Purpose: To evaluate the long-term efficacy of bevacizumab for the treatment of chronic diffuse diabetic macular edema after various previous treatments. Methods: A total of 126 patients (mean age: 66 years) with chronic diffuse diabetic macular edema were consecutively incorporated in this prospective, noncomparative case series. Inclusion was performed independently from the size of edema, retinal thickness, visual acuity (VA), age, metabolic control, type of diabetes, or type of previous treatments. The patients underwent a complete eye examination including best-corrected VA with ETDRS charts, slit lamp examination, intraocular pressure measurement, stereoscopic biomicroscopy of the macula, retinal thickness measurement using optical coherence tomography (OCT), fluorescein angiography, and fundus photography. All patients were treated with repeated intravitreal injections of bevacizumab (1.25 mg). Patients were observed in intervals of 4–12 weeks for a period of up to 6–12 months. Results: All patients had received various previous treatments such as laser treatment (62% focal laser treatment, 38% panretinal laser treatment), vitrectomy (11%), or intravitreal injection of triamcinolone (41%). All patients completed 6 months and 59 patients (47%) completed 12 months of follow-up; within this period 48% had received at least three intravitreal injections of bevacizumab. Mean diameter of foveal avascular zone was 858 ± 341 μm. At baseline mean VA was 40.3 ETDRS letters (0.82 logMAR Snellen VA) and mean central retinal thickness on OCT was 463 μm. Throughout follow-up VA changes were not significant with a mean change of −1.6 ETDRS letters after 6 months, but significant with +5.1 ETDRS letters after 12 months. Mean central retinal thickness (OCT) decreased to 374 μm after 6 months (P < 0.001) and to 357 μm after 12 months (P < 0.001). Changes of retinal thickness and visual acuity did not correlate. No other factors investigated, such as age, central retinal thickness, or previous treatments, were predictive for a change of VA. Macular ischemia was not exacerbated as a result of the treatment. Conclusion: Even in cases with chronic diffuse ischemic diabetic macular edema, a long-term decrease of central retinal thickness can be observed following repeated intravitreal injections of bevacizumab. In these patients, mean decrease in retinal thickness is aligned with a gain in mean VA. Treatment with bevacizumab at an earlier stage of diabetic macular edema without ischemia may be associated with an even better functional outcome.

Purpose. To evaluate systematically the staining characteristics and safety of potential new dyes for intraocular surgery. methods. Six dyes were included in the investigation: light green SF (LGSF) yellowish, E68, bromophenol blue (BPB), Chicago blue (CB), rhodamine 6G, rhodulinblau-basic 3 (RDB-B3). All dyes were dissolved and diluted in a balanced saline saline solution. The light-absorbing properties of each dye were measured at a concentration of 0.05% between 200 and 1000 nm. Staining characteristics were examined by staining lens capsule tissue and epiretinal membranes (ERMs), removed intraoperatively, with dye concentrations of 1.0%, 0.5%, 0.2%, and 0.05%. Enucleated porcine eyes (postmortem time, 9 hours) were also stained. Dye-related toxicity was evaluated by a colorimetric test (MTT) measuring the inhibition of retinal pigment epithelium (RPE) cell proliferation (ARPE-19 and primary human RPE cells, passages 3–6). Cell viability was also quantified based on a two-color fluorescence cell-viability assay. Dyes were investigated in concentrations of 0.2% and 0.02%. results. All dyes investigated in this study stained human lens capsules, removed intraoperatively; ERMs, peeled during macular pucker surgery; and enucleated porcine eyes, depending on the concentration applied. The long-wavelength absorption maximum of the dyes was within the range of 527 to 655 nm at concentrations of 0.05%. Rhodamine G6 and RDB-B3 showed adverse effects on ARPE-19 cell proliferation at a concentration of 0.2% and were excluded from further investigation in primary RPE cells. The remaining four dyes showed no toxic effect on ARPE-19 and primary RPE cell proliferation at concentrations of 0.2% and 0.02%. Cell viability was affected by LGSF yellowish (0.2%) and CB (0.2% and 0.02%). Two dyes (E68 and BPB) showed no relevant toxicity in vitro. conclusions. The systematic evaluation of dyes for intraocular use seems mandatory. In this study four dyes were identified with effective staining characteristics, with two of these dyes having no detectable toxic effect on RPE cells in vitro.

