Pradeep Venkatesh

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10−9). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10−12) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.

Ophthalmic manifestations of HIV infections in India in the era of HAART: analysis of 100 consecutive patients evaluated at a tertiary eye care center in India.

Purpose: To evaluate ophthalmic manifestations in patients with Human Immunodeficiency Virus (HIV) infection in the era of highly active antiretroviral therapy (HAART) at the apex institute for eye healthcare in India. Method: This prospective study was undertaken between October 2004 and December 2005. A complete ophthalmological and systemic examination was performed on each patient. Relevant investigations were carried out in selected patients. Results: One hundred consecutive HIV infected patients (199 eyes) were examined for ophthalmic manifestations. Of these 17% (17/100) had Category A HIV infection (asymptomatic or acute HIV or persistent generalized lymphadenopathy), 23%(23/100) had Category B HIV infection (symptomatic, not A or C), 60%(60/100) had Category C HIV infection (AIDS indicator condition).76%(70/100) were male and 24%(24/100) were female. The median age of patients was 34 years and 52%(52/100) were in the fourth decade. 68%(68/100) patients were on HAART. 45% (45/100) patients had ophthalmic manifestations, the most common being cytomegalovirus (CMV) retinitis (20%) (20/100). Retinal detachment was seen in 70% (14/20) of CMV retinitis patients. HIV vasculopathy was seen in 11% (11/100) of patients. Other lesions included immune recovery uveitis (IRU) (5%)(5/100), acute retinal necrosis (ARN) (3%)(3/100), choroiditis (2%)(2/100), neuro-ophthalmic manifestations (12%)(12/100), complicated cataract (6%)(6/100), keratouveitis (1%)(1/100) and corneal ulcer (1%)(1/100). 7%(7/100) patients presented to us with ophthalmic manifestation as the only presenting sign of HIV infection. Amongst those who had ophthalmic involvement, about 50% (19/40) patients had CD4 count below 100 cells/micro liter and 70% (28/40) patients had CD4 count below 200 cells/micro liter. Conclusions: CMV Retinitis (20%) (20/100) is still the most common manifestation of HIV infection in this series, even in the era of HAART, and is more common than HIV vasculopathy. Immune recovery uveitis is appears to be more common with the introduction of HAART in absence of affordable anti CMV therapy in India. 7% (7/100) of patients present with ophthalmological features as the initial manifestation of HIV. As before, most (70%) (28/40) of the ophthalmic manifestations of HIV infection are present when CD4 count is less than 200 cells/micro liter.

STUDY OF THE FIRST CONTACT MANAGEMENT PROFILE OF CASES OF INFECTIOUS KERATITIS A HOSPITAL BASED STUDY

Purpose. To study the management pattern and examine the role of cultures and antibiotic sensitivity testing in infectious keratitis. Methods. A retrospective analysis of the demographic, clinical, and microbiological data was performed in 100 consecutive patients with infectious keratitis. The main parameters evaluated were nature of first contact with the health care services, investigations undertaken, treatment initiated, and the time interval between presentation to the first medical contact and to our center. Finally, the reports of culture and antibiotic sensitivity testing undertaken at our center were evaluated. Results. In 70% of cases, ophthalmologists in independent practice were the first medical contact. Direct microscopy of the corneal scraping was undertaken in only 6% of cases, whereas culture and sensitivity studies had not been performed in any of the patients. Forty-six percent of the patients were prescribed 0.3% ciprofloxacin eyedrops in an inadequate dosage. Broad-spectrum fortified antibiotics eye drops had not been prescribed in any of the cases. At our center, positive cultures were obtained in 73.86% of cases and the most common organism isolated was coagulase-negative Staphylococcus (33.84%), followed by Pseudomonas aeruginosa (15.38%). A large number of the isolates demonstrated resistance to the recommended antibiotic therapy. Conclusions. Failure to implement standard management protocol for infectious keratitis at first contact is a major factor contributing to ocular morbidity in India.

