Odorant Receptor 51E2 Agonist ß-ionone Regulates RPE Cell Migration and Proliferation.

The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand ß-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.

Using Electronic Health Records to Build an Ophthalmologic Data Warehouse and Visualize Patients' Data.

PURPOSE: To develop a near-real-time data warehouse (DW) in an academic ophthalmologic center to gain scientific use of increasing digital data from electronic medical records (EMR) and diagnostic devices. DESIGN: Database development. METHODS: Specific macular clinic user interfaces within the institutional hospital information system were created. Orders for imaging modalities were sent by an EMR-linked picture-archiving and communications system to the respective devices. All data of 325 767 patients since 2002 were gathered in a DW running on an SQL database. A data discovery tool was developed. An exemplary search for patients with age-related macular degeneration, performed cataract surgery, and at least 10 intravitreal (excluding bevacizumab) injections was conducted. RESULTS: Data related to those patients (3 142 204 diagnoses [including diagnoses from other fields of medicine], 720 721 procedures [eg, surgery], and 45 416 intravitreal injections) were stored, including 81 274 optical coherence tomography measurements. A web-based browsing tool was successfully developed for data visualization and filtering data by several linked criteria, for example, minimum number of intravitreal injections of a specific drug and visual acuity interval. The exemplary search identified 450 patients with 516 eyes meeting all criteria. CONCLUSIONS: A DW was successfully implemented in an ophthalmologic academic environment to support and facilitate research by using increasing EMR and measurement data. The identification of eligible patients for studies was simplified. In future, software for decision support can be developed based on the DW and its structured data. The improved classification of diseases and semiautomatic validation of data via machine learning are warranted.

The influence of a specific ophthalmological electronic health record on ICD-10 coding.

BACKGROUND: A specific Electronic Health Record (EHR) for ophthalmology was introduced in an academic center in Germany. As diagnoses coding corresponding to the International Classification of Diseases Version 10 (ICD-10) is mandatory for billing reasons in Germany, we analyzed whether a change occurred in the diversity and number of diagnoses after the EHR introduction. The number of patients was also analyzed. Proper diagnoses coding is of the utmost importance for further data analysis or billing. METHODS: Graphical User Interfaces (GUIs) were created by using Advanced Business Application Programming language in EHR "i.s.h.med." Development of an EHR was conducted in close collaboration between physicians and software engineers. ICD-10 coding was implemented by using a "hit list" and a search engine for diagnoses. An observational analysis of a 6-month period prior to and after the introduction of an ophthalmological specific EHR was conducted by investigating the diversity and number of diagnoses in various ophthalmological disease categories and the number of patient consultations. RESULTS: During the introduction of a specific ophthalmological EHR, we observed a significant increase in the emergency department cases (323.9 vs. 359.9 cases per week), possibly related to documentation requirements. The number of scheduled outpatients didn't change significantly (355.12 vs. 360.24 cases per week). The variety of diagnoses also changed: on average, 156.2 different diagnoses were made per week throughout our hospital before the EHR launch, compared to 186.8 different diagnoses per week thereafter (p < 0.05). Additionally, a significantly higher number of diagnoses per case and per week were observed in both emergency and subspecialty outpatient clinics (1.15 vs. 1.22 and 1.10 vs. 1.47, respectively). CONCLUSIONS: An optimized EHR was created for ophthalmological needs and for simplified ICD-10 coding. The implementation of digital patient recording increased the diversity of the diagnoses used per case as well as the number of diagnoses coded per case. A general limitation to date is the suboptimal precision of ICD-10 coding in ophthalmology. Correct coding is of utmost importance for future data analysis.

Evaluation of Changes in Human Corneas After Femtosecond Laser-Assisted LASIK and Small-Incision Lenticule Extraction (SMILE) Using Non-Contact Tonometry and Ultra-High-Speed Camera (Corvis ST).

