Management of macula-on giant retinal tear detachments- outcome of pars-plana-vitrectomy with silicone oil versus gas tamponade.

BACKGROUND: To compare the outcome of eyes with a macula-on giant retinal tear (GRT) detachment treated with pars-plana-vitrectomy (PPV) depending on the used endotamponade. METHODS: All consecutive cases with a macula-on GRT-associated rhegmatogenous retinal detachment (RRD) managed with PPV between 2007 and 2022 were retrospectively assessed depending on the selected endotamponade. By reviewing medical charts and surgical protocols the pre- and intraoperative parameters were analysed in detail. The number of vitreoretinal (VR) procedures needed for reattachment, the redetachment rate and the functional outcome were evaluated. Eyes treated with primary silicone oil (SO) tamponade were compared to eyes with primary gas tamponade. Cases with pre-existing conditions affecting outcome e.g. macula-off situation, history of trauma, status after complicated cataract surgery, former VR surgery or proliferative vitreoretinopathy grade C or higher were excluded. RESULTS: Overall, 51 eyes of 45 patients with a macula-on GRT detachment were treated with PPV and SO (n = 32; 63%) or gas (n = 19; 37%) endotamponade in the observed period. Eyes with primary SO tamponade underwent on average 2.3 (SD 0.8) VR procedures and had a redetachment rate of 13% (n = 4). Eyes with gas tamponade showed a higher redetachment rate of 32% (n = 6) with a mean number of 1.6 (SD 1.0) PPV procedures. Postoperative best-corrected visual acuity (BCVA) was significantly better in eyes with primary gas tamponade (mean logMAR BCVA 0.32; SD 0.30) compared to eyes with SO (mean logMAR BCVA 0.60; SD 0.42; p = 0.008). CONCLUSIONS: Surgical management of GRT-associated RRDs is complex. In clinical routine often SO is used as endotamponade. Because of known disadvantages (second procedure necessary for SO removal, unexplained SO-related visual loss, secondary glaucoma, SO emulsification) some VR surgeons prefer a gas tamponade. In our cohort, eyes with a gas compared to SO tamponade showed higher redetachment rates. However, the final postoperative BCVA was significantly better in eyes with gas compared to SO tamponade. TRIAL REGISTRATION: The trial protocol was approved by the local ethics committee on 25th of November 2022 (Ethikkommission der Universität Regensburg, Votum 22-3166-104).

Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1.

INTRODUCTION: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. METHODS: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. RESULTS: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0-70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2-0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. CONCLUSION: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV.

Characteristics of Bilateral Retinal Detachment.

INTRODUCTION: Rhegmatogenous retinal detachment (RD) is still a sight-threatening and potentially blinding disease, especially if both eyes are affected. The purpose of this study is analysing the specific characteristics of bilateral rhegmatogenous RD. METHODS: The files of all 5,791 consecutive eyes undergoing vitreoretinal surgery for uncomplicated RD in a single tertiary retinal centre between January 2005 and June 2021 were retrospectively reviewed. RESULTS: A total of 300 patients (600 eyes) had bilateral retinal detachment. Interval between initial and subsequent RD surgery was 2.6 ± 2.8 (mean ± SD, median 1.5) years. Symptoms were reported by the patients for 20 ± 75 (median 5) days before presentation in the initial eye and 12 ± 32 (median 4) days in the subsequent eye. 220 patients were male (73%), and mean age at initial RD was 55 years. 183 (61%) of the initial RD eyes were phakic. In the initial eye, more patients had a detached macula, worse visual acuity, and more quadrants involved. Primary anatomic success rate was higher in the subsequent eye (90%) compared to the initial eye (83%). There was no difference in the reattachment rate of fellow eyes with primary failure in the first eye (91%) compared to those with primary success in the first eye (90%). There was a high symmetry between the eyes in terms of type of retinal break, number of breaks, and presumed localization of the causative retinal break. CONCLUSION: Patients with bilateral RD were more commonly male and younger than the group of all RD patients. The proportion of pseudophakia was not different. The majority of fellow eye RD occurred within 2 years after the RD in the first eye. Second eye RD was less advanced and had a better anatomical repair rate. Despite their experience in the first eye and despite typical symptoms, patients presented only after a mean of 12 days with RD in the second eye. RD in the initial and the subsequent eye showed a high symmetry. The anatomic result in the first eye is not a predictor for the anatomic result in the subsequent eye.

