Outcome of combined trabeculectomy with cataract surgery in patients on prostaglandin analogs and aqueous suppressants.

PURPOSE: To compare the effect of prostaglandin analogs (PGA) against other glaucoma medications (non-PGA) on the intraocular pressure (IOP) outcomes of combined trabeculectomy with phacoemulsification, and the conjunctival cell profile in persons with primary open-angle (POAG) and pseudoexfoliation glaucoma (PXFG). METHODS: A prospective cohort study was conducted among 116 patients with POAG or PXFG on glaucoma medications for a minimum of 3 months undergoing glaucoma triple procedure. Patients were divided into two groups (PGA and non-PGA) based on preoperative exposure to PGA. IOP outcomes were assessed for up to 2 years. Conjunctival biopsy specimens were obtained at the time of surgery, and histopathological analysis was performed. RESULTS: Forty-two patients were in the PGA group, 67 were in the non-PGA group, and seven were lost to follow-up. The non-PGA group had lesser mean postoperative IOP and needed fewer postoperative medications compared to the PGA group in all visits up to 2 years. The non-PGA group had better complete success rate (50.7% vs. 14.3%, P < 0.001). Kaplan-Meier survival estimates showed a significant difference in cumulative complete success rate between non-PGA (67%) and PGA (26%) by 24 months ( P < 0.001). The Cox proportional model showed the type of drug to be significantly associated with surgical failure. Histopathological analysis revealed that the PGA group had higher numbers for each type of inflammatory cell (except mast cells) compared to the non-PGA group. CONCLUSION: Patients on PGA are likely to have a higher postoperative IOP and may need more medications for IOP control after a glaucoma triple procedure.

Glaucoma drainage device implantation in a pregnant woman with axenfeld-rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a rare disease characterized by anterior segment anomalies with or without glaucoma. A 28-year-old antenatal female diagnosed with ARS presented with uncontrolled intraocular pressures (IOPs) and advanced glaucoma despite maximal medical therapy and progressive vision loss during her third trimester. The refractory and progressive nature of the disease, with useful vision in one eye, necessitated immediate surgical intervention, following which there was successful control of IOP, lasting till the final follow-up at 18 months. We discuss the role of glaucoma surgery, for an ARS patient with refractory glaucoma during the third trimester with a comprehensive review of literature.

Evaluation of the agreement and reliability of Transpalpebral Tonometers compared with Goldmann Applanation Tonometer - A systematic Review and Meta-Analysis Protocol.

In 2020, the global prevalence of glaucoma was estimated to be 76 million and it was projected to increase to 111.8 million by 2040. Accurate intraocular pressure (IOP) measurement is imperative in glaucoma management since it is the only modifiable risk factor. Numerous studies have compared the reliability of IOP measured using transpalpebral tonometers and Goldmann applanation tonometry (GAT). This systematic review and meta-analysis aims to update the existing literature with a reliability and agreement comparison of transpalpebral tonometers against the gold standard GAT for IOP measurement among individuals presenting for ophthalmic examinations. The data collection will be performed using a predefined search strategy through electronic databases. Prospective methods-comparison studies published between January 2000 and September 2022 will be included. Studies will be deemed eligible if they report empirical findings on the agreement between transpalpebral tonometry and Goldmann applanation tonometry. The standard deviation and limits of agreement between each study and their pooled estimate along with weights and percentage of error will be reported using a forest plot. Cochrane's Q test and the I2 statistic will be used to assess heterogeneity, and the publication bias will be investigated using a funnel plot, Begg's and Egger's tests. The review results will provide additional evidence on the reliability of transpalpebral tonometers that, in turn, could possibly assist practitioners to make informed decision about using it as a screening or diagnostic device for clinical practice, outreach camps, or home-based screening. Institutional Ethics Committee registration number: RET202200390. PROSPERO Registration Number: CRD42022321693.

Intraocular Pressure Control Following Phacoemulsification in Eyes With Pre-existing Aurolab Aqueous Drainage Implant.

PURPOSE: The aim was to investigate intraocular pressure (IOP) control after phacoemulsification in adult glaucomatous eyes with a functioning nonvalved Aurolab Aqueous Drainage Implant (AADI) compared with eyes that did not have cataract extraction post-AADI. METHODS: In this retrospective study, we reviewed records of 47 patients (47 eyes) who had a clear corneal phacoemulsification after AADI placement with a minimum of 2 years of follow up. The control group included 89 patients (89 eyes) who had a functional AADI at 1 year, minimum of 3 years of follow up post-AADI implantation, and no cataract extraction. The main outcome measure was failure (IOP >21 mm Hg or increased by >20% from prephacoemulsification level requiring at least 1 additional glaucoma medication, IOP ≤5 mm Hg, reoperation for glaucoma, or loss of light perception vision). RESULTS: The median interval between AADI and phacoemulsification was 11.5 months (range: 4 to 68 mo), and the mean follow-up time after phacoemulsification was 35.6±6.4 months. The cumulative probability of failure was 14% (95% confidence interval=6%-31%) in the phaco group and 6% (95% confidence interval=3%-13%) in the control group at 2 years (P=0.11). Mean IOP was reduced from 16.5±4.5 mm Hg preoperatively to 15.4±4.7 mm Hg at 2 years after phacoemulsification (P=0.10). Mean LogMAR visual acuity improved from 1.1±0.6 preoperatively to 0.6±0.7 at 2 years after phacoemulsification (P<0.001). CONCLUSIONS: In eyes with a pre-existing AADI, phacoemulsification resulted in visual improvement without a significant rise in IOP or increased risk of AADI failure after 2 years follow up.

