma. Many mutations have been discovered in Cytochrome P450 1B1 (CYP1B1) gene to be responsible for causing PCG, and there are still a lot of mutations to be discovered. In this review, we will discuss the genetic aspects of PCG and the most frequent mutations responsible for PCG in Pakistani children. PCG can be handled by decreasing IOP either by medication or by surgery. Genetic counselling plays a significant role in the establishment of proper management of PCG.

Primary congenital glaucoma (PCG) continues to be an important cause of visual impairment in children despite advances in medical and surgical treatment options. The progressive and blinding nature of the disease, together with the long lifespan of the affected population, necessitates a thorough understanding of the pathophysiology of PCG and the development of long-lasting treatment options. The first part of this review discusses the genetic features and makeup of this disorder, including all currently identified genetic loci (GLC3A, GLC3B, GLC3C and GLC3D) and relevant protein targets important for trabecular and Schlemm canal dysgenesis. These target molecules primarily include CYP1B1, LTBP2, and TEK/Tie2 proteins. Their potential roles in PCG pathogenesis are discussed with the purpose of bringing the readers up to date on the molecular genetics aspect of this disorder. Special emphasis is placed on functional implications of reported genetic mutations in the setting of PCG. The second part of the review focuses on various modifications and refinements to the traditional surgical approaches performed to treat PCG, including advances in goniotomy and trabeculotomy ab externo techniques, glaucoma drainage implant surgery and cyclodiode photocoagulation techniques that ultimately provide safer surgical approaches and more effective intraocular pressure control in the 21st century.

Purposes: Recent studies have suggested that loss-of-function mutations of the tunica intima endothelial receptor tyrosine kinase (TEK) are responsible for approximately 5% of primary congenital glaucoma (PCG) cases in diverse populations. However, the causative role of TEK mutations has not been studied in Chinese PCG patients. Here, we report the mutation spectrum of TEK after screening a large cohort of PCG patients of Chinese Han origin and analyze the identified variants in functional assays.Methods: TEK-targeted next-generation sequencing (NGS) was performed in 200 PCG patients. Candidate variants were prioritized by mutation type and allele frequency in public datasets. Plasmids containing wild type and identified variants of TEK were constructed and used to assess protein expression, solubility, receptor auto-phosphorylation, and response to ligand stimulation in cell-based assays.Results: Ten missense and one nonsense heterozygous variants were detected by NGS in 11 families. The clinical features of TEK variants carriers were comparable to that of TEK-mutated patients identified in other populations and CYP1B1-mutated individuals from in-house database. Functional analysis confirmed four variants involving evolutionarily conserved residues to be loss-of-function, while one variant (p.R1003H) located in tyrosine kinase domain seemed to be an activating mutation. However, our results did not support the pathogenicity of the other five variants (p.H52R, p.M131I, p.M228V, p.H494Y, and p.L888P).Conclusion: We provide evidence for TEK variants to be causative in Chinese PCG patients for the first time. Attention needs to be paid to TEK mutations in future genetic testing.