A Prospective Controlled Trial to Evaluate the Adjunctive Role of Posterior Subtenon Triamcinolone in the Treatment of Diffuse Diabetic Macular Edema

The aim of the present prospective controlled trial was to evaluate the adjuvant role of posterior subtenon triamcinolone in the treatment of diffuse diabetic macular edema (DDME). Thirty one (31) eyes with DDME were divided into an interventional group subjected to grid laser photocoagulation and 0.5 mL of 40 mg/mL posterior subtenon triamcinolone, and a noninterventional group subjected to grid laser photocoagulation only. Best-corrected visual acuity, contrast sensitivity, and intraocular pressures were assessed at presentation, and at 6, 12, and 24 weeks after intervention. The interventional group showed a statistically significant (p < 0.05) change in both mean best corrected visual acuity, from 20/160 to 20/100 (two-line increase on Early Treatment Diabetic Retinopathy Study (ETDRS)) (p = 0.024), and mean contrast sensitivity, from 0.9 to 1.09 (p = 0.01), at the end of 24 weeks. A significant rise in intraocular pressure was not described in any of the patients in either group. Posterior subtenon triamcinolone injection is a useful and safe adjunct to the conventional management of diabetic macular edema.

Management of Coats disease with bevacizumab in 2 patients.

Coats disease, first described by George Coats in 1907, is characterized by telangiectatic and aneurysmal blood vessels associated with intraretinal and subretinal exudation, and progresses to exudative retinal detachment and rubeosis iridis with painful secondary glaucoma, if left untreated.1 Even after various treatments, the visual prognosis is dismal because of persistent foveal subretinal fluid, exudation, and (or) fibrosis.2 Elevated vascular endothelial growth factor (VEGF) levels in Coats disease, and rapid response to pegaptanib sodium, have been reported recently by Sun et al.3 However, the more commonly used anti-VEGF agent, bevacizumab (Avastin, Genentech Inc, San Francisco, Calif.), has not been studied in this retinal vascular disease. We report the results of intravitreal bevacizumab in 2 cases of Coats disease. Two girls (14 and 16 years old) presented with unilateral Coats disease with macular edema and exudates of more than 6 months’ duration. A complete evaluation was done, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). After taking informed consent, intravitreal bevacizumab (1.25 mg/0.05 mL) was injected as primary treatment in both patients. While the first patient had no change in visual acuity (hand movement) and persistent macular edema, the second patient had vision improvement from hand movement to 20/800 and a

Subthreshold Micropulse Diode Laser and Double Frequency Neodymium: YAG Laser in Treatment of Diabetic Macular Edema: A Prospective, Randomized Study Using Multifocal Electroretinography

OBJECTIVE The purpose of this study was to compare the efficacy of subthreshold micropulse diode (SDM) laser with double-frequency neodymium YAG (Nd:YAG) laser in treatment of clinically significant diabetic macular edema. METHODS Forty-six eyes of 33 patients with clinically significant macular edema (CSME) caused by diabetic retinopathy were randomized to either SDM (810?nm) laser or the conventional double-frequency Nd:YAG (532?nm) laser. Primary outcome measures were: change in the central macular thickness as measured by optical coherence tomography (OCT) and change in macular retinal sensitivity measured using multifocal electroretinography (MfERG). Secondary outcomes were: change in best corrected visual acuity (BCVA) and contrast sensitivity. RESULTS The group was divided in half, with 23 eyes assigned to SDM laser and 23 eyes assigned to double-frequency Nd:YAG laser. Mean follow-up period was 6 months. No statistically significant difference was noted in either the primary or the secondary outcome measures between the two groups. Macular thickness decreased from the baseline measures of 298.5?49.3 and 312.9?45.8??m to 274.9?62.9 and 286.7?32.8??m in the SDM laser and Nd:YAG laser groups, respectively. On MfERG, P1 implicit wave time delay at baseline changed from 46.27?4.9 to 45.27?3.4?ms in the SDM group and from 46.55?4.9 to 45.27?4.1?ms in the Nd:YAG group. MfERG recordings of 18 of the 23 eyes treated with double-frequency Nd:YAG laser showed areas of signal void as compared to 4 eyes treated with the SDM laser. CONCLUSIONS SDM laser photocoagulation showed an equally good effect on visual acuity, contrast sensitivity, and reduction of diabetic macular edema (DME) as compared to conventional Nd:YAG laser photocoagulation. MfERG recordings, however, suggest that SDM laser results in better preservation of electrophysiological indices.

