TEK gene-related primary congenital glaucoma: Phenotypic features and mutational spectrum in a Mexican cohort of 10 unrelated families.

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

The correlation of anterior segment structures in primary congenital glaucoma by ultrasound biomicroscopy with disease severity and surgical outcomes.

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

Childhood glaucoma profile in a Southwestern Ethiopia tertiary care center: a retrospective study.

BACKGROUND: Childhood glaucoma is a major cause of childhood blindness worldwide. The profile of childhood glaucoma has not been well characterized in sub-Saharan Africa. Thus, this study was designed to describe demographics, clinical features, managements of childhood glaucoma, and improvements in visual acuity (VA) and intraocular pressure (IOP) from baseline to final visit. METHODS: This retrospective study included glaucoma patients below 18 years old who were diagnosed between September 2019 to August 2022. Childhood glaucoma diagnosis and classification was made as per the Childhood Glaucoma Research Network Classification (CGRN). RESULTS: A total of 105 children (181 eyes) were diagnosed with glaucoma. The most common type of childhood glaucoma was primary congenital glaucoma (PCG) constituting (42%, n = 76 eyes, 95% confidence interval (CI), 34.7-49.5%; P = 0.037), followed by glaucoma suspect (22.1%, n = 40 eyes, 95% CI, 16.3-28.9%; P < 0.001) and juvenile open-angle glaucoma (JOAG) (15.5%, n = 28 eyes, 95% CI, 10.5-21.6%; P < 0.001). While the most common type of secondary glaucoma was steroid-induced glaucoma, followed by glaucoma following cataract surgery. Bilateral glaucoma was found in 72.4% (n = 76 children, 95% CI, 62.8-80.7%; P < 0.001) of children. In both primary and secondary glaucoma, boys were affected more than girls, in ratio of 2:1 and 2.7:1, respectively. The mean age at presentation for patients with PCG was 2.7 years. Close to 93.4% (71) of PCG eyes were managed surgically, of which majority underwent combined trabeculotomy and trabeculectomy (CTT). Most of secondary glaucoma cases were treated medically. Overall, 85.3% (111) of eyes had successful control of IOP ≤ 21 mmHg. CONCLUSION: PCG was the most common type of childhood glaucoma. One of a well-recognized challenge in developing countries, late presentation of patients with PCG, was also observed in our study. Which highlights, the need of increasing access to eye-care service and awareness of childhood glaucoma as a major public health issue. Steroid-induced glaucoma was the most common type of secondary glaucoma; appropriate measures should be taken to prevent this preventable glaucoma.

Outcomes of gonioscopy-assisted transluminal trabeculotomy in primary congenital glaucoma treatment: a retrospective study.

BACKGROUND: This retrospective study aimed to evaluate the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in Chinese patients with primary congenital glaucoma (PCG) and identify factors influencing surgical success. METHODS: Fourteen patients (24 eyes) diagnosed with PCG who underwent gonioscopy-assisted transluminal trabeculotomy were recruited, and data on intraocular pressure (IOP), antiglaucoma medication, surgery-related complications, and additional treatments were collected during preoperative and postoperative visits. Surgical success was defined as IOP ≤ 21 mmHg and a reduction of > 30% from baseline, with (partial success) or without (complete success) antiglaucoma medication. RESULTS: Mean preoperative IOP was 30.41 ± 6.09 mmHg. At the final visit, mean IOP reduction was 16.1 ± 9.1 mmHg (52%), and 19 of 24 eyes were topical medication-free. IOP was significantly decreased at each postoperative visit compared with baseline (P < 0.05 for all time points). Cumulative proportions of complete and partial success were 79.2% and 95.8%, respectively, at three years postsurgery. Patients without prior antiglaucoma procedures, without postoperative IOP spikes, and those undergoing complete trabeculotomy exhibited improved surgical prognosis. No permanent vision-threatening complications occurred in the 24 eyes by the end of the respective follow-ups. CONCLUSION: Gonioscopy-assisted transluminal trabeculotomy emerged as a safe and effective procedure for PCG treatment, characterized by outstanding IOP reduction efficacy and high surgical success rates.

Long-term follow-up results and visual outcomes of childhood glaucoma in the black sea region of turkey.

