Potential Involvements of Cilia-Centrosomal Genes in Primary Congenital Glaucoma.

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

Treatment Outcomes of Primary Combined Trabeculotomy With Trabeculectomy in Early Onset Glaucoma With Sturge-Weber Syndrome.

PRCIS: In eyes with Sturge-Weber syndrome (SWS) with early onset glaucoma, primary combined trabeculotomy with trabeculectomy (CTT) had a good intermediate-term success rate and minimal postoperative complications. DESIGN: Retrospective cohort study. OBJECTIVE: To report the intermediate-term outcomes of primary CTT in early onset glaucoma with SWS. PATIENTS AND METHODS: This study included 49 eyes of 49 children (1997-2020) with SWS and early onset glaucoma who underwent primary CTT with at least 1-year postoperative follow-up. Success was defined as complete when intraocular pressure was >5 mm Hg and ≤16 mm Hg under general anesthesia or ≤21 mm Hg in the clinic without antiglaucoma medications (AGMs) and as qualified with AGM. RESULTS: The median age (interquartile range) at CTT was 0.58 (0.19, 8.3) years. The median postoperative follow-up was 4.7 years (2.5, 9). The majority were male children (31/49, 63%). Epilepsy was noted in 7 (14.3%) and diffuse choroidal hemangioma in 17 children (35%). At diagnosis, 37 eyes(75%), had corneal edema, and the mean (±SD) horizontal corneal diameter was 12.8 ± 0.7 mm. Postoperatively, the median intraocular pressure decreased from 26 (22, 30) mm Hg to 16 (12, 20) mm Hg ( P < 0.0001) and the median number of AGM reduced from 1 (0,1) to 0 (0,1; P < 0.01). Complete success probability of CTT was 86% (76, 96) at 1 year and 64% (49, 84) at 5 years. Qualified success was 98% (94, 100) at 1 year and 89% (78, 100) at 5 years. A larger cup-to-disk ratio ( P < 0.005) was associated with a higher risk of surgical failure. Postoperative complications were noted in 9 eyes (18%), all resolved with conservative management except one eye with a retinal detachment that ended in phthisis bulbi. CONCLUSION: CTT as a primary procedure showed good long-term efficacy and safety in SWS with early onset glaucoma.

Profile of Newly Diagnosed Childhood Glaucoma in India: Indian Childhood Glaucoma Study (ICGS) Group 1.

OBJECTIVE: To report the profile of newly diagnosed childhood glaucoma using the Childhood Glaucoma Research Network (CGRN) classification, presenting over 1 year from across centers in India. DESIGN: Prospective observational multicentric study. SUBJECTS: Newly diagnosed children aged < 18 years diagnosed with childhood glaucoma according to CGRN criteria presenting between January and December 2019 to 13 centers across India. METHODS: All children underwent a comprehensive ocular examination, including examination under anesthesia for younger children, and were diagnosed with childhood glaucoma as per CGRN. Data were entered in a standard Excel chart. Refraction and visual acuity assessments were done when feasible. MAIN OUTCOME MEASURES: The profile of newly diagnosed childhood glaucoma in different parts of India and the severity of glaucoma at presentation. RESULTS: A total of 1743 eyes of 1155 children fulfilled the definition of glaucoma and were analyzed. Primary congenital glaucoma (PCG) comprised the single largest group (34.4%), most of which were infantile onset (19%). Neonatal-onset PCG comprised 6.2% of all glaucoma. Secondary glaucoma constituted 53.4% of all glaucoma, one-half of which were acquired conditions (28%), followed by isolated ocular anomalies (14.7%), glaucoma after cataract surgery (6.7%), and glaucoma with nonacquired systemic diseases (4.5%). Of the 1743 eyes with glaucoma, all 3 parameters for severity grading were available in 842 eyes, of which 501 (59.5%) eyes presented with mild, 320 (38%) with moderate, and 21 (2.5%) with severe glaucoma. Nearly one-third of the children (28.5%) were not brought back for follow-up after the initial treatment given. CONCLUSIONS: Our study has one of the largest numbers of consecutive children with glaucoma classified according to the CGRN classification. Despite a widely diverse population, the profile of childhood glaucoma was relatively uniform across India. Childhood glaucoma is a significant problem in India, primarily treated in tertiary care hospitals. The data presented may be the tip of the iceberg because we have only reported the children who reached the hospitals offering treatment for this challenging disease. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

Corneal Endothelial Features in Patients Operated for Primary Congenital Glaucoma.

