The development of age-related macular degeneration (AMD) is influenced by risk factors that contribute to inflammatory processes, cellular stress responses, and a dysregulation of the complement system. Given the incomplete understanding of the pathogenesis of AMD and the necessity for novel therapeutics, biomarker studies investigating aqueous humour from the anterior chamber of the eye serve as a valuable tool. This pilot study aimed to assess inflammatory mediators and complement components in aqueous humour of non-exudative AMD patients in comparison with a control group. The aqueous humour of 12 non-exudative AMD patients and 21 control subjects was collected during cataract surgery. Levels of 78 inflammatory proteins and complement components were measured using multiplex immunoassays. The influence of sex or smoking on the AMD status was assessed using Pearson’s chi-square test. Biomarker levels between AMD patients vs. controls, smokers vs. non-smokers, and females vs. males were compared. Parametric datasets were analysed using independent-means t-test, while non-parametric data analysis was conducted utilising Wilcoxon’s rank-sum test. Spearman’s correlation investigated associations between drusen volume and biomarker levels, as well as biomarker levels and subject age. All examined 78 immunological factors were detectable in aqueous humour. The proteins were categorised into high, medium, and low level groups. Aqueous humour contained high levels of complement proteins, including iC3b, FH/FHL-1, C4B, and FI. Non-exudative AMD patients exhibited decreased levels of C4 (P = 0.020), IL-10 (P = 0.033), and FI (P = 0.082). A positive correlation was observed between drusen volume and CCL4 levels (rS = 0.78, P = 0.013). Furthermore, smokers demonstrated significantly increased levels of pro-inflammatory proteins (CCL7, IL-7; P = 0.027, P = 0.030). MMP-1 was positively correlated with age (rS = 0.44, P = 0.010), while sex differences were observed in FB (P = 0.027) and C4B (P = 0.036) levels. This pilot study presents an initial overview of inflammation-associated biomarkers in the aqueous humour, highlighting potential roles for C4 and IL-10 in the development of non-exudative AMD. A larger, more-focused follow-up study is in progress to further investigate biomarkers localised to the eye and refine our understanding of AMD.

Overview of the retropupillary implantation of iris claw intraocular lenses (ArtisanA (R),Ophtec, Groningen, Niederlande and Verisyse(TM),AMO, Santa Ana CA).A literature search and review of implantation techniques, patient selection, potential complications and management strategies.This approach has the advantage of a simple implantation technique, an anatomically correct implantation site (as compared to endocapsular implantation) and a relatively low complication rate. An intact iris is, however, a prerequisite for this technique. Ischemic vitreoretinopathies, such as diabetes or vascular occlusive entities, as well as uveitis might be considered as contraindications.The retropupillary implantation of iris claw intraocular lenses is an interesting and especially time-effective rehabilitation technique for aphakia.

Purpose To evaluate a multivariable model predicting the individual probability of successful intravitreal ocriplasmin (IVO) treatment in eyes with vitreomacular traction (VMT). Methods Data from three prospective, multicenter IVO studies (OASIS, ORBIT, and INJECT) were pooled. Patients were included if they were treated for a symptomatic VMT without a full-thickness macular hole. A prediction model for VMT resolution using the factors 'age' and 'horizontal VMT diameter' was validated by receiver operating characteristic analysis and according to grouped prediction after calibration. Multivariable regression analysis was performed to check robustness and explore further improvements. Results Data from 591 eyes was included. In the univariate analysis all key factors (age, gender, VMT diameter, lens status, ERM) significantly correlated to treatment success. The prediction model was robust and clinically applicable to estimate the success rate of IVO treatment (AUC of ROC: 0.70). A refinement of the model was achieved through a calibration process. Conclusion The developed multivariable model using 'horizontal VMT diameter' and 'age' is a valid tool for prediction of VMT resolution upon IVO treatment.

