Influence of the Size of the Foveal Avascular Zone on Functional and Morphological Parameters in Patients with Early-Stage Diabetic Retinopathy.

Purpose: To correlate functional and morphological parameters with foveal avascular zone's (FAZ) size in diabetic patients with mild to moderate stage nonproliferative diabetic retinopathy. Methods: Monocentric and prospective study of a consecutive case series of diabetic patients. Medical history, best corrected visual acuity (BCVA), best corrected high/low contrast visual acuity (BChcVA/BClcVA), mean sensitivity (MS) and mean defect (MD) in central visual field testing, and FAZ size in fluorescein-angiography (FAG) were recorded. Macular thickness (central point thickness CPT, central subfield thickness CST) and volume measurements (central subfield volume CSV, total macular volume) were taken from SD-OCT (6x6mm ETDRS-grid). Groups were categorised as presenting FAZ sizes smaller (G1) or larger (G2) than 0.35mm2. Smallest (Q1) and largest quartiles (Q3) were also compared. Results: Thirty-six of 40 patients were included. MS differed significantly between G1 (n = 6) and G2 (n = 30), and BChcVA/BClcVA as well as TMV correlated significantly with FAZ size in correlation analysis. Mean HbA1c tended to be lower in G1 than G2. Patients in G1 were slightly older than in G2. Treatment period with insulin was shorter in G1/Q1 than in G2/Q3. CPT and TMV were lower in G1/Q1 than in G2/Q3. Our analysis of the FAZ in terms of patient age, HbA1c, disease duration and insulin therapy duration revealed no significance. That lack of significance also applies to BCVA, MS, MD, CPT, CST and CSV. Conclusion: As significantly associated, contrast sensitivity, central visual field parameters and potentially retinal thickness or volume seem to be suitable to detect early macular ischaemia. However, we failed to establish any correlation between FAZ and BCVA.

Incidence and risk factors for macular oedema after primary rhegmatogenous retinal detachment surgery: a prospective single-centre study.

PURPOSE: To assess the incidence of cystoid macular oedema (CME) diagnosed by spectral domain optical coherence tomography (SD-OCT) after primary rhegmatogenous retinal detachment (RRD) surgery. METHODS: From April 2016 to October 2017, 150 eyes of 150 patients presenting with primary RRD were included consecutively in this prospective single-centre study. Patients with the following characteristics were excluded: previous vitreoretinal surgery, combined cataract surgery, preoperatively presentation with any intraocular or systemic inflammatory condition, visible macular oedema or epiretinal membrane (ERM) on funduscopy. SD-OCT (Spectralis, Heidelberg Engineering) was conducted 3 and 6 weeks after surgery. RESULTS: One hundred and twenty-eight of the 150 patients completed the study, of whom 107 (age: 61.7 ± 11.5 years, mean ± SD) showed successful retinal attachment during follow-up visits. The most frequent operation method was scleral buckling (54.2%), followed by vitrectomy (25.2%) and the combination of both techniques (20.6%). Postoperative SD-OCT revealed CME, neurosensory detachment and ERM in 18.7, 31.8 and 32.7% of all cases, respectively. The risk of postoperative CME was significantly elevated in patients with ERM (42.9 versus 6.9%, p < 0.001). In addition, patients with initial detachment of the macula had more postoperative CME (26.5 versus 11.1%, p = 0.044). BCVA improvement was significantly lower in patients with CME compared to patients without 6 weeks after surgery for macula-on RRD. CONCLUSIONS: This prospective study confirmed that postoperative CME is a frequent complication after RRD surgery; we identified ERM and macula-off RRD as potential risk factors. As CME potentially delays visual recovery, postoperative follow-ups should include SD-OCT.

The urgency of surgical treatment for rhegmatogenous retinal detachment.

The ideal timing of surgery in patients with rhegmatogenous retinal detachment has been discussed for decades. The study situation has improved in recent years so that recommendations can now be made. When the macula is detached, surgical treatment of the retinal detachment should be undertaken within a few days. When the macula is still attached, the near fovea and bullous superotemporal detachment should be classified as an emergency. When planning the operation environmental factors must also be considered, meaning that the performance of the intervention by an experienced surgical team is usually more important for the final result than the retinal condition alone. Influencing factors are discussed in this article and recommendations for dealing with these emergency patients are discussed.