PURPOSE: To evaluate theoretical biomechanical advantages of human corneas treated with small incision lenticule extraction (SMILE) compared with femtosecond laser-assisted LASIK (FS-LASIK) Patients and methods: In a prospective, comparative, non-randomized, consecutive case series patients with moderate to high myopia and/or astigmatism underwent corneal refractive surgery. Patients either received standard FS-LASIK or SMILE. Preoperatively and up to 3 months postoperatively data were analyzed including tomography with Pentacam HR, Goldmann tonometry, non-contact tonometry, and deformability of the cornea using an ultra-high-speed camera (Corvis ST). Data were analyzed and p < 0.05 was considered as statistically significant (t-test). RESULTS: Seventy-three patients (128 eyes) were treated. Forty-eight eyes of 29 patients underwent FS-LASIK and 80 eyes of 44 patients underwent SMILE. Preoperative spherical equivalent (SE) was -3.23 ± 1.64 D (FS-LASIK group) and -4.83 ± 1.63 D (SMILE group) (p < 0.0001). Almost all parameters obtained by Corvis ST between preoperative and postoperative measurements showed significant changes after refractive surgery. Significant changes were seen between both groups postoperatively. However, matched pair subgroup analysis (n = 69; 26 eyes FS-LASIK; 43 eyes SMILE) of eyes with initially equal pachymetry, intraocular pressure, SE, and difference of pre- to postoperative pachymetry (p>0.05), showed no significant changes in parameters measured with Corvis ST (p>0.05). CONCLUSIONS: Corneal biomechanical parameters measured preoperatively with Corvis ST showed significant differences postoperatively in total and in both groups. In subgroup analysis with homogenous groups, FS-LASIK showed no significant changes in biomechanical data measured with Corvis ST compared with SMILE.

Evaluation of the New "SAVE" Protocol in Diabetic Macular Edema Over the Course of Anti-VEGF Treatment.

BACKGROUND: To evaluate a recently established grading protocol for diabetic macular edema (DME) over the course of intravitreal anti-VEGF treatment with ranibizumab. METHODS: Fluorescein angiography images and optical coherence tomography scans before treatment and after 3 monthly applied intravitreal ranibizumab injections were retrospectively graded for each included study eye according to the recently introduced "SAVE" grading protocol ("S"= subretinal fluid; "A"= "area of retinal thickening"; "V"="vitreo-retinal abnormalities"; "E"="etiology of leakage focal versus non-focal") and correlated with best-corrected visual acuity (BCVA) in letters (lett). RESULTS: Five of the 39 included study eyes had subretinal fluid ("S") before treatment which resolved during treatment. BCVA of study eyes with an initial retinal thickening smaller than one disc diameter ("A") was non-significantly higher compared to patients with a retinal thickening greater than one disc diameter (34.0 ± 17.9 lett versus 25.3 ± 13.3 lett, p=0.236) but became significant during treatment (40.5 ± 10.0 lett versus 28.3 ± 13.1 lett, p=0.004). No difference in BCVA was observed between patients with or without vitreo-retinal abnormalities ("V") before and during therapy. BCVA in patients with focal leakage ("E") was significantly higher than in patients with non-focal leakage before (33.1 ± 12.3 lett versus 23.3 ± 13.3 lett, p=0.017) and during (38.9 ± 10.9 lett versus 26.3 ± 12.6 lett, p=0.002) therapy. CONCLUSIONS: Applying the grading protocol "SAVE", focal leakage ("E") was the only retrospectively observed parameter which significantly correlated with a better BCVA before therapy and over the course of treatment in patients with fovea-involving DME.

Dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia.