Rhegmatogenous retinal detachment repair-does age, sex, and lens status make a difference?

PURPOSE: To analyze the correlation between lens status, age, and sex in the epidemiology and success rates of rhegmatogenous retinal detachment (RRD) surgery. METHODS: The files of all consecutive patients undergoing vitreoretinal surgery for uncomplicated RRD between Jan 2005 und Dec 2020 were retrospectively reviewed. Successful outcome was defined as no retinal redetachment occurring within 3 months after surgery. RESULTS: 5502 eyes with uncomplicated primary RRD were included. Mean age of the patients was 61.1 years (± 13.6 SD). In the age group over 40 years, a male predominance was found. The percentage of pseudophakic RRD increased from 25 to 40% during the 15 years observation period. In the age group 50 to 69 years, patients with pseudophakic detachments were male in 786 out of 1079 cases (72.9%). In the same age group, 1285 of 2110 (60.9%) patients with phakic RRD were male. Overall, primary success rate after one procedure was 91.2% (5018 of 5502). In the phakic eyes, the primary success rate was higher in those eyes that underwent combined phacovitrectomy (93.0%), compared to those without simultaneous cataract surgery (88.7%; p = 0.002). CONCLUSION: The ratio of male and female patients with RRD varies between age groups. The proportion of pseudophakic RRD has increased within 15 years. The male predominance in RRD is stronger in pseudophakic than in phakic eyes. In phakic eyes with RRD, a combined phacovitrectomy yielded better anatomical results.

Genetic Association Analysis of Anti-VEGF Treatment Response in Neovascular Age-Related Macular Degeneration.

Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been FDA-approved in 2004, and since then has helped tens of thousands of patients worldwide to preserve vision. Still, treatment responses vary widely, emphasizing the need for genetic biomarkers to robustly separate responders from non-responders. Here, we report the findings of an observational study compromising 179 treatment-naïve nAMD patients and their reaction to treatment after three monthly doses of anti-VEGF antibodies. We show that established criteria of treatment response such as visual acuity and central retinal thickness successfully divides our cohort into 128 responders and 51 non-responders. Nevertheless, retinal thickness around the fovea revealed significant reaction to treatment even in the formally categorized non-responders. To elucidate genetic effects underlying our criteria, we conducted an undirected genome-wide association study followed by a directed replication study of 30 previously reported genetic variants. Remarkably, both approaches failed to result in significant findings, suggesting study-specific effects were confounding the present and previous discovery studies. Of note, all studies so far are greatly underpowered, hampering interpretation of genetic findings. In consequence, we highlight the need for an extensive phenotyping study with sample sizes exceeding at least 15,000 to reliably assess anti-VEGF treatment responses in nAMD.

The learning curve of retinal detachment surgery.

PURPOSE: To investigate the learning curve of vitreoretinal (VR) surgeons beginning training in retinal detachment (RD) surgery. METHODS: The files of all consecutive patients undergoing VR surgery for uncomplicated RD between Jan 2005 und Mar 2020 were retrospectively reviewed. Successful outcome was defined as no retinal redetachment within 3 months after surgery. RESULTS: Ten surgeons started their VR career during this period. Together, these 10 surgeons performed 3786 RD operations (mean 379; median 251; range 71-1053). Primary success rate after one operation was 90% (3420 of 3786). When starting to operate retinal detachments, VR surgeons had a primary success rate of about 80%. Redetachment rates steadily decreased and stabilized at just under 10% after about 200 operations. Beginners needed more than twice the time for the procedure compared to experienced surgeons. The individual learning curves varied widely. In our series, female surgeons seem to have a faster learning curve. CONCLUSION: RD surgery performed by VR surgeons in training had acceptable results. With increasing experience, success rates continuously improve reaching stable levels after approximately 200 operations. The training of VR surgeons requires considerable resources.

Spectral Domain Optical Coherence Tomography Allows the Unification of Clinical Decision Making for the Evaluation of Choroidal Neovascularization Activity.