[The modified treat and extend scheme with injection blocks in intravitreal injection treatment : Retrospective analysis from the routine clinical application]. / Das modifizierte Treat-and-Extend-Schema mit Injektionsblöcken in der IVOM-Therapie : Retrospektive Analyse aus der täglichen klinischen Anwendung.

BACKGROUND: Regular treatment with intravitreal operative medication injections (IVOM) and the associated frequent check-ups are a major challenge for many patients, which can lead to treatment discontinuation. The aim of the modified treat and extend (TAE) in blocks scheme is to achieve stable retinal and visual outcomes with as few control visits as possible and thus to minimize the burden for the individual patient. METHODS: This monocentric retrospective study examined the treatment courses of 387 patients with neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion, who were treated by three blocks of intravitreal injections in the TAE regimen. The primary endpoint was achieving an injection interval of 12 weeks. RESULTS: Intravitreal injections in TAE blocks significantly reduced retinal thickness and improved visual acuity. On average, a treatment interval of 2 months was achieved across the various indications. CONCLUSION: Intravitreal injections in TAE blocks of three injections can reduce patients' burden and lead to stable retinal and visual results.

[The urgency of surgical treatment for rhegmatogenous retinal detachment]. / Dringlichkeit der operativen Versorgung bei der rissbedingten Netzhautablösung.

The ideal timing of surgery in patients with rhegmatogenous retinal detachment has been discussed for decades. The study situation has improved in recent years so that recommendations can now be made. When the macula is detached, surgical treatment of the retinal detachment should be undertaken within a few days. When the macula is still attached, the near fovea and bullous superotemporal detachment should be classified as an emergency. When planning the operation environmental factors must also be considered, meaning that the performance of the intervention by an experienced surgical team is usually more important for the final result than the retinal condition alone. Influencing factors are discussed in this article and recommendations for dealing with these emergency patients are discussed.

Risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study.

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.

Real-World Data: Ranibizumab Treatment For Retinal Vein Occlusion In The OCEAN Study.

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.

[Complications in sutured scleral fixation of artificial lens implantation]. / Komplikationen bei skleranahtfixierter Kunstlinsenimplantation.

BACKGROUND: Sutured scleral fixation of an artificial posterior chamber lens is a frequently used method for the treatment of eyes with poor or absent capsular support; however, the complication profile is often considered unfavorable. OBJECTIVE: To analyze the postoperative complication profile. METHODS: In this monocentric and retrospective analysis of a consecutive case series of patients with standardized sutured scleral fixation of a posterior chamber lens between 2007 and 2017, the documented complications were categorized as a permanent threat to visual acuity, such as endophthalmitis, choroidal hemorrhage, retinal detachment and clinically relevant but without a permanent threat to visual acuity, such as hemorrhage and hypotension. Additionally, the time point when complications first occurred was categorized into the 3 periods 0-3, 4-30 and ≥31 days. RESULTS: This is the largest patient collective of a study with scleral fixation of a posterior chamber lens published so far. A total of 338 eyes from 338 patients were included in the study (women 47%) and the median postoperative follow-up period was 60 days (range 1-5833 days). In 68% of the patients at least 1 complication was documented. Complications with a permanent threat to visual acuity occurred in 3% (n = 10) of the patients. The most frequent clinically relevant complications were intraocular hypotension ≤10 mm Hg (35%; n = 119), pupil decentration (28%; n = 93), hyphema, iris or vitreous hemorrhage (10%; n = 34), secondary glaucoma (9%; n = 32) and iris capture (5%; n = 17). Of the complications 41% occurred within the first 3 days and 70% within the first 30 days. Revision surgery was carried out in 4.5% (n = 15) of the patients. CONCLUSION: Although complications occurred in two thirds of the interventions, the number of permanent complications with a permanent threat to visual acuity was low. Scleral fixation of an artificial posterior chamber lens is still a justifiable intervention.

Lipid Emulsion-Based OCT Angiography for Ex Vivo Imaging of the Aqueous Outflow Tract.