PURPOSE: To investigate long-term visual outcomes and factors associated with low vision in patients with childhood glaucoma. MATERIALS AND METHODS: A retrospective review was conducted on the medical records of pediatric glaucoma patients at the Ondokuz Mayis University Ophthalmology Clinic from 2005 to 2023. The patients were categorized into three groups: primary congenital glaucoma (PCG), secondary childhood glaucoma, and glaucoma following cataract surgery (GFCS). Groups were analyzed regarding visual acuity (VA), ocular conditions and comorbidities, and the cause of visual impairment. The study also investigated the potential risk factors associated with visual impairment. RESULTS: A total of 105 eyes of 60 patients with a mean age of 9.7 ± 5.5 years were included in the study. The mean VA in logMAR was 0.59 ± 0.52. At the final follow-up, 34.1% had good VA (≥ 20/50), 29.5% had moderate VA (20/50-20/200), and 36.4% had poor VA (< 20/200). The final mean intraocular pressure (IOP) was 16.2 ± 6.2 mmHg. Amblyopia was the leading cause of vision loss (38.2%), followed by glaucomatous damage (36.4%). Patients with GFCS had a higher rate of visual impairment (42.4%) and refractive error. The results of the regression analysis showed that low vision was associated with undergoing more than two surgeries, high IOP at baseline, high initial and final cup-to-disc (C/D) ratio, and high initial central corneal thickness (CCT) (CI 95%, p = 0.018, p= 0.017, p = 0.013, p = 0.003, p = 0.001, respectively). CONCLUSION: Good VA can be achieved in 34.1% of childhood glaucoma cases. However, the VA prognosis may be worse in patients with GFCS. Achieving good visual outcomes in childhood glaucoma requires timely and effective treatment, consideration of risk factors, and management of amblyopia and ocular comorbidities.

Long-term Outcomes in Patients Undergoing Surgery for Primary Congenital Glaucoma between 1991 and 2000: A Single-Center Database Study.

PURPOSE: To estimate the long-term surgical and visual outcomes in patients with primary congenital glaucoma (PCG) who completed at least 20 years of follow-up. DESIGN: Retrospective study. PARTICIPANTS: Two hundred twenty eyes of 121 patients undergoing surgery for PCG between January 1991 and December 2000 and who returned for a follow-up visit from January 2021 through January 2022. METHODS: Retrospective review of medical records of patients who underwent primary combined trabeculotomy-trabeculectomy (CTT) without mitomycin C as an initial procedure. Success was defined as complete when intraocular pressure (IOP) was ≥ 6 mmHg and ≤ 21 mmHg without glaucoma medication and as qualified when up to 2 glaucoma medications were required. Failure was defined as uncontrolled IOP with more than 2 glaucoma medications, need for a second IOP-lowering procedure, chronic hypotony (IOP < 6 mmHg on 2 consecutive visits), or any sight-threatening complication. A mixed-effects model using maximum likelihood estimation was used in estimation of eye-based variables and to make comparisons between different visits. Kaplan-Meier survival analysis was used to estimate the probabilities of surgical and functional successes. Cox proportional hazards regression using sandwich clustered estimation was used to evaluate risk factors for failure and poor visual outcome. MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of patients who demonstrated complete success over the 20-year follow-up. Secondary outcome measures included rate of surgical failure and need for reoperation for glaucoma, visual acuity, refractive errors, risk factors for poor outcome, and complications. RESULTS: Kaplan-Meier survival analysis revealed 1-year, 10-year, and 20-year complete success rates of 90.7%, 78.9%, and 44.5%, respectively. In univariate analysis, surgical failure was higher among patients with any additional non-glaucoma intraocular surgery. None of the clinical parameters were associated significantly with failure in multivariable analysis. Overall, the proportion of eyes with good, fair, and poor visual outcomes was 33.2%, 16.4%, and 50.4%, respectively. Myopia was seen in 68.9% eyes. Twenty-eight eyes of those who underwent primary CTT (14.4%) required second surgery for IOP control. No significant intraoperative complications occurred. Six eyes required enucleation because of painful blind eye. CONCLUSIONS: In this large cohort of patients with PCG, CTT is a useful procedure. It provides good IOP control and moderate visual recovery that remained over a 20-year follow-up after surgery. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma.

