Clinical and experimental links between diabetes and glaucoma

Glaucoma is a leading cause of blindness. It is a multifactorial condition, the risk factors for which are increasingly well defined from large-scale epidemiological studies. One risk factor that remains controversial is the presence of diabetes. It has been proposed that diabetic eyes are at greater risk of injury from external stressors, such as elevated intraocular pressure. Alternatively, diabetes may cause ganglion cell loss, which becomes additive to a glaucomatous ganglion cell injury. Several clinical trials have considered whether a link exists between diabetes and glaucoma. In this review, we outline these studies and consider the causes for their lack of concordant findings. We also review the biochemical and cellular similarities between the two conditions. Moreover, we review the available literature that attempts to answer the question of whether the presence of diabetes increases the risk of developing glaucoma. At present, laboratory studies provide robust evidence for an association between diabetes and glaucoma.

Phacoemulsification combined with posterior capsulorhexis and anterior vitrectomy in the management of malignant glaucoma in phakic eyes

Purpose: To describe sequential phacoemulsification-intraocular lens (IOL) implantation-posterior capsulorhexis-anterior vitrectomy in the management of phakic malignant glaucoma. Methods: Twenty consecutive patients (25 eyes) with phakic malignant glaucoma were enrolled at the Zhongshan Ophthalmic Center, Sun Yat-sen University. All patients underwent phacoemulsification, IOL implantation and posterior capsulorhexis together with anterior vitrectomy via a clear corneal paracentesis. Visual acuity, intraocular pressure (IOP), anterior chamber depth (ACD), surgical complications and medications required after the surgery were recorded. Results: After surgery, the mean LogMAR visual acuity and ACD increased significantly (visual acuity from -1.56 ± 1.17 to -0.54 ± 0.81, p < 0.001; ACD from 0.367 ± 0.397 mm to 2.390 ± 0.575 mm, p < 0.001), and mean IOP decreased significantly (from 39.6 ± 10.6 mm Hg to 14.5 ± 4.1 mmHg, p < 0.001). No serious perioperative complications occurred, and only five eyes required topical glaucoma medications after surgery. Conclusion: Combined phacoemulsification-IOL implantation-posterior capsulorhexis-anterior vitrectomy surgery is a safe and effective method for treating patients with phakic malignant glaucoma. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Modeling and reasoning with qualitative comparative clinical knowledge

The number of clinical trials reports is increasing rapidly due to a large number of clinical trials being conducted; it, therefore, raises an urgent need to utilize the clinical knowledge contained in the clinical trials reports. In this paper, we focus on the qualitative knowledge instead of quantitative knowledge. More precisely, we aim to model and reason with the qualitative comparison (QC for short) relations which consider qualitatively how strongly one drug/therapy is preferred to another in a clinical point of view. To this end, first, we formalize the QC relations, introduce the notions of QC language, QC base, and QC profile; second, we propose a set of induction rules for the QC relations and provide grading interpretations for the QC bases and show how to determine whether a QC base is consistent. Furthermore, when a QC base is inconsistent, we analyze how to measure inconsistencies among QC bases, and we propose different approaches to merging multiple QC bases. Finally, a case study on lowering intraocular pressure is conducted to illustrate our approaches.

Medical versus surgical interventions for open angle glaucoma.

BACKGROUND: Open angle glaucoma (OAG) is a common cause of blindness.

OBJECTIVES: To assess the effects of medication compared with initial surgery in adults with OAG.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2012), Biosciences Information Service (BIOSIS) (January 1969 to August 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Zetoc, the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 August 2012. The National Research Register (NRR) was last searched in 2007 after which the database was archived. We also checked the reference lists of articles and contacted researchers in the field.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing medications with surgery in adults with OAG.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for missing information.

MAIN RESULTS: Four trials involving 888 participants with previously untreated OAG were included. Surgery was Scheie's procedure in one trial and trabeculectomy in three trials. In three trials, primary medication was usually pilocarpine, in one trial it was a beta-blocker.The most recent trial included participants with on average mild OAG. At five years, the risk of progressive visual field loss, based on a three unit change of a composite visual field score, was not significantly different according to initial medication or initial trabeculectomy (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54 to 1.01). In an analysis based on mean difference (MD) as a single index of visual field loss, the between treatment group difference in MD was -0.20 decibel (dB) (95% CI -1.31 to 0.91). For a subgroup with more severe glaucoma (MD -10 dB), findings from an exploratory analysis suggest that initial trabeculectomy was associated with marginally less visual field loss at five years than initial medication, (mean difference 0.74 dB (95% CI -0.00 to 1.48). Initial trabeculectomy was associated with lower average intraocular pressure (IOP) (mean difference 2.20 mmHg (95% CI 1.63 to 2.77) but more eye symptoms than medication (P = 0.0053). Beyond five years, visual acuity did not differ according to initial treatment (OR 1.48, 95% CI 0.58 to 3.81).From three trials in more severe OAG, there is some evidence that medication was associated with more progressive visual field loss and 3 to 8 mmHg less IOP lowering than surgery. In the longer-term (two trials) the risk of failure of the randomised treatment was greater with medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; hazard ratio (HR) 7.27, 95% CI 2.23 to 25.71). Medications and surgery have evolved since these trials were undertaken.In three trials the risk of developing cataract was higher with trabeculectomy (OR 2.69, 95% CI 1.64 to 4.42). Evidence from one trial suggests that, beyond five years, the risk of needing cataract surgery did not differ according to initial treatment policy (OR 0.63, 95% CI 0.15 to 2.62).Methodological weaknesses were identified in all the trials.