Purpose: Contrast agents applicable for optical coherence tomography (OCT) imaging are rare. The intrascleral aqueous drainage system would be a potential application for a contrast agent, because the aqueous veins are of small diameter and located deep inside the highly scattering sclera. We tested lipid emulsions (LEs) as candidate OCT contrast agents in vitro and ex vivo, including milk and the anesthetic substance Propofol. Methods: Commercial OCT and OCT angiography (OCTA) devices were used. Maximum reflectivity and signal transmission of LE were determined in tube phantoms. Absorption spectra and light scattering was analyzed. The anterior chamber of enucleated porcine eyes was perfused with LEs, and OCTA imaging of the LEs drained via the aqueous outflow tract was performed. Results: All LEs showed a significantly higher reflectivity than water (P < 0.001). Higher milk lipid content was positively correlated with maximum reflectivity and negatively with signal transmission. Propofol exhibited the best overall performance. Due to a high degree of signal fluctuation, OCTA could be applied for detection of LE. Compared with blood, the OCTA signal of Propofol was significantly stronger (P = 0.001). As a proof of concept, time-resolved aqueous angiography of porcine eyes was performed. The three-dimensional (3D) structure and dynamics of the aqueous outflow were significantly different from humans. Conclusions: LEs induced a strong signal in OCT and OCTA. LE-based OCTA allowed the ability to obtain time-resolved 3D datasets of aqueous outflow. Possible interactions of LE with inner eye's structures need to be further investigated before in vivo application.

Bevacizumab versus bevacizumab and macular grid photocoagulation for macular edema in eyes with non-ischemic branch retinal vein occlusion: results from a prospective randomized study.

BACKGROUND: 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). METHODS: Prospective, randomized, monocentric study. Thirty-two patients were included. Initially, all eyes in both groups received three monthly injections of BEV, followed by additional injections if re-treatment criteria were met. In the BEV + GRID group, photocoagulation was performed 2 weeks after the first BEV injection and laser re-treatment was allowed. The follow-up was 38 weeks. Main outcome measures were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Changes of foveal avascular zone (FAZ) and of retinal ischemia, as well as the number of injections were also evaluated. RESULTS: Sixteen eyes were randomized into each group. At baseline, BCVA was similar in both groups (BEV + GRID: 20/71; BEV: 20/60; P = 0.51). At 38 weeks, BCVA significantly improved in the two groups (BEV + GRID gain of 9 ± 11.2 letters and 16.25 ± 10.08 letters in the BEV) with no difference between them (P < 0.06). With regard to anatomical findings, initial CRT in BEV + GRID was 496.2 µm ± 138.4 µm and 538.9 µm ± 156.9 µm in BEV (P < 0.1697). At 38 weeks, CRT decreased in both groups significantly, 98.2 µm in the BEV + GRID (P = 0.02) and 141.7 µm in the BEV group (P = 0.01), with no significant difference between groups (P < 0.17). The area of FAZ a significantly increased in both groups (41% (P = 0.04) in BEV + GRID; 35% (P = 0.03) in BEV) during the study and the grade of peripheral ischemia remained unchanged. The mean number of injections was 3.8 (range 3-6) with no significant difference between groups. CONCLUSIONS: Our data demonstrate a beneficial effect of bevacizumab in ME in eyes with BRVO. A loading phase of three injections led to a significant improvement in vision in both groups, which persisted at week 38. Additional grid laser photocoagulation exhibited no beneficial functional or anatomical effect during the study, nor did it reduce the number of injections. The FAZ area increased significantly in both groups, but overall retinal ischemia did not. Further studies investigating more numerous eyes and longer follow-up are needed to confirm these data.

Comparison of ranibizumab versus dexamethasone for macular oedema following retinal vein occlusion: 1-year results of the COMRADE extension study.

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.

Atrial fibrillation in retinal vascular occlusion disease and non-arteritic anterior ischemic optic neuropathy.

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.

Intravitreal Sustained-Release Steroid Implants for the Treatment of Macular Edema following Surgical Removal of Epiretinal Membranes.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implant for the treatment of postoperative persistent cystoid macular edema (CME) following macular pucker surgery. METHODS: In this multicenter study, we retrospectively reviewed the data of 37 patients (39 eyes) who had been treated with intravitreal dexamethasone implant (Ozurdex®) for persistent CME following macular pucker surgery. Main outcome measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: All eyes underwent spectral domain optical coherence tomography examination within 130 days after implantation. We observed a significant decrease in mean CRT from 519.9 to 392.9 µm (p < 0.0001). By this time, mean BCVA had improved from 0.60 to 0.43 logMAR (p = 0.003). Seventeen eyes (43.6%) required at least 1 repeat injection of dexamethasone. Of these, 8 (47%) eyes received a total number of 3 or more dexamethasone injections. CONCLUSION: Intravitreal dexamethasone implant injection is an effective treatment option for persistent CME following macular pucker surgery.