The primary objective was to create and establish a new formula that predicts the individual probability of macular hole closure for eyes with full thickness macular holes (FTMH) accompanied by vitreomacular traction (VMT) which received enzymatic vitreolysis using intravitreally administered ocriplasmin. The secondary objective was to evaluate the forecast reliability of a previously published formula for VMT resolution in VMT-only eyes (Odds IVO-Success = e Intercept × OR years × OR ln(µm) ; Probability IVO-Success = Odds IVO-Success /(Odds IVO-Success + 1)) on VMT resolution using the current dataset of eyes with FTMH accompanied by VMT. Retrospective analysis of the OASIS, ORBIT, and INJECT-studies. Patients with FTMH and VMT with complete information (n = 213) were included. The effect of gender, age, FTMH diameter, lens status and the presence of epiretinal membranes (ERM) on FTMH closure was assessed using separate univariate logistic regression analyses. With regard to VMT release separate univariate regression analyses were carried out and results were compared with formerly published data of VMT resolution in eyes with VMT only. Overall, 126 eyes (63%) experienced VMT resolution within 28 days. Younger age (p < 0.0001) and VMT diameter (p = 0.041) had a significant impact on VMT release. Overall, 81 eyes (38%) treated with ocriplasmin showed FTMH closure within 28 days. Univariate analysis of the different predictors analyzed revealed that FTMH diameter < 250 µm had a significant impact on treatment success (p = 0.0495). It was not possible to calculate and establish a new multivariate formula that can predict the individual FTMH closure probability for eyes with FTMHs and VMT. However, the results of VMT release prediction in eyes with FTMHs accompanied by VMT matched the prediction of VMT release in eyes with VMT only when using the previously published formula. All in all, predictors for calculating the individual probability of VMT resolution on the one hand and FTMH closure on the other hand are different suggesting diverse pathophysiological mechanisms.

Introduction: The aim of this study was to evaluate the prevalence of back pain among German ophthalmologists, to investigate the relationship towards age, gender, various profession-related factors, to correlate localization of pain to subspecialties, and to explore individual therapeutic and coping strategies. Methods: In this prospective, cross-sectional survey, a 9-item questionnaire was sent via mail to all members of the German professional association of ophthalmologists “Berufsverband der Augenärzte Deutschlands e.V. (BVA).” Responses were analyzed according to a pre-specified analysis plan. Results: From a total of 5,954 members contacted, 1,861 copies (31%) were received back, of which 1,807 (30%) were suitable for analysis. 913 (51%) participants were female and 876 (48%) were male, with a median age of 50 years (interquartile range: 44; 57). 1,464 ophthalmologists (81%) reported current back problems, considerably more than had been reported in the general population or in other medical specialties. Older age, female gender, and higher number of professional years appeared to be risk factors for developing back pain. Overall, neck pain was the leading symptom in 951 attendees (65%) but differed between ophthalmologists who primarily performed conservative treatment (cervical spine) and those who performed surgery (mainly lumbar spine). 1,037 participants (71%) link their complaints to their occupational activity. Exercising and back training were reported as common strategies for prevention and coping with the problem. Recommendations for improvement were mainly ergonomic optimization of the working place. Conclusions: The prevalence of back pain complaints in German ophthalmologists is high. Neck pain (65%) was the leading localization, followed by low back pain (53%) and shoulder (38%) problems, which might emphasize a special back pain complaint profile in ophthalmologists. Low back pain seems to be more common in ophthalmologists with surgical specialization than in those with mainly medical tasks. The high prevalence of back pain in ophthalmologists should be communicated with employers, the industry, and professional societies to develop and implement a strategy to prevent occupational-related musculoskeletal disorders and preserve the ability to work and the quality of life.

Glaucoma poses the second largest cause of severe visual impairment and loss of vision worldwide. Despite the progress in both pharmaceutical and surgical treatments, the attempts to decrease intraocular pressure and prevent progression of glaucomatous optic neuropathy fail in many cases. Hence there is a high demand for additional complementary methods, which can reduce intraocular pressure and improve ocular blood flow as well as mental well-being. On the basis of literature research, the study results published so far on the effectiveness of psychotherapeutical methods in glaucoma therapy will be presented here. The methods of autogenic training, hypnosis and music therapy have already been demonstrated to have a positive effect on intraocular pressure, ocular blood flow and psychological well-being of patients affected by glaucoma. With these methods being not only effective but also cost-efficient, free of side effects and easily administered, they could gain importance in terms of an adjuvant treatment option for patients with glaucoma. However, regular ophthalmological examinations still remain obligatory.