PURPOSE: To evaluate the prevalence of dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia. SETTING: Department of Ophthalmology, Ludwig-Maximilans Universität, München, Germany. DESIGN: Retrospective study. METHODS: Two groups of patients were screened retrospectively over a 5-year period for the inclusion criterion of severe retrobulbar hematoma after retrobulbar or parabulbar injection. The first group consisted of emergency cases referred to the clinic. A second group of patients had received retrobulbar block at the hospital. All cases were collected and screened for the presence of antiplatelet therapy. RESULTS: Among roughly 160 000 patient records screened, 3 patients with grade IV retrobulbar hematoma were identified. Two of these patients were taking dual antiplatelet medications and 2 were on anticoagulation therapy during the time of retrobulbar or peribulbar anesthesia. None of the cases showed single medication platelet inhibition. The visual acuity of all patients stayed low at the 6-month follow-up (1.2 logMAR in 1 patient and no light perception in 2 patients). CONCLUSIONS: Retrobulbar hematoma is a rare but severe complication of retrobulbar anesthesia. With the high prevalence of dual platelet inhibition found in these cases, a prospective controlled trial seems unethical. In these high-risk patients, surgery should be performed under topical anesthesia if possible or general anesthesia if necessary. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Dexamethasone implant as an effective treatment option for macular edema due to Irvine-Gass syndrome.

PURPOSE: To investigate the effectiveness and safety of a dexamethasone implant (Ozurdex) to treat pseudophakic macular edema (Irvine-Gass syndrome). SETTING: Department of Ophthalmology, Ludwig-Maximilians-University Munich, Munich, Germany. DESIGN: Prospective nonrandomized study. METHODS: Preoperatively and in 12 monthly postoperative intervals, a complete ophthalmic examination was performed in study patients, including measurement of corrected distance visual acuity (CDVA) using the standard Early Treatment Diabetic Retinopathy Study chart, intraocular pressure, foveal thickness using spectral-domain optical coherence tomography (SD-OCT), and retinal sensitivity (mean defect depth) using microperimetry. Morphological aspects of the inner segment-outer segment junction and visual function were correlated. RESULTS: Twenty-three eyes (23 patients) with pseudophakic macular edema after uneventful cataract surgery were included. The mean duration of macular edema before treatment with a dexamethasone implant was 5.4 months (range 2 to 8 months). The CDVA increased in all patients from 30.2 letters ± 4.3 (SD) at baseline to 50.4 ± 4.9 letters at 12 months (P = .0016), regardless of the time of macular edema duration. Foveal thickness decreased from 520.8 ± 71.4 µm to 232.7 ± 26.6 µm (P < .002). Retinal sensitivity (mean defect depth) increased significantly over a 12-month follow-up, correlating positively with a restored inner segment-outer segment junction on SD-OCT analyses. No relevant adverse events were reported, and 9 recurrences occurred with a peak after 3 months and required a second dexamethasone implant injection. CONCLUSION: The dexamethasone implant was safe and effective in treating pseudophakic macular edema regardless of the duration of the edema. FINANCIAL DISCLOSURE: Drs. Mayer and Haritoglou are consultants to Allergan, Inc. No author has a financial or proprietary interest in any material or method mentioned.

Functional and Morphological Correlations before and after Video-Documented 23-Gauge Pars Plana Vitrectomy with Membrane and ILM Peeling in Patients with Macular Pucker.

Purpose. To assess functional and morphological alterations following video-documented surgery for epiretinal membranes. Methods. Forty-two patients underwent video-documented 23-gauge vitrectomy with peeling of epiretinal (ERM) and inner limiting membrane (ILM). Patient assessment was performed before and 3 and 6 months including best corrected visual acuity (BCVA), slit lamp biomicroscopy, SD-OCT, and central 2° and 18° microperimetry. In addition, all video-documented areas of peeling on the retinal surface were evaluated postoperatively using an additional focal 2° microperimetry. Retinal sensitivity and BCVA were correlated with morphological changes (EZ and ELM) in the foveal region and in regions of membrane peeling. Results. Overall, BCVA increased from 0.6 (±0.2) to 0.2 (±0.2) logMAR after 6 months with an increase in retinal sensitivity (17.9 ± 2.7 dB to 26.8 ± 3.1 dB, p < 0.01). We observed a significant correlation between the integrity of the EZ but not of the ELM and the retinal sensitivity, overall and in peeling areas (p < 0.05). However, no significant correlation between alterations in the area of peeling and overall retinal sensitivity regarding visual acuity gain could be observed after 6 months (p > 0.05). In contrast, overall postoperative retinal sensitivity was significantly decreased in patients with a visual acuity gain lower than 2 lines (p < 0.05) correlating with EZ defects seen in OCT. Conclusions. Mechanical trauma of epiretinal membrane and ILM peeling due to the use of intraocular forceps may affect the outer retinal structure. Nevertheless, these changes seem to have no significant impact on postoperative functional outcome.