AUTHORS' CONCLUSIONS: Primary surgery lowers IOP more than primary medication but is associated with more eye discomfort. One trial suggests that visual field restriction at five years is not significantly different whether initial treatment is medication or trabeculectomy. There is some evidence from two small trials in more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with more glaucoma progression than surgery. Beyond five years, there is no evidence of a difference in the need for cataract surgery according to initial treatment.The clinical and cost-effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared with primary surgery is not known.Further RCTs of current medical treatments compared with surgery are required, particularly for people with severe glaucoma and in black ethnic groups. Outcomes should include those reported by patients. Economic evaluations are required to inform treatment policy.

Surveillance for ocular hypertension: An evidence synthesis and economic evaluation

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways.

DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model.

SETTING: Primary and secondary care.

PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences).

INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community.

MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs).

RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence.

LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates.

CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment.

FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

Transcameral suture to prevent tube-corneal touch after glaucoma drainage device implantation: a new surgical technique

PURPOSE: To report a new technique to correct tube position in anterior chamber after glaucoma drainage device implantation.

PATIENT AND METHODS: A patient who underwent a glaucoma drainage device implantation was noted to have the tube touching the corneal endothelium. A 10/0 polypropylene suture with double-armed 3-inch long straight needle was placed transcamerally from limbus to limbus, in the superior part of the eye, passing the needle in front of the tube.

RESULTS: The position of the tube in the anterior chamber was corrected with optimal distance from corneal endothelium and iris surface. The position remained satisfactory after 20 months of follow-up.

CONCLUSIONS: The placement of a transcameral suture offers a safe, quick, and minimal invasive intervention for the correction of the position of a glaucoma drainage device tube in the anterior chamber.

Cannabinoids and glaucoma

Glaucoma is one of the leading causes of blindness in the world. In spite of the diverse therapeutic possibilities, new and better treatments for glaucoma are highly desirable. Cannabinoids effectively lower the intraocular pressure (IOP) and have neuroprotective actions. Thus, they could potentially be useful in the treatment of glaucoma. The purpose of this article is to provide the reader with an overview of the latest achievements in research into the potential use of cannabinoids for glaucoma.

Influence of YAG laser posterior capsulotomy on preexisting glaucoma

Purpose. To evaluate the effects of a YAG laser posterior capsulotomy on intraocular pressure (IOP) in glaucoma patients. Methods. We retrospectively studied 69 patients who underwent posterior capsulotomy following cataract or combined cataract-glaucoma surgery and who had a minimum follow-up of six months. We assessed IOP control, number of glaucoma medications required, and need for additional glaucoma surgery following capsulotomy as clinical outcomes. We defined an "unfavorable result" as: a =5 mm Hg sustained rise in IOP, a need for additional glaucoma medications, and/or a need for additional glaucoma surgery. We calculated Kaplan-Meier event rate curves for these "unfavorable results." Mean follow-up was 24.4 ± 12.3 months. Results. 6.3% of patients had an IOP rise of =5 mm Hg one hour post capsulotomy. The actuarial (Kaplan-Meier) rate of any "unfavorable result" was 11.6% at 4 months, 38.1% at 12 months, 46.1% at 24 months, and 52.1% at 36 months following capsulotomy. Conclusions. Progression of glaucoma after YAG capsulotomy is common and may be accelerated by the laser procedure.

Surgical technique:Complex glaucoma case requiring molteno drainage tube extension

A 42-year-old man has been under long-term follow-up since he was a child for congenital glaucoma and buphthalmos in both eyes. His left eye best corrected visual acuity (BCVA) was counting fingers, due to end-stage glaucoma. He was on maximal medical therapy with an intraocular pressure (IOP) maintained at mid to low twenties. His right eye, the only seeing eye, had a BCVA of 6/9. This eye had undergone multiple glaucoma laser and surgical procedures, including an initial first Molteno drainage device inserted superonasally that failed in April 2003 due to fibrotic membrane over the tube opening. As a result, he subsequently had a second Molteno drainage device inserted inferotemporally. To further maximize his vision he had an uncomplicated cataract extraction and intraocular lens implant in December 2004, after which he developed postoperative cystoid macular edema and corneal endothelial failure. He underwent a penetrating keratoplasty in the right eye thereafter in March 2007. After approximately a year, the second Molteno device developed drainage tube retraction, which was managed surgically to maintain optimum IOP in the right eye. His right eye vision to date is maintained at 6/12. © 2011 Mustafa and Azuara-Blanco.

