Advances in genetic characterization and genes of juvenile open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Juvenile open angle glaucoma(JOAG)is a subtype of primary open angle glaucoma(POAG)that severely affects the quality of life of young patients and has a high disability rate. While JOAG is commonly considered an autosomal dominant disease, it has been found to have a diverse mode of inheritance, including autosomal recessive inheritance in specific populations. The variable genetic predisposition of JOAG may be attributed to the co-regulation of several key disease-causing genes, such as MYOC, CYP1B1, and CPAMD8. Mutations in these genes are closely associated with various biological processes in ocular tissues, including cellular metabolic regulation, oxidative stress response, and abnormal induction of programmed death. Therefore, a comprehensive study of the causative genes associated with JOAG is crucial to understanding the specific genetic background of disease onset, progression, and clinical phenotype. This knowledge will provide a strong foundation for early identification and screening of high-risk populations. The objective of this review is to focus on the genetic characterization and genetic studies of JOAG. Through a systematic review of the relevant literature, we summarize the causative genes and their mutations associated with JOAG and explore their potential applications and value in advancing research in the field, aiming to provide valuable insights for the diagnosis and treatment of JOAG.

A rare optineurin mutation in an Indian family with coexistence of JOAG and PCG

Purpose: This study focused on the genetic screening of Myocilin (MYOC), Cytochrome P450 family 1 subfamily B member 1 (CYP1B1), Optineurin (OPTN), and SIX homeobox 6 (SIX6) genes in a family with coexistence of primary congenital glaucoma (PCG) and juvenile open?angle glaucoma (JOAG). Methods: Sanger sequencing was used to examine the coding region of all four genes. Six different online available algorithms were used for the pathogenicity prediction of missense variant. Structural analysis was done using Garnier–Osguthorpe–Robson (GOR), PyMol, ChimeraX, and Molecular Dynamic (MD) Simulations (using Graphics Processing Unit (GPU)?enabled Desmond module of Schrödinger). Results: There were a total of three sequence variants within the family. All seven algorithms determined that a single mutation, G538E, in the OPTN gene is pathogenic. The loops connecting the strands became more flexible, as predicted structurally and functionally by pathogenic mutations. Mutations create perturbations and conformational rearrangements in proteins, hence impairing their functioning. Conclusion: In this study, we describe a North Indian family in which members were having JOAG and PCG due to a rare homozygous/ heterozygous mutation in OPTN. The coexistence of two types of glaucoma within a single pedigree suggests that certain OPTN mutations may be responsible for the onset of different glaucoma phenotypes.

Clinical and demographic profile of patients less than 40 years of age presenting to glaucoma services at a tertiary care eye hospital in South India

Purpose: To study the clinical and demographic profile of patients less than 40 years of age presenting to glaucoma services including the reasons for referral. Methods: Patients in the age group of 5 to 39 years, visiting the glaucoma clinic, who were either suspected to have glaucoma or who had been newly/previously diagnosed with glaucoma were included in the study. After informed written consent, basic demographic details of the participants including age, gender, education, socioeconomic status, and family history were obtained. A comprehensive ophthalmological evaluation was performed by glaucoma specialists. Results: The proportion of glaucoma in the study population (n = 384) was found to be 31.25%, and the incidence of glaucoma among new patients was found to be 11.9%. Among all glaucomas (n = 120), 44.2% of patients had secondary glaucomas, 27.5% had primary glaucomas, and 28.3% had congenital glaucomas. Also, 67.3% of all glaucoma patients were males. Newly diagnosed glaucoma patients presented with a mean intraocular pressure (IOP) of 32.9 mmHg and mild–moderate disc damage with a mean cup?disc ratio of 0.65. Nearly one?third of them had a presenting visual acuity worse than 5/60. The most common reason for referral was raised IOP. Univariate and multivariate analysis revealed that the odds of developing glaucoma were less in females (P = 0.04) and in patients with a higher standard of living index (P < 0.001). Conclusion: One?third of the patients had glaucoma and another one?third were suspects. Secondary glaucomas are more common than primary/congenital glaucomas. A comprehensive eye evaluation is a must, especially in those with predisposing factors.

Comparison of anterior chamber angle parameters and iris structure of juvenile open-angle glaucoma and pigmentary glaucoma

Purpose: To compare the quantitative measurements of the anterior chamber angle (ACA) and iris parameters in patients with juvenile open?angle glaucoma (JOAG), pigmentary glaucoma (PG), and healthy controls using anterior segment optical coherence tomography (AS?OCT). Methods: This was a retrospective, cross?sectional study of 25 eyes with JOAG, 25 eyes with PG, and 25 control eyes. Anterior chamber depth, angle?opening distance 500 and 750, trabecular–iris space 500 and 750, scleral spur angle, iris thickness (IT, measured at the thickest part), and iris bowing were obtained using AS?OCT (Visante” OCT 3.0 Model 1000, Carl Zeiss Meditec, Inc). Results: The quantitative ACA parameters were found to be significantly higher in JOAG and PG patients compared to healthy controls (P < 0.001); there was no significant difference between the eyes with JOAG and PG (P > 0.05). In eyes with JOAG and PG, there was significantly backward bowing of the iris in temporal and nasal angles compared to control subjects (P < 0.001). Median iris bowing was not significantly different between the patients with JOAG and PG (P > 0.05). The temporal and nasal angle iris thickness were significantly thinner in eyes with JOAG than the eyes with PG (P < 0.001) and age?matched control subjects (P < 0.001). The median IT did not differ between the patients with PG and control subjects (P > 0.05). In patients with JOAG, the intraocular pressure (IOP) was inversely correlated with IT (r = ?0.43, P < 0.05). Conclusion: AS?OCT provided quantitative data on the ACA and iris parameters in JOAG and PG. The evaluation of the ACA and iris structures using AS?OCT revealed higher ACA measurements and posterior bowing of the iris in patients with JOAG and PG. Furthermore, the patients with JOAG were found to have thinner IT than the ones with PG and healthy controls