Erufosine, a phosphoinositide-3-kinase inhibitor, to mitigate posterior capsule opacification in the human capsular bag model.

PURPOSE: To determine whether erufosine alone or erufosine-loaded intraocular lenses (IOLs) can inhibit growth of human lens epithelial cells after a single administration in the human capsular bag model. SETTING: Laboratory for Cell Biology, Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. DESIGN: Experimental study. METHODS: Sixteen human cadaver eyes had sham cataract surgery. The capsular bag was transferred into cell culture. The tissue was exposed to the half maximum inhibitory concentrations of erufosine alone for 72 hours; solvent-only tissue served as a control. Erufosine is a potent inhibitor of phosphoinositide-3-kinase, a downstream kinase with major implications in posterior capsule opacification (PCO) pathogenesis. The IOLs were soaked with erufosine and implanted in the capsular bags; unsoaked IOLs served as controls. For both settings, the time until confluence of the capsular bag was measured. Cell growth was observed and photodocumented. RESULTS: Erufosine as a single therapeutic agent increased the time until confluence of the capsular bag, but not significantly compared with the control. When IOLs were soaked with erufosine, a long-term prophylactic effect was observed in this organ model for PCO, which is known to closely reflect the clinical situation. CONCLUSION: Erufosine-soaked IOLs effectively inhibited PCO formation as seen in long-term organ culture and might become of clinical relevance. FINANCIAL DISCLOSURES: Drs. Kampik and Eibl-Lindner are inventors of IOLs treated with alkylphosphocholines for pharmacological after-cataract prophylaxis, patent international application PCT/EP2010/051490. No other author has a financial or proprietary interest in any material or method mentioned.

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio.

PURPOSE: Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress. METHODS: ARPE-19 cells were treated with 1-100 µM idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono- and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated ß-galactosidase (SA-ß-Gal) activity were investigated under exposure to hydrogen peroxide (H2O2). RESULTS: Idebenone concentrations from 1 to 20 µM showed no toxic effects on ARPE-19 cells. When cells were treated with H2O2, pretreatment with 5, 7.5, 10, and 20 µM idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-ß-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H2O2. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H2O2-induced apoptosis, not necrosis. CONCLUSION: In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio.

Comparison of 1-day versus 1-hour application of topical neomycin/polymyxin-B before cataract surgery.

PURPOSE: To compare the efficacy of 2 prophylaxis regimens before cataract surgery using topical antibiotics (1 hour before surgery versus the day before), both with povidone-iodine, with regard to reducing the preoperative conjunctival bacterial load. SETTING: Tertiary ophthalmic referral center, Munich, Germany. DESIGN: Prospective comparative case series. METHODS: Eyes were treated with topical antibiotics and their conjunctival sac flush irrigated using 10 mL of povidone-iodine 1.0%. All eyes were randomized to receive either 4 applications of topical 3500 IU/mL neomycin sulfate/6000 IU/mL polymyxin-B sulfate within 1 hour preoperatively (Group 1) or on the day before surgery (Group 2). Conjunctival specimens were obtained at 4 timepoints: T0C untreated fellow eye (control), T0 surgery eye (after antibiotic prophylaxis but before povidone-iodine irrigation), T1 after povidone-iodine, and T2 at the conclusion of surgery. All specimens were inoculated onto blood and chocolate-blood agar and into thioglycollate broth. RESULTS: One hundred thirty-three eyes of 133 consecutive patients were included (Group 1, 64 eyes; Group 2, 69 eyes). The antibiotic regimens were equally effective in reducing the aerobic and microaerophilic conjunctival flora (Group 1, P=.028; Group 2, P=.000), but had no significant effect on anaerobic bacteria (Group 1, P=.201; Group 2, P=.117). Flush irrigation of the conjunctival sac using 10.0 mL povidone-iodine 1.0% significantly decreased the conjunctival bacterial load in both groups. CONCLUSION: Topical neomycin/polymyxin-B was equally effective in reducing the conjunctival bacterial load whether given 1 day or 1 hour before surgery. The greatest effect was achieved by irrigating the conjunctival sac using povidone-iodine. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Association between anatomical resolution and functional outcomes in the mivi-trust studies using ocriplasmin to treat symptomatic vitreomacular adhesion/vitreomacular traction, including when associated with macular hole.