Purpose: Primary congenital glaucoma (PCG) is a potentially blinding disease, and the search for the best surgical option always remains. This study investigated the efficacy of Bent Ab-Interno Needle Goniectomy (BANG) compared to the established standard of traditional goniotomy., Design: Parallel-group randomized controlled trial., Participants: Infants with PCG aged 1 month to 1 year with similar clinical features in both eyes., Intervention: The 2 eyes of eligible patients were randomized to either goniotomy or BANG using a 25-gauge needle bent as a reverse cystitome, and the surgeries were done on the same day in both eyes. Postoperatively each infant was followed up for a minimum period of 1 year., Main Outcome Measures: The primary outcomes measured were intraocular pressure (IOP) control and the requirement for antiglaucoma medications (AGMs). The secondary outcome measures included corneal clarity enhancement, axial length stability, incidence of surgical complications, or the need for repeat surgery., Results: Eight infants with both eyes eligible, were included. In each infant, 1 eye was randomized to BANG and the other to conventional goniotomy. The mean age was 7.6 ± 3.6 months. There was no significant difference in the mean preoperative IOP (16.8 ± 8.87 mm Hg vs. 17 ± 6.0 mm Hg; P = 0.48) in eyes randomized to goniotomy or BANG. The mean number of AGMs (1.7 ± 1.11 vs. 2 ± 0.81 respectively; P = 0.26) were similar in both groups. Postoperatively, the IOP at 6 months (14.05 ± 4.1 vs. 16.2 ± 4.07; P = 0.22) and 1 year (15.3 ± 3.4 vs. 17.1 ± 3.0; P = 0.15) were similar in eyes that underwent goniotomy or BANG respectively. Both procedures demonstrated significant improvements in corneal clarity and maintained normal axial length growth. However, the BANG group required slightly more AGMs than the goniotomy group. There were no serious complications in either group. Both eyes of 1 patient required repeat surgery for IOP control and underwent a combined trabeculotomy with trabeculectomy at 9 months and 1 year postoperatively, respectively., Conclusions: This study indicates that goniotomy remains an effective surgical treatment for PCG. The absence of discernible superiority in IOP control or overall outcomes implies that the added complexity of excising the trabecular meshwork in BANG may not confer additional benefits over the established approach., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the long-term visual outcomes in children with primary congenital glaucoma and determined the factors associated with the final visual outcomes. Methods: Medical records of children with primary congenital glaucoma between 2005 and 2016, seen at Seoul National University Children's Hospital in South Korea, were reviewed. The minimum follow-up period after surgery for primary congenital glaucoma was 3 years. Visual acuity (VA) was categorized into good (≧20/70) and poor (< 20/70). Factors including age, VA, refractive errors, intraocular pressure (IOP), laterality, and cup-to-disc (C/D) ratio were compared between the groups. Results: A total of 71 eyes of 44 patients were included. The patients' age at the time of surgery was 14.7 ± 12.2 months. The mean IOP was 28.3 ± 7.0 mmHg. During 6.7 ± 2.7 years of mean follow-up after surgery, 39 eyes (54.9%) needed occlusion treatment. After occlusion, patients with lower IOP values, lesser additional surgeries, reversal of optic disc cupping, and better initially measured VA achieved a better visual outcome. At the final assessment, the mean age was 7.8 ± 2.6 years, and the mean VA gain was 15.0 ± 19.4 letters. There were 44 eyes (62.0%) with VA ≧20/70. Conclusions: In children with primary congenital glaucoma, IOP control and the optic disc configuration over time are important factors associated with visual outcome. Regular follow-up and correction of refractive errors—along with occlusion for those with difference in VA between the two eyes—might be helpful for achieving better visual outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To estimate carrier frequencies of CYP1B1 mutations p.Gly61Glu and p.Arg368His, respectively, in Talesh and the east of Guilan province in Iran with a maximum error of 2%. Previously, it was shown that these CYP1B1 mutations may be relatively prevalent in these regions. Methods: Population-based screenings were performed. DNA was extracted from saliva samples of 1036 individuals from Talesh and 3029 individuals from the east of Guilan. P.Gly61Glu and p.Arg368His screenings were performed, respectively, by RFLP and ARMS-based PCR protocols. For confirmation, the DNA of individuals with mutations was sequenced using the Sanger protocol. Results: Nine individuals from Talesh (0.86%; 95%CI: 0.45--1.64%) carried the p.Gly61Glu mutation, and 73 from the east of Guilan (2.41%; 95%CI: 1.91--3.04%) carried p.Arg368His. There was no significant difference in frequencies between urban and rural regions of the various cities, nor among four cities within the east of Guilan. Conclusion: The frequencies of p.Gly61Glu carriers in Talesh and of p.Arg368His carriers in the east of Guilan were within the 95% confidence interval of a previous study based on screenings of fewer individuals. The reliability of the recent estimates is higher, as the confidence interval for p.Gly61Glu decreased from 6.5% to 1.19% and the interval for p.Arg368His decreased from 4% to 1.13%. Based on the new findings, the maximum expected frequency of p.Gly61Glu carriers in Talesh is 1.64%, and of p.Arg368His carriers in the east of Guilan is 3%. The need for performing premarital screenings in the respective cities can be evaluated. [ABSTRACT FROM AUTHOR]