Purpose The goal of this study was to analyze the incidence of perioperative bleeding complications in rhegmatogenous retinal detachment. The handling of perioperative anticoagulation during vitreoretinal surgery remains controversial, since the risk of bleeding complications by its continuation has to be balanced against the risk of progression of retinal detachment and the risk of thromboembolic events when anticoagulation is interrupted. Nevertheless, only few studies have investigated the risk of perioperative bleeding complications in an emergency such as retinal detachment surgery. Methods We therefore examined the rate of all perioperative hemorrhages and separately the rate of only severe bleedings during vitrectomy, scleral buckling with or without drainage of subretinal fluid (SRD), or combined procedures due to retinal detachment in patients undergoing different types of perioperative anticoagulation including acetylsalicylic acetate (ASA), clopidogrel, heparin, low molecular weight heparin, and phenprocoumon. Results This retrospective single-center study included 893 patients with primary rhegmatogenous retinal detachment, n = 192 on anticoagulation and n = 701 serving as control without anticoagulation. Our analysis revealed no significantly increased rate of perioperative hemorrhages under anticoagulation with ASA 100 mg (all, 11.4%; severe, 5.0%) or phenprocoumon (all, 11.6%; severe, 2.3%) compared with controls (all, 13.0%; severe, 5.4%). However, frequencies of bleeding complications varied markedly regarding the type of surgical procedure: Scleral buckling plus SRD showed the highest rates of hemorrhages (all, 18.9%; severe, 9.1%) with significant difference (P < 0.001) compared with scleral buckling without SRD (all, 3.8%; severe, 0.6%) and vitrectomy (all, 9.2%; severe, 1.5%), respectively. Furthermore, subretinal bleeding was the most common type of perioperative hemorrhage. Conclusions The data suggest not to stop ASA therapy prior to vitreoretinal surgery. Furthermore, we found no evidence of an increased risk for perioperative bleedings in patients under anticoagulation with vitamin-k antagonists with an INR within the sub-therapeutic range. SRD during scleral buckling procedure should be avoided as possible and regardless of any type of anticoagulation.

The objective of the study was the investigation of the effects of intravitreal bevacizumab (BEV) with or without additional macular grid laser photocoagulation (GRID) for macular edema (ME) secondary to branch retinal vein occlusion (BRVO).

Josep Callizo 1 Focke Ziemssen 2 Thomas Bertelmann Nicolas Feltgen 3 Jessica Vögeler Mirja Koch Nicole Eter Sandra Liakopoulos Steffen SchmitzValckenberg Georg Spital 1Department of Ophthalmology, GeorgAugust University, Goettingen, Germany; 2Center for Ophthalmology, Eberhard Karl University of Tuebingen, Tuebingen, Germany; 3Georg-August-University Goettingen, University Eye Hospital, Goettingen, Germany; 4Novartis Pharma GmbH, Clinical Research, Nuremberg, Germany; 5Department of Ophthalmology, University of Muenster Medical Center, Muenster, Germany; 6Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany; 7Department of Ophthalmology, University of Bonn, Bonn, Germany; 8Augenzentrum Am St. Franziskus Hospital, Muenster, Germany Purpose: The non-interventional OCEAN study (NCT02194803) evaluated frequency and monitoring of ranibizumab injections for retinal vein occlusion (RVO) in routine practice in Germany. Methods: RVO patients (including branch and central RVO (BRVO/CRVO)) receiving ranibizumab were included. Best-corrected visual acuity (BCVA) testing, imaging and treatment were performed at the investigators’ discretion and documented over 24 months. Results: Overall, 744 RVO patients (27% BRVO, 16% CRVO, remaining unspecified RVO) were included. For 74% of patients, data were available for the 12-month visit and for 56% for the 24-month visit. Mean baseline BCVA was 52.0 Early Treatment for Diabetic Retinopathy Study (ETDRS) letters (BRVO: 55.9, CRVO: 43.9). BCVA improved rapidly within the first 3 months, reaching 64.3 letters at 12 months and 64.7 at 24 months. CRVO patients showed less improvement than those with BRVO. Patients received a median of 4 (5) injections over 12 (24) months, with 100% of patients receiving injections at baseline, 70% at Month 1 and 81% at Month 2. Overall, 40% of patients demonstrated a ≥15 letter increase within the first 3 months (42% BRVO, 46% CRVO). Patients with low initial BCVA (<50 letters) showed greater improvement than patients with higher baseline BCVA. Due to considerable loss to follow-up, the number of injections and optical coherence tomography (OCT) examinations were not associated with the change in BCVA. Conclusion: Patients with RVO in routine practice in Germany received fewer injections and fewer OCT examinations than in clinical trials. CRVO patients showed less and later improvement compared to BRVO patients.