PURPOSE: This prospective observational clinical study investigated the benefits of spectral domain optical coherence tomography for specialists and residents in the management of neovascular age-related macular degeneration (AMD). PROCEDURES: The study involved 49 eyes of 44 patients. Patients were advised to present for reevaluation 4 weeks after the administration of the loading dose of vascular endothelial growth factor (VEGF)-inhibitors (3 intravitreal injections every 4 weeks after diagnosis). They were examined by residents (3-4 years' experience in ophthalmology) and specialists (> 5 years' experience). Each examiner evaluated the clinical situation and the spectral domain optical coherence tomography (SD-OCT) scan. After each evaluation, the examiners independently stated if further anti-VEGF treatment was recommended. The "true outcome" was defined as the specialist decision based on clinical evaluation and SD-OCT. RESULTS: Specialists and residents did not significantly differ in their accuracy in deciding on the correct treatment (p = 0.705 and p = 1), with or without the aid of SD-OCT. Both groups benefited from using SD-OCT to support their recommendations (p = 0.001 and p = 0.0002) and achieved a similar level of accuracy (p = 1 for difference). CONCLUSIONS: Residents benefited more than specialists by using SD-OCT to substantiate their recommendation on how to manage exudative AMD after the administration of the loading dose.

[Dietary Supplements and "Lifestyle"]. / Nahrungsergänzungsmittel und "Lifestyle".

Currently, for non-exudative age-related macular degeneration (AMD), therapy is not possible-in contrast to the exudative form. Many patients hope for a preventive effect and a slower progression of the disease from the dietary supplements on the market. The substances contained in them are supposed to reduce the oxidative environment in the outer retina and, thereby, slow down the cell damage and the progression of AMD. The Age-Related Eye Disease Studies (AREDS) examined certain supplements for their effectiveness in reducing the risk of AMD progression. They are the only interventional large-scale, prospective, randomized and controlled clinical trials and are repeatedly used as the basis for dietary supplementation in AMD. This article discusses the rationale for the use of certain ingredients of AREDS supplements and critically examines the results of AREDS. Furthermore, the modern term "lifestyle" will be discussed in the context of AMD as a possibility to influence the progression of this disease.

Intravitreal anti-VEGF treatment for subretinal neovascularisation secondary to type 2 idiopathic juxtafoveolar telangiectasia.

PURPOSE: To assess the long-term outcome of patients with subretinal neovascular membrane (SRNVM) secondary to type 2 idiopathic juxtafoveolar telangiectasia (IJT) receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: A total of 14 eyes of 12 patients treated with intravitreal anti-VEGF for SRNVM related to type 2 IJT were retrospectively assessed. RESULTS: Nine men and 3 women with a mean age of 66 years (SD 12, range 47-87 years) were diagnosed with IJT-related SRNVM. On average, 6.8 injections (SD 5.5, range 3-18) were given per eye. Ten eyes were treated with ranibizumab, 3 eyes with bevacizumab and 1 eye received both substances. The median follow-up after the last injection was 31 months (IQR: 18, 48). In 6 eyes, BCVA improved by 1-4 lines (mean Δ +2.0 lines), 1 eye remained stable and 7 eyes showed decline of vision by 1-5 lines (mean Δ -2.1 lines). The baseline central foveal thickness was significantly reduced from a mean of 323 (SD 87) to 266 µm (SD 71 µm) at the last follow-up visit (p = 0.001). CONCLUSIONS: SRNVM development is a severe complication of type 2 IJT. Since the establishment of intravitreal anti-VEGF treatment laser coagulation and PDT have lost significance. Intravitreal anti-VEGF therapy seems to be safe and effective for the treatment of IJT-related SRNVM. Frequently multiple intravitreal injections are necessary for stabilisation.

Classification and characterization of acute macular neuroretinopathy with spectral domain optical coherence tomography.