Purpose: To examine agreement between intraocular pressure (IOP) measurements made using the rebound tonometer Icare ic200 (RT200) and the Perkins handheld applanation tonometer (PAT) in patients with primary congenital glaucoma (PCG). The impacts of several covariables on measurements using the two devices were also assessed. Materials and Methods: Intraocular pressure measurements were made in a single session in 86 eyes of 86 patients with PCG (46 under anaesthesia, 40 in the office). The order was RT200 then PAT. The variables age, central corneal thickness (CCT), corneal state and anaesthesia were recorded in each patient. Data were compared by determining interclass correlation coefficients (ICC) for each tonometer and representing the differences detected as Bland–Altman plots. Effects of covariables were assessed through univariate and multivariate regression. Results: Mean IOP difference between tonometers (RT200 minus PAT) was 1.26 mmHg (95%: 0.22–2.31). Absolute agreement (ICC) was 0.73 (95% CI: 0.62–0.82). Lower and upper limits of agreement (95%) were −8.06 mmHg (95% CI: −9.87 to −6.25) and 10.59 mmHg (95% CI: 8.77–12.40), respectively. The tonometers showed systematic differences (a = −4.63 mmHg; 95% CI: −9.11 to −1.44) and proportional differences; for each mmHg increase in PAT‐IOP, the RT200 reading increased by 1.28 mmHg (b = 1.28; 95% CI: 1.12–1.53). None of the variables tested as predictors were able to explain differences between the tonometers. Conclusions: Despite the good overall agreement between both tonometers, caution should be taken in high values of IOP, considering the interchangeability of its readings as systematic and proportional differences appear to exist between both methods. [ABSTRACT FROM AUTHOR]

Introduction: Primary congenital glaucoma is a rare vision-threatening condition of children. Primary congenital glaucoma though a rare disease it is the most common cause of childhood glaucoma with potency to cause blindness. This study was undertaken to find the prevalence of the children with primary congenital glaucoma under 3 years of age in a tertiary care hospital. Methods: This was a descriptive cross-sectional study conducted at a tertiary eye center in Nepal in children (≤ 3 years) presented in the outpatient department of a tertiary eye hospital between June 2017 and June 2020. The study was approved by the hospital review committee and adhered to the declaration of Helsinki. A convenient sampling method was used. Point estimate at 95% Confidence Interval was calculated with frequency distribution. Data analysis was conducted using Statistical Package for the Social Sciences. Results: Out of total children under 3 years who presented to the outpatient department, 46 (0.31%) at 95% Confidence Interval (0.30-0.32) had primary congenital glaucoma. Among them, 30 children (65.2%) had bilateral involvement. Mean intraocular pressure was 42.40±8.15mm Hg. The mean age of initial presentation, horizontal corneal diameter, and axial length were 12.07±8.9 months, 12.95±1mm, and 23.89±1.7mm respectively. Consanguinity was observed in 12 (26%) children. Conclusions: From the study, we conclude that there was a low prevalence of primary congenital glaucoma among children under 3 years of age who presented to the outpatient department in a tertiary care hospital.

Newborn primary congenital glaucoma (PCG) is an important subtype of PCG. Affected patients manifest specific signs that facilitate its recognition at birth and become important in the determination of appropriate treatment for this severe expression of PCG. Objective clinical evidence supports the occurrence of spontaneous resolution of PCG, explanation for which is unknown. Its mechanism could be related to continued postnatal development of the angle structures in eyes possessing milder angle abnormalities. The anterior segment findings are similar to those of patients with treated PCG such as normal intraocular pressures (IOPs), the optic nerve damage is stable, and filtration angles possess mild or moderate abnormalities. We describe a case of spontaneously resolved PCG in an 8 yearold female presenting with large cornea, Haab's striae, and normal IOP in one eye. Literature review shows limited data about such a case report being described from the Indian subcontinent.

