Krishna S. Kishor

Endophthalmitis: state of the art

Endophthalmitis is an uncommon diagnosis but can have devastating visual outcomes. Endophthalmitis may be endogenous or exogenous. Exogenous endophthalmitis is caused by introduction of pathogens through mechanisms such as ocular surgery, open-globe trauma, and intravitreal injections. Endogenous endophthalmitis occurs as a result of hematogenous spread of bacteria or fungi into the eye. These categories of endophthalmitis have different risk factors and causative pathogens, and thus require different diagnostic, prevention, and treatment strategies. Novel diagnostic techniques such as real-time polymerase chain reaction (RT-PCR) have been reported to provide improved diagnostic results over traditional culture techniques and may have a more expanded role in the future. While the role of povidone-iodine in prophylaxis of postoperative endophthalmitis is established, there remains controversy with regard to the effectiveness of other measures, including prophylactic antibiotics. The Endophthalmitis Vitrectomy Study (EVS) has provided us with valuable treatment guidelines. However, these guidelines cannot be directly applied to all categories of endophthalmitis, highlighting the need for continued research into attaining improved treatment outcomes.

Incidence of bleb-associated endophthalmitis in the United States

Purpose To evaluate the 5-year incidence rate of blebitis and bleb-associated endophthalmitis in the United States. Methods In this retrospective cross-sectional study, we utilized a large commercial health insurance claim-based database during 2007–2011 and identified all patients who had a record of trabeculectomy in 2007. These patients were followed until the end of 2011. During the follow-up period, all incidences of blebitis, confirmed bleb-associated endophthalmitis, and presumed bleb-associated endophthalmitis were recorded. Kaplan–Meier survival analysis was utilized to calculate 5-year cumulative incidence rates of blebitis and bleb-associated endophthalmitis following trabeculectomy procedures. Results Among the 1,461 trabeculectomies included in our analysis, eight cases of blebitis, five cases of confirmed bleb-associated endophthalmitis, and eight cases of presumed bleb-associated endophthalmitis were identified. We found that the 5-year cumulative incidence of blebitis was 0.55%±0.19%. The 5-year cumulative incidence of bleb-associated endophthalmitis was 0.45%±0.2% when only confirmed cases were included and 1.3%±0.34% when presumed cases were also added to the analysis. The mean time from procedure to diagnosis was 45 months for blebitis and 33 months for bleb-associated endophthalmitis. Conclusion Blebitis and bleb-related endophthalmitis are uncommon in the United States. The 5-year cumulative incidence was 0.55% for blebitis and 0.45%–1.3% for bleb-associated endophthalmitis.

Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration

BACKGROUND Age-related macular degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell type involved in AMD, the retinal pigment epithelium, expresses a G protein–coupled receptor that, in response to its ligand, L-DOPA, up-regulates pigment epithelia–derived factor, while down-regulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD. METHODS We used retrospective analysis to compare the incidence of AMD between patients taking vs not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (approximately 17,000 and approximately 20,000) and the Truven MarketScan outpatient and databases (approximately 87 million) patients. We used International Classification of Diseases, 9th Revision codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription. RESULTS In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3, and 71.3 in 3 independent retrospective cohorts. Age-related macular degeneration occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (odds ratio 0.78; confidence interval, 0.76–0.80; P <.001). Similar results were observed for neovascular AMD (P <.001). CONCLUSIONS Exogenous L-DOPA was protective against AMD. L-DOPA is normally produced in pigmented tissues, such as the retinal pigment epithelium, as a byproduct of melanin synthesis by tyrosinase. GPR143 is the only known L-DOPA receptor; it is therefore plausible that GPR143 may be a fruitful target to combat this devastating disease.