Objective: To identify the genetic variants in the CYP1B1 gene associated with Primary Congenital Glaucoma (PCG) and to predict its pathological effect. Method: A descriptive study was conducted in the time period of nine months (September 2021-May 2022) after the ethical approval was taken from The Children Hospital and Institute of Child Health (CH & ICH). Two milliliters of the blood sample from PCG-affected individuals were collected in EDTA vacutainers and genomic DNA was extracted by a phenol-chloroform method. The semi-quantification of extracted DNA was done by agarose gel electrophoresis. PCR amplification was performed by specific primers of CYP1B1 gene then termination sequencing (di-deoxy) was done to detect the genetic variants. Different bioinformatics tools such as BLAST, Ensembl, Clustal Omega, Polyphen and SIFT were used for the further analysis of mutation causing the disease. Result: A total of 85% of patients were bilaterally affected, while 15% were unilaterally affected. Mutation analysis identified five non related known variants. Two missense mutations (c.355 G/T p.A119S and c.685G/A p.E229K) occurred in 94% patients and intragenic SNP occurred in 29% patients along with the 1% somatic (c.693C/A p.F231L) and stop gained mutation (c.840C/A p.C280*). Conclusion: Genetic analysis in the current study showed that 85% of PCG affected patients were due to the CYP1B1 mutation, and disease heterogeneity might be reduced through genetic counseling.

Long-Term Visual Outcomes of Primary Congenital Glaucoma in China.

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.

Approach to childhood glaucoma: A review.

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.

Visual outcomes and associated factors of primary congenital glaucoma in children.

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.

Long-term structural and functional outcomes of primary congenital glaucoma.

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.

Retinal nerve fibre layer thickness measurements in childhood glaucoma: the role of scanning laser polarimetry and optical coherence tomography.

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.

The Epidemiological and Clinical Findings from the Latvian Registry of Primary Congenital Glaucoma and Evaluation of Prognostic Factors.

Background and objectives: primary congenital glaucoma (PCG) is a rare, potentially blinding disease that affects children worldwide. The aim of the study was to describe the epidemiological and clinical characteristics, outcomes for newly diagnosed patients with PCG, as well as evaluate the prognostic factors that are related to the outcomes. Materials and Methods: a retrospective cohort study was conducted at a tertiary referral centre among patients diagnosed with PCG. Evaluation of the clinical data was performed preoperatively at three, six, and 12 months after the surgery and at the last follow-up. Results: during the 15 years of follow-ups, 24 eyes of 18 patients were diagnosed with PCG. Unilateral and bilateral PCG constituted 50% of cases each. A slight male predominance was observed (55.6% vs. 44.4%), with a relative risk of 1.3. The incidence of PCG was 1:19,033 live births. The mean age of the patients at the time of diagnosis was 10.1 ± 10.0 months, with a diagnostic delay of 2.0 ± 1.9 months. Furthermore, 75% of patients indicated an enlargement of an eyeball, followed by excessive tearing (58.3%) and corneal opacity (41.7%). After 85.9 ± 51.2 months, the mean intraocular pressure (IOP) value was 14.6 ± 4.9 mmHg. Surgical treatment provided sufficient IOP control in 75% of PCG cases at the last follow-up visit. The only prognostic factor that was related to the outcome of IOP control that was statistically significant was axial length at the time of diagnosis. Conclusions: the incidence of PCG in Latvia was 5.3 patients per 100,000 live births. PCG was more common among males than females with a relative risk of 1.3. The enlargement of an eyeball was the leading clinical sign.

Genetic analysis of patients with primary congenital glaucoma.

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).

Visual evoked potentials changes with surgery in primary congenital glaucoma: a pilot study.

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.

Mutational analysis of CYP1B1 gene in Iranian pedigrees with glaucoma reveals known and novel mutations.

