UNASSIGNED: To compare the surgical outcomes of trabeculectomy with and without anti-metabolites in patients with juvenile open-angle glaucoma (JOAG).
UNASSIGNED: This retrospective comparative case series included 98 eyes of 66 patients with JOAG who underwent either trabeculectomy without anti-metabolites (group A, n = 53 eyes) or with anti-metabolites (group B, n = 45 eyes) with a minimum of 2 years follow-up. The main outcome measures were intra-ocular pressure (IOP), number of glaucoma medications, visual acuity, additional surgical interventions, surgical complications, and risk factors for failure. Surgical failure was defined as IOP >18 mmHg or failure to reduce IOP by <30% from the baseline value or IOP ≤5 mmHg or re-operation for refractory glaucoma or a complication or loss of light perception vision.
UNASSIGNED: The mean post-operative IOP reduced significantly from baseline at all post-operative visits until 6 months and thereafter. The cumulative probability of failure at 2 years was 28.7% in group A [95% confidence interval (CI) = 17.6-44.8%] and 29.1% in group B (95% CI = 17.1-46.7%) (P = 0.78). Surgical complications occurred in 18 eyes (34%) in group A and 19 eyes (42%) in group B. Re-operations for glaucoma or complications were performed in two eyes (3.8%) in group A and two eyes (4.4%) in group B. Cox-hazard regression model revealed male gender (HR = 0.29; P = 0.008), baseline high IOP (HR = 0.95; P = 0.002), and an increased number of pre-operative glaucoma medications (HR = 2.08; P = 0.010) as significant factors associated with failure.
UNASSIGNED: : Our study results on trabeculectomy in JOAG revealed a success of 71% in both groups at 2 years follow-up. There was no significant difference in success or failure rates between the two groups. The risk factors for poor surgical outcome in JOAG were male gender, baseline high IOP, and an increased number of glaucoma medications.

Background and objective The majority of glaucoma patients are asymptomatic and are usually diagnosed at an advanced stage of the disease. This study aimed to assess the outcomes of glaucoma screening among known first-degree relatives of primary glaucoma patients. Materials and methods This study involved primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG), and juvenile open-angle glaucoma (JOAG) patients who attended the glaucoma clinic at the Hospital Universiti Sains Malaysia between January 2014 and December 2015. First-degree relatives of the patients underwent a preliminary eye-screening evaluation, including visual acuity (Snellen chart), intraocular pressure (IOP) measurement (air-puff tonometry), and non-mydriatic fundus photography. Patients with visual acuity worse than 6/12, IOP measuring more than 21 mmHg or a difference of more than 3 mmHg between the eyes, and a vertical cup-disc ratio (VCDR) of 0.7 or higher were given a comprehensive eye examination. Results Seventy indexed glaucoma patients were recognized, and 368 first-degree relatives were identified. Forty-five relatives underwent the preliminary screening. Of these, 29 showed normal findings (62%), one had corneal pathology (2%), and 16 (36%) underwent a complete eye examination after failing the initial screening. Among the indexed JOAG group, five relatives (11%) were diagnosed as having JOAG; two were treated medically, while the remaining three required surgical intervention. Conclusion Opportunistic glaucoma screening of high-risk groups, especially JOAG is a feasible and cost-effective way to detect early glaucoma and prevent irreversible blindness. However, improvement in our healthcare system, including the involvement of multicentre clinics in other states in screening initiatives, is required to promote and facilitate the response to screening opportunities.

Juvenile-onset open-angle glaucoma (JOAG) is a subset of primary open-angle glaucoma that is diagnosed before 40 years of age. The disease may be familial or non-familial, with proportions varying among different populations. Myocilin mutations are the most commonly associated. JOAG is characterized by high intraocular pressures (IOP), with many patients needing surgery. The mean age at diagnosis is in the 3rd decade, with a male preponderance. Myopia is a common association. The pathophysiology underlying the disease is immaturity of the conventional outflow pathways, which may or may not be observed on gonioscopy and anterior segment optical coherence tomography. The unique optic nerve head features include large discs with deep, steep cupping associated with high IOP-induced damage. Progression rates among JOAG patients are comparable to adult primary glaucomas, but as the disease affects younger patients, the projected disability from this disease is higher. Early diagnosis, prompt management, and life-long monitoring play an important role in preventing disease progression. Gene-based therapies currently under investigation offer future hope.