PURPOSE: To classify and characterize AMN lesions with SD-OCT during a follow-up as long as 5 years. METHODS: Retrospective study of 14 patients (18 eyes) with special focus on SD-OCT. We measured thickness of inner nuclear layer (INL), outer retinal layer (ONL), and hyperreflective band at baseline and during follow-up. AMN lesions were classified as type 1 and type 2. RESULTS: Of 14 patients (six males, eight females, mean age 29.7 years), three patients (four eyes) had type 1 and nine (12 eyes) had type 2. Two patients did not meet the criteria for AMN type 1 or 2 and were therefore classified as new subtype of AMN. In all patients, statistically significant thinning of ONL and INL was observable. Mean ONL of all patients was 90.2 ± 7.81 and 72.3 ± 15.64 µm (p < 0.05) during follow-up; mean INL was 54.4 ± 10.71 and 37.5 ± 6.18 µm (p < 0.05) in the course. In the subgroup analysis in AMN type 2, the thinning of both ONL and INL was also statistically significant (mean ONL: 87.4 ± 6.02 and 71.6 ± 12.7 µm (p < 0.05); mean INL: 48.5 ± 5.04 and 38.5 ± 5.6 µm (p < 0.05)) in the course. CONCLUSION: SD-OCT allows for classification, characterization, and further understanding of AMN lesions. Up to now, this is one of the largest AMN case series differentiating into different subtypes and following up for up to 5 years. Furthermore, we describe a new AMN subtype characterized by initially clinically visible yellowish parafoveal lesions, subtle pigmentary changes at late stage, lack of classic dark appearance on IR reflectance, involvement of RPE/Bruch's complex, and disruption of ellipsoid zone and interdigitation zone. The patients suffered from a prolonged visual impairment and paracentral scotomata. We propose the term AMN type 3 or "paracentral acute outer maculopathy."

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

[Ocular side effects of modern oncological therapy : Immunological checkpoint and MEK/BRAF signal transduction inhibitors]. / Okuläre Nebenwirkungen moderner onkologischer Therapie : Immunologische Checkpoint- und MEK/BRAF-Signaltransduktionsinhibitoren.

In recent years, checkpoint inhibitors have revolutionized the treatment of previously untreatable malignant tumors, significantly improving the life expectancy as well as quality of life in many cases. Checkpoint inhibitors comprise a group of drugs with different mechanisms of action. These include immunological checkpoint inhibitors (iCPI) and intracellular signal transduction inhibitors; however, both substance classes can cause inflammatory or toxic ocular side effects. The frequency of intraocular inflammation (uveitis) is reported to be ca. 1-2%, toxic side effects were observed in up to more than 50% of the patients treated with signal transduction inhibitors. In the following article the main mechanisms of these forms of treatment are characterized. Furthermore, this article presents the currently most frequently used therapeutic agents and their typical ophthalmological side effects to increase awareness and to draw attention to these still rare but increasingly more frequent findings.

Visual and morphological outcomes of bevacizumab (Avastin®) versus ranibizumab (Lucentis®) treatment for retinal angiomatous proliferation.

Retinal angiomatous proliferation (RAP) is a variant of exudative age-related macular degeneration with particularly bad prognosis. The purpose of this work is to describe the long-term functional and morphological outcome of patients treated with intravitreal bevacizumab and ranibizumab. Retrospective case series of 16 eyes treated with bevacizumab and 19 eyes treated with ranibizumab. All patients received initially three intravitreal injections of bevacizumab (1.25 mg/0.05 ml) or ranibizumab (0.5 mg/0.05 ml) every 4 weeks. Follow-up ranged from 1 to 7 months after the third injection. Complete ophthalmologic examination including best-corrected visual acuity (VA), optical coherence tomography, fluorescein angiography, and in selected cases, indocyanine green angiography was performed. Triple intravitreal injections resulted in improvement of VA in bevacizumab-treated as well as in ranibizumab-treated patients; logarithm of the minimal angle of resolution (logMAR) 0.84 before treatment and 0.67 at month 9, and logMAR 0.75 before treatment and 0.59 at month 9, respectively. Central macular thickness (CMT) in the bevacizumab group improved from 363.67 ± 47.4 µm at baseline to 328 ± 49.77 µm at month 6 (p = 0.03) and 301 ± 129.69 at month 9 (p = 0.35). CMT in the ranibizumab group improved from 545.62 ± 167.39 µm at baseline to 395.88 ± 169.37 µm at month 6 and 411.83 ± 212.41 µm at month 9 (p = 0.03, p = 0.05, respectively). Patients with RAP might benefit from both intravitreal bevacizumab and ranibizumab treatments with stabilization of VA over a longer period of time. Close follow-up should nevertheless be performed in this special subgroup because of the high recurrence rate.