Risk of progression in macula-on rhegmatogenous retinal detachment.

PURPOSE: To identify factors that may lead to a rapid progression in macula-on rhegmatogenous retinal detachment (RRD), in particular, those that may lead to macular involvement. METHODS: Observational, prospective, single-center study. Patients referred for surgery due to primary rhegmatogenous retinal detachment with the macula on between 2009 and 2013 were included. Relevant factors analyzed included age, time delay until surgery, lens status, myopia, the detachment's location and configuration as well as number, size and type of retinal breaks. Eyes underwent optical coherence tomography to detect macular detachment. A multivariate analysis was performed to investigate the effect of several factors in the progression of retinal detachment. RESULTS: A total of 116 eyes of 116 patients were included. Mean time delay between admission and surgery was 1.8 ± 1.4 days. Progression was observed in 19.8% of the eyes. Of those, 47.8% presented macular detachment. Ten of the 11 (90.9%) eyes presenting progression involving the macula also exhibited a bullous configuration, which was the only parameter that correlated significantly with detachment progression in patients with (p = 0.0036) and without (p = 0.0014) macular involvement. CONCLUSIONS: For the first time in a prospective trial, a bullous configuration was found to be a highly significant predictor for progression in macula-on detachments. Our data support prompt surgery in patients diagnosed with bullous macula-on RRD.

Efficacy and safety of a fixed bimonthly ranibizumab treatment regimen in eyes with neovascular age-related macular degeneration: results from the RABIMO trial.

PURPOSE: 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. METHODS: This was a 12-month, phase IV, single center, randomised, non-inferiority study. Following three initial monthly injections, patients were randomised to receive either ranibizumab bimonthly (RABIMO group) or ranibizumab PRN (PRN group) (n = 20 each). Main outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of injections, and adverse events (AEs). RESULTS: BCVA [median (interquartile range, IQR)] increased significantly in both groups after 12 months [RABIMO group +8.5 (14); PRN group +6.5 (16) ETDRS letters] when compared to baseline (p < 0.0001; p = 0.0085). At month 12, the RABIMO treatment regimen was non-inferior to the PRN scheme (∆BCVA = 3.5 ETDRS letters; p < 0.0001). CRT was significantly reduced in both groups after the 12-month study period (p < 0.0001 each), with no significant difference between groups (p = 0.6772). Number of overall injections [median (IQR)] was 8 (0) in the RABIMO versus 4 (5) in the PRN group (p = 0.0037). Three patients in the RABIMO group received one additional unscheduled injection. We observed no significant differences between groups in the number of patients with reported SAEs/AEs (RABIMO group n = 6/15; PRN group n = 7/13) (p = 0.7357/p = 0.4902). CONCLUSIONS: We found no evidence of significant functional or anatomical differences between the RABIMO and PRN treatment regimens. However, the RABIMO group's number of injections was twice as high as the PRN group's (protocol-driven). In light of potential side effects, the fixed bimonthly treatment regimen might not be advisable for routine clinical care, but it might be a worthwhile treatment option if monthly monitoring is not possible. Eudra-CT number: 2009-017324-11.

Predictors of prognosis and treatment outcome in central retinal artery occlusion: local intra-arterial fibrinolysis vs. conservative treatment.

INTRODUCTION: The study analyses patients' risk factors to determine prognostic and predictive factors in patients with acute central retinal artery occlusion (CRAO) treated in the randomized European Assessment Group for Lysis in the Eye (EAGLE) Study with local intra-arterial fibrinolysis (LIF) or conservative standard treatment (CST). These data could improve patient selection for either method. METHODS: Post hoc statistical analysis of effects of risk factors on overall best corrected visual acuity (BCVA [logarithm of the minimum angle of resolution (logMAR)]) at baseline and month 1 (prognostic effect) and on the difference between outcome of CST and LIF (predictive effect) was conducted. RESULTS: Seventy two of 84 EAGLE datasets were included. Prognostic effect: Patients with coronary heart disease (CHD) presented worse BCVA at baseline (0.39 logMAR, p = 0.0097). Patients with time from occlusion to treatment <12 h showed a trend to better vision gain at month 1 (-0.23 logMAR, p = 0.086), similarly smoking (-0.24 logMAR, p = 0.077). Predictive effect: Age (<60 years favours LIF -0.54 logMAR; >70 years favours CST 0.28 logMAR; interaction p = 0.070) and CHD (favours CST 0.44 logMAR; interaction p = 0.073) might be predictors of therapeutic outcome. There were no strong effects in multivariate analysis. CONCLUSION: CHD, time from occlusion to treatment and smoking influence BCVA at baseline and at month 1 (prognostic effect). Patients treated within 12 h are more likely to profit from treatment. In multivariate analysis, there is no clear trend to benefit from LIF even in patients with young age, no CHD and early treatment. Based on this preliminary report on a rather small sample size, we do not recommend LIF in CRAO patients.