Corneal biomechanical properties in primary open angle glaucoma and normal tension glaucoma

PURPOSE: To determine and compare the corneal biomechanical properties between eyes with primary open angle glaucoma (POAG) and eyes with normal tension glaucoma (NTG). PATIENTS AND METHODS: Prospective cross-sectional study. Consecutive eligible POAG and NTG patients attending the Glaucoma Clinic had assessment of their corneal biomechanical properties-corneal hysteresis (CH) and corneal resistance factor (CRF)-using the Ocular Response Analyzer by an observer masked to the diagnosis. Exclusion criteria included previous intraocular surgery, corneal pathology, inflammatory connective tissue disease, and refraction of 5-dimensional or over. If both eyes were eligible, then the right eye was used for analysis. The main outcome measures were corneal hysteresis and CRF measurements. Data analysis was performed using the t test and general linear model. RESULTS: Eighty-one patients (80 whites) were analyzed. Forty had NTG, whereas 41 had POAG. Thirty-five were females. There was a statistically significant difference in mean CH (NTG 9.6±1.3 mm Hg; POAG 9.0±1.4 mm Hg; P=0.01), but not in mean CRF (NTG 9.9±1.4; POAG 10.8±1.7; P=0.06). The highest recorded Goldmann applanation intraocular pressure (IOP) was statistically significantly associated with lower CH (P=0.01) and higher CRF (P=0.02). CONCLUSIONS: There was a small but statistically significant difference in the mean CH between POAG and NTG (CH was higher in NTG). The highest recorded Goldmann applanation IOP was also statistically significantly correlated with lower CH and higher CRF, suggesting that alterations to the corneal biomechanical properties may occur as a result of chronic raised IOP in POAG. © 2008 by Lippincott Williams & Wilkins.

Methods to objectify reversibility of glaucomatous cupping

Lowering intraocular pressure in adults with glaucoma may be associated with an improvement in appearance of the optic nerve head. The stage of disease, the amount of intraocular pressure reduction, and the age of the patient probably influence the occurrence of this event. The clinical relevance of 'reversal' has not been established with certainty. The reversibility of glaucomatous cupping can be detected by subjective and qualitative means (examination of the patient or of fundus photographs) or by quantitative techniques such as photogrammetry, computerized image analysis, and scanning laser tomography. Clinical and experimental studies are providing new information about the behavior of the optic nerve head tissues in response to changes in intraocular pressure.

Cannabinoids and glaucoma - A review

Glaucoma is one of the leading causes of blindness in the world. A wide range of therapeutic possibilities to control the disease and prevent glaucomatous optic nerve damage with subsequent loss of vision already exist. In a relatively high proportion of patients, medical and/or surgical therapies are contraindicated or become non-effective. The purpose of this article is to provide an overview on the latest achievements in the research of potential use of cannabinoids in glaucoma. Methods: The literature on recent basic science research on cannabinoids and a range of research studies using cannabinoids under different preparations and ways of application was reviewed. Conclusions: Cannabinoids effectively lower the intraocular pressure. Newer research findings allow a better understanding of the different possible mechanisms of action of cannabinoids on IOP. Future progress in different research fields concerning possible clinical applications of cannabinoids may offer better preparations with less or possibly no undesired side effects.

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation

Purpose: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. Setting: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Methods: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. Results: Mean follow-up was 16.7 months ± 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperativety, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). Conclusion: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

Malignant glaucoma after diode laser cyclophotocoagulation

PURPOSE: To report a case of malignant glaucoma after diode laser cyclophotocoagulation. METHOD: Case report. RESULTS: A 45-year-old man with uncontrolled secondary glaucoma in his right eye after corneoscleral graft and cataract extraction underwent diode laser cyclophotocoagulation. The right eye was aphakic, with an intact posterior capsule. Two weeks later, the patient presented with blurred vision, edematous cornea, and flat anterior chamber. The posterior capsule was touching the endothelium. Intraocular pressure was 20 mm Hg. Repeated Nd:YAG laser capsulotomy was effective in reversing the malignant glaucoma attack, and the anterior chamber deepened. CONCLUSION: Malignant glaucoma can occur after diode laser cyclophotocoagulation.

Effect of cataract extraction on SITA perimetry in patients with glaucoma

PURPOSE: To evaluate the effect of cataract extraction on Swedish Interactive Thresholding Algorithm (SITA) perimetry in patients with coexisting cataract and glaucoma. PATIENTS AND METHODS: This is a retrospective noncomparative interventional study. Thirty-seven consecutive patients with open-angle glaucoma who had cataract extraction alone or combined with trabeculectomy were included. All patients had SITA-standard 24-2 visual fields before and after the surgery. The main outcome measures were changes in mean deviation (MD) and pattern standard deviation (PSD). Additionally, changes in best-corrected visual acuity, intraocular pressure, and number of glaucoma medications were also studied. RESULTS: Visual field tests were performed 3.9±4.4 months before surgery and 4.1±2.8 months after surgery. Mean visual acuity improved after the surgery, from 0.41±0.21 to 0.88±0.32 (P