ISRCTN12125882 - Influence of topical anti-VEGF (Ranibizumab) on the outcome of filtration surgery for glaucoma - Study Protocol

<p>Abstract</p> <p>Background</p> <p>Excessive wound healing, with scarring of the episcleral tissue or encapsulation of the filtering bleb is the main reason for failure in trabeculectomy. Ranibizumab, an inhibitor of the Vascular Endothelial Growth Factor (VEGF), is seen as a promising candidate to prevent or treat extensive wound healing. We describe the design of a two phased study, i) assessing the local tolerability and safety of topical ranibizumab and ii) assessing the efficacy of topical ranibizumab against placebo in patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and intra ocular lens (IOL) implantation.</p> <p>Methods/Design</p> <p>In the first phase five patients that had trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be treated with topical ranibizumab (Lucentis^®) eye drops (2 mg/ml) four times daily for one month. The treatment will be started at the first postoperative day. Patients will be assessed for local and systemic side effects using a standardised schedule. In the second phase, after successful completion of phase 1, consenting eligible patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be randomised to either receive topical ranibizumab eye drops (2 mg/ml) four times daily for 1 month or placebo (BSS 4x/d for 1 month). Patients will be reviewed weekly for 4 weeks until conjunctival sutures are removed. Further follow up examinations are planned after 3 and six months. Assessment of differences in the intraocular eye pressure will be considered primary, and bleb appearance/vascularisation using a standardized photography and the Moorfields bleb grading system, postoperative intraocular pressure and conjunctival wound healing problems will be considered secondary outcome parameters.</p> <p>Discussion</p> <p>Anti-VEGF-antibodies might be more effective in preventing scaring and might have fewer toxic side effects than the currently used anti-metabolites and may replace them in the long term.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN12125882">ISRCTN12125882</a></p

Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment Modalities

In branch retinal vein occlusion (BRVO), abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal hematological factors constitute the primary mechanism of vessel occlusion. In general, BRVO has a good prognosis: 50–60% of eyes are reported to have a final visual acuity (VA) of 20/40 or better even without treatment. One important prognostic factor for final VA appears to be the initial VA. Grid laser photocoagulation is an established treatment for macular edema in a particular group of patients with BRVO, while promising results for this condition are shown by intravitreal application of steroids or new vascular endothelial growth factor inhibitors. Vitrectomy with or without arteriovenous sheathotomy combined with removal of the internal limiting membrane may improve vision in eyes with macular edema which are unresponsive to or ineligible for laser treatment

Antioxidants protect Trabecular meshwork Cells from hydrogen peroxide-induced cell death

Purpose: To examine the protective effects of antioxidants in cultured trabecular meshwork (TM) cells exposed to oxidative stress. Methods: Primary porcine TM cells were pretreated with 50 lM resveratrol, 0.2 mM urate, 1 mM ascorbate, 1 mM reduced glutathione (rGSH), or 1 mM q-coumarate followed by exposure to hydrogen peroxide (0.5-4 mM). Cell metabolism was determined by mitochondrial enzyme activity and cell viability by uptake of the vital dye calcein, a fluorescent calcium binding dye. Reactive oxygen species (ROS), which may reflex oxidative damage, were determined by 2 0 7 0 -dichlorofluorescein diacetate. Results: Trabecular meshwork cell metabolism was reduced to 72 6 5% of control levels with 1 mM hydrogen peroxide (H 2 O 2 ) treatment. TM cells that co-incubated with ascorbate (85% 6 5%), q-coumarate (98 6 11%) or rGSH (103 6 17%) had significantly increased metabolism compared to 1 mM H 2 O 2 treatment. Resveratrol significantly increased TM cell metabolism at both 2 mM (102 6 14% live) and 4 mM H 2 O 2 (27 6 12% live), with H 2 O 2 -treated cultures containing mostly metabolically inactive cells (3% at 2 mM; 2% at 4 mM). Similar results were obtained in cell viability assays. Ascorbate and resveratrol, but not q-coumarate or rGSH, decreased ROS levels in TM cells exposed to a sublethal dose of H 2 O 2 (0.5 mM). Urate had no protective effect against H 2 O 2 damage in any of the assays. Conclusions: Increased oxidative damage was demonstrated in the TM of patients with primary open angle glaucoma. The antioxidants (resveratrol, ascorbate, qcoumarate) and the antioxidant enzyme cofactor (rGSH) protected TM cells from H 2 O 2 -induced damage. Translational Relevance: Future experiments are needed to determine whether addition of antioxidants may maintain TM cell viability in vivo. Antioxidants could be applied either topically or coupled with extended-release vehicles for intraocular injection to reduce free radical formation leading to enhanced therapeutic outcomes. Ultimately, studies using animal models could determine whether application of antioxidants can ameliorate progression in diseases such as glaucoma and macular degeneration

Fibrin glue‐assisted glaucoma drainage device surgery

AIM: To describe the use of fibrin glue as a suture substitute for portions of glaucoma drainage device (GDD) surgery. METHODS: Retrospective non‐randomised case–control study reviewing 28 consecutive cases of GDD implantation using traditional suture material compared with 14 consecutive cases of GDD implantation using Tisseel fibrin glue (Baxter AG, Vienna, Austria) for portions of the procedure. The fibrin glue was used to close the conjunctiva, secure the pericardium patch graft and secure the tube to the sclera. Three‐month follow‐up data for each group as well as data on operating times, postoperative conjunctival inflammation, drugs used for glaucoma and intraocular pressure (IOP) were evaluated. Statistical analysis was carried out using analysis of variance. RESULTS: The mean (SD) age of the patients in the suture group (17 men and 11 women) was 56.6 (10.5) years and that in the Tisseel‐assisted group (8 men and 6 women) was 54.7 (8.6) years (p = 0.56). No significant differences were observed in IOP levels at any time point between the two groups. No significant differences were found for the need for postoperative glaucoma drops or postoperative complication rates in both groups. Conjunctival inflammation was more pronounced in the suture group (p = 0.002) using a standard scale for comparison. The mean (SD) time of surgery was significantly less for the Tisseel‐assisted group, 15.0 (3.11) min, than for the suture group, 25.93 (4.04) min (p<0.001). CONCLUSIONS: Tisseel fibrin glue seems to be a safe substitute for some of the sutures used in GDD surgery. Use of Tisseel seems to have no effect on IOP control or complications, whereas it considerably improved postoperative conjunctival inflammation and reduced time of surgery. Further studies are needed to better understand the role of fibrin glue in GDD implantation

The Role of Artificial Intelligence in the Diagnosis and Management of Glaucoma

Glaucomatous optic neuropathy is the leading cause of irreversible blindness worldwide. Diagnosis and monitoring of disease involves integrating information from the clinical examination with subjective data from visual field testing and objective biometric data that includes pachymetry, corneal hysteresis, and optic nerve and retinal imaging. This intricate process is further complicated by the lack of clear definitions for the presence and progression of glaucomatous optic neuropathy, which makes it vulnerable to clinician interpretation error. Artificial intelligence (AI) and AI-enabled workflows have been proposed as a plausible solution. Applications derived from this field of computer science can improve the quality and robustness of insights obtained from clinical data that can enhance the clinician\u27s approach to patient care. This review clarifies key terms and concepts used in AI literature, discusses the current advances of AI in glaucoma, elucidates the clinical advantages and challenges to implementing this technology, and highlights potential future applications