Sushil Vasudevan

Antifibrotic Activity of Bevacizumab on Human Tenon's Fibroblasts In Vitro

PURPOSE To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenons capsule fibroblasts (HTFs) in an in vitro model of wound healing. METHODS Fibroblasts were cultured in RPMI media, and bevacizumab was administered at a concentration ranging from 0.25 to 12.5 mg/mL. Fibroblast viability and cell death were assessed using the MTT colorimetric assay, lactate dehydrogenase assay, BrdU assay, and live/dead assay. Fibroblast contractility was assessed in floating collagen gels. Morphologic changes were assessed by transmission electron microscopy. Antifibrosis activities were compared with 5-fluorouracil. RESULTS Bevacizumab induced a significant dose-related reduction of HTF cell number at 12.5 mg/mL at 72 hours (P < 0.05). Under serum-free conditions, bevacizumab induced significant fibroblast cell death at concentrations greater than 7.5 mg/mL (P < 0.05). Bevacizumab caused a moderate inhibition of fibroblast gel contraction from baseline (P < 0.05). Scanning electron microscopy revealed marked vacuolization in bevacizumab-treated fibroblasts. CONCLUSIONS Bevacizumab disrupted fibroblast proliferation, inhibited collagen gel contraction ability, and induced fibroblast cell death at concentrations greater than 7.5 mg/mL in serum-free conditions. These results demonstrated that bevacizumab inhibited a number of fibrosis activities in culture. These activities may underpin the antifibrosis effect proposed in vivo.

Neuroprotection in glaucoma

Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications.

Acute Primary Angle Closure Attack Does Not Cause an Increased Cup-to-Disc Ratio

PURPOSE To determine if an increased cup-to-disc ratio (CDR) and retinal nerve fiber layer (RNFL) loss occur after acute primary angle closure (APAC). DESIGN Prospective, observational case series. PARTICIPANTS Twenty participants with unilateral APAC provided 20 affected eyes and 20 fellow eyes (controls) for analysis. METHODS After initial presentation, participants attended 3 further assessments over a 12-month period (visit 2, within 2 weeks; visit 3, 2-3 months; and visit 4, 6-12 months), in which they underwent the following investigations: Heidelberg Retinal Tomography (Heidelberg Engineering, Dossenheim, Germany), optical coherence tomography of the RNFL and macula, and automated perimetry. MAIN OUTCOME MEASURES Cup-to-disc ratio, optic cup area, neuroretinal rim area, RNFL thickness, macular thickness, and volume. RESULTS There was no change from visits 2 to 4 in CDR (0.46 ± 0.17 vs. 0.47 ± 0.20; P = 0.94), neuroretinal rim area (1.64 ± 0.55 vs. 1.64 ± 0.57; P = 0.96), or other optic nerve head parameters analyzed in eyes with APAC. The mean overall RNFL thickness decreased from 106.6 ± 17.9 μm to 92.9 ± 18.3 μm between visits 2 and 3 (P<0.01) in affected eyes. The superior quadrant RNFL thickness decreased from 134.8 ± 25.9 μm to 113 ± 25.7 μm (P<0.01), and the inferior quadrant RNFL thickness decreased from 139.1 ± 28.4 μm to 115.6 ± 24.9 μm (P<0.01). There was no significant change in macular thickness or volume. CONCLUSIONS This study demonstrated that an increase in CDR does not occur after APAC that is treated promptly, although RNFL loss does occur.

Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension

Steroid‐induced ocular hypertension is currently treated in the same way as primary open‐angle glaucoma. However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans‐resveratrol in rats with steroid‐induced ocular hypertension and involvement of adenosine receptors (AR) in intraocular pressure (IOP) lowering effect of trans‐resveratrol.

Posterior revision for failed blebs: long-term outcomes.

AimTo report the long-term efficacy and safety of same site revision trabeculectomy with mitomycin application via a posterior approach. MethodsA noncomparative retrospective case series of consecutive revision trabeculectomies performed for inadequate bleb function between March 2003 and March 2007 by a single surgeon. Surgery involved a posterior/fornix incision with opening of the scleral flap posteriorly at the same site as previous surgery and application of 0.2 to 0.4 mg/mL mitomycin. ResultsFifty-seven eyes were followed for an average of 33±15 months. Mean baseline intraocular pressure (IOP) reduced from 21.5±6.5 to 11.2±4.4 and 8±3.6 mm Hg at 1 and 5 years, respectively (P<0.001). On Kaplan-Meier survival analysis the probability of maintaining IOP ⩽15 mm Hg without medication at the end of 1 year was 95% (n=57) and at 3 (n=36) and 5 years (n=7) was 84%. Eighty-five percent of patients were on no antiglaucoma drops at last follow-up. Four cases required a second procedure (7%), transient choroidal effusions occurred in 4 eyes (7%), corneal decompensation in 1 eye (1.7%), and ptosis in 1 (1.7%). ConclusionsPosterior approach to surgical revision of failed filtration surgery is an effective procedure with good long-term control of IOP.

Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats

Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress. These effects of tocotrienol invlove reduced NFκB activation, lower iNOS expression, restoration of ATP level, ATPase activities, calpain activity and lens protein levels.

Effects of adding tocotrienol-tocopherol mixed fraction and vitamin C supplementation on coronary risk biomarkers in patients with hypercholesterolaemia with moderate coronary risk.

Article history: Received on: 07/01/2016 Revised on: 07/02/2016 Accepted on: 24/03/2016 Available online: 30/04/2016 This study was a prospective clinical trial to investigate the effects of adding combined tocotrienol-tocopherol mixed fraction (TTMF) and vitamin C (TTMF+C) supplementation on coronary biomarkers in non-statin and statin treated patients with hypercholesterolaemia (HC) with moderate coronary risk. A total of 35 patients were randomised at baseline into one of two groups, (G1) TTMF+C (320mg TTMF plus 500mg vitamin C) alone daily and (G2) TTMF+C (320mg TTMF plus 500mg vitamin C) plus atorvastatin 10 mg daily. The entire supplementation were taken for 12 months. Fasting serum samples were taken at baseline, 2weeks, 3months, 6months and 12months post-randomisation and analysed for inflammatory biomarkers; high sensitivity Creactive protein (hsCRP) and interleukin-6 (IL6). Combination of TTMF and vitamin C supplementation leads to neutral effects on lipid profiles and inflammation; with no added benefit in statin-treated HC patients with moderate coronary risk. This neutral effects may be attributed to the tocopherol composition in TTMF which could possibly attenuate any potential beneficial effects of tocotrienols. Clinical studies using pure tocotrienols in the absence of tocopherols would further confirm this.

Nasal chondroma presenting as hypertelorism.

Purpose To report a rare case of nasal chondroma presenting as hypertelorism. Case Report We report a case of a 16-year-old boy with a large calcified mass arising from the posterior nasal cavity presenting as hypertelorism. Surgical excision was done, and the histopathological examination revealed a chondroma. The hypertelorism resolved postoperatively. Conclusions Nasal chondroma may also present innocuously as hypertelorism as in this case.