Strabismus Surgery Reoperation Rates With Adjustable and Conventional Sutures

PURPOSE To determine the association of strabismus surgery reoperation rates with adjustable or conventional sutures. DESIGN Retrospective cross-sectional study. METHODS setting: Review of a large national private insurance database. STUDY POPULATION Adults aged 18-89 having strabismus surgery between 2007 and 2011. INTERVENTION Adjustable vs conventional suture strabismus surgery. OUTCOME MEASURE Reoperation rate in the first postoperative year. RESULTS Overall, 526 of 6178 surgical patients had a reoperation (8.5%). Reoperations were performed after 8.1% of adjustable suture surgeries and after 8.6% of conventional suture surgeries (P = .57). Of the 4357 horizontal muscle surgeries, reoperations were performed after 5.8% of adjustable suture surgeries, and after 7.8% of conventional suture surgeries (P = .02). Of the 1072 vertical muscle surgeries, reoperations were performed after 15.2% of adjustable suture surgeries and after 10.4% of conventional suture surgeries (P = .05). Younger age (18-39 years) was associated with a lower reoperation rate (P ≤ .02). The significant multivariable predictors of reoperation for horizontal surgery were adjustable sutures (odds ratio [OR] 0.69, 95% confidence interval 0.52-0.91), monocular deviation (OR 0.64), complex surgery (OR 1.63), and unilateral surgery on 2 horizontal muscles (OR 0.70, all P ≤ .01). Adjustable sutures were not significantly associated with reoperation rates after vertical muscle surgery (multivariable OR 1.45, P = .07). CONCLUSIONS Adjustable sutures were associated with significantly fewer reoperations for horizontal muscle surgery. Adjustable sutures tended to be associated with more reoperations for vertical muscle surgery, but this observation was not statistically significant in the primary analysis after controlling for age.

Predicting Development of Glaucomatous Visual Field Conversion Using Baseline Fourier-Domain Optical Coherence Tomography

PURPOSE To predict the development of glaucomatous visual field (VF) defects using Fourier-domain optical coherence tomography (FD OCT) measurements at baseline visit. DESIGN Multicenter longitudinal observational study. Glaucoma suspects and preperimetric glaucoma participants in the Advanced Imaging for Glaucoma Study. METHODS The optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) were imaged with FD OCT. VF was assessed every 6 months. Conversion to perimetric glaucoma was defined by VF pattern standard deviation (PSD) or glaucoma hemifield test (GHT) outside normal limits on 3 consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. Predictive accuracy was measured by the area under the receiver operating characteristic curve (AUC). RESULTS Of 513 eyes (309 participants), 55 eyes (46 participants) experienced VF conversion during 41 ± 23 months of follow-up. Significant (P < .05, Cox regression) FD OCT risk factors included all GCC, NFL, and disc variables, except for horizontal cup-to-disc ratio. GCC focal loss volume (FLV) was the best single predictor of conversion (AUC = 0.753, P < .001 for test against AUC = 0.5). Those with borderline or abnormal GCC-FLV had a 4-fold increase in conversion risk after 6 years (Kaplan-Meier). Optimal prediction of conversion was obtained using the glaucoma composite conversion index (GCCI) based on a multivariate Cox regression model that included GCC-FLV, inferior NFL quadrant thickness, age, and VF PSD. GCCI significantly improved predictive accuracy (AUC = 0.783) over any single variable (P = .04). CONCLUSIONS Reductions in NFL and GCC thickness can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma patients.

Incidence of postoperative suprachoroidal hemorrhage after glaucoma filtration surgeries in the United States.

Purpose To report the 3-month incidence rates of postoperative suprachoroidal hemorrhage after glaucoma filtration surgeries and to examine the subsequent surgical treatments in these eyes. Methods This is a retrospective study using the nationally pooled, insurance claim-based MarketScan databases from the years 2007–2011. Patients with records of trabeculectomy and/or tube shunt procedures were identified, and all cases of “definite” (ie, properly coded) and “suspected” (possibly miscoded) postoperative suprachoroidal hemorrhage occurring within 3 months of their glaucoma filtration procedures were captured along with the surgical interventions used for this condition. Kaplan–Meier survival analysis was used to evaluate the 3-month incidence rates of suprachoroidal hemorrhage, and regression analysis was applied to calculate the odds ratios, confidence intervals, and P-values. Results There were 17,843 trabeculectomies and 9,597 tube shunt surgeries identified. Among these, there were 107 cases (247 including “suspected” cases) of postoperative suprachoroidal hemorrhage within 3 months of trabeculectomy and 113 cases (255 including “suspected” cases) within 3 months of tube shunt procedures. The 3-month cumulative incidence rate of postoperative suprachoroidal hemorrhage ranged from 0.6%±0.06% to 1.4%±0.09% after trabeculectomy and 1.2%±0.11% to 2.7%±0.16% after tube shunt surgery. Postoperative suprachoroidal hemorrhage was almost twice as likely to occur after tube shunt surgeries than after trabeculectomies for both “definite” and “definite” plus “suspected” cases (odds ratio, 1.98; 95% confidence interval, 1.51–2.58; P<0.001; and odds ratio, 1.95; 95% confidence interval, 1.63–2.32; P<0.001, respectively). Among the 502 “definite” and “suspected” cases of postoperative suprachoroidal hemorrhage, 32.9% (165 cases) had a treatment record of choroidal tap and 8.8% (44 cases) had a treatment record of pars plana vitrectomy. Conclusion In this sample, the 3-month cumulative incidence rate of postoperative suprachoroidal hemorrhage was 0.6%–1.4% after trabeculectomy and 1.2%–2.7% after tube shunt procedures, and the majority of the cases appeared to be managed without further surgery. Postoperative suprachoroidal hemorrhage was almost twice as likely to occur after tube shunt surgeries as after trabeculectomies.