Incidence and Outcomes of Suprachoroidal Hemorrhage Following Aurolab Aqueous Drainage Implant in Adult and Pediatric Glaucoma.

PRCIS: Postoperative suprachoroidal hemorrhage (PSCH) is an infrequent but devastating complication after nonvalved aqueous drainage implant surgery and demonstrated a bimodal distribution. The final outcomes of either conservative management or surgical drainage of the hemorrhage remained poor. PURPOSE: The aim was to report the incidence and outcomes of eyes developing PSCH after undergoing Aurolab aqueous drainage implant (AADI) surgery for adult and pediatric refractory glaucomas. MATERIALS AND METHODS: In this retrospective series, case files of all patients who underwent AADI between May 2012 and December 2019 were retrieved from an electronic database. A PSCH was defined as the presence of hemorrhagic choroidal detachment, confirmed by ultrasound B scan, occurring in a closed system in the postoperative period. RESULTS: Of the 986 eyes that underwent AADI during the study period, 7 (0.7%), developed PSCH (95% confidence interval=0.3-1.6%). There were no differences in the preoperative parameters between those with and without PSCH. Of these, 4 were seen in pediatric eyes (4/288, 1.4%) and 3 in adult eyes (3/698, 0.4%) (P<0.01). Four eyes (57%) had PSCH in the immediate postoperative period (ie, between 24 and 48 h of AADI surgery), while the remaining 3 had onset ranging from 6 to 7 weeks after surgery. Anatomic risk factors were present in all eyes including hypotony (n=4), myopia (n=3), microcornea (n=2), microphthalmos (n=1), postvitrectomy (n=1), and staphyloma (n=1). Visual acuity improved in only 1 (14%) eye while 3 (43%) eyes developed phthisis bulbi, all in the pediatric age group. CONCLUSIONS: PSCH is a rare complication following AADI and is seen in <1% eyes. The incidence is higher in the pediatric age group. Visual and anatomic outcomes are dismal following PSCH with globe salvage possible in only about half these eyes.

Intermediate-Term Outcomes of an Affordable Aqueous Drainage Implant in Adults with Refractory Glaucoma.

PURPOSE: To report the outcomes of Aurolab Aqueous Drainage Implant (AADI) (Aurolab, Madurai, India) surgery in adults with refractory glaucoma. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Patients 18 years of age or older who underwent AADI surgery between January 2012 and December 2015 for refractory glaucoma with a minimum follow-up of 2 years. METHODS: Case records of eligible patients were evaluated for demographics, best-corrected visual acuity (BCVA), and indication for AADI surgery. The intraocular pressure (IOP) and the number of antiglaucoma medications (AGMs) were recorded at baseline, at 1, 3, 6, 9, 12, 18, and 24 months, and at the last visit after 24 months if any from the case files. Complications during or at any time point after surgery were also recorded. MAIN OUTCOME MEASURES: Cumulative failure rate of the AADI was defined as IOP > 18 mmHg or not reduced by 30% below baseline on 2 consecutive follow-up visits after 3 months, IOP ≤ 6 mmHg on 2 consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light perception vision. RESULTS: A total of 158 eyes of 158 patients with a mean age of 45.4±17.4 years and mean follow-up of 41.9±14.7 months were included in the analysis. Secondary open-angle glaucoma (n = 71, 45%) was the most common form of glaucoma. The mean preoperative IOP was 34.7±9.9 mmHg with 3.2±0.7 AGMs. At 1 year, the mean IOP decreased to 15.10±6.7 mmHg with 1.5±1.1 medications, and this was maintained at 2 years. Kaplan-Meier estimates showed that the cumulative probability of failure was 9.5% (95% confidence interval [CI], 5.8-15.2) at 1 year, 27.8% (95% CI, 21.5-35.5) at 2 years, 38.9% (95% CI, 31.1-47.8) at 3 years, and 50.1% (95% CI, 40.5-60.6) at 4 years. Forty-seven complications were observed in 38 eyes (24%), most of which were transient and did not require surgical intervention. The AADI tube exposure (n = 1), retraction (n = 1), plate exposure (n = 1), and plate displacement (n = 1) were seen rarely. CONCLUSIONS: The AADI appears to have good efficacy and safety for managing eyes with refractory glaucoma. Longer follow-up studies are required to determine long-term cumulative failure rates.