PURPOSE: To compare the corneal endothelial cell morphology using specular microscopy imaging between primary congenital glaucoma (PCG) and age-matched healthy controls, and to determine if the endothelial cell parameters vary among different subtypes of PCG. DESIGN: Retrospective case-control study. PARTICIPANTS: One hundred forty-five eyes of 145 patients operated for PCG between 1991 and 2018 and who returned for a follow-up visit between June 2021 and May 2022. Three hundred and nineteen age-matched healthy individuals constituted the control group. METHODS: Corneal endothelial cell layer analysis was performed with EM-3000 (Tomey) noncontact specular microscope. Patients were categorized according to the clinical subtypes of PCG (neonatal, infantile, and late-onset) based on the Childhood Glaucoma Research Network classification. MAIN OUTCOME MEASURES: Specular microscopic parameters, including endothelial cell density (ECD), average cell size, coefficient of variation (CV), and maximum and minimum cell size, were compared with that of the control group. RESULTS: Mean ± standard deviation (SD) age of patients at endothelial imaging was 13.5 ± 6.54 years, and there was a male preponderance (n = 88, 61%). The majority of the patients had infantile-onset PCG (n = 67, 46%). Eyes with PCG demonstrated a significantly lower ECD compared with controls (2158.7 ± 636.5 vs. 2840.9 ± 232.5 cells/mm2; P < 0.0001). Other endothelial cell parameters were also significantly worse in PCG compared with controls. The mean ± SD ECD was 2344.3 ± 544.3, 2131.9 ± 626.4, and 2054.2 ± 714.0 cells/mm2 in neonatal onset, infantile, and late-onset PCG groups, respectively. Although the ECD was lowest in the late-onset PCG group, there was no significant difference in the ECD between the 3 subgroups. Except for CV, all the endothelial cell parameters were significantly worse in eyes with Haab striae than in eyes without. CONCLUSIONS: Patients with PCG have significantly lower ECD compared with healthy controls. Furthermore, other endothelial cell parameters were also significantly worse in the PCG group. These changes in the corneal endothelium in patients with PCG should be considered in long-term medical and surgical management. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Glaucoma management in congenital ectropion uveae: Surgical outcomes from a large tertiary referral center in South India.

PURPOSE: To evaluate the long-term outcomes of glaucoma management in patients with congenital ectropion uveae (CEU) over a period of three decades at a single large referral tertiary eye care center. METHODS: Retrospective chart review of all patients with CEU treated surgically from 1990 to 2019 was performed. Primary combined trabeculotomy-trabeculectomy (CTT), trabeculectomy with and without mitomycin-C (MMC) (0.2 mg/mL for 1 min) and transscleral cyclophotocoagulation (TSCPC) were performed. Intraocular pressure (IOP) ≥6 and ≤16 mmHg without medications was considered as complete success and IOP≤ 16 mmHg with the use of upto 2 medications as qualified success. RESULTS: A total of 26 eyes of 21 patients were identified with a median age of 7 years (range, 6 days to 19 years) at the time of glaucoma surgery. Median follow-up was 51.1 months (range, 7-244.6 months). Primary CTT was performed in 17 eyes (65%), trabeculectomy in 5 eyes (19%) with application of MMC in 2 eyes, and 3 eyes (12%) underwent TSCPC. One painful blind eye (4%) underwent evisceration. Mean IOP reduced from 30.8 ± 7.6 mmHg on a mean of 1.3 ± 0.8 glaucoma medications preoperatively to a mean IOP of 15.2 ± 5.9 mmHg (P < 0.0001) on a mean of 0.2 ± 0.5 medications postoperatively at final follow-up (P = 0.0009). Complete success was achieved in 20 eyes, and qualified success in 2 eyes. CONCLUSIONS: CTT is a safe and efficacious primary procedure for management of early-onset glaucoma in CEU. Trabeculectomy with or without adjuvant MMC is a viable second line of treatment in late-onset glaucoma with CEU for IOP control.

Illuminated Microcatheter Passage Assisted Circumferential Trabeculotomy and Trabeculectomy (IMPACTT): An improved surgical procedure for Primary Congenital Glaucoma.

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

Co-existing lacrimal drainage anomalies in eyes with congenital Glaucoma.