PURPOSE: To evaluate visual function in patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction including when associated with macular hole after ocriplasmin treatment, and the association between resolution of the underlying condition and improvement in visual function. METHODS: Six hundred and fifty-two patients from 2 Phase 3 trials received a single intravitreal injection of ocriplasmin 125 µg (n = 464) or placebo (n = 188). Mean and categorical changes from baseline in best-corrected visual acuity and 25-item Visual Function Questionnaire scores were used to evaluate visual function. Subgroups with VMA resolution and full-thickness macular hole closure were compared. RESULTS: Overall, 42% of patients who achieved VMA resolution at Day 28 had a ≥2-line improvement in best-corrected visual acuity at Month 6, and 20% had a ≥3-line improvement. Likewise, 69% of patients with nonsurgical full-thickness macular hole closure at Day 28 had a ≥2-line improvement at Month 6, and 48% had a ≥3-line best-corrected visual acuity improvement. Mean improvements in 25-item Visual Function Questionnaire scores were associated with achieving VMA resolution and nonsurgical full-thickness macular hole closure. CONCLUSION: In patients with symptomatic VMA/vitreomacular traction, VMA resolution and nonsurgical full-thickness macular hole closure were each associated with improvements in visual function. Resolving the underlying anatomical condition in symptomatic VMA/vitreomacular traction will increase the probability of achieving a clinically meaningful improvement in visual function.

Safety profile of ocriplasmin for the pharmacologic treatment of symptomatic vitreomacular adhesion/traction.

PURPOSE: To report the safety of intravitreal ocriplasmin injection based on 2 Phase 3 clinical trials in patients with symptomatic vitreomacular adhesion/vitreomacular traction, including when associated with full-thickness macular holes. METHODS: Safety analyses were based on 2 completed Phase 3 studies assessing intravitreal ocriplasmin injection. Adverse events (AEs), serious AEs, and suspected adverse drug reactions are reported. The authors also report AEs of special interest from 8 other completed Phase 2 studies and 2 ongoing studies. RESULTS: A total of 465 eyes were injected with ocriplasmin (125 µg), and 187 eyes were treated with placebo injection in Phase 3 studies. Overall AE rate was 69.0% in the placebo group and 76.6% for ocriplasmin-treated patients. Most AEs were in the study eye, mild or moderate in severity, and transient. All suspected adverse drug reactions were ocular; the majority was nonserious, of mild intensity, and transient. CONCLUSION: Intravitreal ocriplasmin injection provides a generally well-tolerated pharmacologic treatment option for patients with symptomatic vitreomacular adhesion/vitreomacular traction, including when associated with full-thickness macular holes ≤400 µm in diameter.

EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model.