Purpose: To investigate the clinical characteristics and long-term outcomes of primary congenital glaucoma (PCG) patients. Methods: In this retrospective, longitudinal, cohort study, PCG patients with reliable visual field (VF) tests and optical coherence tomography (OCT) were included. Disease progression was detected using guided progression analysis with OCT and the change analysis of mean deviation (MD) slope with VF tests. Factors associated with the disease progression and visual prognosis were analyzed. Results: Twenty-nine eyes from 11 bilateral and 7 unilateral PCG patients were enrolled. LogMAR visual acuity declined (0.15 vs. 0.40, P < 0.001). The change rate of the average retinal nerve fiber layer thickness was − 0.83 ± 1.45 µm/year, and 28% of eyes showed glaucoma progression on OCT. The median of the MD slope was 0.16 (− 1.19 to 1.07) dB/year, and 14% of eyes showed glaucoma progression on the VF test. Higher average intraocular pressure (IOP) (P = 0.046) and IOP fluctuation (P = 0.031) predicted disease progression. None of the fellow eyes of unilateral PCG patients developed glaucoma during the follow-up. At last, 59% of eyes had visual acuity > 20/70, and 31% had MD > − 6 dB. Patients with worse baseline visual acuity (P = 0.027), worse baseline MD (P < 0.001), and smaller neuroretinal rim area (P < 0.001) showed worse final MD values. Conclusions: Aggressive IOP control is necessary to prevent structural and functional decline in PCG patients. Their fellow eyes are not at risk of glaucoma. Baseline neuroretinal rim area can predict the functional outcome. [ABSTRACT FROM AUTHOR]

Purpose: To determine the common gene mutation in patients with primary congenital glaucoma (PCG) in the Southeast region of Turkey via genetic analysis and to evaluate whether there were other gene mutations in these patients. Methods: A total of 25 patients with PCG were included in this study. We performed sequence analysis including all exons of cytochrome p450 1B1 (CYP1B1), myocilin (MYOC), forkhead box C1 (FOXC1), and paired-like homeodomain 2 (PITX2) genes of the obtained samples. Further, we analyzed the results using the Nextgen analysis program. Results: The CYP1B1 gene mutation was detected in 20 (80%) of 25 patients, and FOXC1 gene mutation was detected in one (4%) patient. The mutation site of nine (45%) of the 20 CYP1B1 genes was found in the second exon. The pathogenic variant (p.Gly61Glu) was observed in 12 (60%) patients (in the first and second exons); the mutation type of six (50%) of these patients was homozygous. The mutation site of one patient with FOXC1 gene mutation was found to be in the first exon; its pathogenic variant was p.Met400lle. The mutation type in this gene was observed to be heterozygous. Lastly, there were no mutations in the MYOC, FOXC1, and PITX2 genes in combination with the CYP1B1 gene mutation. Conclusion: The most common cause of PCG in our region is the CYP1B1 gene mutation, and the most frequent pathogenic variant is c.182G > A (p.Gly61Glu). We also determined that the CYP1B1 gene mutation was alone and did not occur with other gene mutations (MYOC, FOXC1, and PITX2). [ABSTRACT FROM AUTHOR]

Background: To evaluate the VEP parameters in operated controlled primary congenital glaucoma (PCG) eyes and compare them to normal age similar children eyes. Methods: A cross-sectional comparative study conducted on 34 (19 right) eyes of 26 (19 males) children operated for PCG and 30 (17 right) eyes of 22 (12 males) age similar control children in a university-based practice. All study participants were subjected to a standard protocol of examination and electrophysiological testing (single flash VEP response, light adapted, pupils not dilated), reporting on the P2 implicit time, N1-P1 and N2-P2 (amplitude). Results: The mean±SD of the age of the study children and controls was 43.22± 33.2 and 55.68± 35.2 months respectively (p=0.217). The mean±SD IOP and cup/disc ratio of the study children were 18.4± 5.2 and 5.2± 3.3mmHg and 0.7± 0.2 and 0.3± 0.3 at presentation and at testing, respectively. The VEP testing was conducted after 21.5± 21.3 months of surgery for PCG. There was no statistically significant differences in P2, N1-P1 and N2-P2 between patients and controls (p=0.941, 0.916,0.945, respectively). There was no statistically significant correlation between most of the clinical characteristics of the study eyes and any of the studied VEP parameters. Conclusion: Operated controlled PCG eyes have VEP parameters that match their normal fellow children. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the surgical success after trabeculotomy for primary congenital glaucoma (PCG) in Denmark in the last 40 years. Methods: Retrospective review of medical files on children who all underwent trabeculotomy as the first surgical intervention between January 1rst, 1977 and December 31, 2016. Information on diagnosis and surgical procedures were extracted. Primary outcome was surgical success was defined as intraocular pressure (IOP) < 21 mmHg without medications one year after surgery. Secondary outcome was the number of reoperations needed. Results: Out of 118 children with PCG, 96 children (144 eyes) had an ab externo trabeculotomy as primary IOP lowering procedure opening Schlemm's channel 4 clock hours into the anterior chamber. Complete surgical success at one year was achieved in 73% (106 of 144 eyes). On the long term, IOP could be controlled by one surgical procedure in 2/3 of children, eight eyes required >5 surgical procedures to control IOP. In 12.1% of children the second glaucoma procedure was performed >5 years after the initial trabeculotomy. There was a tendency towards greater risk of needing a second procedure in patients < 3 months of age at primary trabeculotomy (hazard ratio, HR, 2.01, 95% CI 0.96–4.22) and in boys (HR 2.02, 95% CI 0.97–4.18) and a lower risk of requiring a third surgery if the second surgery was trabeculectomy with MMC. Conclusion: Dedicated follow‐up of patients with PCG is essential as the disease may continue to progress even after years of quiescence and some children need multiple surgeries to control IOP. Additional glaucoma procedures are required in 1/3 of children and boys and younger patients seem to be at greater risk. [ABSTRACT FROM AUTHOR]