OBJECTIVE: To assess the clinical relevance of myocilin (MYOC) gene variants as risk factors for glaucoma in literature and to estimate their prevalence in different populations.
METHODS: We reviewed the literature for published MYOC variants in glaucoma patients and estimated their prevalence in general population using gnomAD and BRAVO databases. We used several bioinformatics tools and the criteria of the American College of Medical Genetics and Genomics (ACMG) to assess the pathogenicity of the variants. We evaluated the carrier frequency of the variants in gnomAD, including its subpopulations.
RESULTS: We found 13 missense and 5 loss-of-function (LOF) reported variants in MYOC that were both probable pathogenic or risk variants and listed in gnomAD. Six likely pathogenic missense variants were p.(Cys25Arg), p.(Gln48His), p.(Gly326Ser), p.(Thr353Ile), p.(Thr377Met) and p.(Gly399Val). They were most prevalent in East and South Asia (frequency, 0.92% and 0.81%, respectively). The most common missense variants were p.(Thr353Ile) (0.91% in East Asia) and p.(Gln48His) (0.79% in South Asia). Five LOF variants were p.(Arg46Ter), p.(Arg91Ter), p.(Arg272Ter), p.(Gln368Ter) and p.(Tyr453MetfsTer11). We considered these glaucoma risk variants. They were most prevalent in the East Asian and the Finnish population (0.93% and 0.33%, respectively).
CONCLUSIONS: Pathogenic MYOC variants appear to be population-associated. Our results highlight allelic heterogeneity of MYOC variants in open-angle glaucoma. Many of the probable pathogenic variants are over-represented in some of the populations causing doubt of their status as monogenic disease-causing variants.

The purpose of this study was to screen juvenile open angle glaucoma (JOAG) patients from Brazil for variants within the MYOC and CYP1B1 genes.
In this study, we evaluated the coding regions of MYOC and CYP1B1 genes in 100 non-related patients with JOAG and 200 controls through Sanger sequencing. We also tested the most frequent single nucleotide variants of CYP1B1 for association with JOAG.
Sixteen different sequence variants in the MYOC gene were observed in JOAG patients: eight variants were described as neutral and eight were identified in 34 out of 100 patients with JOAG and no controls, thus being considered damaging. In the CYP1B1 gene, nine neutral variants and two damaging alterations were found among JOAG patients. No association between CYP1B1 variants and JOAG was detected.
While MYOC damaging alterations were highly prevalent (34%), CYP1B1 damaging variants were less frequent (2%) in this cohort of Brazilian JOAG patients.

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C>G, p.(Pro989Arg); c.5235T>G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 (LTBP2) segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles.

Primary open-angle glaucoma (POAG) is one of the most important disease in ophthalmology with high prevalence and risk of irreversible blindness. If diagnosed before the age of 35, it is usually categorized as juvenile open-angle glaucoma (JOAG). The WDR36 gene is reckoned as one of the major causative genes of POAG, and had been studied to be related to the pathogenesis of POAG in the literature. We have selected 61 JOAG patients and 61 JOAG-free individuals, and by next-generation sequencing method, the WDR36 gene of the subjects were analyzed. We identified 26 variations exclusively in JOAG group. Among these 26 variations, there were 3 noteworthy variations. First, a novel variation c.460-650A>G was found in our study which might cause premature termination of splicing of the conserved domain in WDR36; second, c.1494+1111G>T (rs13178997) had significantly different frequency in our JOAG patients compared to the reference frequency on NCBI; third, a variation c.710+30C>T (rs10038177) was found in our study, which had already been reported to be related to high-pressure glaucoma. We offer the profile of WDR36 in JOAG in Taiwan population, and we suggest that WDR36 gene is involved in the pathogenesis of JOAG as a subordinate modifier gene.