PURPOSE: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) which represents a potential pharmacological target for PCO prevention. In this in vitro study, we assessed the effect and biocompatibility of Gefitinib in PCO prophylaxis. METHODS: The effect of Gefitinib on the key pathological features of PCO was assessed in vitro. We determined growth in the human capsular bag model, prepared from sixteen cadaver eyes that underwent sham cataract surgery. Furthermore, two lens epithelial cell lines, HLE-B3 and FHL-124, were used to determine concentration-based effects on cell proliferation. In addition, cell-migration, matrix-contraction, and cell spreading were investigated. To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on six different human ocular cell types from the anterior and posterior segment of the eye. RESULTS: Gefitinib significantly increased the time until confluence of the capsular bag compared to controls (p < 0.001)). In both human lens epithelial cell lines (HLE-B3 and FHL-124), proliferation decreased significantly and as equally strong after incubation with Gefitinib (p < 0.001), as did chemotactic migration (p = 0.004), matrix contraction (p = 0.001), and cell-spreading (p = 0.001). At the IC50 concentration, Gefitinib was well tolerated by six different human ocular cell types of the anterior and posterior segment. CONCLUSION: The specific EGFR inhibitor Gefitinib might become of clinical relevance in PCO prophylaxis as it attenuated cellular growth and other pathological PCO factors in the ex vivo human capsular bag model and in two human lens epithelial cell lines, while showing good biocompatibility in vitro.

Epiretinal membrane characteristics correlate with photoreceptor layer defects in lamellar macular holes and macular pseudoholes.

PURPOSE: To report on epiretinal membrane (ERM) characteristics and photoreceptor layer integrity of lamellar macular holes (LMHs) and macular pseudoholes (MPHs), and to compare with clinical course in operated and untreated eyes. METHODS: We consecutively reviewed the charts of patients with LMH and MPH between 2003 and 2013. For clinical analysis, we included 87 eyes (48 with LMH, 39 with MPH) with a minimum follow-up of 6 months. Of these, we included 64 eyes (37 with LMH, 27 with MPH) for high-resolution spectral domain optical coherence tomography analysis with examinations fulfilling the required resolution and quality of optical coherence tomography images. Epiretinal membranes were termed "typical tractional ERM" if presenting with contractive properties, or "atypical epiretinal tissue" if presenting as epiretinal material of homogeneous medium reflectivity without contractive properties. Integrity or discontinuity of the inner and outer segment (IS/OS) and the external limiting membrane (ELM) was evaluated by differentiating between "defect present" and "defect absent." RESULTS: In eyes with LMH, atypical epiretinal tissue presented in 29%, typical tractional ERMs were seen in 57%, and a combination of both in 14%. In contrast, eyes with MPH rarely presented atypical epiretinal tissue, and typical tractional ERMs were found in 89%. Comparing cases with LMH, eyes with atypical epiretinal tissue showed significantly more defects of the IS/OS and the ELM than eyes with typical tractional ERM. Both IS/OS and ELM defects correlated with a significant lower best-corrected visual acuity. Defects of the IS/OS were seen in 41% of LMH and 11% of MPH. Defects of the ELM revealed in 27% of LMH and in 11% of MPH. Operated eyes with disrupted IS/OS but intact ELM had significant better best-corrected visual acuity than eyes with defects in both layers. CONCLUSION: Atypical epiretinal tissue is related to the presence of photoreceptor layer defects and to poor visual acuity. It seems that integrity of the ELM is most important for functional recovery after surgery in both LMH and MPH. The presence of atypical epiretinal tissue in eyes with LMH may represent differences in the pathogenesis compared with MPH, and might have therapeutic implications for the proceeding with macular surgery in selected cases.

Incidence of postoperative endophthalmitis from 1990 to 2009 using povidone-iodine but no intracameral antibiotics at a single academic institution.

