Whole-genome sequencing unravels novel genetic determinants and regulatory pathways associated with triamcinolone acetonide-induced ocular hypertension.

Glucocorticosteroids commonly used to treat certain ocular inflammatory conditions cause an unwarranted elevation in intraocular pressure (IOP) leading to steroid-induced ocular hypertension (OHT). This study aims to identify novel genetic variants in the Indian population associated with steroid responsiveness, specifically to that of intravitreal Triamcinolone acetonide (TA) injections, which leads to OHT in 27% of the TA-treated Indian subjects. Genetic determinants and pathways regulating TA-OHT progression were investigated by applying whole-genome sequencing (WGS) on DNA extracted from 53 blood samples that included TA responders and non-responders. Sequencing analysis yielded 45 intronic and 49 exonic variants to be associated with TA-OHT, which are known to play a vital role in eye, heart, brain, and bone deformities. Of these, the most significant genetic variant associated with TA-OHT was further considered for molecular dynamics (MD) simulation studies. Variants in the CRPPA, PLOD1, ARHGAP1, TIMELESS and TNFSF4 genes were found to be directly implicating TA-OHT. Furthermore, these genes were enriched in pathways associated with cardiomyopathy, focal adhesion, extracellular matrix, and actin cytoskeleton reorganization. MD simulation studies revealed that the top significant variant (rs141625803) in the CRPPA gene possesses a high pathogenic and structurally destabilizing effect. Thus, novel genetic variants that could be significantly associated with the TA-OHT progression were identified in this study. Validation of these targets in a larger cohort of patients along with their functional analysis would inform on the disease, thereby adding to the existing knowledge on the pathophysiology of TA-OHT.

A comparative analysis of surgical outcome in uveitic and non-uveitic steroid-induced glaucoma in children.

Purpose: To compare outcomes of surgical management of uveitic glaucoma (UG) and steroid-induced glaucoma (SIG) in children in terms of intraocular pressure (IOP) control, visual acuity, and associations for failure. Methods: This was a retrospective case-control study of consecutive UG (cases) and non-uveitic SIG (controls) in children <18 years of age who underwent surgery between January 2005 and December 2017. Results: Primary trabeculectomy with mitomycin C (MMC) was performed in 12 cases (mean age: 9.2 ± 4.3 years) and 40 controls (mean age: 10.4 ± 3.7 years) (P = 0.33). Primary phaco-trabeculectomy with MMC was performed in 11 cases (mean age: 11.4 ± 4.7 years) and 16 controls (mean age: 10.4 ± 3.4 years) (P = 0.57). IOP control (P = 0.26), visual acuity (P = 0.97), number of glaucoma medications (P = 0.06), and survival rates (49% cases vs. 68% controls at 5 years; P = 0.22) were similar between the two groups following trabeculectomy. Survival rates in the phaco-trabeculectomy group at 5 years were 68% cases vs. 69% controls (P = 0.71). IOP was higher (P = 0.008) and visual acuity was worse (P = 0.02) in cases at the last visit. Associations for failure (univariate analysis) were younger age (OR: 6.29, 95% CL: 1.43, 27.67; P = 0.03) and male gender (OR: 4.79, 95% CL: 1.09, 20.97; P = 0.04). On multivariate analysis, younger age (OR: 11.985, 95% CL: 1.071, 134.153; P = 0.04) remained significant. Preoperative number of uveitic attacks was protective on univariate (OR: 0.75, 95% CL: 0.48, 1.15; P = 0.1) and multivariate analyses (OR: 0.49, 95% CL: 0.24, 0.09; P = 0.04). Conclusion: Outcomes of trabeculectomy between cases and controls were similar in our series. However, phaco-trabeculectomy in pediatric uveitic eye group fared worse than eyes with SIG.

Synthesis and Characterization of a Novel Peptide Targeting Human Tenon Fibroblast Cells To Modulate Fibrosis: An Integrated Empirical Approach.