AIM: To evaluate the occurrence of co-existing congenital nasolacrimal duct obstruction (CNLDO) and other lacrimal anomalies in eyes with congenital glaucoma (CG). METHODS: Retrospective analysis of children aged ≤1-year with co-existing CG and CNLDO seen between 1998 and 2019, treatment interventions and outcomes. RESULTS: During the study period, 1993 children had CG and 6203 children had CNLDO, among the children aged 1-year or less. Of these, 51 children (73 eyes) had co-existing CG and CNLDO. The prevalence of CNLDO in CG was 2.5% (51/1993) and the prevalence of CG among CNLDO was 0.8% (51/6203). Median age (Interquartile range, IQR) was 53 days (IQR: 8, 155), when they were diagnosed with CG. Among the children with CNLDO, 68 eyes (93.1%) had simple CNLDO, and 5 eyes (6.9%) had complex CNLDO. Associated lacrimal anomalies were present in 7/73 eyes, including congenital lacrimal fistula in two eyes, upper punctal agenesis and upper mid-canalicular obstruction in two eyes each, and upper single canalicular-wall hypoplasia in one eye. Lacrimal syringing and probing were successful in 69/72 eyes (95.8%), and failed in 3 eyes (4.2%). These 3 eyes had complex CNLDO and underwent Dacryocystorhinostomy (DCR) with Mitomycin-C and intubation. Sixty-two eyes underwent combined trabeculotomy and trabeculectomy, and two eyes underwent trabeculectomy. Median age at glaucoma surgery was 87 days (IQR: 54, 193). Median time delay for glaucoma surgery after probing was 18 days (IQR: 12, 35). CONCLUSION: Among children aged ≤1-year presenting with congenital glaucoma coexisting lacrimal drainage anomalies was noted in 2.5% and simple CNLDO was the commonest. Early intervention is of paramount importance to prevent sight-threatening intraocular infection with CNLDO, and to minimize the delay of glaucoma surgery. The outcomes of lacrimal probing were excellent, however complex CNLDO required DCR.

Outcomes of trabeculectomy in eyes with refractory acute primary angle-closure in Indian eyes.

PURPOSE: To report the outcomes of trabeculectomy in eyes with refractory acute primary angle-closure attack. METHODS: Patients with acute primary angle-closure attack and who underwent trabeculectomy for medically uncontrolled intraocular pressure within 2 months of presentation were retrospectively analyzed. Primary outcome was intraocular pressure (IOP). Secondary outcome measures were visual acuity, number of antiglaucoma medication (AGM), complications, and risk factors for failure of trabeculectomy. RESULTS: Thirty-five eyes of 31 patients with median (interquartile range) follow-up of 3 (0.5, 9) years were included in the study. Median age at presentation was 55 (47, 60) years. Median duration of symptoms at presentation was 10 (4, 16) days and median time from presentation to surgery was 13 (6, 25) days. Median IOP reduced from 42 (36, 46) to 13 (12, 16) mmHg (P < 0.001) and median number of AGM reduced from 3 (1, 3) to 0 (0, 0) after trabeculectomy at the end of 1 year. The probability of complete and qualified success was 88% (95% confidence interval [CI]: 72%-95%) and was 97% (95% CI: 81%-99%) at 1 year, respectively. Failure was noted in six eyes. Subsequent cataract surgery was needed in 13 eyes (37%) with a median duration from trabeculectomy being 6.75 (1, 11) years. None of the preoperative, intraoperative, or postoperative factors tested were associated with failure (P > 0.10 for all associations on Cox proportional hazard regression analysis). CONCLUSION: In medically unresponsive cases of acute primary angle-closure attack, primary trabeculectomy seems safe and effective in Indian eyes.

Outcomes of Management of Glaucoma in Phacomatosis Pigmentovascularis Over the Last Three Decades: A Single-Center Experience.