To evaluate phenotypic differences among familial and non-familial JOAG patients.
First degree relatives of unrelated JOAG patients were screened for glaucoma and ocular hypertension. JOAG probands were grouped as familial or non-familial and phenotypic differences in terms of age of onset, gender, baseline untreated IOP, presence angle dysgenesis, and refractive error was compared between the two groups.
Out of 368 unrelated JOAG patients, 134 in whom all first degree relatives had been examined were included in the study. The non-familial JOAG (n = 96) had similar age of onset as familial JOAG (n = 38); (p = 0.076) but had greater male preponderance (p = 0.046), and had the higher baseline IOP (p = 0.044) compared to familial JOAG. However, on adjustment using the Bonferroni correction, the observed differences were not found to be significant. Both groups had similar proportion of patients with angle dysgenesis (p = 0.46) and high myopia (p = 0.72).
Non-familial JOAG were not found to be phenotypically different from the familial JOAG patients in this cohort.

OBJECTIVE: Glutathione S transferase (GST) polymorphisms have been considered risk factors for the development of glaucoma. The aim of the present study was to investigate the association of glutathione S-transferase GSTT1 and GSTM1 genotypes with juvenile open-angle glaucoma (JOAG) in Indian patients.
METHODS: A case-control study was performed to investigate the associations of GSTM1 and GSTT1 in juvenile open-angle glaucoma. The genotype of GSTM1 and GSTT1 were determined in 73 juvenile open-angle glaucoma patients, and 70 controls matched by age and sex by polymerase chain reaction method. We also performed a meta-analysis of sixteen published studies on GSTM1 and GSTT1 and evaluated the association between the GSTM1 and GSTT1 polymorphisms and glaucoma (JOAG & POAG). Published literature from PubMed and other databases were retrieved. All studies evaluating the association between GSTM1 and GSTT1 polymorphisms and glaucoma (JOAG & POAG) risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.
RESULTS: In the present study, we observed there is no association of GSTM1 (OR=0.680; 95% CI=0.323-1.433; p=0.311) or GSTT1 (OR=0.698; 95% CI=0.307-1.586; p=0.391) with JOAG. In the present meta-analysis, significantly increased glaucoma (JOAG & POAG) risk was found among subjects carrying GSTM1 null genotype (OR=1.177; 95% CI=1.028-1.348; p=0.018) but not among subjects carrying GSTT1 deletion genotype (OR=1.186; 95% CI=0.992-1.417; p=0.061).
CONCLUSIONS: The present case-control study found that GSTM1 and GSTT1 polymorphism are not associated with JOAG risk in North Indian population. The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with glaucoma (JOAG & POAG) risk. To the best of our knowledge, this is the first study in the world to investigate role of GSTM1 and GSTT1 polymorphisms with JOAG susceptibility. Given the limited sample size, the associations between GST polymorphism and glaucoma risk needs further investigation.

Glaucoma is one of the primary causes of visual impairment and blindness in the world. It is characterized by the damage to the optic nerve head and visual field loss. Variants in CYP1B1 are the most common cause of glaucoma in different world populations. We studied a consanguineous Pakistani family in which three affected individuals had a severe form of glaucoma with members in one generation diagnosed with juvenile-onset open angle glaucoma at 27 years of age, while the members of the next generation were affected with primary congenital glaucoma with onset at birth. Sequencing of CYP1B1 revealed a homozygous transition variant, c.182G>A, p.G61E which co-segregated with the disease phenotype. This variant has been previously reported to cause both recessively and dominantly inherited PCG and JOAG in different populations. However, this reported for the first time in Pakistani PCG and JOAG patients in a homozygous state. This is also the first ever report of a CYP1B1 variant segregating in a consanguineous family with co-existence of JOAG and PCG in two subsequent generations. This observation of different phenotypes due to an identical mutation suggests that primary congenital glaucoma and juvenile-onset open angle glaucoma can both be caused by homozygosity for the same mutation. It also indicates the reduced penetrance of the variant in those affected due to p.G61E mutation and further implies that modifiers have a role in controlling the time of onset of the disorder.