Evaluation of genetic polymorphisms in clusterin and tumor necrosis factor-alpha genes in South Indian individuals with pseudoexfoliation syndrome.

PURPOSE: The aim of this study was to explore the potential association of genetic variants across clusterin (CLU) and tumor necrosis factor-alpha (TNF-α) genes in South Indian individuals with pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG). MATERIALS AND METHODS: A total of 523 individuals including 299 unrelated cases (150 PEXS and 149 PEXG) and 224 age- and ethnically-matched healthy controls were recruited for genetic analysis. Six single-nucleotide polymorphisms (SNPs) including, five CLU SNPs (rs11136000, rs2279590, rs9331888, rs9331931, rs3087554) and one promoter SNP (rs1800629) of TNF-α were genotyped in all study subjects. Genotyping of CLU SNPs were performed using the TaqMan allelic discrimination assay while TNF-α SNP was genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis. Association analysis was performed by determining the distributions of genotype and allele frequencies, Hardy-Weinberg equilibrium, and chi-square p values and odds ratios as implemented in the Golden Helix SNP & Variation Suite (SVS). RESULTS: Five CLU SNPs did not show any significant differences in allele frequencies between patients and control subjects (rs3087554, p = 0.919, OR = 1.01, 95% CI: 0.77-1.33; rs2279590, p = 0.432, OR = 1.12, 95% CI: 0.84-1.51; rs9331931, p = 0.310, OR = 1.24, 95% CI: 0.81-1.89; rs11136000, p = 0.072, OR = 1.31, 95% CI: 0.97-1.76; rs9331888, p = 0.911, OR = 1.01, 95% CI: 0.78-1.31). The investigation of TNF-α SNP established a significant association with PEXS and PEXG (p = 0.042, OR = 0.61, 95% CI: 0.38-0.99). However, this association did not remain significant after Bonferroni correction. CONCLUSIONS: Our data suggest that genetic variants in CLU and TNF-α genes do not play a major role in the development of PEXS and PEXG in the South Indian population.

Evaluation of SNPs on chromosome 2p with primary open angle glaucoma in the South Indian cohort.

PURPOSE: Glaucoma comprises a heterogeneous group of optic neuropathies with a complex genetic basis. It is the second leading cause of irreversible blindness in the world. This study investigates the association of SNPs on chromosome 2p with primary open angle glaucoma (POAG) in a Southern Indian population. METHODS: Case-control analysis was performed using 220 unrelated POAG cases and 220 age-matched unaffected controls recruited through the Aravind Eye Hospital and its outlying clinics. Five SNPs (rs1533428, rs12994401, rs10202118, rs11125375, and rs11889995) on chromosome 2p were evaluated in these two groups and genotyped using Taq Man SNP genotyping assay. Statistical analysis was performed using the SVS program package by Golden Helix to identify the distributions of allele and genotype frequencies, Fisher exact test P values, and odds ratios and to check Hardy-Weinberg equilibrium. RESULTS: Among the five SNPs screened, SNP rs10202118, showed a P = 0.026 for the basic allelic test, P = 0.004 for the genotypic test, and P = 0.0014 for the recessive model. The second suggestive marker was rs11125375, which also showed P = 0.033 for the recessive model. The associated SNPs formed a common disease haplotype. The remaining three SNPs showed insignificant association in this study population. CONCLUSIONS: This was the first study to demonstrate the association of SNPs on chromosome 2p in patients with POAG in the Indian population. The two tagging SNPs (rs10202118 and rs11125375) on chromosome 2p are the most likely sites underlying the significant association with POAG in this study population.

Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds.

PURPOSE: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. METHODS: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. RESULTS: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. CONCLUSIONS: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies.

A review of genetic and structural understanding of the role of myocilin in primary open angle glaucoma.

Primary open angle glaucoma (POAG) is the most common form of glaucoma and the second leading cause of blindness in the world. Discovery of the candidate gene MYOC (TIGR/MYOC) encoding the protein myocilin, believed to have a role in cytoskeletal function, might play a key role in understanding the pathogenesis of POAG. MYOC is expressed in many ocular tissues, including trabecular meshwork (TM), a specialised eye tissue essential in regulating intraocular pressure (IOP). Later it was shown to be the trabecular meshwork inducible-glucocorticoid response protein (TIGR). Mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma (JOAG). The unprocessed myocilin with signal peptide is a 55-kDa protein with 504 amino acids. Mature myocilin is known to form multimers. Wild type myocilin protein is normally secreted into the trabecular extracellular matrix (ECM) and there appears to interact with various ECM materials. It is believed that the deposition of high amounts of myocilin in trabecular ECM could affect aqueous outflow either by physical barrier and/or through cell-mediated process leading to elevation of IOP. The N-terminal region of the myocilin has sequence similarity to myosin (muscle protein) and the C-terminal of the protein has an olfactomedin-like domain. Structural and genetic studies of the MYOC gene and its protein product along with molecular modeling could lead to better understanding of the pathogenesis of POAG. This review highlights the current understanding of myocilin and the relevance of genetic and structural work.