PURPOSE: To report the clinical outcomes of glaucoma management in patients with phacomatosis pigmentovascularis (PPV) treated over a period of 3 decades. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-five eyes of 38 patients (21 unilateral and 17 bilateral) with glaucoma in PPV managed at one institution between January 1990 and December 2019 with a minimum follow-up of 1 year. METHODS: Medical records of children with glaucoma in PPV were reviewed, and demographic and clinical data were collected. Surgical interventions included primary combined trabeculotomy-trabeculectomy (CTT), trabeculectomy with mitomycin C (MMC), and transscleral cyclophotocoagulation (TSCPC). Complete success was defined as intraocular pressure (IOP) ≥ 6 and ≤ 16 mmHg without medications and qualified success as IOP ≤ 16 mmHg with the use of up to 2 medications. MAIN OUTCOME MEASURES: Intraocular pressure, best-corrected visual acuity (BCVA), corneal clarity, antiglaucoma medications at preoperative and postoperative visits (last visit), and complications. RESULTS: Median age was 4 months (range, 0.2-252 months) at the time of glaucoma surgery. Thirty-nine eyes (74%) had primary CTT, 10 eyes (19%) had trabeculectomy with MMC, and 4 eyes (7%) with advanced glaucoma had TSCPC. Two eyes (3.6%) received medical treatment. Preoperative IOP reduced from a mean of 25.7 ± 8.4 mmHg on 0.8 ± 0.6 medications to 14.6 ± 5.2 mmHg on 0.4 ± 0.5 medications (P < 0.0001) at last follow-up after surgery (77.7 ± 56.5 months). Thirty-seven eyes (67.3%) required medications preoperatively, and 22 eyes (40%) required medications at the last follow-up. Of 25 patients with available BCVA at last follow-up, 9 (36%) had ≥ 20/60; of these, 6 had > 20/40. Four of 10 eyes that underwent trabeculectomy with MMC developed retinal detachment and were managed surgically; however, all of these eyes had poor visual outcomes. There was no incidence of bleb leakage, bleb-related infection, or endophthalmitis. CONCLUSIONS: Combined trabeculotomy-trabeculectomy is safe and effective as a primary procedure for management of glaucoma in PPV. Trabeculectomy augmented with MMC as a second procedure was associated with a higher rate of complications.

Combined trabeculotomy-trabeculectomy for primary congenital glaucoma: long-term experience from a tertiary referral centre in a developing nation.

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.

Quality of Life and Life Satisfaction in Young Adults with Primary Congenital Glaucoma.

PURPOSE: Little is known about quality of life (QoL) and life satisfaction (LS) of treated primary congenital glaucoma (PCG) patients in adulthood. The purpose of this study was to assess the QoL and LS and their predictors among young adults treated for PCG during early childhood. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-two participants with PCG (mean age, 22.5 years; standard deviation [SD], 4.6); 52% were male; 94% bilateral) recruited at L V Prasad Eye Institute. METHODS: Participants were asked to complete the 26-item World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire (items related to satisfaction with general health, physical, psychological, social relations, and environmental aspects) and the 5-item Satisfaction with Life Scale (SWLS) in the clinic visit. Clinical data including visual acuity (VA) and visual fields (VFs) were collated from medical records. Rasch analysis was used to optimize the psychometric properties, with higher scores indicating a higher degree of QoL and LS, for both the questionnaires. Linear regression models were used to examine associations between overall QoL and LS (in separate models), and sociodemographic and clinical variables. MAIN OUTCOME MEASURES: The QoL and LS were measured using Rasch-transformed scores from the WHOQOL-BREF questionnaire and SWLS, respectively. RESULTS: Response rate was 93%. The overall mean (SD) Rasch-scaled scores for QoL were 0.93 (1.11) and 0.87 (1.32) for environment domain and 0.41 (1.56) logits for LS. Better QoL was significantly related to rural residence and higher education in both univariable and multivariable analyses and explained 13% variance. Higher LS was significantly related to marital status, unilateral affliction, and higher education in univariable analyses. However, multivariable regression analysis showed that only marital status was independently associated with higher LS and explained 8.8% of variance. Clinical and treatment variables (VF, surgical interventions, medications) were not independent predictors of QoL/LS. CONCLUSIONS: Our results suggest that QoL and LS of treated patients with PCG during adult life are generally good and appear to be driven by factors other than clinical indices. Educational achievement appears to be linked to better QoL and LS, and clinicians should emphasize the importance and need for education in the continued care of these patients.

Outcomes of Primary Combined Trabeculotomy and Trabeculectomy in Early-Onset Glaucoma in Children with Congenital Aniridia.