Purpose: To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. Methods: Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient “positive.” The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. Results: The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up (“true positive”) and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME (“true negative”). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. Conclusion: Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.

Introduction: To evaluate the effect of α-lipoic acid (ALA) on the occurrence of diabetic macular edema. Methods: Randomized, double-blind, placebo-controlled, multicenter, multinational study. Patients were randomized to the treatment group with 600 mg ALA per day or the placebo group. Every 6 months stereo fundus photographs, HbA1c levels, and an ophthalmological examination were documented. The primary endpoint was the occurrence of clinically significant macular edema (CSME) within a follow-up period of 2 years. Results: We randomized 235 patients with type II diabetes mellitus into the treatment group (mean age 58.0 years) and 232 into the placebo group (mean age 57.9 years). Mean HbA1c level was 8.1, with no significant differences between the treatment (mean 8.2, SD ± 1.35) and placebo groups (mean 8.1, SD ± 1.29). HbA1c values remained constant over time. In the treatment and placebo groups, 84 and 86 patients (35.7 and 37.1%) had insulin-dependent diabetes mellitus (IDDM) with a median duration of diabetes of 9.3 versus 9.0 years in the placebo group. Visual acuity remained unchanged during the entire trial. Concerning the primary endpoint, the study provided a negative result, i.e. 26/235 patients in the treatment group and 30/232 patients in the placebo group developed CSME. Confirmatory intention-to-treat analysis of the primary endpoint revealed no statistically significant difference between groups (log-rank test, p = 0.7108, HR = 0.9057 with CI = 0.5355–1.5317). Median follow-up was identical (2.00 years). Conclusions: A daily dosage of 600 mg ALA does not prevent the occurrence of CSME in IDDM patients.

A 66 year old male patient had undergone cataract surgery and lens implantation on both eyes 20 months earlier. Six months after cataract surgery a retinal detachment was seen in the left eye which was first treated with pars plana vitrectomy and gas tamponade (15% C₂F₆). After a period of 4 months, a redetachment occurred and silicone oil (Acri.Sil-ol 5000, 5000 cps, Acri.Tec, Hennigsdorf, Germany) was used as a permanent tamponade. Postoperative visual acuity was 20/500 in the left eye. Twelve months later, the patient was referred to our institution for further evaluation of a temporal hemianopia of sudden onset in the right eye (fig 1A) and for treatment of elevated intraocular pressure in the left eye. At presentation, visual acuity was 20/20 in the right eye and light perception in the left eye. Intraocular pressure was in a normal range in the right eye and elevated to 35 mm Hg in the left eye despite local antiglaucomatous monotherapy using latanoprost (Xalatan). Emulsified silicone oil was detected in the anterior chamber angle during gonioscopy of the left eye. Funduscopy revealed a glaucomatous excavation and atrophy of the optic nerve in the left eye with a cup-disc ratio of 1.0 (fig 1B); the retina was attached, with the silicone oil filling of the globe being incomplete. Magnetic resonance imaging (MRI) of the brain was then performed for further evaluation. T1 weighted MRI scan revealed a hyperintensive signal in the left vitreous cavity characteristic for silicone oil.² An identical hyperintensive signal was also observed in the left optic nerve and the left half of the optic chiasm (fig 1C); in contrast, in T2 weighted sections the silicone located in the optical system and in the vitreous cavity appeared hypointensive (fig 1D). In order to prevent a further progression of the visual field defect of the right eye, a decompression of the optic nerve seemed prudent. After informed consent, the patient underwent left subfrontal craniotomy and the left optic nerve and the optic chiasm were explored. No oil was found in the subarachnoid space or in the brain tissue. Therefore, the left optic nerve at the transition to the optic chiasma was slit open and the intrachiasmatic and intranerval silicone oil was removed by smooth suction and irrigation. The nerve was completely hollowed out by the oil with only thin perineural structures remaining (fig 2A, B, C). At the end the small opening in the nerve was covered with a collagen fleece coated with fibrin glue (Tachocomb H, Nycomed Pharma GmbH, Unterschleissheim, Germany). The neurosurgical intervention was performed without intraoperative or postoperative complications. In addition, a re-vitrectomy with gas tamponade was performed to remove the silicone oil from the vitreous cavity of the left eye. One month later, a regression of the visual field defect in the right eye was observed (fig 2D) and best corrected visual acuity was 20/32. Intraocular pressure in the left eye was normal without treatment after surgery.