Increased Desmosine in the lens capsules is associated with augmented elastin turnover in Pseudoexfoliation syndrome.

Pseudoexfoliation syndrome (PXF) is an idiopathic disease with a high prevalence rate. The elastosis disorder is contributed by genetic and non-genetic factors. Elastin dysregulation associated with the disease mechanism is incompletely understood. This study evaluated the molecules of the elastogenesis machinery in PXF. Lens capsule and aqueous humor (aqH) samples (age/sex-matched) were collected from the eyes with PXF alone and PXF with glaucoma (PXF-G) undergoing Extra Capsular Cataract Extraction (ECCE) surgery. The Elastin turnover was assessed by estimating Desmosine levels in the lens capsules by HPLC analysis. Expression of elastogenesis genes [EMILIN1, CLU, FBN1, FN1, FBLN5, FBLN4 and LOXL1] were evaluated in the lens capsule by qPCR while the proteins were assessed in aqH by western blot analysis. The Desmosine content in the lens capsules were 3-fold and 6-fold elevated in PXF (P = 0.02) and PXF-G (P = 0.01) respectively compared to the cataract-alone, indicating increased elastin degradation. A significant increase in the transcript levels of the CLU, FBLN4, EMILIN1, FBLN5, FN1, FBN1, LOXL1 along with significant changes in protein expression of CLU, FBLN5, FBN1 and LOXL1 signified up-regulation of the elastogenesis machinery. The study provides direct evidence of augmented elastin degradation and turnover in the lens capsule of PXF marked by increased Desmosine content and the expression of proteins involved in mature elastin formation.

Outcome of repeat trabeculectomy with mitomycin C in isolation or combined with phacoemulsification.

Purpose: To evaluate the effectiveness of repeat trabeculectomy with Mitomycin C (MMC) in isolation or combined with phacoemulsification, and to identify risk factors for failure over 1 year. Methods: Retrospective review of 113 eyes of 113 patients (49 primary open angle, 27 primary angle closure, 37 secondary glaucoma) who underwent repeat trabeculectomy with MMC (isolated trabeculectomy 75 and phacotrabeculectomy 38). The primary outcome measure was intraocular pressure (IOP) at 1 year follow-up. Three IOP criteria were chosen to measure success A) IOP ≤21 mmHg and ≥20% reduction from baseline. B) IOP ≤17 mmHg and ≥20% reduction from baseline. C) IOP ≤14 mmHg. Results: Mean IOP decreased from 24.5 ± 8.8 mmHg to 16.4 ± 7.6 mmHg 1 year after repeat trabeculectomy. The mean number of medications reduced from 2.9 ± 1.0 to 0.6 ± 1.0. Complete success with trabeculectomy versus phacotrabeculectomy for criterion A was 60% vs 55.3%, criterion B 54.7% vs 50.0% and criterion C 40.0% vs 28.9%. IOP ≤14 mmHg was more likely with trabeculectomy than phacotrabeculectomy (P = 0.047). On regression analysis, duration between surgeries ≤4 years (P = 0.018) and secondary glaucoma (P = 0.046) were identified as risk factors for surgical failure with criterion A. Younger age (P = 0.042), fornix based flap (P = 0.058), and phacotrabeculectomy (P = 0.042) for criterion C. Conclusion: Repeat trabeculectomy with MMC is successful at lowering IOP and decreasing number of antiglaucoma medications. Low IOP levels are less likely with phacotrabeculectomy.

Needle stick injuries in a tertiary eye-care hospital: Incidence, management, outcomes, and recommendations.

PURPOSE: The purpose of this study is to assess the incidence, management, and outcomes for needle stick injuries (NSIs) in a tertiary eye-care hospital and provide appropriate recommendations for its prevention. METHODS: This was a retrospective database review of NSI recorded between 2010 and 2015 at a tertiary eye care center. All staff members who had NSI were managed with standard treatment protocol. The mode, location, health-care workers affected and/or at risk for NSI were analyzed. RESULTS: One hundred and forty NSI were reported between 2010 and 2015, with ophthalmic fellows under training encountering maximum needle pricks (n = 33; 24%), followed by nursing staff (n = 32; 23%), and consultants (n = 30; 21%). Location wise, the highest incidence of NSI was found in the operating room (n = 94; 67%), followed by the laboratory (n = 17; 12%), and patients' ward (n = 14; 10%). Maximum pricks (n = 10; 20%) occurred while passing sharp instruments, anterior segment surgeons (n = 23; 79%) being affected more than posterior segment surgeons (n = 6; 21%). None of the NSI incidents was attributed to anti-VEGF injections. None of the subjects with NSI had seroconversion to hepatitis B surface antigen, human immunodeficiency virus, or hepatitis C virus in the 5-year study period. CONCLUSIONS: NSI is the most commonly encountered in the operating room among training personnel while passing sharp instruments, especially anterior segment surgeons. A proper needle/sharp disposal mechanism, documentation of adverse event, on-going staff training, and prompt prophylactic treatment are essential components of the protocol for NSI management.