Purpose: The non-interventional OCEAN study (NCT02194803) evaluated frequency and monitoring of ranibizumab injections for retinal vein occlusion (RVO) in routine practice in Germany. Methods: RVO patients (including branch and central RVO (BRVO/CRVO)) receiving ranibizumab were included. Best-corrected visual acuity (BCVA) testing, imaging and treatment were performed at the investigators' discretion and documented over 24 months. Results: Overall, 744 RVO patients (27% BRVO, 16% CRVO, remaining unspecified RVO) were included. For 74% of patients, data were available for the 12-month visit and for 56% for the 24-month visit. Mean baseline BCVA was 52.0 Early Treatment for Diabetic Retinopathy Study (ETDRS) letters (BRVO: 55.9, CRVO: 43.9). BCVA improved rapidly within the first 3 months, reaching 64.3 letters at 12 months and 64.7 at 24 months. CRVO patients showed less improvement than those with BRVO. Patients received a median of 4 (5) injections over 12 (24) months, with 100% of patients receiving injections at baseline, 70% at Month 1 and 81% at Month 2. Overall, 40% of patients demonstrated a >= 15 letter increase within the first 3 months (42% BRVO, 46% CRVO). Patients with low initial BCVA (<50 letters) showed greater improvement than patients with higher baseline BCVA. Due to considerable loss to follow-up, the number of injections and optical coherence tomography (OCT) examinations were not associated with the change in BCVA. Conclusion: Patients with RVO in routine practice in Germany received fewer injections and fewer OCT examinations than in clinical trials. CRVO patients showed less and later improvement compared to BRVO patients.

Purpose: To compare ischemia-related clinical outcomes in patients treated with either ranibizumab pro re nata (PRN) or single dexamethasone implant in the Branch Retinal Vein Occlusion (COMRADE-B) or Central Retinal Vein Occlusion (COMRADE-C) trials. Methods: A post-hoc analysis of the Phase IIIb, 6-month, multicenter, double-masked, randomized, COMRADE-B and COMRADE-C trials. Change over 6 months in retinal ischemia status (central avascular [CA] zone and peripheral nonperfusion [PNP]), mean best-corrected visual acuity (BCVA), the development of shunt vessels and neovascularization, and frequency of laser therapy were assessed in retinal vein occlusion (RVO) patients treated with either ranibizumab 0.5 mg PRN or single dexamethasone 0.7 mg implant, as per European labels, in the COMRADE-B (N = 244; ranibizumab, 126, dexamethasone, 118) or COMRADE-C (N = 243; ranibizumab, 124, dexamethasone, 119) trials. BCVA progression in ischemic vs. non-ischemic patients based on the ischemia assessment at month 6 was carried out. Results: Visual acuity (VA) gains from baseline to month 6 were higher with ranibizumab than with dexamethasone in both patients with central ischemia and those with peripheral retinal nonperfusion, independent of the type of RVO (branch or central). The presence of CA and PNP had a significant impact on VA gain over 6 months in CRVO patients (p < .0001), while there was no significant impact in BRVO. Ranibizumab was associated with less new ischemia than dexamethasone. Central RVO patients treated with dexamethasone received more laser treatments over the 6 months than those treated with ranibizumab, while there was no difference in the frequency of laser therapy between the branch RVO treatment groups. Conclusions: VA gain over six months in ranibizumab-treated RVO patients is not affected by ischemia, and is associated with less development of new ischemia during the first 6 months of treatment and equal or fewer laser treatments than dexamethasone implant.

To assess the efficacy of intravitreally injected tissue plasminogen activator (t-PA, Alteplase [Actilyse®]) to induce posterior vitreous detachment (PVD) in eyes with recent onset of retinal vein occlusion (RVO).

In daily practice, vitreomacular traction (VMT) is described by the horizontal diameter of its attachment site implying a regular round shape of VMT. We investigated the deviation from this circular area of vitreous traction in patients with VMT.