[Retinal detachment surgery: trends over 15 years]. / Ablatiochirurgie: Trends über 15 Jahre.

INTRODUCTION: The aim of the study was to investigate the changes in the treatment of patients with retinal detachment over the past 15 years. METHOD: Files of all 5101 patients hospitalized for retinal detachment surgery between January 2005 and March 2020 were retrospectively analyzed. RESULTS: The number of retinal detachment surgeries over the past 15 years increased continually from 150 to 600 per annum. During the summer months an increased incidence of retinal detachment of approximately 20% could be observed compared to the winter months. Anatomical success rates of emergency surgery carried out at weekends were not lower than those of scheduled routine procedures performed during the week. The relative proportion of buckle surgery decreased significantly from more than 60% down to 5% between 2005 and 2019. While initially an additional encircling buckle was employed in most cases of primary vitrectomy, this technique has almost completely disappeared in recent years without a deterioration of success rates. Liquid silicone tamponade was applied less frequently over the years. The overall anatomical success rates showed a slight trend towards improved results over the past 15 years. CONCLUSION: The strategies for surgical repair of retinal detachment have changed considerably in recent years: less buckle surgery, more vitrectomy, less add-on encircling buckles and less silicone tamponade. A slight trend towards better anatomical success rates could be observed.

Bevacizumab versus ranibizumab in the treatment of exudative age-related macular degeneration.

The purpose of this article is to describe functional and morphological short-term results in patients with exudative age-related macular degeneration (AMD) of all subtypes, treated with intravitreal bevacizumab versus intravitreal ranibizumab. This was a retrospective case-controlled series of 30 patients treated with intravitreal bevacizumab and 30 patients treated with intravitreal ranibizumab for exudative AMD. All patients received three initial injections every 4 weeks. Best corrected visual acuity (BCVA) as well as greatest linear dimension (GLD) of the CNV in fluorescein angiography and central retinal thickness (CRT) in optical coherence tomography (OCT) were monitored 2-4 months after last injection. BCVA stabilized and slightly increased from logMAR 0.74 to 0.62 in the bevacizumab group, and from logMAR 0.76 to 0.58 in the ranibizumab group (P < 0.05 for each group). No statistical difference was seen between both groups at any time-point. CRT was significantly reduced in both groups at last follow-up. In contrast, GLD did not change significantly. Patients with exudative AMD of all subtypes benefit from intravitreal anti-VEGF injections. No significant difference between bevacizumab and ranibizumab is seen in the short-term follow-up.

Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance in a Noninterventional Trial.

AIM: The prospective, noninterventional OCEAN study assessed the safety of intravitreal ranibizumab injections for treatment of neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion under real-world conditions in Germany. METHODS: Adults receiving ≥1 ranibizumab (0.5 mg) injections were recruited by 369 ophthalmologists and followed for 24 months. Information on adverse events (AEs) was reported by the treating physician or detected by the data management team. Collected information included observed AE, AE start and end date, intensity, causal relationship, outcome, severity, suspected drug, and actions taken. RESULTS: 2,687 AEs were reported for 1,176 of the 5,781 patients who had received a total of 32,621 injections: 27.4% nonserious AEs, 30.3% serious AEs, 27.3% nonserious adverse drug reactions (ADRs), and 15.0% serious ADRs. Most patients reported no AEs (79.7%) or only 1 AE (10.3%). AEs were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). The most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%). AEs occurred most frequently after 3 or 4 injections (1,129 of 2,687 AEs). The proportion of AEs in the SOC Eye disorders decreased slightly with increasing number of injections, from 39.8% of events after 1 or 2 injections to 29.1% after 5 or more injections. Rates of the most frequently reported PTs did not show any consistent increase with increasing number of injections. A decrease in overall AE rates was observed over the study course. CONCLUSIONS: The results did not raise any new safety concerns for ranibizumab. The findings allow conclusions to be drawn on how pharmacovigilance data can be collected even more effectively in real-world studies to facilitate discussion on benefit-risk ratio.