Fibrosis is the primary factor influencing the prognosis of glaucoma post-trabeculectomy surgery, an eye condition characterized by increased intraocular pressure (IOP). Despite advancements in surgical procedures and aftercare, it continues to be a serious impediment. During the clinical intervention of scarring, fibrosis is managed by using topical application of combined antifibrotic drugs (mitomycin C). But still, scarring remains a key problem due to minimal drug penetration and nonbioavailability. In this study, we synthesized a cell-specific peptide for modulating scarring in human tenon fibroblasts undergoing epithelial-mesenchymal transition (EMT). The peptide was also conjugated with mitomycin C in order to investigate the effect of the drug conjugation on human tenon fibroblasts from the nanofiber composite system and to evaluate the fibrosis process. Peptide VRF2019 was identified using a subtractive proteomics approach, including solubility, cell penetration, and amphipathic properties. The peptide structure was determined using circular dichroism spectroscopy. The peptide and drug was conjugated using N-ethyl-N'-(3-(dimethylamino)propyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry, and the conjugation efficiency was evaluated using high-pressure liquid chromatography. The conjugated product and polycaprolactone (PCL) were electrospun to form a composite nanofiber, which was tested for cytotoxicity and drug release on human tenon fibroblast cells. The modeled VRF2019 peptide structure formed an α-helical structure with all residues spanning the allowed regions of the Ramachandran plot. Subsequent molecular dynamics simulations also demonstrated its membrane penetration potential. The peptide uptake was also studied in human tenon fibroblast cells. High-pressure liquid chromatography (HPLC) and mass spectrometry measurements confirmed peptide-drug conjugation and stability. Furthermore, scanning electron microscopy (SEM) investigation revealed the structure and size of the PCL composite nanofiber. We infer from early research that the PCL composite nanofiber matrix can greatly increase drug delivery and bioavailability.

Vogt-Koyanagi-Harada Disease in Pre-school Children.

PURPOSE: To report the management and outcome of VKH disease in a 4-year-old boy with a review of literature on VKH in preschool children (3 to 5 years). METHOD: Retrospective chart and literature review. RESULT: A 4-year-old boy presented with visual acuity of light perception in both eyes with panuveitis, secondary cataracts and intraocular pressure (IOP) of ≥40 mmHg in both eyes. He was started on oral corticosteroid, immunosuppressive and underwent glaucoma filtering surgery and lensectomy with vitrectomy after adequate control of intraocular inflammation. Over time his IOP was again uncontrolled even with maximum anti-glaucoma medications, and he underwent Ahmed glaucoma valve (AGV) implantation, and he gained a visual acuity of 20/60 in both eyes with aphakic correction at the last visit. CONCLUSION: Paediatric VKH follows an aggressive disease phase and requires a comprehensive multispeciality management approach.

Effect of immediate shallow anterior chamber after Ahmed glaucoma valve implantation on intermediate-term intraocular pressure control.

Purpose: To evaluate the incidence of shallow anterior chamber in the early postoperative period following Ahmed glaucoma valve (AGV) implantation and its effect on the hypertensive phase (HP), intermediate-term intraocular pressure (IOP) control, and success rate. Methods: A retrospective analysis of 369 eyes of 360 patients who underwent AGV implantation between January 2005 and January 2020 with a minimum follow-up of 2 months was performed. Twenty-six patients developed shallow anterior chamber (AC) within 8 weeks following surgery (cases). They were compared with 39 randomly selected controls (no shallow AC post AGV). HP (IOP spike >21 mmHg), use of ocular hypotensive medications, and other associations were compared. Results: Incidence of shallow AC post AGV was 7% (95% confidence interval [CI] 4, 9). The onset of shallow AC was 3 ± 2.1 days and resolved within 6 ± 4.7 days. Hypotony (12 [47%] vs. 1 [2.5%], P 0.0001) and choroidal detachment (CD; 7 [27%] vs. 3 [8%], P 0.03) were more common in cases compared to controls. The HP occurred in 11 (43%) cases versus 13 (34%) controls (P 0.4). Cases required more ocular hypotensive medications than controls at the end of 8 weeks (1.1 ± 1 vs. 0.5 ± 0.5, P 0.01). There was no significant difference in the qualified success between the groups at 1 year. Conclusion: The development of postoperative shallow AC post AGV implantation was not detrimental to IOP control at 1 year. However, there is a need to monitor the occurrence of HP in these eyes.

Elucidating the Therapeutic Potential of Cell-Penetrating Peptides in Human Tenon Fibroblast Cells.

