Automated iris volume analysis and trabecular meshwork length using anterior segment optical coherence tomography - Application in pseudoexfoliation and pseudoexfoliation glaucoma.

Purpose: The aim of this study was to evaluate differences in the iris and angle parameters in psuedoexfoliation syndrome (PXF) and pseudoexfoliation glaucoma (PXG) using anterior segment optical coherence tomography (ASOCT). Methods: Patients with PXF or PXG were compared using ASOCT with primary open-angle glaucoma POAG eyes as controls in this noninterventional comparative study conducted at a tertiary eye care center in East India. All angle parameters, TM length, and iris thickness were analyzed from the enhanced depth imaging (EDI) single scans obtained. Quadrant scans were used for the calculation of iris volume using a custom-built in-house software. In particular, the software performs multiple operations including edge detection, connected components, and thresholding to localize and segment the iris. Differences in the iris volume/thickness and TM length in PXF and PXG with POAG were analyzed. Results: A total of 225 eyes were included, which included 75 PXG and 98 PXF cases and 52 POAG with a mean age of 67 ± 9.7 years at presentation. The algorithm repeatability and reproducibility was also established with correlation coefficients more than 99% which was substantiated with Bland-Altman plots. The iris volume (calculated in 197 images of 225 eyes) did not differ significantly in PXF and PXG eyes, although both had significantly greater volume compared to POAG eyes. The iris volume or other angle parameters including TM length did not correlate with clinical variables such as IOP, age, or visual field indices. Conclusion: Iris parameters or TM length do not explain pathogenesis of glaucoma in pseudoexfoliation.

Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation.

PURPOSE: To investigate the microRNA (miRNA) profile in patients with different stages of pseudoexfoliation (PXF). METHODS: Peripheral blood of patients with PXF (naïve to medical therapy and with no systemic disease/drugs) with ocular hypertension (OHT) and pseudoexfoliation glaucoma (PXG) was evaluated in triplicate for miRNA profiling using polymerase chain reaction (PCR) arrays. Those identified in the discovery stage were validated with evaluation of serum transforming growth factor-ß1 (TGF-ß1) levels by ELISA. The downstream targets of TGF-ß1 and unfolded protein response (UPR) were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Predicted targets of the identified miRNA and KEGG pathway analysis were done using miRbase and DIANA tools mirPathv3.1. RESULTS: We found hsa-miR-122-5p, hsa-miR-124-3p and hsa-miR-424-5p to be upregulated in PXG targeting 3 specific pathways namely TGF-ß1, fibrosis/ECM and proteoglycan metabolism with common effectors like SMAD/3/2. The unfolded protein response (UPR) genes were significantly downregulated in all stages of PXF suggesting this as the key mechanism for protein aggregates in PXF syndrome. Serum TGF-ß1 was significantly upregulated as disease progressed to later stages in PXG. This elevation in advanced stages was associated with significantly differential expression of downstream pathways and fibrotic genes in OHT compared to PXG predominantly through the SMAD3, a canonical pathway marker. CONCLUSION: Circulatory miRNA differentially regulating TGF-ß1 and downstream targets including UPR genes may be the key mechanisms for glaucoma onset in PXF.

Visual impairment in pseudoexfoliation from four tertiary centres in India.

PURPOSE: To analyse the disease burden of pseudoexfoliation (PXF) disease stages from East and South India. DESIGN: Prospective hospital based study of patients seen at 4 tertiary centres. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Consecutive old and new patients of pseudoexfoliation with normal intraocular pressure (IOP), raised IOP (PXF with Ocular hypertension, OHT) and irreversible disc/field changes (pseudoexfoliation glaucoma, PXG) seen from April 2016-March 2017 at a tertiary centre in Odisha, East India and 3 centres in Andhra Pradesh and Telangana, South India, recruited into the prospective study were screened for baseline characteristics. METHODS: The clinical and demographic details including visual acuity, laterality, intraocular pressure (IOP) with details of medical/surgical therapy at presentation were collected from the hospital database at all 4 centres. INTERVENTION OR EXPOSURE: The World Health Organization WHO visual criteria were used for defining visual impairment/absolute blindness in different disease stages. OUTCOME MEASURES: The visual impairment/blindness rates with comorbidities in the anterior/posterior segment in PXF, OHT and PXG at baseline were compared and the influence of age, IOP fluctuations and laterality was analysed using multivariate logistic regression. RESULTS: Of 6284 PXF eyes (of 3142 patients) included from all centres, OHT and PXG was seen in 2.1% and 29% respectively which included 3676 (>50%) bilateral PXF eyes. Reversible visual impairment rates caused by PXF associated co-morbidities in PXF and OHT were 33% and 26% respectively with cataract being the major cause (67% in PXF and 74% in OHT). Irreversible blindness rate was higher in bilateral PXG eyes (30.5%) compared to bilateral PXF (23.2%) or bilateral OHT (21.6%) with overall absolute blindness rates of 28.2% at presentation. Older age (p<0.001), bilaterality and higher baseline IOP were significantly associated with higher rates of blindness in PXF eyes. CONCLUSION AND RELEVANCE: Pseudoexfoliation is associated with ≥30% visual impairment across all stages and 28% absolute blindness rate which is a huge hidden burden of glaucoma. Adequate disease staging and assessment of comorbidities is required for accurate prognostication at baseline and reducing avoidable pseudoexfoliation blindness.

