Amod Gupta

Sustained Delivery Fluocinolone Acetonide Vitreous Inserts Provide Benefit for at Least 3 Years in Patients with Diabetic Macular Edema

OBJECTIVE To assess long-term efficacy and safety of intravitreal inserts releasing 0.2 μg/d (low dose) or 0.5 μg/d (high dose) fluocinolone acetonide (FAc) in patients with diabetic macular edema (DME). DESIGN Two randomized, sham injection-controlled, double-masked, multicenter clinical trials. PARTICIPANTS Subjects with persistent DME despite ≥1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). METHODS Subjects received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. MAIN OUTCOME MEASURES Percentage of patients with improvement of ≥15 letters from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. RESULTS At month 36, the percentage of patients who gained ≥15 in letter score using the last observation carried forward method was 28.7% (low dose) and 27.8% (high dose) in the FAc insert groups compared with 18.9% (P = 0.018) in the sham group, and considering only those patients still in the trial at month 36, it was 33.0% (low dose) and 31.9% (high dose) compared with 21.4% in the sham group (P = 0.030). Preplanned subgroup analysis demonstrated a doubling of benefit compared with sham injections in patients who reported duration of DME ≥3 years at baseline; the percentage who gained ≥15 in letter score at month 36 was 34.0% (low dose; P<0.001) or 28.8% (high dose; P = 0.002) compared with 13.4% (sham). An improvement ≥2 steps in the Early Treatment Diabetic Retinopathy Study retinopathy scale occurred in 13.7% (low dose) and 10.1% (high dose) compared with 8.9% in the sham group. Almost all phakic patients in the FAc insert groups developed cataract, but their visual benefit after cataract surgery was similar to that in pseudophakic patients. The incidence of incisional glaucoma surgery at month 36 was 4.8% in the low-dose group and 8.1% in the high-dose insert group. CONCLUSIONS In patients with DME FAc inserts provide substantial visual benefit for up to 3 years and would provide a valuable addition to the options available for patients with DME.

Long-term Benefit of Sustained-Delivery Fluocinolone Acetonide Vitreous Inserts for Diabetic Macular Edema

OBJECTIVE To assess the efficacy and safety of intravitreal inserts releasing 0.2 μg/day (low dose) or 0.5 μg/day (high dose) fluocinolone acetonide (FA) in patients with diabetic macular edema (DME). DESIGN Two parallel, prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trials. PARTICIPANTS Subjects with persistent DME despite at least 1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). METHODS Subjects received study drug or sham injection at baseline and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. MAIN OUTCOME MEASURES The primary outcome was the percentage of patients with improvement from baseline best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Trial (ETDRS) letter score of 15 or more at month 24. Secondary outcomes included other parameters of visual function and foveal thickness (FTH). RESULTS The percentage of patients with improvement from baseline ETDRS letter score of 15 or more at month 24 was 28.7 and 28.6 in the low- and high-dose insert groups, respectively, compared with 16.2 in the sham group (P = 0.002 for each). Benefit occurred for both doses compared with sham at 3 weeks and all subsequent time points. The mean improvement in BCVA letter score between baseline and month 24 was 4.4 and 5.4 in the low- and high-dose groups, respectively, compared with 1.7 in the sham group (P = 0.02 and P = 0.016). At all time points compared with sham, there was significantly more improvement in FTH. Subjects requiring cataract surgery were more frequent in the insert groups, and their visual benefit was similar to that of subjects who were pseudophakic at baseline. Glaucoma requiring incisional surgery occurred in 3.7%, 7.6%, and 0.5% of the low-dose, high-dose, and sham groups, respectively. CONCLUSIONS Both low- and high-dose FA inserts significantly improved BCVA in patients with DME over 2 years, and the risk-to-benefit ratio was superior for the low-dose insert. This is the first pharmacologic treatment that can be administered by an outpatient injection to provide substantial benefit in patients with DME for at least 2 years.

Presumed tubercular serpiginouslike choroiditis: clinical presentations and management.