Correlation of Aqueous Humor Lysyl Oxidase Activity with TGF-ß Levels and LOXL1 Genotype in Pseudoexfoliation.

PURPOSE: Pseudoexfoliation (PXF) is a microfibrillopathy involving disordered elastogenesis. Abnormal extracellular matrix (ECM) production underlies the pathophysiology of PXF. The enzyme Lysyl oxidase (LOX) and its isoforms are known to cross-link the elastin and collagen. Though the etiopathogensis of PXF is not well understood, studies report on the genetic risk involving LOXL1 gene. This study aims to screen LOXL1 coding variants rs1048661 and rs3825942 in the South Indian population and the implication of the single nucleotide polymorphism (SNP) with LOX activity. The levels of transforming growth factor ß (TGF-ß) in aqueous humor and its correlation with the LOX activity were also examined. METHODS: Blood, plasma, and aqueous aspirates were prospectively collected from PXF cases with and without glaucoma and cataract cases as controls. DNA was extracted from 48 PXF cases without glaucoma, 12 PXF cases with glaucoma, and 40 age-matched cataract-alone controls without PXF/glaucoma for analyzing LOX SNPs. LOX activity was measured in aqueous humor and plasma of 30 PXF cases without glaucoma, 24 age-matched cataract-alone controls without PXF/glaucoma, and 14 PXF cases with glaucoma. Protein levels of LOX, LOXL1, LOXL2, and total TGF-ß were estimated in plasma and aqueous humor by ELISA. RESULTS: The specific activity of LOX in aqueous humor was found to be significantly lowered in PXF cases compared with cataract-alone controls (p = 0.014). This decrease in LOX activity in PXF cases was associated with high-risk GG haplotype. However, this was not statistically significant and a larger sample size is warranted. TGF-ß1 and TGF-ß2 negatively correlated with LOX activity in aqueous humor (p = 0.028; p = 0.046, respectively). CONCLUSIONS: The LOXL1 SNPs, rs1048661 and rs3825942, are associated with PXF in the South Indian population correlating with lowered LOX activity in the aqueous humor. The increased level of total TGF-ß in the aqueous humor of PXF cases is possibly associated with LOX regulation which needs further investigation.

Diurnal intraocular pressure fluctuation and its risk factors in angle-closure and open-angle glaucoma.

PURPOSE: To evaluate intraocular pressure (IOP) fluctuation during office hours and its predictive factors in untreated primary angle-closure suspects (PACS); post-iridotomy primary angle closure (PAC) and primary angle-closure glaucoma (PACG) eyes with or without IOP-lowering medication(s) as appropriate and medically treated primary open-angle glaucoma (POAG) eyes. METHODS: One-hundred seventeen eyes (29 PACS, 30 PAC, 28 PACG, and 30 POAG) of 117 patients were included in this cross-sectional study. The subjects underwent hourly IOP measurements with Goldmann tonometer from 0800 to 1700 hours. Subjects with PAC and PACG had laser peripheral iridotomy at least 2 weeks prior to the inclusion. SD of office-hour IOP readings was the main outcome measure. RESULTS: IOP fluctuation differed between the groups (P=0.01; Kruskal-Wallis Test). Post hoc Mann-Whitney U-tests showed significantly less IOP fluctuation in PACS compared with PACG (P<0.01). Peak office-hour IOP was observed in the morning in untreated subjects and in the early afternoon in treated subjects. A stepwise linear regression model identified the presence of peripheral anterior synechiae (PAS), thickness of lens, large vertical cup-to-disc ratio (VCDR), and PAC category as significant predictive factors associated with office-hour IOP fluctuation. CONCLUSIONS: Diurnal IOP fluctuation in asymptomatic PACSs was less than that in treated PACG subjects and was at least comparable to that in treated PAC and POAG subjects. The greater the amount of PAS, the thicker the lens, the larger the VCDR, the greater was the IOP fluctuation during office hours.

Comparison of saccadic reaction time between normal and glaucoma using an eye movement perimeter.

AIM: To compare the saccadic reaction time (SRT) in both the central and peripheral visual field in normal and glaucomatous eyes using eye movement perimetery (EMP). MATERIALS AND METHODS: Fifty-four normal and 25 glaucoma subjects underwent EMP and visual field testing on the Humphrey Field Analyser (HFA) 24-2 program. The EMP is based on infrared tracking of the corneal reflex. Fifty-four test locations corresponding to the locations on the 24-2 HFA program were tested. SRTs at different eccentricities and for different severities of glaucoma were compared between normal and glaucoma subjects. RESULTS: Mean SRT was calculated for both normal and glaucoma subjects. Mann-Whitney U test showed statistically significant (P < 0.001) differences in SRT's between normal and glaucoma subjects in all zones. CONCLUSION: SRT was prolonged in eyes with glaucoma across different eccentricities.