Cell-penetrating peptides (CPPs) have been widely used as vehicles for delivering therapeutic molecules to the site of action. Apart from their delivering potential, the biological effects of CPPs have not been explored in detail. JTS-1 is a CPP that has been reported to have gene delivery functions, although its biological role is yet to be determined. Hence, in this study, we revealed the biological mechanism such as its uptake mechanism and immunogenic potential and function using primary human tenon fibroblast (TF) cells collected from patients undergoing glaucoma trabeculectomy surgery. Our results showed that the JTS-1 peptide has an α-helical structure and is nontoxic up to 1 µM concentration. It was found to be colocalized with early endosome (Rab5), recycling endosome (Rab7), and Rab11 and interacted with major histocompatibility complex (MHC) class I and II. The peptide also affected actin polymerization, which is regulated by cofilin phosphorylation and ROCK1 localization. It also inhibited TF cell proliferation. Therefore, the JTS-1 peptide could be used as a possible therapeutic agent for modifying the fibrosis process, where TF proliferation is a key cause of surgery failure.

A deep dive into the latest European Glaucoma Society and Asia-Pacific Glaucoma Society guidelines and their relevance to India.

Glaucoma is the second leading cause of blindness in India. Despite advances in diagnosing and managing glaucoma, there is a lack of India-specific clinical guidelines on glaucoma. Ophthalmologists often refer to the European Glaucoma Society (EGS) and Asia-Pacific Glaucoma Society (APGS) guidelines. A group of glaucoma experts was convened to review the recently released EGS guideline (fifth edition) and the APGS guideline and explore their relevance to the Indian context. This review provides the salient features of EGS and APGS guidelines and their utility in Indian scenario. Glaucoma diagnosis should be based on visual acuity and refractive errors, slit-lamp examination, gonioscopy, tonometry, visual field (VF) testing, and clinical assessment of optic nerve head, retinal nerve fiber layer (RNFL), and macula. The intraocular pressure target must be individualized to the eye and revised at every visit. Prostaglandin analogues are the most effective medications and are recommended as the first choice in open-angle glaucoma (OAG). In patients with cataract and primary angle-closure glaucoma (PACG), phacoemulsification alone or combined phacoemulsification and glaucoma surgery are recommended. Trabeculectomy augmented with antifibrotic agents is recommended as the initial surgical treatment for OAG. Laser peripheral iridotomy and surgery in combination with medical treatment should be considered in high-risk individuals aged <50 years. In patients with phakic and PACG, phacoemulsification alone or combined phacoemulsification and glaucoma surgery are recommended. Visual acuity, VF testing, clinical assessment of the optic disc and RNFL, and tonometry are strongly recommended for monitoring glaucoma progression.

Using artificial intelligence for diabetic retinopathy screening: Policy implications.

Artificial intelligence (AI) has evolved over the last few years; its use in DR screening has been demonstrated in multiple evidences across the globe. However, there are concerns right from the data acquisition, bias in data, difficulty in comparing between different algorithm, challenges in machine learning, its application in different group of population, and human barrier to AI adoption in health care. There are also legal and ethical concerns related to AI. The tension between risks and concerns on one hand versus potential and opportunity on the other have driven a need for authorities to implement policies for AI in DR screening to address these issues. The policy makers should support and facilitate research and development of AI in healthcare, but at the same time, it has to be ensured that the use of AI in healthcare aligns with recognized standards of safety, efficacy, and equity. It is essential to ensure that algorithms, datasets, and decisions are auditable and when applied to medical care (such as screening, diagnosis, or treatment) are clinically validated and explainable. Policy frameworks should require design of AI systems in health care that are informed by real-world workflow and human-centric design. Lastly, it should be ensured that healthcare AI solutions align with all relevant ethical obligations, from design to development to use and to be delivered properly in the real world.

Incidence of presumed steroid response in contralateral eye of patients who underwent glaucoma filtration surgery.