PURPOSE: To report clinical features and treatment outcomes of primary combined trabeculotomy with trabeculectomy (CTT) in congenital aniridia with glaucoma in children 3 years of age or younger. DESIGN: Retrospective study. PARTICIPANTS: Sixty-six eyes of 35 children with congenital aniridia and early-onset glaucoma who underwent CTT between May 1997 and June 2015 were included. METHODS: Success was defined as complete when intraocular pressure (IOP) was more than 5 mmHg and less than or equal to 21 or 16 mmHg without antiglaucoma medications (AGMs), and qualified when AGMs were required. Eyes needing repeat surgery for IOP control were considered as failures. MAIN OUTCOME MEASURES: IOP control and number of AGMs. RESULTS: The median age at presentation of 35 children was 26 days (interquartile range [IQR], 7-106 days). There were 22 males (62.9%) and 13 females (37.1%). Parental consanguinity was noted in 11 children (31.4%). Aniridia was total in 52 eyes and partial in 14 eyes. At presentation, there was corneal edema in 30 eyes (45.4%), enlarged corneal diameter in 32 eyes (48.5%), nystagmus in 15 children (23%), limbal stem cell deficiency in 1 eye, cataract in 9 eyes (13.6%), and foveal hypoplasia in 4 eyes. After CTT, median IOP was reduced significantly (P < 0.0001). Corneal edema cleared in 12/30 eyes and cleared with scar in 18/30 eyes. Median follow-up was 5.33 (IQR, 3.05-7.59) years. At latest follow-up, median number of AGMs was 1 (IQR, 0-2) and median visual acuity in logarithm of minimum angle of resolutions (n = 34 eyes) was 1.35 (IQR, 0.80-2.78). The probability of complete success for IOP ≤ 21 mmHg was 79.9% at 1 year and 62.3% between 2 and 10 years; for IOP ≤ 16 mmHg, it was 78.6% at 1 year and decreased to 51.9% at 10 years. Qualified success for IOP ≤ 21 mmHg at 1 year was 82.6% and 81% over 10 years; for IOP ≤ 16 mmHg, it was 81.4% at 1 year and decreased to 63.1% at 10 years. Seven eyes (10.6%) required repeat intervention for IOP control with median time of 3.17 years (IQR, 0.92-6.56) from first surgery. CONCLUSIONS: CTT showed good success in children with congenital aniridia with early-onset glaucoma.

Cross-Diagnostic Validity of the Congenital Glaucoma Caregiver's Quality of Life Questionnaire (CarCGQoL).

Purpose: The Caregiver's Congenital Glaucoma QoL (CarCGQoL) questionnaire was proposed as a measure of QoL of caregivers with children with primary congenital glaucoma (PCG). Support for its psychometric properties among other diagnostic groups is required for scores to be interpreted in the same manner across groups. Therefore we investigated the measurement properties and cross-diagnostic validity of the CarCGQoL questionnaire among caregivers of children with congenital cataract, retinopathy of prematurity (ROP), and blinding corneal disorders. Methods: Eight hundred ninety-one caregivers (mean age, 28.3 years; 76% mothers) of children with congenital cataract (n = 407), ROP (n = 272), and blinding corneal disorders (n = 212) completed the CarCGQoL questionnaire. Rasch analysis was used to investigate the psychometric properties. Unidimensionality (by principal components analysis of residuals, PCA) was examined for each group and for pooled sample. Differential item functioning (DIF) was investigated to explore whether bias in responses to the questionnaire existed for certain subgroups as compared to the reference group (PCG). Results: Across groups, six items necessitated removal because of misfit (two common and four uncommon), after which three different versions of the questionnaire emerged. Measurement precision was adequate for each group and for the pooled sample (0.80). Unidimensionality was observed, albeit with some DIF. Regardless of the level of QoL, caregivers in the pooled sample were more likely to endorse two items reflecting ability to face child's disease, and interest to pursue leisure activity, as compared with caregivers of children with PCG. Conclusions: Care must be taken when data from the CarCGQoL questionnaire from different pediatric ocular conditions are pooled, given the presence of DIF between the reference group (PCG) and the pooled sample. Translational Relevance: When evaluating the impact of interventions on the caregiver's QoL using the CarCGQoL questionnaire in a pooled sample of pediatric ocular conditions, cross-diagnostic DIF must be taken into account.

Management outcomes of secondary glaucoma due to retinopathy of prematurity: A 19-year prospective study at a tertiary eye care Institute. The Indian Twin cities ROP Screening (ITCROPS) database report number 8.