PURPOSE: To correlate the incidence of postoperative endophthalmitis with changes in the preoperative prophylaxis over a 20-year period. SETTING: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. DESIGN: Retrospective chart review. METHODS: Patients diagnosed with postoperative endophthalmitis from 1990 to 2009 after intraocular surgery performed at the same institution were included. Because of changes in the preoperative prophylaxis during the study period, 3 groups were formed for data analysis: Period 1 (1990 to 1992), no standardized prophylaxis regimen; period 2 (1993 to 1998), preoperative topical medication, povidone-iodine 10.0% periorbitally, and 1 drop of povidone-iodine 1.0% in the conjunctiva sac; and period 3 (1999 to 2009), similar to period 2 except with irrigation of the conjunctival sac with 10 mL of povidone-iodine 1.0%. RESULTS: The overall rate of postoperative endophthalmitis was 0.113% (77/68,323) for all intraocular surgeries. It decreased significantly from 0.291% (16/5505) in period 1 to 0.170% (33/19,413) in period 2 to 0.065% (28/43,405) in period 3 (P < .001). In cataract surgery, the overall rate of postoperative endophthalmitis was 0.125% (30/24,034). It decreased in each subsequent period, from 0.338% (9/2662) in period 1 to 0.224% (15/6696) in period 2 to 0.041% (6/14,676) in period 3 (P < .001). Coagulase-negative Staphylococcus was the most commonly isolated organism (47.4%). CONCLUSIONS: The rate of postoperative endophthalmitis decreased over a 20-year period at a single academic institution. Although multiple factors might have contributed to this decline, implementation of a preoperative prophylaxis protocol using copious povidone-iodine might have been the most important contributor. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Intravitreal ranibizumab versus isovolemic hemodilution in the treatment of macular edema secondary to central retinal vein occlusion: twelve-month results of a prospective, randomized, multicenter trial.

PURPOSE: This is a prospective, randomized, multicenter, investigator-initiated trial to evaluate the 12-month effectiveness of isovolemic hemodilution (IH) with prompt versus deferred intravitreal injections (IVI) of ranibizumab 0.5 mg for the treatment of macular edema secondary to early central retinal vein occlusion (CRVO). METHODS: Eyes with macular edema due to CRVO having occurred not more than 8 weeks previously received either monthly ranibizumab IVI in combination with IH (group I, n = 28) or IH alone (group II, n = 30). From month 2 to 12, the patients in both groups could be treated with monthly intravitreal ranibizumab. The main outcome variables were gain of visual acuity and the course of central retinal thickness as measured with optical coherence tomography. RESULTS: At 12 months, eyes in group I on average gained +28.1 (±19.3) letters compared to +25.2 (±20.9) letters in group II (p = 0.326). This result was achieved with significantly fewer injections in group II. Additionally, 30% of the eyes in group II did not need ranibizumab IVI during the 12 months of the trial. CONCLUSION: Ranibizumab IVI in addition to IH proved to be highly effective in increasing visual acuity and reducing macular edema secondary to CRVO. Initial IH in early CRVO may be a first treatment option in patients anxious about IVI.

Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema.

OBJECTIVE: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME). RESEARCH DESIGN AND METHODS: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12. RESULTS: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001). CONCLUSIONS: Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.

Role of wide-field autofluorescence imaging and scanning laser ophthalmoscopy in differentiation of choroidal pigmented lesions.

AIM: To evaluate the diagnostic properties of wide-field fundus autofluorescence (FAF) scanning laser ophthalmoscope (SLO) imaging for differentiating choroidal pigmented lesions. METHODS: A consecutive series of 139 patients were included, 101 had established choroidal melanoma with 13 untreated lesions and 98 treated with radiotherapy. Thirty-eight had choroidal nevi. All patients underwent a full ophthalmological examination, undilated wide-field imaging, FAF and standardized US examination. FAF images and imaging characteristics from SLO were correlated with the structural findings in the two patient groups. RESULTS: Mean FAF intensity of melanomas was significantly lower than the FAF of choroidal nevi. Only 1 out of 38 included eyes with nevi touched the optic disc compared to 31 out of 101 eyes with melanomas. In 18 out of 101 melanomas subretinal fluid was seen at the pigmented lesion compared to none seen in eyes with confirmed choroidal nevi. In "green laser separation", a trend towards more mixed FAF appearance of melanomas compared to nevi was observed. The mean maximal and minimal transverse and longitudinal diameters of melanomas were significantly higher than those of nevi. CONCLUSION: Wide-field SLO and FAF imaging may be an appropriate non-invasive diagnostic screening tool to differentiate benign from malign pigmented choroidal lesions.