PURPOSE: The aim of this study was to report the incidence of presumed steroid response in contralateral eye of patients who underwent glaucoma filtration surgery. METHODS: We reviewed records of 298 glaucoma patients (147 PACG [primary angle-closure glaucoma], 129 POAG [primary open-angle glaucoma], and 22 JOAG [juvenile open-angle glaucoma]) who underwent either trabeculectomy alone or trabeculectomy with cataract extraction. All patients received prednisolone acetate 1% eye drop postoperatively in the operated eye for up to 6 to 8 weeks. The contralateral eye received the same antiglaucoma medications as before. Information collected included age, sex, number of antiglaucoma medications in the fellow eye preoperatively, and VFI (visual field index). The preoperative intraocular pressure (IOP) in the contralateral eye was taken as the baseline. The maximum IOP recorded postoperatively up to a follow-up period of 6 to 8 weeks was noted. A steroid response was defined as rise in the IOP by ≥6 mmHg. RESULTS: In this study, 298 eyes of 298 glaucoma patients were included. The mean age of patients was 60.1 ± 13.7 years. The mean number of antiglaucoma medications in the fellow eye pre-operatively was 2.4 ± 1.2. Mean preoperative and postoperative IOP in the fellow eye were 17.46 ± 7 and 19.37 ± 7.1 mmHg, respectively. Sixty-three eyes out of 298 eyes (21.14%) showed a rise in IOP by 6 mmHg. The maximum IOP difference noted was 15 mmHg. The average time interval to the defined steroid response was 16.13 days. The majority showed a steroid response within 19 days. CONCLUSION: Steroid response is a significant factor leading to elevated IOP postoperatively in the contralateral eye as well.

Topical timolol for the treatment of conjunctival pyogenic granulomas: Outcomes and effect on intraocular pressure.

PURPOSE: To report the clinical outcomes of 0.5% timolol maleate eye drops for the treatment of conjunctival pyogenic granuloma (PG) and its effect on intraocular pressure (IOP). METHODS: In this retrospective study, consecutive patients with conjunctival pyogenic granuloma between January 2019 and September 2019 were prescribed 0.5% timolol maleate eye drops twice a day and followed up for 8 weeks. IOPs were measured before treatment, while on treatment and 6 weeks after treatment. RESULTS: A total of 12 patients with conjunctival PGs were treated with 0.5% timolol maleate eye drops. Patients ranged from 7 to 72 years with a mean age of 31.1 years. Eleven (11/12; 91.6%) patients had complete resolution of pyogenic granulomas after a mean duration of treatment of 4.4 weeks (range: 3-6 weeks). One patient had a persistent PG, which showed sub-optimal resolution at 6 weeks of treatment and was surgically excised. The mean IOP of the affected eye at presentation was 15.1 mm Hg (range: 10 to 20 mm Hg; SD: ±2.9 mm Hg). One week after initiating therapy, the mean IOP was 12.1 mm Hg (range: 8-16 mm Hg; SD: ±2.4 mm Hg). The mean reduction IOP compared to the baseline IOP was statistically significant (p = 0.02). No adverse events were noted in any of the patients. CONCLUSION: Topical timolol is effective in the treatment of conjunctival pyogenic granulomas with no major side effects. There is a significant reduction in IOP while on treatment which is reversible and returns to baseline following completion of therapy.

Phacoemulsification in eyes with long anterior zonules.

PURPOSE: To study the safety of phacoemulsification in eyes with long anterior zonules (LAZs). SETTING: Institute. DESIGN: Retrospective interventional case series. METHODS: All patients with clinically proven LAZs who had undergone phacoemulsification by a single surgeon from January 2014 to December 2018 were included. All cases of LAZs with cataract extraction by procedures other than phacoemulsification or combined with any other ocular surgery were excluded. Sixty-five eyes of 52 patients were analyzed. Phacoemulsification with capsulorhexis that involves sacrificing the LAZs was performed. The primary outcome measures were the incidence of capsulorhexis extension or the need to rescue intraoperatively and the rate of intraoperative complications. Secondary outcomes assessed were the percentage of eyes within ±0.5 diopters (D) and ±1 D of the target refraction. RESULTS: Sixty-five eyes (52 patients) were analyzed; the mean age of patients was 67.3 ± 7.4 years. The successful completion of an adequately sized capsulorhexis without extension or rescue was seen in 100% of cases. The incidence of intraoperative complications was 1.5% (posterior capsular rupture in 1 eye). The mean postoperative corrected distance visual acuity was 0.05 ± 0.1 (logarithm of the minimum angle of resolution) at a mean of 26.8 ± 7.6 days. The mean spherical equivalent was -0.15 ± 0.7 D. Eyes within ±0.5 D and ±1.00 D of the target refraction were 77% and 94%, respectively. CONCLUSIONS: Phacoemulsification in eyes with LAZs can be safely performed through an adequately sized capsulorhexis by sacrificing, ie, cutting or breaking, the anteriorly inserted zonules 360 degrees without significant intraoperative complications.