PURPOSE: Primary congenital glaucoma (PCG) (OMIM#231,300) can be caused by pathogenic sequence variations in CYP1B1, LTBP2, MYOC and PXDN genes. The purpose of this study was to investigate mutations in the CYP1B1 gene in families affected with primary congenital glaucoma (PCG) using linkage analysis and Sanger sequencing. METHODS: A total number of four families with nine affected PCG patients during six months were included in this study. The mutations were identified by homozygosity mapping to find the linked loci and then direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA obtained from affected family members and their parents. Moreover, bioinformatic tools were applied to study mutation effect on protein structure and function. RESULTS: A total of four mutations were identified, and three of these were novel. Two were missense mutations: One was truncating mutation, and the other was an in-frame deletion. Mutations in CYP1B1 could fully explain the PCG phenotype in all of the patients. Also, the bioinformatic study of the mutations showed the structure of the protein is affected, and it is well conserved among similar species. CONCLUSION: In this study, we identified 4 CYP1B1 mutations, 3 of which were novel. In silico analysis of identified mutations confirmed their molecular pathogenicity. A similar analysis will help understand the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG. CLINICAL TRIALS REGISTRATION: Not relevant.

Viscocanalostomy combined with nearly 360-degree suture trabeculotomy for the treatment of primary congenital glaucoma: a preliminary report of a novel technique for trabeculotomy.

PURPOSE: The aim of this study was to determine the preliminary efficacy and safety of a novel technique for trabeculotomy for the treatment of primary congenital glaucoma (PCG). METHODS: This retrospective interventional study was conducted on patients with PCG. Pliability test was performed among 5/0 and 6/0 polypropylene sutures and the flexible illuminated microcatheter. Viscocanalostomy was first performed and the Schlemm's canal was identified. Then, suture trabeculotomy was completed except the region for viscocanalostomy. The preoperative and follow-up data were recorded and analyzed. Success criteria were defined as intraocular pressure (IOP) ≤ 21 mmHg without (complete success) or with medications (qualified success). RESULTS: 5/0 polypropylene suture was an appropriate option for cannulation of Schlemm's canal. A total of 33 eyes from 23 consecutive patients were included with a mean follow-up of 9.3 ± 3.6 months (range 6-18 months). Circumferential cannulation by suture was successfully performed in 28 eyes (84.8%) of 18 patients. Mean IOP decreased from 33.9 ± 9.4 mmHg preoperatively to 10.5 ± 3.5 mmHg at 6 months (p < 0.001) and 11.3 ± 4.1 mmHg at 9 months (p < 0.001). Complete success rate was 92.9% [95% confidence interval (CI:0.83-1.03)] and 87.5% (CI:0.69-1.06) at 6 months and 9 months, respectively. Hyphema was found in 5 eyes (17.9%), all of which were absorbed within 1 week. No other complications were observed. CONCLUSIONS: Viscocanalostomy combined with nearly 360-degree suture trabeculotomy as a novel technique controls IOP in patients with PCG without any severe complications. It is suitable for extended applications because of accurate identification of Schlemm's canal and low cost.

Severity of visual field defects in primary congenital glaucoma and their risk factors.

PURPOSE: The primary objective of the study was to assess the frequency and severity of visual field defects (VFD) in primary congenital glaucoma (PCG). The secondary objective was to ascertain any associated risk factors. METHODS: An ambispective review of patients with PCG on follow-up with a 'target' intraocular pressure (IOP) of ≤ 15 mmHg. Age, sex, laterality, duration of follow-up, baseline IOP, baseline cup-disc ratio (CDR), central corneal thickness (CCT), age during filtering surgery, second surgery if any, yearly IOP, glaucoma medications and best corrected visual acuity from 2013 (year 1) to the final review and final CDR were noted down. Children ≥ 5 years of age with best corrected visual acuity ≥ 6/60 were subjected to manual kinetic Goldmann perimetry, and visual field defects (VFD) were identified. RESULTS: Seventy-one of 90 eyes completed a reliable kinetic perimetry. The mean age of children was 12.34 ± 4.86 years, and the mean follow-up duration was 10.77 ± 4.69 years. Baseline IOP and CDR were 29.07 ± 8.83 mmHg and 0.66 ± 0.22, respectively. 86.67% of eyes underwent a trabeculotomy + trabeculectomy with mitomycin-C. Thirty-one eyes (34.44%) required a second surgery, 25 of which were bleb revisions and 3 trabeculectomies. Mean IOP and CDR during last visit were 10.23 ± 2.76 mmHg and 0.52 ± 0.25, p < 0.001 as compared with baseline. On Goldmann perimetry, 19 eyes, 26.76%, had defects, arcuate scotoma being most frequent. On the Fisher exact test, a baseline/final CDR > 0.8, undergoing just a trabeculectomy with MMC, needing ≥ 2 glaucoma medications on review or a repeat trabeculectomy was associated with greater severity of VFD. On univariate logistic regression, eyes that needed a bleb revision [OR, 95% CI 9.75 (2.66-35.67), p = 0.001], a repeat trabeculectomy with mitomycin-C [OR (CI) 18 (1.31-245.58), p = 0.03] and final CDR of > 0.8 [OR (CI) 23.1 (3.7-144.21), p = 0.001] were associated with VFD. On multivariable regression analysis, female sex [OR (CI) 18 (2.01-161.04), p = 0.01] was identified as the single most important risk factor for development of a VFD. CONCLUSION: At a 'target' IOP of ≤ 15 mmHg, 26.76% of PCG eyes manifested a VFD over 10 years. Baseline and/or final CDR > 0.8, necessity for ≥2 medications or a repeat glaucoma surgery, and female sex were identified as risk factors for development and greater severity of glaucomatous VFD.