Ultrasound biomicroscopy findings of 25 G Transconjuctival sutureless (TSV) and conventional (20G) pars plana sclerotomy in the same patient

BackgroundTransconjunctival Sutureless Vitrectomy (TSV) is a recent advancement in vitreo-retinal surgical techniques involving the use of 25 G instruments through self-sealing sclerotomies. It has been hypothesized that there may be less chance of vitreous and retinal herniation in the scleral wound as compared to conventional sclerotomy incision. However there are no reports on differences in 20 gauge and 25 gauge sclerotomies using ultrasound biomicroscopy (UBM). We report herein the differences in sclerotomies undertaken with 20 gauge (G) and 25 gauge instruments in the same patient.Case presentationUltrasound biomicroscopy of the sclerotomy sites was done in the same patient in whom both 20 G and 25 G sclerotomies had to be constructed during pars plana vitrectomy and the differences were studied.On day 2, we observed a wide gape at the site that had been enlarged using a 20G MVR blade. In contrast, the other two sites made transconjunctivally using the 25G trocar showed only a mild gape. Significant gape continued to persist at the subsequent evaluations on day 7 and day 14 only at the port, which had been enlarged.ConclusionHealing of a 25 G sclerotomy is expectedly quite rapid, with inability to detect the site of sclerotomy in a short duration of 2 weeks post-operatively. This is as opposed to conventional sclerotomies, which might take up to 6–8 weeks post-operatively for complete opposition.

Comparative evaluation of diode laser versus argon laser photocoagulation in patients with central serous retinopathy: a pilot, randomized controlled trial [ISRCTN84128484].

BackgroundTo evaluate the efficacy of diode laser photocoagulation in patients with central serous retinopathy (CSR) and to compare it with the effects of argon green laser.MethodsThirty patients with type 1 unilateral CSR were enrolled and evaluated on parameters like best corrected visual acuity (BCVA), direct and indirect ophthalmoscopy, amsler grid for recording scotoma and metamorphopsia, contrast sensitivity using Cambridge low contrast gratings and fluorescein angiography to determine the site of leakage.Patients were randomly assigned into 2 groups according to the statistical random table using sequence generation. In Group 1 (n = 15), diode laser (810 nm) photocoagulation was performed at the site of leakage while in Group 2 (n = 15), eyes were treated with argon green laser (514 nm) using the same laser parameters. Patients were followed up at 4, 8 and 12 weeks after laser.ResultsThe mean BCVA in group 1 improved from a pre-laser decimal value of 0.29 ± 0.14 to 0.84 ± 0.23 at 4 weeks and 1.06 ± 0.09 at 12 weeks following laser. In group 2, the same improved from 0.32 ± 0.16 to 0.67 ± 0.18 at 4 weeks and 0.98 ± 0.14 at 12 weeks following laser. The improvement in BCVA was significantly better in group 1 (p < 0.0001) at 4 weeks. At 4 weeks following laser, all the patients in group1 were free of scotoma while 6 patients in group 2 had residual scotoma (p < 0.05). The mean contrast sensitivity in group 1 improved from pre-laser value of 98.4 ± 24.77 to 231.33 ± 48.97 at 4 weeks and 306.00 ± 46.57 at 12 weeks following laser. In group 2, the same improved from 130.66 ± 31.95 to 190.66 ± 23.44 at 4 weeks and 215.33 ± 23.25 at 12 weeks. On comparative evaluation, a significantly better (p < 0.001) improvement was noted in group 1.ConclusionDiode laser may be a better alternative to argon green laser whenever laser treatment becomes indicated in patients with central serous retinopathy in terms of faster visual rehabilitation and better contrast sensitivity. In addition, diode laser also has the well-recognized ergonomic and economic advantages.