INTRAOCULAR PRESSURE OUTCOMES AFTER SURGERY FOR RHEGMATOGENOUS RETINAL DETACHMENT IN SCHWARTZ SYNDROME.

PURPOSE: To study intraocular pressure (IOP) outcomes after surgery for rhegmatogenous retinal detachment in Schwartz syndrome. METHODS: We reviewed records of 32 eyes of 32 patients with Schwartz syndrome (patients with rhegmatogenous retinal detachment, IOP above 21 mmHg, and open angles without angle recession, chronic steroid use or other secondary causes of increased IOP) who had undergone surgical treatment consisting of scleral buckling or vitrectomy. Intraocular pressure, number of medication, best-corrected visual acuity were compared at baseline and postsurgery visits and also studied association of various factors on long-term IOP. RESULTS: The median duration of rhegmatogenous retinal detachment was 2 months, and the inter quartile range was 1 to 12 months. Follow-up was 15 months (inter quartile range: 7-33 months). Sixteen (50%) had prior ocular trauma. Baseline IOP was 35 ± 8 mmHg, and 12% (4/32) of patients were on IOP-lowering medication at presentation. At the final visit, mean IOP was 17 ± 6 mmHg and 59% patients (19/32) required additional IOP-lowering medication or surgery for IOP control. CONCLUSION: Surgical management of rhegmatogenous retinal detachment resulted in significant reduction in IOP. At the final visit, 41% did not require any IOP-lowering medication or surgical intervention for IOP control.

Risk factors and outcomes of management of delayed suprachoroidal haemorrhage following Ahmed glaucoma valve implantation in children.

AIMS: To assess the incidence, risk factors and outcomes of management of delayed suprachoroidal haemorrhage (DSCH) in children who had undergone Ahmed glaucoma valve implantation. METHODS: A retrospective case-control study of eyes which developed DSCH in children <18 years of age who underwent surgery between January 2009 and December 2017 with a follow-up of at least 2 months was performed. Nine cases were compared with 27 age, gender and surgeon matched controls who had undergone surgery during this period. RESULTS: The incidence of DSCH was 4.7% (95% CL 1.5% to 7.7%, 9 eyes of 191 children). There were no significant differences between cases and controls in baseline details except for the number of intraocular pressure (IOP) lowering medications (p=0.01) and follow-up period (p=0.001). Risk factors identified on univariate analysis (p≤0.1) were axial length (p=0.02), diagnosis of primary congenital glaucoma (p=0.05), postoperative hypotony (p=0.07) and aphakia (p=0.1). None of them were found to be significant on multivariate analysis. Five eyes, three with retinal apposition and two with retinal detachment, underwent surgical drainage. There were no significant differences in the outcomes of eyes which underwent drainage compared with those which did not. Failures, defined as IOP>18 mm Hg despite use of medications, loss of light perception, phthisis or removal of the implant were more frequent in cases (three eyes, 33.3%) compared with controls (four eyes, 14.8%) (p=0.002). CONCLUSIONS: None of the risk factors analysed in our series proved to be significant. Failures were more common in eyes with choroidal haemorrhage, despite surgical intervention.

Lowered Decorin With Aberrant Extracellular Matrix Remodeling in Aqueous Humor and Tenon's Tissue From Primary Glaucoma Patients.