PURPOSE: To report the clinical presentation and management outcomes of glaucoma in the "Indian Twin cities retinopathy of prematurity (ROP) Screening database." METHODS: All children with diagnosis of ROP and glaucoma between 1997 and 2016 from a prospective database were included. Glaucoma was classified as open when anterior chamber (AC) was deep, closed when AC was shallow or flat and neovascular when there was extensive iris neovascularization. ROP was classified based on International classification of ROP. RESULTS: The prevalence of secondary glaucoma in our cohort was 1.36% (82 eyes of 6000 children). Eighty-two eyes of 54 children with secondary glaucoma due to ROP where included in this study. The distribution of glaucoma among the ROP stages included, stage V (58.5%), stage 1V (24.3%), stage III (2.4%) and stage II (1.2%) eyes. Median (interquartile range) duration from birth to glaucoma diagnosis was 7.8 (4.2, 24.9) months. Type of glaucoma was angle closure in 39 (47.6%), open angle in 35 (42.7%) and neovascular in 8 (9.8%) eyes. Retinal interventions included vitreoretinal surgery in 59 (72%), retinal laser in 14 (17%) and intravitreal bevacizumab injection in 19 (23.1%) eyes. The mean (±standard deviation) IOP at presentation was 22.6 ±11.8 mm Hg. Glaucoma was managed medically in 66 (76%) and surgically in 16 (19.5%) eyes. The mean follow up for the entire cohort was 1.14±2.24 years. At final visit, 37% eyes with ROP and glaucoma had ambulatory vision with mean IOP of 16.0±8.1 mm Hg and 56 eyes (68.2%) needed glaucoma medications. CONCLUSION: In this large ROP cohort, 1.36% eyes developed secondary glaucoma. Majority of them had stage V or IV ROP and 1/5 of them needed glaucoma surgery. Around 1/3rd of the ROP eyes with glaucoma had ambulatory vision.

Primary Congenital Glaucoma: Trends in Presentation Over 3 Decades at a Tertiary Eye Care Center in India.

PRECIS: In this study, huge time delay was observed between first primary congenital glaucoma (PCG) symptom recognition by parents to ophthalmological diagnosis and this delay was unchanged over time. Bilateral affliction and mean presenting intraocular pressure (IOP) remained unaltered. PURPOSE: To compare the trends in presentation of patients with PCG over 3 different time periods at 10-year intervals (1998, 2008, and 2018) managed by a single surgeon at one of the largest tertiary eye care centers in South India. METHODS: Retrospective analysis of 313 eyes of 172 patients diagnosed to have PCG and treated at the L V Prasad Eye Institute (LVPEI) between January and December of the 3 specified years. Data collected included age at symptom recognition and at presentation, sex, affected eye, signs and symptoms, time between onset of symptoms and diagnosis (diagnostic delay), corneal clarity, and IOP. RESULTS: Of the 172 patients, 48 (27.9%), 76 (44.2%), and 48 (27.9%) belonged to 1998, 2008, and 2018, respectively. Bilateral affliction (79% to 84%) was common and there was no sex predilection. The median age at recognition of first symptoms by caregivers/parents was 1 day (interquartile range, 1 to 30), and at diagnosis was 120 days (interquartile range, 30 to 378). Overall, presentation to LVPEI was delayed by >3 months in 80 (46.5%) children, and there was no statistically significant difference in the duration of delay over time (P=0.13). There was no significant difference in the mean presenting IOP over time (P>0.05). CONCLUSIONS: We provide unique single center-based information of trends in the presentation of patients with PCG over 3 decades. Diagnostic delay was common, and a large number of characteristics of patients with PCG in South India have remained unchanged, particularly, age at onset and at diagnosis and laterality.

Loss of PRSS56 function leads to ocular angle defects and increased susceptibility to high intraocular pressure.

Glaucoma is a leading cause of blindness, affecting up to 70 million people worldwide. High intraocular pressure (IOP) is a major risk factor for glaucoma. It is well established that inefficient aqueous humor (AqH) outflow resulting from structural or functional alterations in ocular drainage tissues causes high IOP, but the genes and pathways involved are poorly understood. We previously demonstrated that mutations in the gene encoding the serine protease PRSS56 induces ocular angle closure and high IOP in mice and identified reduced ocular axial length as a potential contributing factor. Here, we show that Prss56-/- mice also exhibit an abnormal iridocorneal angle configuration characterized by a posterior shift of ocular drainage structures relative to the ciliary body and iris. Notably, we show that retina-derived PRSS56 is required between postnatal days 13 and 18 for proper iridocorneal configuration and that abnormal positioning of the ocular drainage tissues is not dependent on ocular size reduction in Prss56-/- mice. Furthermore, we demonstrate that the genetic context modulates the severity of IOP elevation in Prss56 mutant mice and describe a progressive degeneration of ocular drainage tissues that likely contributes to the exacerbation of the high IOP phenotype observed on the C3H/HeJ genetic background. Finally, we identify five rare PRSS56 variants associated with human primary congenital glaucoma, a condition characterized by abnormal development of the ocular drainage structures. Collectively, our findings point to a role for PRSS56 in the development and maintenance of ocular drainage tissues and IOP homeostasis, and provide new insights into glaucoma pathogenesis.