Objective: To report the flash visual evoked potential (VEP) findings in children with primary congenital glaucoma (PCG) before and after successful surgical control of the intraocular pressure (IOP). Methods: The study enrolled children presenting with PCG to the Ophthalmology Department of Alexandria Main University Hospital in the period between June and December 2019. All study participants were subjected to a standard protocol of examination, to confirm the diagnosis of PCG. The child was then referred for flash VEP testing. Peaks were designated as negative and positive waves in a numerical sequence (N1, P1, N2, P2, N3 and P3). The child was then scheduled for surgery within 1 week of presentation. Postoperative VEP testing was scheduled as soon as feasible and was conducted in the same way as the preoperative VEP testing. Results: The study was conducted on 11 (four right) eyes of eight (five males) children. The mean ± standard deviation of the age of the study children at presentation and at postoperative VEP testing was 3.5 ± 1.6 and 5.1 ± 3.0 months, respectively. The study eyes mean ± standard deviation IOP at presentation and at postoperative VEP testing was 23.0 ± 6.7 and 8.3 ± 2.4 mmHg, respectively (p < 0.0001). There were a statistically insignificant reduction in P2 implicit time (p = 0.235) and a statistically insignificant increase in each of N1–P1 (p = 0.15) and N2–P2 (p = 0.67) amplitudes postoperatively than preoperatively. Conclusions: IOP elevation in PCG adversely affects the optic nerve function, but, at least in the short term, has no permanent detrimental effect on the optic nerve function as evidenced by the improvement in the VEP parameters. [ABSTRACT FROM AUTHOR]

An asymptomatic 3-year-old child presented with megalocornea, mild corneal haze, high intraocular pressure, and advanced optic disc damage in both eyes. The child was taken up for trabeculectomy and trabeculotomy in the right eye and trabeculectomy alone in the left eye. Due to the failure of the procedure in the right eye, Aurolab aqueous drainage implant was placed. The asymptomatic nature of the child led to the late presentation with advanced disc damage. Therefore, awareness of subtle signs of congenital glaucoma is crucial among the pediatricians for proper screening and referral.

AIM: To identify the novel mutation alleles in the CYP1B1 gene of primary congenital glaucoma (PCG) patients at Shandong Province of China, and investigate their correlation with glaucomatous features. METHODS: The DNA from the peripheral blood of 13 congenital glaucoma patients and 50 ethnically matched healthy controls from the affiliated hospital of Qingdao University were extracted. The coding region of the CYP1B1 gene was amplified by PCR and direct DNA sequencing was performed. Disease causing-variants were analyzed by comparing the sequences and the structures of wild type and mutant CYP1B1 proteins by PyMOL software. RESULTS: Two missense mutations, including A330F caused by c.988G>T&c.989C>T, and R390H caused by c.1169G>A, were identified in one of the 13 PCG patients analyzed in our study. A330F mutation was observed to be novel in the Chinese Han population, which dramatically altered the protein structure of CYP1B1 gene, including the changes in the ligand-binding pocket. Furthermore, R390H mutation caused the changes in heme-protein binding site of this gene. In addition, the clinical phenotype displayed by PCG patient with these mutations was more pronounced than other PCG patients without these mutations. Multiple surgeries and combined drug treatment were not effective in reducing the elevated intraocular pressure in this patient. CONCLUSION: A novel A330F mutation is identified in the CYP1B1 gene of Chinese PCG patient. Moreover, in combination with other mutation R390H, this PCG patient shows significant difference in the CYP1B1 protein structure, which may specifically contribute to severe glaucomatous phenotype.