Purpose: To evaluate the inflammatory cytokine, growth factors, extracellular matrix (ECM) remodeling genes, profibrotic and antifibrotic molecules in patients undergoing glaucoma filtration surgery (GFS). Additionally, the effect of preoperative antiglaucoma medications (AGMs) and postoperative bleb status were related to these parameters. Methods: Tenon's tissue and aqueous humour (AH) were collected from 207 patients undergoing GFS with primary open-angle glaucoma (POAG) (n = 77), primary angle-closure glaucoma (PACG) (n = 62), and cataract controls (n = 68). Monocyte chemoattractant protein-1 (MCP-1), connective tissue growth factor (CTGF), transforming growth factor ß1/2 (TGF-ß1/2), lysyl oxidase (LOX), lysyl oxidase L2 (LOXL2), elastin (ELN), collagen type 1 α 1 (COL1A1), secreted protein acidic and rich in cysteine (SPARC), α-smooth muscle actin (α-SMA), and decorin (DCN) were determined in tenon's tissue by real-time PCR and in AH using ELISA. Results: A significant increase was observed in the transcripts of MCP-1, TGF-ß2, and SPARC in POAG and PACG (P < 0.05); CTGF, TGF-ß1, LOX, LOXL2, ELN, COL1A1, and α-SMA in PACG (P < 0.05) compared with control. DCN transcript was significantly decreased in POAG and PACG (P < 0.05) compared with control. The protein levels of CTGF, TGF-ß1/ß2, ELN, SPARC, and LOXL2 was significantly elevated in POAG and PACG (P < 0.05); DCN was decreased (P < 0.05) compared with control. These parameters showed significant association with duration of preoperative AGMs and postoperative bleb status. Conclusions: This study demonstrates increased expression of growth factors and ECM molecules, both at protein and transcript levels in GFS patients. A decreased DCN in AH seems striking, and if restored might have a therapeutic role in minimizing postoperative scarring to improve GFS outcome.

Phacotrabeculectomy in Eyes With Uveitic Glaucoma: A Retrospective Case-Control Study.

PRECIS: Phacotrabeculectomy with adjunctive mitomycin C is a good option for the management of coexisting cataract and glaucoma. Strict preoperative control of inflammation and close follow-up are essential in the management of eyes with uveitic glaucoma (UG). PURPOSE: The purpose of this study was to compare the outcomes of phacotrabeculectomy with adjunctive antimetabolites in the management of patients with UG and patients with primary open-angle glaucoma (POAG). MATERIALS AND METHODS: A retrospective case-control study of 112 patients with UG and 120 patients with POAG who underwent phacotrabeculectomy with mitomycin C and had a follow-up of ≥12 months between January 2000 and June 2015 was performed. Patients who had undergone intraocular surgery or cyclodestructive procedures earlier were excluded. The primary outcome was intraocular pressure (IOP) control; secondary outcomes included visual acuity and complication rates. RESULTS: IOP control was similar at the final visit in the UG group (14.52±6.74 mm Hg) and the POAG group (14.39±4.18 mm Hg) (P=0.867). Kaplan-Meier survival analysis showed a cumulative probability of survival (IOP: 6 to 18 with or without medications) in 71% and 77% at the end of 5 years (P=0.094) in the UG and POAG groups, respectively. Visual outcomes were worse in the UG group (0.5±0.68 logMAR units), as compared with the POAG group (0.27±0.47 logMAR units) (P=0.002). Complications such as cystoid macular edema (P=0.025) and posterior capsular opacification (P=0.004) were more common in the UG group. Recurrence of inflammation occurred in 34 eyes (30.04%) in the UG group. CONCLUSION: Meticulous control of perioperative and postoperative inflammation could have contributed to the favorable long-term outcomes of phacotrabeculectomy in UG, as compared with POAG.

The Outcomes of a Comprehensive Program for Maintenance of Goldmann Applanation Tonometer.