Beyond Intraocular Pressure: Visual Functioning and Quality of Life in Primary Congenital Glaucoma and Secondary Childhood Glaucoma.

PURPOSE: To compare the visual functioning (VF) and vision-related QoL (VRQoL) of children 8-18 years old treated for primary congenital glaucoma (PCG) and secondary childhood glaucoma. DESIGN: Cross-sectional study. METHODS: A total of 309 children 8-18 years old treated for PCG and secondary childhood glaucoma between 2000 and 2010 by a single pediatric glaucoma specialist were prospectively enrolled at LV Prasad Eye Institute, Hyderabad, India. Children completed 2 questionnaires, the LV Prasad Functional Vision Questionnaire-II (LVP-FVQ-II), and the Impact of Vision Impairment-Children (IVI-C) questionnaire. Rasch-calibrated scores from both these questionnaires were used to compare the VF and VFQoL between the 2 groups. RESULTS: Mean ages of the children were 12.2 and 12.6 years in the PCG (53%, median age at diagnosis = 5 months) and secondary glaucoma groups (47%, median age at diagnosis = 3 years), respectively. A majority (80%) of children had bilateral glaucoma and underwent filtering surgery (83%). Mean better eye logMAR visual acuity (VA) was comparable between PCG and secondary childhood glaucoma groups (0.49 vs 0.52, respectively; P = 0.59). Children with PCG reported significantly better VF and VRQoL than secondary childhood glaucoma patients. Unadjusted and adjusted childhood glaucoma group comparisons revealed secondary childhood glaucoma to be associated with worse VF and VRQoL compared to PCG (difference for VF, -0.83; 95% confidence interval [CI], -1.34 to 0.31; P = 0.002; 0.39; 95% CI, 0.16-0.62; P = 0.001 for VRQoL). CONCLUSIONS: Results show that children with treated PCG experience significantly better VF and VRQoL than those with secondary childhood glaucoma, despite comparable VA and IOP.

Profile of childhood glaucoma at a tertiary center in South India.

PURPOSE: To describe the prevalence of various types of childhood glaucomas, their clinical features and treatment methods. METHODS: We prospectively included consecutive children with glaucoma presenting to glaucoma clinic for the first time between March 2013 and May 2014. We classified childhood glaucomas as per the classification proposed by Congenital Glaucoma Research Network. RESULTS: Of the 275 children (449 eyes) with glaucoma during this period, primary glaucomas constituted 56% (n = 252 eyes of 145 children), including 169 eyes (37.64%) of 97 children with primary congenital glaucoma (PCG), 16 eyes (3.56%) of 10 children with infantile glaucoma, and 67 eyes (14.9%) of 38 children with juvenile open angle glaucoma. Among these, 85% (214 eyes of 107 children) had bilateral involvement. Secondary glaucomas constituted 44%; they were glaucoma associated with ocular anomalies 18% (n = 80 eyes), glaucoma associated with acquired conditions (steroid induced and traumatic glaucoma) 14% (n = 61 eyes), glaucoma following congenital cataract surgery 7.6% (n = 34 eyes), and glaucoma associated with systemic or syndromic conditions 5% (n = 22 eyes). In primary glaucomas, boys and girls were equally affected (1:1), and more boys (3.8:1) had acquired glaucomas. Close to 80% PCG eyes were managed surgically with combined trabeculotomy and trabeculectomy (CTT). Majority of secondary glaucomas were managed medically. CONCLUSION: In our cohort, PCG was the most common childhood glaucoma and CTT was the most common surgery performed in these eyes. Steroid-induced and traumatic glaucomas were the most common acquired glaucomas; appropriate measures should be taken to avert these preventable glaucomas in children.