AIM: To identify CYP1B1 gene mutations and evaluate their possible role as a prognostic factor for success rates in the surgical management of Egyptian congenital glaucoma patients. METHODS: Totally 42 eyes of 29 primary congenital glaucoma patients were operated on with combined trabeculotomy/trabeculectomy with mitomycin-C and followed up at 1d, 1wk, 1, 6 and 12mo postoperatively. Genomic DNA was extracted from peripheral blood leukocytes. Coding regions of CYP1B1 gene were amplified using 13 pairs of primers, screened for mutations using single-strand conformation polymorphism followed by sequencing of both strands. Efficacy of the operation was graded as either a success [maintaining intraocular pressure (IOP) less than 21 mm Hg with or without anti-glaucoma medication], or a failure (IOP more than 21 mm Hg with topical antiglaucoma medications). RESULTS: Seven novel mutations out of a total of 15 different mutations were found in the CYP1B1 genes of 14 patients (48.2%). The presence of CYP1B1 gene mutations did not correlate with the failure of the surgery (P=0.156, odds ratio=3.611, 95%CI, 0.56 to 22.89); while the positive consanguinity strongly correlated with failure of the initial procedure (P=0.016, odds ratio=11.25, 95%CI, 1.57 to 80.30). However, the Kaplan-Meier survival analysis revealed a significantly lower time of IOP control in the subgroup with mutations in CYP1B1 versus the congenital primary glaucoma group without mutations (log rank test, P=0.015). CONCLUSION: Seven new CYP1B1 mutations are identified in Egyptian patients. Patients harboring confirmed mutations suffered from early failure of the initial surgery. CYP1B1 mutations could be considered as a prognostic factor for surgery in primary congenital glaucoma.

AIM: To evaluate the outcome of the initial and the redo-surgeries for primary congenital glaucoma (PCG) correlated to its degree of severity. METHODS: A retrospective study involved patients with PCG presented between 2010 and 2018. Medical records were reviewed to assess the degree of the preoperative severity according to the intraocular pressure (IOP), corneal diameter and corneal edema. Success and failure rates were calculated for both first and redo-surgeries at 6 and 12mo respectively then correlated to the severity of the cases. RESULTS: Complete records were retrieved for 272 eyes (153 patients) with PCG: 43 eyes were mild, 136 moderate and 93 severe. Combined trabeculotomy and trabeculectomy (CTT) had the highest success rate in moderate (96.4%) and severe cases (59.3%) while trabeculotomy had the highest success rate in mild cases (96.3%). Medical records of 88 eyes (63 patients) with recurrent PCG were analyzed, most with severe presentation (59 eyes). Ahmed glaucoma valve (AGV) was used in 67 (76%) eyes and augmented trabeculectomy in 21 (24%) eyes. At 12mo, there was no statistically significant difference between both surgeries in total success rate (P=0.256). For mild cases, success rate was 100% for both surgeries. Severe cases had higher success rates following AGV (87%) than augmented trabeculectomy (20%). Preoperative severity of the disease was an independent factor affecting the failure rate in secondary trabeculectomy but not in AGV. Patients younger than 24mo had higher probabilities of failure following both redo-surgeries with hazard ratio =1.325 and 0.37 for augmented trabeculectomy and AGV respectively. CONCLUSION: Preoperative assessment of the severity of eyes with PCG helps in the selecting the optimal primary and secondary surgery. For first surgery, trabeculotomy is more effective in mild cases whereas; CTT and augmented subscleral trabeculectomy (SST) are appropriate for moderate and severe cases. AGV proved to be superior to augmented SST in severe recurrent cases.