Vascular networks in retinal arterial macroaneurysms.

Retinal arterial macroaneurysms (MA) are a rare pathology, often associated with old age, arterial hypertension, artherosclerosis, and retinal vein occlusions. Here, we present two unusual cases of MA in patients with arterial hypertension, that displayed small vascular networks at the site of the MA on angiography. Resulting exudative changes and the networks themselves regressed after laser treatment, and visual acuity improved. Those vascular networks might represent collateral vessels forming as a rare sequel after spontaneous occlusion of the MA.

The RELATION study: efficacy and safety of ranibizumab combined with laser photocoagulation treatment versus laser monotherapy in NPDR and PDR patients with diabetic macular oedema.

PURPOSE: To assess efficacy and safety of intravitreal ranibizumab 0.5 mg plus laser (COMBI) versus laser monotherapy (LASER) in patients with visual impairment due to diabetic macular oedema (DME) in either nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) and to analyse the relevance of inner versus outer retinal thickness. METHODS: In this double-masked, multicentre phase IIIb study, patients (N = 128) were randomized (2:1) to receive COMBI (n = 85) versus LASER (n = 43). Patients received four initial monthly injections of ranibizumab 0.5 mg (COMBI) or sham (LASER) followed by pro re nata (PRN) injections. In both groups, patients received laser at baseline and additional laser at 3 monthly intervals, as needed. The study was started in 2010 and was prematurely terminated due to approval of ranibizumab for DME. RESULTS: The least squares (LS) mean change in mean best-corrected visual acuity (BCVA) from baseline to month 12 was higher in the COMBI (6.5) versus LASER (2.3) group (LS mean difference: 4.2 [95% CI 0.9; 7.4] letters, p = 0.01, primary end-point). There was also a tendency in the same direction for the subgroup of 26 patients with PDR (LS mean difference 14.7, p = 0.11). Mean central retinal thickness decreased by 107.3 µm in the COMBI group and by 80.3 µm in the LASER group from baseline to month 12 (p = 0.28). Ranibizumab was well tolerated. CONCLUSION: This study showed that ranibizumab plus laser is a valuable treatment option for the management of DME. Patients with DME in PDR might also benefit from combined therapy compared to laser alone.

Intravitreal Ranibizumab Therapy for Diabetic Macular Edema in Routine Practice: Two-Year Real-Life Data from a Non-interventional, Multicenter Study in Germany.

INTRODUCTION: 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. METHODS: Adults with DME receiving ≥ 1 ranibizumab (0.5 mg) injections were recruited by 250 ophthalmologists. Best-corrected visual acuity (VA) testing, imaging and treatments were performed according to the investigators' routine practice and documented over 24 months. RESULTS: The full analysis set included 1226 participants. Mean baseline VA was 60.6 [95% CI: 59.7; 61.5] Early Treatment Diabetic Retinopathy Study letters. VA improved by ≥ 15 letters in 21.5% and 23.5% of the participants at 12 months and 24 months, respectively. They received a mean number of 4.42 [95% CI: 4.30; 4.54] injections in the first year and 5.52 [95% CI: 5.32; 5.73] injections over 24 months, which was markedly lower than in clinical trials. Only 33.4% of the participants received an upload with four initial monthly injections as recommended by the German ophthalmologic societies. Time-to-event analyses that account for missing data inherent to a non-interventional study design demonstrated that participants receiving ≥ 7 injections in the first year had a faster response, but the duration of the response was shorter compared to the subgroups receiving 1-3 and 4-6 injections. Serious adverse events were reported for 143/1250 (11.4%) participants in the safety population. CONCLUSION: Under-treatment is a major problem of DME anti- vascular endothelial growth factor therapy under real life conditions. Despite fewer injections given compared to randomised controlled trials with a consequently reduced overall mean visual gain, a profound functional improvement (≥ 15 letters) was achieved over 2 years in 23.5% of eyes with DME. TRIAL REGISTRATION NUMBER: NCT02194803, ClinicalTrials.gov. FUNDING: Novartis Pharma GmbH, Nuremberg, Germany.