PURPOSE Choroiditis, choroidal tubercles, and tuberculomas are well known ocular manifestations of systemic tuberculosis. The present series aimed to report the occurrence of serpiginouslike choroiditis of presumed tubercular origin. DESIGN Retrospective, noncomparative, interventional case series. PARTICIPANTS Eleven eyes in seven consecutive patients with a diagnosis of choroidal tuberculosis simulating serpiginous choroiditis were studied between 1997 and 2000. TESTING AND INTERVENTION: All patients had their fundus photographs taken at the time of initial presentation as well as during follow-up. All patients underwent a Mantoux skin test and chest radiography. In addition, five patients had their aqueous or vitreous humor subjected to polymerase chain reaction (PCR) for Mycobacterium tuberculosis. Sputum examination, biopsy, or both were carried out whenever recommended by the pulmonologist. Systemic antituberculosis chemotherapy was instituted in combination with treatment for ocular inflammation. MAIN OUTCOME MEASURE Therapeutic response and visual improvement. RESULTS There were five men and two women ranging in age from 17 to 32 years. Clinical presentations included three morphologic variants; multifocal progressive choroiditis showing wavelike progression to confluent, diffuse lesions resembling serpiginous choroiditis (three eyes); diffuse choroiditis characterized by diffuse plaquelike choroiditis with an amoeboid pattern suggestive of serpiginous choroiditis at initial presentation (four eyes); and mixed variety where opposite eyes had mixed features (four eyes). All patients had strongly positive Mantoux skin test results and positive chest radiograph results. The PCR results from aqueous and vitreous humor in four samples was positive for Mycobacterium tuberculosis; one had sputum positive for acid-fast bacilli, whereas two had histopathologic evidence of tuberculosis from cervical or parahilar lymph nodes. Treatment was associated with resolution of choroidal lesions and visual improvement. Final visual acuity of 20/30 or better was achieved in five eyes. CONCLUSIONS Choroidal tuberculosis may present as multifocal progressive or diffuse choroiditis resembling serpiginous choroiditis. It is important to recognize these presentations because these eyes show good response to systemic antituberculosis chemotherapy.

Ocular Signs Predictive of Tubercular Uveitis

PURPOSE To determine ocular signs predictive of tubercular uveitis. DESIGN Retrospective, nonrandomized, comparative interventional case study. METHODS Three hundred eighty-six patients with active uveitis were treated at a tertiary care single-center uveitis practice. Uveitis was presumed to be tubercular in patients who showed evidence of latent or manifest tuberculosis without any other known cause and who did not show recurrence of uveitis after 12 months of antitubercular therapy. One hundred eighty-two patients who thus obtained clinical diagnoses of presumed tubercular uveitis were enrolled in group A. Two hundred four patients with uveitis resulting from a nontubercular cause were enrolled in group B. Patients were monitored for the presence of types of keratic precipitates (mutton fat or fine), posterior synechiae (broad based or filiform), iris nodules, snowballs, snow banking, vasculitis (with or without choroiditis), serpiginous-like choroiditis, and other types of posterior uveitis (choroidal abscess, retinochoroiditis, or exudative retinal detachment) which were compared between the 2 groups. Statistical analysis was carried out at a 5% level of significance. The main outcome measures were clinical signs significantly associated with tubercular uveitis. RESULTS Broad-based posterior synechiae, retinal vasculitis with or without choroiditis, and serpiginous-like choroiditis were seen significantly more commonly in patients with tubercular uveitis. Filiform posterior synechiae were more frequent in eyes with nontubercular uveitis. CONCLUSIONS Broad-based posterior synechiae, retinal vasculitis with or without choroiditis, and serpiginous-like choroiditis in patients with latent or manifest tuberculosis in tuberculosis-endemic areas are suggestive of a tubercular cause of uveitis and merit specific treatment.