Outcomes of Ahmed glaucoma valve FP8 versus FP7 in adult secondary glaucoma.

AIM: To compare the outcomes of Ahmed glaucoma valve (AGV) pediatric FP8 versus the large-sized adult FP7 implants in an adult secondary glaucoma. METHODS: Patients who underwent AGV implantation from January 2011 to December 2016 for adult secondary glaucoma (due to causes other than post-vitreoretinal/buckle surgery glaucoma) with a follow-up of 6 months were included for this retrospective study. Success was defined as IOP > 6 mm Hg and < 21 mm Hg without any loss of vision, with or without the need of anti-glaucoma medications or additional procedures for control of IOP. Hypertensive phase was defined as IOP > 21 mmHg at any visit in the first 6 months of postoperative follow-up period, while failure was defined as IOP > 21 mm Hg even after medications or additional procedures, need of removal of implant or loss of light perception. Cumulative survival rates and intraoperative or postoperative complications along with IOP profiles were compared between the implants. RESULTS: Of 43 patients, 19 patients underwent FP7 and 24 patients underwent FP8 Ahmed Glaucoma valve implantation. The IOP significantly reduced in both groups from baseline (31 ± 8.2 mm Hg in FP7 eyes and 37 ± 13.1 mm Hg in FP8 eyes) by a mean of 64 ± 23.5% in FP8 and 64 ± 21.5% in FP7 group, respectively, p = 0.8 with comparable final IOP of 16.5 mm Hg and 16.9 mm Hg, respectively, p = 0.9. Both groups had 75% qualified success rates at 20 months after surgery with similar rates of need for postoperative medications or incidence of hypertensive phase. The FP8 eyes had more frequent conjunctiva-related complications in eyes with prior surgeries and preoperative conjunctival scarring while the other complications were similar in the two groups. CONCLUSION: Surgical outcomes of adult FP7 and pediatric FP8 AGV in adult secondary glaucoma seem to achieve similar IOP control and success rates. This suggests that smaller-sized FP8 can be used in adult glaucoma with good surgical outcomes albeit with careful case selection in eyes with extensive preoperative scarring to avoid conjunctival thinning-related complications postoperatively.

Clinical spectrum of pseudoexfoliation syndrome-An electronic records audit.

PURPOSE: To evaluate different clinical variants of pseudoexfoliation syndrome and their risk of developing ocular hypertension (OHT) or glaucoma (PXG). DESIGN: Cross sectional hospital based study. SETTING: All patients seen at glaucoma services of a tertiary eye care center in east India. METHODS: Electronic medical records search of hospital database including consecutive new and old cases seen during April 2013 to March 2015 was done to retrieve case sensitive words including pseudoexfoliation, PXF, PEX, PXG and pseudoexfoliative glaucoma over any part of the clinical electronic sheet of the patient. All demographic and clinical details including laterality, the pattern of deposits, need for medicines and disc damage at presentation was compared in eyes with radial pigmentary, classical or combined forms of PXF phenotypes. RESULTS: Of 110313 PXF patients seen during the period of 2013-2015, a total of 2297 eyes of 1150 PXF patients were identified including 525 unilateral PXF (meaning a total of 1775 PXF eyes with 625 patients having bilateral disease, n = 1250 eyes, other clinically normal eye, n = 522) at presentation. Of 525 unilateral PXF eyes, 105 had OHT and 131 had glaucoma while bilateral cases had more >50% (675 eyes of 1250 eyes) with glaucoma. Glaucoma with significant changes in IOP with or without disc damage was seen in 32% of pigmentary and 39% of classical PXF forms with eyes with combined forms of PXF having around 50% with glaucoma at presentation compared to other forms, p<0.001. CONCLUSION: Different phenotypic variants of PXF in this Indian cohort was associated with 30-50% risk of OHT or glaucoma respectively. Adequate care is required while examining the pattern of PXF in each case to prognosticate each patient/eye.