Management of complications in glaucoma surgery.

Surgical option for glaucoma is considered when other modalities are not working out to keep the intraocular pressure under control. Since the surgical procedures for glaucoma disrupt the integrity of the globe, they are known to produce various complications. Some of those complications can be vision-threatening. To minimize the morbidity, it is very important that one should know how to prevent them, recognize them and treat them. The objective of this article is to provide insight into some of those complications that will help the ophthalmologists in treating glaucoma patients in their clinical practice.

Anterior chamber angle assessment using gonioscopy and ultrasound biomicroscopy.

PURPOSE: Comparison of anterior chamber angle measurements using ultrasound biomicroscopy (UBM) and gonioscopy. METHODS: Five hundred subjects were evaluated for grading of angle width by the Shaffer method. UBM was done in the same group to document angle width, angle opening distance (AOD 500), and anterior chamber depth. Biometric parameters were documented in all subjects. UBM and gonioscopic findings were compared. RESULTS: A study was conducted in 282 men and 218 women with a mean age of 57.32 +/- 12.48 years. Gonioscopic grading was used to segregate occludable (slit-like, grades 1 and 2) from nonoccludable (grades 3 and 4) angles. Subjective assessment by gonioscopy resulted in an overestimation of angle width within the occludable group when compared with values obtained by UBM. This did not affect the segregation of occludable versus nonoccludable angles by gonioscopy. Biometric parameters in eyes with occludable angles were significantly lower in comparison with eyes with nonoccludable angles, except for lens thickness. AOD 500 correlated well with angle width. CONCLUSIONS: We concluded that clinical segregation into occludable and nonoccludable angles by an experienced observer using gonioscopy is fairly accurate. However, UBM is required for objective quantification of angles, and AOD 500 can be a reliable and standard parameter to grade angle width.

Comparison of low-dose intraoperative mitomycin-C vs 5-fluorouracil in primary glaucoma surgery: a pilot study.

BACKGROUND AND OBJECTIVE: This study was undertaken to compare the efficacy and safety of low-dose intraoperative application of mitomycin-C (MMC) with that of 5-fluorouracil (5-FU) in primary trabeculectomy. PATIENTS AND METHODS: A non-randomized prospective study was performed between August 1994 and November 1995. Thirty-two eyes of 16 consecutive patients who underwent trabeculectomy for uncontrolled glaucoma of various causes form the study group. The mean age was 46.8 +/- 9.9 years. The first eye received MMC (0.2, 0.4 mg/ml), fellow eye received 5-FU (50 mg/ml), for 1 minute intraoperatively. Bleb characteristics and intraocular pressure (IOP) control were analyzed. Success of surgery based on IOP control was measured by 3 different criteria: IOP less than 21 mm Hg; IOP less than 21 mm Hg with more than 30% reduction; and IOP less than 16 mm Hg with more than 30% reduction. RESULTS: Mean preoperative IOP was 31.4 +/-12.7 mm Hg in MMC group and 27.8+/- 8.8 mm Hg in 5-FU group. Mean follow-up in MMC group was 16.12 +/- 8.17 months; in 5-FU group 13.37 +/- 8.19 months. At last follow-up all 5-FU blebs were nonischemic, while 4 eyes in the MMC group showed nonischemic blebs, and 12 eyes had ischemic blebs. There was no statistically significant difference between MMC group and 5-FU group success rates with all 3 criteria. Success rates were: IOP less than 21 mm Hg; 100% in both groups; IOP less than 21 mm Hg with more than 30% reduction; MMC group 93.8%, 5-FU group 75%; less than 16 mm Hg with more than 30% reduction; MMC group 87.5%, 5-FU group 68.8%. CONCLUSIONS: Low-dose intraoperative MMC and 5-FU can provide control of IOP in primary trabeculectomy, 5-FU group showed more non-ischemic blebs.

The role of artificial drainage devices in glaucoma surgery.

The use of artificial drainage devices (ADDs) or "setons" in glaucoma surgery is generally restricted to patients with refractory glaucoma at high risk for failure from conventional filtration surgery. ADDs, both valved and nonvalved are currently available in this country. Recently, some of these devices have been propogated as primary treatment even for primary glaucomas. This article examines the role of ADDs in the modern management of the glaucomas. Specific indications for ADDs and methods to reduce the complication of overfiltration are discussed. The use of antimitotics, such as 5-fluorouracil or mitomycin, with traditional filtration has decreased the indications for ADDs. The literature and our experience confirm that currently there is no role for use of ADDs as a primary procedure in most glaucomas.