Ab interno vs ab externo microcatheter-assisted trabeculotomy for primary congenital glaucoma with clear cornea.

IMPORTANCE: This is the first comprehensive comparison between ab interno approach and ab externo approach for microcatheter-assisted trabeculotomy in primary congenital glaucoma with clear cornea. BACKGROUND: Ab externo microcatheter-assisted trabeculotomy is considered to be the gold standard for primary congenital glaucoma. The novel ab interno approach would intuitively be similar to ab externo approach for microcatheter-assisted trabeculotomy in eyes with clear cornea; however, there is no evidence yet. DESIGN: Non-contemporary comparison of retrospective case series. PARTICIPANTS: Fifty-eight and fifty-seven consecutive primary congenital glaucoma eyes with clear corneas underwent ab interno and ab externo microcatheter-assisted trabeculotomy, respectively. METHODS: Retrospective comparison of clinical outcomes. MAIN OUTCOME MEASURES: Surgical success was defined as a postoperative intraocular pressure of ≤21 mmHg with at least a 30% reduction from preoperative IOP with or without the use of anti-glaucoma medication (qualified and complete success, respectively). RESULTS: The qualified success rate (87.9% vs 82.2%, P = .40) and complete success rates (81.0% vs 73.3%, P = .32) were comparable between groups. Complications were minimal and comparable. Less than 360° trabeculotomy (P = .009) and a higher number of previous surgeries (P = .03) were both associated with worse surgical outcomes. CONCLUSIONS AND RELEVANCE: Ab interno approach provide good and comparable outcomes as ab externo approach for microcatheter-assisted trabeculotomy in primary congenital glaucoma eyes with clear cornea. It should be considered as the initial choice in these patients with the benefit of sparing conjunctiva. Successful trabeculotomy with either technique during the first attempt is critical to overall success and underscores the need for proficiency before independent practice.

Risk factors for primary congenital glaucoma in the National Birth Defects Prevention Study.

Primary congenital glaucoma (PCG) is a rare but serious birth defect. Genetic mutations have been implicated in the development of PCG, but little is known about nongenetic risk factors. This study investigates potential risk factors for PCG in the National Birth Defects Prevention Study (NBDPS), a large population-based case-control study of major birth defects in the United States. The analysis includes case infants with PCG (N = 107) and control infants without birth defects (N = 10,084) enrolled in NBDPS from birth years 2000-2011. Pregnancy/infant clinical characteristics, demographics, and parental health history were collected through maternal interview. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to examine associations with all PCG cases and isolated PCG cases without other major malformations. Associations with all the cases included term low birth weight (<2,500 g; aOR = 2.80, CI 1.59-4.94), non-Hispanic black maternal race/ethnicity (aOR = 2.42, CI 1.42-4.13), maternal history of seizure (aOR = 2.73, CI 1.25-5.97), maternal antihypertensive use (aOR = 3.60, CI 1.52-8.53), and maternal sexually transmitted infection (aOR = 2.75, CI 1.17-6.44). These factors were also associated with isolated PCG, as was maternal use of nonsteroidal anti-inflammatory drugs (aOR = 2.70, CI 1.15-6.34). This study is among the first to examine a wide array of potential risk factors for PCG in a population-based sample.