PURPOSE:The COMRADE studies are the first randomized controlled head-to-head trials comparing the efficacy and safety of intravitreal ranibizumab versus dexamethasone (DEX) in patients with macular oedema secondary to retinal vein occlusion (RVO). The COMRADE extension trial was designed to provide additional 6-month data of patients who completed the core studies.METHODS:In this open-label, phase IV study patients who completed the COMRADE core studies were prospectively enrolled. Overall, 92 branch RVO (BRVO) patients (ranibizumab 52, DEX 40) and 83 central RVO (CRVO) patients (ranibizumab 61, DEX 22) were treated, and 94.6% of BRVO patients and 97.6% of CRVO patients completed the extension study. Patients were assigned to the same treatment group as in the core studies. Patients were monitored monthly and received either 0.5 mg ranibizumab or a 0.7 mg DEX implant as needed.RESULTS:Over the course of the extension, treatment-emergent adverse events (TEAEs) of the study eye occurred in 55.8% of BRVO patients on ranibizumab and in 62.5% of those on DEX. Among CRVO patients, 65.5% in the ranibizumab group and 59.1% in the DEX group developed TEAEs. Overall, elevated intraocular pressure (IOP) was more frequent with DEX than ranibizumab treatment. Mean average change in best-corrected visual acuity (BCVA) in BRVO patients was significantly better for ranibizumab than DEX (p = 0.0249). The CRVO results were consistent with BRVO's, although not significant (p = 0.1119).CONCLUSION:When used according to the European labels, ranibizumab revealed a better ocular safety profile and produced greater average BCVA gains than DEX. By the end of the additional 6-month study period, this difference in BCVA was more pronounced in BRVO as in CRVO patients. The main limitation of the COMRADE studies was that DEX patients received only a single intravitreal treatment during the first 6 months, which is presumably not adequate. However, frequent DEX implants could lead to more steroid-related side effects, especially to an increased intraocular pressure.

The prospective, non-interventional OCEAN study examined the use of intravitreal ranibizumab injections for the treatment of diabetic macular oedema (DME) in a real-world setting in Germany.

BACKGROUND/AIMS:To evaluate predictive factors for the treatment success of ocriplasmin and to use these factors to generate a multivariate model to calculate the individual probability of successful treatment.METHODS:Data were collected in a retrospective, multicentre cohort study. Patients with vitreomacular traction (VMT) syndrome without a full-thickness macular hole were included if they received an intravitreal injection (IVI) of ocriplasmin. Five factors (age, gender, lens status, presence of epiretinal membrane (ERM) formation and horizontal diameter of VMT) were assessed on their association with VMT resolution. A multivariable logistic regression model was employed to further analyse these factors and calculate the individual probability of successful treatment.RESULTS:167 eyes of 167 patients were included. Univariate analysis revealed a significant correlation to VMT resolution for all analysed factors: age (years) (OR 0.9208; 95% CI 0.8845 to 0.9586; p<0.0001), gender (male) (OR 0.480; 95% CI 0.241 to 0.957; p=0.0371), lens status (phakic) (OR 2.042; 95% CI 1.054 to 3.958; p=0.0344), ERM formation (present) (OR 0.384; 95% CI 0.179 to 0.821; p=0.0136) and horizontal VMT diameter (µm) (OR 0.99812; 95% CI 0.99684 to 0.99941, p=0.0042). A significant multivariable logistic regression model was established with age and VMT diameter.CONCLUSION:Known predictive factors for VMT resolution after ocriplasmin IVI were confirmed in our study. We were able to combine them into a formula, ultimately allowing the calculation of an individual probability of treatment success with ocriplasmin in patients with VMT syndrome without FTHM.

To evaluate prospectively the efficacy and safety of a fixed bimonthly ranibizumab treatment regimen (RABIMO) in eyes with neovascular age-related macular degeneration (nAMD) and to compare these results with a pro re nata (PRN) treatment scheme.

BACKGROUND:Patients with retinal vascular occlusion disease have an increased risk for ischemic stroke and share some risk factors with cerebrovascular disease. The purpose of this study was to analyze the prevalence of atrial fibrillation (AF) in subjects with retinal vascular occlusive disease and anterior ischemic optic neuropathy and to compare these data to an ischemic stroke group.METHODS:Prospective, observational single-center trial. Subjects with retinal artery occlusion (RAO), retinal vein occlusion (RVO) and anterior ischemic optic neuropathy (AION) were included. Patients with ischemic stroke (IS) from a previous observational trial were used as control. Investigation included 7-day Holter ECG, echocardiography, duplex ultrasonography of the carotid arteries, and 24-hour blood pressure monitoring. Further vascular risk factors were documented.RESULTS:During the 1-year study period, 101 patients were recruited. The control group with ischemic stroke consisted of 272 subjects. At inclusion, the prevalence of AF was 12% (RAO), 10.2% (RVO), 11.1% (NAION) and 15.8% (IS). The final prevalence after Holter ECG rose to 16% (RAO), 18.4% (RVO), 14.8% (NAION) and 26.5% (IS). No significant difference was measured between groups.CONCLUSIONS:We detected a similar prevalence of AF in all groups. RVO patients tended to exhibit a higher AF detection rate and lower number needed to screen than RAO and NAION. The detection of AF rose considerably via Holter ECG. As a consequence, we recommend prolonged ECG monitoring in patients with acute ophthalmic vascular diseases.