Cardiovascular Risk Factors in Central Retinal Artery Occlusion: Results of a Prospective and Standardized Medical Examination.

PURPOSE: To analyze the underlying risk factors in patients with nonarteritic central retinal artery occlusion (CRAO) in a well-defined and homogenous group of patients enrolled in the European Assessment Group for Lysis in the Eye (EAGLE) study. DESIGN: Analysis of the cardiovascular risk factors in a prospective, randomized clinical trial. PARTICIPANTS: Seventy-seven EAGLE patients with nonarteritic CRAO. METHODS: Analysis of vascular risk factors and underlying diseases detected by questionnaire and standardized physical examination within 1 month after occlusion. MAIN OUTCOME MEASURES: The standardized physical examination included carotid Doppler ultrasonography, echocardiography, electrocardiography, blood pressure monitoring, pulse rate, urine analysis, body mass index analysis, and laboratory tests. RESULTS: Seventy-seven of 84 patients had complete datasets for analysis. Fifty-two (67%) patients had cardiovascular risk factors in their medical history, and comprehensive phenotyping identified at least 1 new risk factor in 60 patients (78%; 95% confidence interval, 67%-87%). Thirty-one (40%) had carotid artery stenosis of at least 70%. Eleven patients experienced a stroke, 5 of those within 4 weeks after the CRAO occurred. Arterial hypertension was found in 56 (73%) patients and was newly diagnosed in 12 (16%) study participants. Cardiac diseases were also highly prevalent (22% coronary artery disease, 20% atrial fibrillation, and 17% valvular heart disease). CONCLUSIONS: Previously undiagnosed vascular risk factors were found in 78% of all CRAO patients. The most meaningful risk factor was ipsilateral carotid artery stenosis. A comprehensive and prompt diagnostic work-up is mandatory for all CRAO patients.

Efficacy and safety of intravitreal therapy in macular edema due to branch and central retinal vein occlusion: a systematic review.

BACKGROUND: Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a systematic review to evaluate efficacy and safety outcomes of intravitreal therapies for macular edema in CRVO and BRVO. METHODS AND FINDINGS: MEDLINE, Embase, and the Cochrane Library were systematically searched for RCTs with no limitations of language and year of publication. 11 RCTs investigating anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) and steroids (triamcinolone, dexamethasone implant) with a minimum follow-up of 1 year were evaluated. EFFICACY CRVO: Greatest gain in visual acuity after 12 months was observed both under aflibercept 2 mg: +16.2 letters (8.5 injections), and under bevacizumab 1.25 mg: +16.1 letters (8 injections). Ranibizumab 0.5 mg improved vision by +13.9 letters (8.8 injections). Triamcinolone 1 mg and 4 mg stabilized visual acuity at a lower injection frequency (-1.2 letters, 2 injections). BRVO: Ranibizumab 0.5 mg resulted in a visual acuity gain of +18.3 letters (8.4 injections). The effect of dexamethasone implant was transient after 1.9 implants in both indications. SAFETY: Serious ocular adverse events were rare, e.g., endophthalmitis occurred in 0.0-0.9%. Major differences were found in an indirect comparison between steroids and anti-VEGF agents for cataract progression (19.8-35.0% vs. 0.9-7.0%) and in required treatment of increased intraocular pressure (7.0-41.0% vs. none). No major differences were identified in systemic adverse events. CONCLUSIONS: Anti-VEGF agents result in a promising gain of visual acuity, but require a high injection frequency. Dexamethasone implant might be an alternative, but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen. The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids. Because comparative data from head-to-head trials are missing currently, clinicians and patients should carefully weigh the benefit-harm ratio.