Purpose: Primary congenital glaucoma (PCG) is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic causes of PCG segregating in 36 large consanguineous Pakistani families. Methods: Ophthalmic examination including fundoscopy, or slit-lamp microscopy was performed to clinically characterize the PCG phenotype. Genomic nucleotide sequences of the CYP1B1 and LTBP2 genes were analyzed with either Sanger or whole exome sequencing. In silico prediction programs were used to assess the pathogenicity of identified alleles. ClustalW alignments were performed to determine evolutionary conservation, and three-dimensional (3D) modeling was performed using HOPE and Phyre2 software. Results: Among the known loci, mutations in CYP1B1 and LTBP2 are the common causes of PCG. Therefore, we analyzed the genomic nucleotide sequences of CYP1B1 and LTBP2, and detected probable pathogenic variants cosegregating with PCG in 14 families. These included the three novel (c.542T>A, c.1436A>G, and c.1325delC) and five known (c.868dupC, c.1168C>T, c.1169G>A, c.1209InsTCATGCCACC, and c.1310C>T) variants in CYP1B1. Two of the novel variants are missense substitutions [p.(Leu181Gln), p.(Gln479Arg)], which replaced evolutionary conserved amino acids, and are predicted to be pathogenic by various in silico programs, while the third variant (c.1325delC) is predicted to cause reading frameshift and premature truncation of the protein. A single mutation, p.(Arg390His), causes PCG in six (~43%) of the 14 CYP1B1 mutations harboring families, and thus, is the most common variant in this cohort. Surprisingly, we did not find any LTBP2 pathogenic variants in the families, which further supports the genetic heterogeneity of PCG in the Pakistani population. Conclusions: In conclusion, results of the present study enhance our understanding of the genetic basis of PCG, support the notion of a genetic modifier of CYP1B1, and contribute to the development of genetic testing protocols and genetic counseling for PCG in Pakistani families.

AIM: To find the CYP1B1 mutations associated with primary congenital glaucoma (PCG) in Pakistani consanguineous pedigrees. METHODS: After getting informed consent, 11 consanguineous pedigrees belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundaries of CYP1B1 gene were directly sequenced. Bioinformatics tools were used to model the mutant protein and predict the effect of novel variants on protein structure and function. RESULTS: Sequencing analysis revealed 5 different CYP1B1 variants in 7 families (7/11; 64%), including two novel variants. A common mutation, p.R390H was found in four families, whereas p.P437L was found once in a family. Two novel variants, a homozygous non sense variant p.L13* and a compound heterozygous variant, p.P350T along with p.V364M were segregating with PCG in two families. All the patients had the variable onset and severity of the disease. The success rate of early clinical interventions was observed dependent on mutation types and position. Two different haplotypes were associated with frequently found mutation, p.R390H. CONCLUSION: Identification of novel CYP1B1 variants reassert the genetic heterogeneity of Pakistani PCG patients. The patients with missense mutations show severe phenotypic presentations and poor vision after surgical interventions as compare to patients with null variants. This may help to better understand the role of CYP1B1 mutations in the development of PCG and its course of pathogenicity.

PURPOSE: To study circumferential trabeculotomy for congenital glaucoma using Glaucolight illuminated microcatheter. METHODS: This was a prospective, uncontrolled, consecutive interventional study of 25 eyes of 25 patients with primary congenital glaucoma (PCG) underwent circumferential trabeculotomy done with an illuminated microcatheter through a period of 18-24 months in ophthalmology department, faculty of medicine, Minia University, Egypt. Patients' data of 12 months' follow-up were recorded. The primary target was the mean intraocular pressure (IOP) study in which complete success was defined as an IOP ≤21 mm Hg and at least a 30% reduction without the use of antiglaucoma drugs and a qualified success when medications were used to reach this aim. The secondary target was studying the corneal diameter and cup disc ratio change. RESULTS: The mean IOP (mm Hg) was reduced from 27.28 ± 3.46 preoperatively to 17.50 ± 5.09 at the final postoperative visit (P < 0.001). The mean follow-up period length was (18 months). A qualified success rate was reached to 88%, complete success in 76% and failure in 12%. No serious surgical complications were observed. CONCLUSION: Circumferential trabeculotomy accomplished by an illuminated microcatheter achieved a significant IOP lowering with either qualified or complete success in most of eyes with no significant ocular complications and it can be the first option in pediatric PCG surgery. [ABSTRACT FROM AUTHOR]