Reproducibility of retinal oxygen saturation in normal and treated glaucomatous eyes

Aim To measure the reproducibility of retinal oxygen saturation (SaO2) levels among treated glaucomatous eyes and normal controls in a prospective non-randomised study. Methods Patients with perimetric glaucoma (PG) and normal controls were included. Exclusion criteria for both groups included visual acuity <20/30, unreliable visual fields, thyroidopathies, hemoglobinopathies, cardiovascular and pulmonary diseases. Retinal oximetry was performed twice consecutively on one randomly selected eye of PG and normal controls using spectrophotometric retinal oximeter (SRO; Oxymap ehf., Iceland). Four main retinal vessel pairs were analysed separately. Coefficients of variability (CoV), coefficients of repeatability (CoR) and intraclass correlation coefficients (ICCs) in arteries (a.SaO2) and veins (v.SaO2) were calculated. Results 23 PG (mean age 68.3±10.8 years) and 22 normal subjects (mean age 61.5±18.2 years; p=0.14) were included. The intraocular pressure and mean ocular perfusion pressure in glaucoma (14.4±4.2 mm Hg; 45.8±5.8 mm Hg) and controls (14.3±3.3 mm Hg; 45.8±6.1 mm Hg) were similar (p >0.05). In the PG group, the a.SaO2 had a CoV of 1.6%, a CoR of 4.7 and an ICC of 0.97; the v.SaO2 had a CoV of 5.9%, a CoR of 8.7 and an ICC of 0.96. In normals, the a.SaO2 had a CoV of 0.98%, a CoR of 3.3 and an ICC of 0.97; the v.SaO2 had a CoV of 4.8%, a CoR of 7.7 and an ICC of 0.93. Conclusions Retinal oximetry measurements using SRO are highly reproducible in both treated glaucomatous and normal eyes.

New Therapeutic Approaches in Diabetic Retinopathy.

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy.

Tamponade in the surgical management of retinal detachment

Despite treatment advances, rhegmatogenous retinal detachment (RD) can have poor visual outcomes even with prompt and appropriate therapy. Pars plana vitrectomy is a leading management modality for the treatment of RD. This procedure is generally accompanied by the use of internal tamponade. Various gases and silicone oils may yield beneficial outcomes. Heavy silicone oils have been approved in some European nations but are not available in the USA. Different tamponade agents have unique benefits and risks, and choice of the agent should be individualized according to the characteristics of the patient and RD, as well as perioperative and postoperative factors.

Eye-related Emergency Department Visits in the United States, 2010

Cataract surgery incidence All participants 2771 1.90* 1.17e3.10* Stratified by sex Females 1540 2.46* 1.25e4.85* Males 1231 1.48 0.74e2.93 Stratified by age group Age < 75 y 1824 2.52* 1.20e5.33* Age 75 y 947 1.41 0.74e2.68 Progression of cortical lens opacity All participants 2609 1.52* 1.08e2.12* Stratified by sex Females 1438 1.67* 1.03e2.71* Males 1171 1.40 0.89e2.20 Stratified by age group Age < 75 y 1738 1.49 0.94e2.36 Age 75 y 871 1.57 0.96e2.58 Progression of posterior subcapsular lens opacity All participants 2673 1.84* 1.25e2.71* Stratified by sex Females 1480 2.27* 1.31e3.94* Males 1193 1.51 0.89e2.58 Stratified by age group Age < 75 y 1768 2.11* 1.22e3.65* Age 75 y 905 1.54 0.88e2.68