Juvenile onset open-angle glaucoma in a large family in Cebu, Philippines

Objective@#This study described the clinical profile of a four-generation Cebuano family with juvenile-onset open-angle glaucoma (JOAG).@*Methods@#Thisis a case series conducted in the out-patient department of Cebu Velez General Hospital. Thirtyeight (38) members in a four-generation family from the northern part of Cebu province were investigated. General medical and ophthalmologic histories were taken. Complete ophthalmologic examination was done.@*Results@#Forty-two (42%) percent of participants examined had increased intraocular pressures (IOP); 15 were diagnosed with JOAG, one had ocular hypertension. There were more females than males affected. Mean age when symptoms were first noted was 14.56 ±6.63 years and mean age at diagnosis was 16.3 ±7.84 years. The most common initial symptom was rainbow or halos around lights (87.5%). Mean refraction was -3.09 ±2.54 diopters for both eyes. Mean IOP on examination was 24.56 ± 20.17 mmHg. Gonioscopy showed open angles with flat iris plane. All affected participants underwent medical treatment and 69% needed surgical interventions.@*Conclusion@#This family demonstrated the typical JOAG phenotype consisting of early age of onset, strong family history with an autosomal dominant pattern of inheritance, myopia, open angles, and increased IOP refractory to medical treatment.

Association between hypertriglyceridemia and open angle glaucoma: A case report

Hypertriglyseridemia is a metabolic disorder that can cause vascular dysfucntion and be causally associated with glaucoma. Herein we present the case of a 16-year-old boy with hypertriglyseridemia with open-angle glaucoma.

Outcomes of trabeculectomy in juvenile open angle glaucoma.

Purpose: This study was aimed at reporting the outcomes of trabeculectomy in primary juvenile open angle glaucoma (JOAG). Design: This study was a retrospective noncomparative case series. Materials and Methods: We included 60 eyes of 41 JOAG patients who underwent primary trabeculectomy without mitomycin-C (MMC) between 1995 and 2007. The primary outcome was success, defined as complete, if intraocular pressure (IOP) was >5 and ≤21 mmHg without medications or qualified if IOP was >5 and ≤21 mmHg with or without antiglaucoma medications. Secondary outcome measures were mean and percentage IOP reduction, complications, and risk factors for the failure of trabeculectomy. Results: The mean (±standard deviation) age at presentation was 24.1 ± 6.8 years (range, 12–35). Mean follow-up was 67 ± 41 months (range, 12–156). At 1 year, the probability of complete success was 92% (n = 56, 95% CI: 81–96%), at 3 years it was 89% (n = 47, 95% CI: 78–95%), and at the end of 5 years, it was 80% (n = 34, 95% CI: 65–89%). The probability of qualified success was 100% (n = 60) at 1 year, 98% (n = 51, 95% CI: 87–100%) at 3 years, and 96% (n = 36, 95% CI: 84–99%) at the end of 5 years. The mean IOP reduced from 35 ± 10 to 13 ± 2.5 mmHg (P < 0.001) after trabeculectomy. There was no serious postoperative complication. Young age was the only significant risk factor associated with the failure (odds ratio = 0.89, P = 0.03). Conclusion: Primary trabeculectomy without MMC has good success rates in JOAG.

Long-Term Outcomes of Trabeculectomy in Korean Patients with Juvenile Open-Angle Glaucoma

PURPOSE: To evaluate the outcomes and prognostic factors of trabeculectomy with mitomycin C in Korean patients with juvenile open-angle glaucoma (JOAG). METHODS: A retrospective review was performed on 29 eyes with JOAG who had undergone trabeculectomy between January 2004 and January 2013. Intraocular pressure (IOP) and postoperative complications were monitored at 1 day preoperatively, at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively, and at final follow-up after postoperative 18 months. Surgical success was defined as a final IOP of <21 mm Hg or <80% of preoperative IOP, regardless of the use of anti-glaucoma medication. Prognostic factors for surgical success or failure were analyzed by the Cox proportional hazards model. RESULTS: Mean (+/- standard deviation) age at trabeculectomy was 24.6 (+/- 8.9) years, and mean follow-up period was 24.3 (+/- 20.8) months. The overall success rate was 82.8% at final follow-up. The Kaplan-Meier cumulative probabilities of surgical success were 100% at 1 year, 87.4% at 2 years, and 78.7% at 3 years postoperatively. The Cox proportional hazards model failed to determine any significant factors that were associated with surgical failure. The three most frequent postoperative complications were immediately postoperative hypotony (n = 19, 65.5%), hypotony maculopathy (n = 8, 27.6%), and encapsulated bleb (n = 8, 27.6%), most of which were resolved after a minor procedure or observation. Two of 8 eyes with encapsulated bleb required a second surgery. There were no vision-threatening severe complications. CONCLUSIONS: Trabeculectomy with MMC may be an effective treatment in Korean JOAG patients.