Prospective evaluation of intravitreal triamcinolone acetonide injection in macular edema associated with retinal vascular disorders

Purpose To evaluate the effect of intravitreal triamcinolone acetonide on visual acuity and macular thickness using optical coherence tomography (OCT) in macular edema associated with various retinal vascular disorders. Methods This prospective nonrandomized clinical interventional study included 81 eyes (76 patients) comprised of Group I, 57 eyes (51 patients) with diabetic macular edema; Group II, 10 eyes (10 patients) with branch retinal vein occlusion; and Group III, 13 eyes (13 patients) with central retinal vein occlusion. All eyes received an intravitreal injection of 4 mg triamcinolone acetonide (with the solvent) in the operation theater under sterile conditions. Results Mean preinjection central macular thickness was 531.84±132 μm in Group I, 458.4±149 μm in Group II, and 750.81±148 μm in Group III. All groups showed a statistically significant decrease in mean central macular thickness at 1 month (300.7±119 μM in Group I, 218.2±99 μm in Group II, and 210.5 ±56 μm in Group III) and 3 months (253.19±109 μm in Group I, 187±47 μm in Group II, and 182±50 μm in Group III) after injection (p<0.05). Mean follow-up was 22±2.4 weeks. Mean visual acuity increased in all three groups (preoperative visual acuity in Group I, 1.2±0.4 logMAR units; Group II, 1.24±0.5 logMAR units; Group III, 1.1 ±0.4 logMAR units; 1 month postinjection in Group I, 0.88±0.3 logMAR units; Group II, 0.67±0.3 logMAR units; Group III, 0.86±0.4 logMAR units; 3 months postinjection in Group I, 0.84±0.4 logMAR units; Group II, 0.59±0.3 logMAR units; Group III, 0.82±0.5 logMAR units) (p<0.05). Forty-one eyes completed 6 months and 20 eyes completed 9 months follow-up. Twelve of 20 (41%) eyes in Group I, 2/6 (33%) eyes in Group II, 3/6 (50%) eyes in Group III, and 8/15 (53%) eyes in Group I, 1/3 (33%) eyes in Group II, and 2/2 (100%) eyes in Group III developed recurrence of macular edema with worsening of visual acuity at 6 and 9 months, respectively. Thirty-three (40.7%) eyes developed IOP elevation (at least one reading > 24 mmHg). One eye developed infective endophthalmitis. Conclusions Intravitreal injection of triamcinolone acetonide may be considered as an effective treatment for reducing macular thickening due to diffuse diabetic macular edema, venous occlusion associated macular edema, and may result in increase in visual acuity at least in the short term. Further follow-up and analysis is required to demonstrate its long-term efficacy.

Comparison of the Efficacy and Safety of Different Methods of Posterior Subtenon Injection

Purpose: To compare the safety and efficacy of different methods of posterior subtenon (PST) injection of corticosteroids in the treatment of cystoid macular edema secondary to intermediate uveitis. Design: Prospective comparative randomized interventional study. Participants: A total number of 30 eyes with cystoid macular edema secondary to intermediate uveitis were examined. Methods: Patients were randomized into 3 treatment groups of 10 eyes each. Each group received PST injection of triamcinolone acetonide 0.5 mL (20 mg) by one of three methods: cannula method (group 1), Smith and Nozik method (group 2), or orbital floor injection method (group 3). Patients underwent Snellens and ETDRS visual acuity (VA) testing, clinical evaluation, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA) at baseline and follow-up visits. Outcome measures: Changes in Snellen and ETDRS VA, OCT retinal thickness and assessments of safety were recorded in follow-up visits. Results: Postintervention patients were followed up at the 1st, 2nd, 6th, and 12th weeks. Statistically significant (p = .00) improvement in VA was present in group1 from 0.25 ± 0.08 (mean ± standard deviation) to 0.75 ± 0.24, in group 2 from 0.29 ± 0.12 to 0.78 ± 0.23, and in group 3 from 0.24 ± 0.10 to 0.72 ± 0.27. Statistically significant decrease in OCT central macular thickness (43.97% in group 1, 32.46% in group 2, and 29.75% in group 3) was noted at 12 weeks. However, the difference between individual groups at each visit did not reach statistical significance. Steroid-induced rise in intraocular pressure was observed in all the three groups with no statistical difference between individual groups. Conclusions: The different methods of PST injection are equally efficacious in terms of improving visual acuity. However, the cannula method achieves the greatest quantitative reduction in macular thickness. As the cannula method is as efficacious as Smith and Nozik method it may be a preferable method to deliver posterior subtenon injection of corticosteroids.