PRECIS: We checked 190 tonometers every month and repaired faulty ones. Calibration error (CE) frequency reduced from 23% to 0.6% at 1 year. Tonometers needing one or >1 CE repair differed in survival but not in age. PURPOSE: The purpose of this study was to report the outcomes of a comprehensive program to maintain calibration status of the Goldmann applanation tonometer. METHODS: This prospective cohort study was carried out at 2 tertiary eye care referral centers. We included 190 slit-lamp mounted Goldmann applanation tonometers (Model AT 900 C/M). Health care providers (error checking and reporting) and clinical engineers (maintenance) participated. The team carried out CE check once a month, and repair of faulty tonometers, if any, within 24 hours. Failure of tonometer was defined as development of unacceptable CE beyond the third repair. The main outcome measures were the frequency of CE and survival function of the tonometer over 1 year. RESULTS: The median age of the tonometers was 10.7 (range, 0.2 to 25.1) years. The total number of repairs was 86. The proportion (95% confidence interval) of faulty tonometers reduced from 23.1% (17.7, 29.6) in the first month to 0.6% (0.1, 3.3) at 1 year (P<0.01). The median age of the tonometer did not differ between those needing (n=63, 9.4 y) and not needing (n=127, 10.7 y; P=0.24) repair. All tonometers requiring 1 CE repair (n=49, 25.7%) survived until 1 year. The survival of tonometers requiring >1 CE repair (n=14, 7.3%) was 40% at 1 year. CONCLUSIONS: Our in-house program maintained 92.6% tonometers error free. Number of repairs rather than age determined the need for replacement/sending back the tonometer to the manufacturer. Our simple and easy to follow maintenance program has the potential for wide application.

Detection of Proteins Associated with Extracellular Matrix Regulation in the Aqueous Humour of Patients with Primary Glaucoma.

Purpose: The protein composition of aqueous humour (AH) has held significant relevance and remains to be the prime sample in the discovery of biomarkers in glaucoma. The purpose of this study is to analyze the AH protein concentrations in primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) and further examine the proteome changes compared to cataract control. Methods: AH was collected from 90 POAG, 72 PACG, 78 cataracts (controls) in this study. The total protein was quantified using Bradford's assay. Samples were subjected to trypsin digestion followed by liquid chromatography-mass spectrometry (LC-MS) for proteomic studies (n = 3 per group). The extracellular matrix has a major influence on the AH outflow, and the regulator proteins osteopontin (OPN), cathepsin D, and cystatin C detected by mass spectrometry are validated in AH samples by Western blot and turbidimetric immunoassay. Results: We observed a significant increase in protein levels of POAG (p = .0009); interestingly, a similar increase in PACG compared to cataract (p < .0001) and POAG (p = .02). Proteomics analysis identified 184, 190, and 299 proteins in control, POAG and PACG. OPN was increased in POAG (p = .0319) and PACG (p = .0103) compared to control. The precursor form of cathepsin D was increased in POAG and decreased in PACG, though not significant compared to control. Cystatin C was also increased in both POAG (p = .0310) and PACG (p = .0125) compared to control. Conclusion: In this study, we report for the first time that PACG cohort had higher total protein compared to controls. A qualitative comparison of proteomes revealed increased numbers of proteins identified in PACG. We assume that elevated levels of OPN and cystatin C in POAG and PACG along with altered cathepsin levels may contribute to ECM aberration in glaucoma.

Prospective analysis of the predictors of glaucoma following surgery for congenital and infantile cataract.

PURPOSE: A prospective longitudinal cohort study was performed to assess the incidence of and risk factors for the development of glaucoma following surgery for congenital/infantile cataract. METHODS: One hundred and one eyes of one hundred and one children, ≤12 years of age who had follow-up of ≥24 months were included. Group I included those who underwent surgery using an anterior approach, group II included those who underwent surgery using a posterior approach, and group III included those who underwent surgery using an anterior approach along with foldable intraocular lens implantation. Standard definitions for glaucoma and glaucoma suspect were used. The Cox proportional hazard model was used to analyze risk factors for glaucoma. RESULTS: Group I: 30 eyes (29.7%); group II: 11 eyes (10.9%); group III 60 eyes (59.4%). The incidence of glaucoma + glaucoma suspect was 7.9% (95% CL: 2.6, 13.2%) in the entire group. The incidence in group I was 16.7% (95% CL 3%, 30%), in group II was 18.2% (95% CL: 0, 41%) and in group III was 1.7% (95% CL: 0, 4.9%). Gonioscopy revealed high iris insertion with grade I (modified Shaffer grading) in one eye each in the glaucoma and glaucoma suspect group and open angles in the rest. Age at surgery of ≤3 months (HR: 6.6, 95% CL: 1.4, 30.6, p = 0.01) was found to be a significant risk factor within the aphakic group. CONCLUSIONS: Younger age at the time of surgery was the only identifiable risk factor for glaucoma.