Role of Anti-Tubercular Therapy in Uveitis With Latent/Manifest Tuberculosis

PURPOSE To assess the role of anti-tubercular therapy in uveitis with latent/manifest tuberculosis (TB). DESIGN Retrospective, interventional case series. METHODS A total of 360 patients from uveitis clinic with following inclusion criteria were studied: 1) complete clinical records of visual acuity, slit-lamp biomicroscopic examination, intraocular pressure, complications if any, and treatment records at the baseline and at all follow-up visits; 2) a documented positive tuberculin skin test (10 mm of induration or more) at 48 to 72 hours; 3) evidence of active uveitis, i.e., cellular reaction in the anterior chamber with or without keratic precipitates, and/or active vitreous inflammation, retinal vasculitis, choroiditis, or neuroretinitis; 4) all known causes of infectious uveitis except TB and known noninfectious uveitic syndromes ruled out; and 5) a minimum one year of follow-up from the initiation of treatment. Of these, 216 patients (Group A) received four-drug anti-tubercular therapy and corticosteroids, and 144 patients (Group B) received corticosteroids alone. The main outcome measure was recurrence of inflammation after minimum six months of initiating treatment in each group. RESULTS Recurrences reduced significantly (P < .001) in Group A (15.74%) as compared to Group B (46.53%) over a median follow-up of 24 and 31 months, respectively. The patients treated with anti-tubercular therapy with corticosteroids had decreased risk of developing recurrence of uveitis by approximately two-thirds as compared to those treated with corticosteroids alone. CONCLUSION Addition of anti-tubercular therapy to corticosteroids in uveitis patients with latent/manifest TB led to significant reduction in recurrences of uveitis.

Retinopathy of prematurity in Asian Indian babies weighing greater than 1250 grams at birth: Ten year data from a tertiary care center in a developing country.

Background: Retinopathy of prematurity (ROP) is an important cause of childhood blindness in developing countries. Aim: To report the spectrum of ROP and associated risk factors in babies weighing > 1250 g at birth in a developing country. Setting and Design: Institutional, retrospective, non-randomized, observational clinical case series. Materials and Methods: Retrospective analysis (10 years) of 275 eyes (138 babies) with ROP. Statistical Analysis: Qualitative data with the Chi-square test. Quantitative data using the unpaired t test or the ANOVA and further tested using multivariate logistic regression. Results: The mean birth weight was 1533.9 g (range 1251 to 2750 g) and the mean period of gestation was 30.9 weeks (range 26 to 35). One hundred and twenty-four of 275 eyes (45.1%) had threshold or worse ROP. Risk factors for threshold or worse disease were, ′outborn babies′ ( P < 0.001), respiratory distress syndrome ( P = 0.007) and exchange transfusion ( P = 0.003). The sensitivity of the American and British screening guidelines to pick up threshold or worse ROP in our study group was 82.4% and 77.4% respectively. Conclusions: Severe ROP is often encountered in babies weighing greater than 1250 g at birth in developing countries. Western screening guidelines may require modifications before application in developing countries.

PCR-positive tubercular retinal vasculitis: clinical characteristics and management.

Background Inflammation of retinal vessels is a known association of systemic tuberculosis. Patients with retinal vasculitis are subjected to extensive but unrewarding systemic workup. Polymerase chain reaction (PCR) is now commonly used to detect DNA of infective organisms including Mycobacterium tuberculosis. This study was undertaken to characterize the clinical characteristics of PCR-positive tubercular retinal vasculitis, so as to determine the clinical presentation, associated systemic features, management, and course of this form of vasculitis. Methods The clinical records of 13 patients seen between 1997 and 1999 with the diagnosis of PCR-positive tubercular retinal vasculitis from the aqueous or vitreous humor were reviewed. Recorded data included age, sex, race, visual acuity, anterior and posterior segment findings, and results of diagnostic evaluations. All received antituberculosis therapy with or without concomitant corticosteroids. Laser scatter photocoagulation was done in eyes with neovascularization. One eye with vitreous hemorrhage was subjected to pars plana vitrectomy. Results There were 9 (69.2%) male and 4 (30.7%) female patients with a median age of 20 years. The disease was bilateral in seven. The most consistent finding was the presence of vitritis in all the eyes followed by vitreous snowball opacities in 17 eyes (89.4%), neovascularization in 11 eyes (57.8%), retinal hemorrhages in 10 eyes (52.6%), neuroretinitis in 10 eyes (52.6%), focal choroiditis in 9 eyes (47.3%), vitreous/preretinal hemorrhage in 5 eyes (26.3%), and serous retinal detachment in 3 eyes (15.7%). Over a median follow-up of 12 months, all showed resolution of vasculitis with no recurrences. Conclusions Polymerase chain reaction–positive tubercular retinal vasculitis had varied associated fundus findings. Its recognition is important so as to order only relevant diagnostic tests.

Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease

PURPOSE To determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis. DESIGN Comparative case series. PARTICIPANTS We included 1147 patients. METHODS All patients with bilateral ocular inflammatory disease presenting to any of 10 uveitis centers in the 3-month period between January 1 and March 31, 2006 (inclusive), were asked to participate. The clinical and historical features of disease were obtained from the participants via direct interview and chart review. Patients were stratified based on whether they were diagnosed with VKH disease or non-VKH uveitis for statistical analysis. MAIN OUTCOME MEASURES Presence or absence of various clinical features in the 2 populations. RESULTS Of 1147 patients, 180 were diagnosed with VKH disease and 967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed with VKH than non-VKH disease compared with other ethnicities. In acute disease, the finding of exudative retinal detachment was most likely to be found in VKH disease with a positive predictive value (PPV) of 100 and negative predictive value (NPV) of 88.4, whereas in chronic disease, sunset glow fundus was most likely to be found, with a PPV of 94.5 and NPV of 89.2. CONCLUSIONS Numerous clinical findings have been described in the past as important in the diagnosis of VKH. The current study reveals that of these, 2 are highly specific to this entity in an ethnically and geographically diverse group of patients with nontraumatic bilateral uveitis. These clinical findings are exudative retinal detachment during acute disease and sunset glow fundus during the chronic phase of the disease.

Fungal endophthalmitis following cataract surgery: clinical presentation, microbiological spectrum, and outcome.

PURPOSE To determine the clinical presentation, microbiological spectrum, and outcome in cases of fungal endophthalmitis following cataract surgery. DESIGN Observational case series. METHODS SETTING Tertiary referral hospital. PATIENTS Retrospective analysis of 27 cases of smear- and culture-proven fungal endophthalmitis. INTERVENTION Pars plana vitrectomy in 18 eyes, where the corneal condition did not preclude the same. All eyes received intravitreal amphotericin B and dexamethasone along with systemic antifungal agents. MAIN OUTCOME MEASURES Functional success: Final visual acuity of 3/60 or better with attached retina. Anatomical success: Final visual acuity of better than light perception with preserved anatomy of globe. RESULTS The majority of the eyes (22 of the 27) had early onset and diffuse presentation (that is, anterior segment as well as posterior vitreous exudates). Substantial corneal involvement was seen in 14 eyes (51.85%). Aspergillus sp. was the most common isolate. Multivariate analysis using forward stepwise logistic regression showed corneal involvement as the single most important risk factor in determining final visual outcome (P =.0429). CONCLUSIONS Early onset and diffuse presentation, which mimics bacterial endophthalmitis, stresses the importance of both bacterial and fungal cultures from intraocular fluids to reach a diagnosis apart from the clinical judgment. Corneal involvement was the most important predictor of outcome in cases of fungal endophthalmitis.

Tubercular posterior uveitis.

Tuberculosis is defined by the Centers for Disease Control (CDC) as a chronic bacterial infection caused by Mycobacterium tuberculosis, characterized pathologically by the formation of granulomas. Themost common site of infection is the lung, but other organs may be involved. The M. tuberculosis spreads by droplet infection from coughing or sneezing. Nearly one third of the world’s population is infected, with an annual incidence approaching 8.7 million patients. There are remarkable geographic variations in the distribution of tuberculosis and 22 countries, including India, China, Indonesia, Bangladesh, Pakistan, Nigeria, Philippines and South Africa, among others, have been identified that contribute 80% of the world’s total burden of tuberculosis. Although mortality from tuberculosis has been known from the prehistoric times, it peaked during the industrial revolution in the west in the mid 19th century aided by poor housing, unsanitary conditions, poverty, and poor personal hygiene, many of which prevail even today in most of the developing countries. Since 1953, when the CDC began its public health surveillance program for tuberculosis in the United States, there has been a 10-fold decrease in the annual incidence of tuberculosis from 53/100,000 in 1953 to 5.2/100,000 in 2002. It, however, remains still very high in several regions of the world. Recent data from India suggest that the case rate may be nearly 187/100,000. Besides, in the last several years, new challenges have emerged in the form of close association of tuberculosis in patients with human immunodeficiency virus (HIV) infection. The association has been so striking that