Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis

Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept.

Methods: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections.

Results: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment.

Conclusions: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent.     

Bilateral same-session intravitreal injections of anti-vascular endothelial growth factors

AIM: To document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.METHODS:A retrospective case series study. Consecutive records of seventy four patients receiving simultaneous bilateral intravitreal injections of either ranibizumab or bevacizumab, between September 2010 and September 2013, were reviewed and the outcomes were assessed. Data collected included number of injections, indications for injections, pre-injection and post-injection visual acuity (VA), pre-injection and post-injection intraocular pressure and ocular and systemic complications/complaints after each injection.RESULTS: A total of 342 injections were administered to 74 patients, with a mean of 4.62 injections per patient. Seventy-three patients received bevacizumab (Avastin; Genentech Inc., South San Francisco, California, USA) alone, and only one patient received both bevacizumab and ranibizumab (Lucentis; Genentech Inc.) distributed between the injections. Pre- and post-injection VA follow-up measurements were available for 65 patients. Mean follow up period was 22mo. The indications for initiating therapy were choroidal neovascular membrane from age-related macular degeneration (3 patients) and diabetic macular edema (71 patients). The mean Snellen VA before each injection was 6/22. The next post-injection follow-up mean Snellen VA was 6/20. One patient had a painful, culture-positive endophthalmitis in one eye 3d after bilateral bevacizumab. Another patient had a painless subconjunctival hemorrhage in one eye. No other ocular or systemic adverse side effects/complaints have been registered in this study group.CONCLUSION:Bilateral same-session intravitreal injections using a separate povidone-iodine preparation, speculum, needle, and syringe for each eye are well-tolerated. None of the subjects in this study requested to switch to alternating unilateral injections. Proper patient counseling as to the risk of complications with this procedure is necessary.     

Safety and complications of intravitreal injections performed in an Asian population in Singapore

There has been a rapid rise in the use of intravitreal injections, such as anti-vascular endothelial growth factor (anti-VEGF) agents, performed over the past few years for the treatment of ocular neovascular diseases. This study aims to review the systemic and ocular adverse events among patients treated at a tertiary eye center over a period of 8 years. A retrospective review of all intravitreal injections of anti-VEGF performed over an 8-year period at a tertiary eye care center in Singapore was done. We report the frequency of systemic and ocular adverse events and compared it among the various anti-VEGF agents. A total of 14 001 intravitreal injections were performed on 2225 patients from January 1, 2007 to December 31, 2014, and this included 9992 bevacizumab (71.4 %), 3306 ranibizumab (23.6 %) and 703 aflibercept (5.0 %) injections. Systemic complications related to treatment were 26 (1.17 %) deaths (from any cause), of which 11 (0.49 %) were from fatal thromboembolic events, 7 (0.31 %) non-fatal thromboembolic events and two (0.09 %) serious non-ocular hemorrhage. Ocular complications included one (0.007 %) endophthalmitis, three (0.021 %) traumatic cataracts, and one (0.007 %) retinal detachment. Rates of death and thromboembolic events were similar among ranibizumab (lucentis), bevacizumab (avastin) and aflibercept (Eylea). The systemic and ocular complications associated with intravitreal injections among Asian patients at a tertiary eye center are relatively low and reflect the safety of the treatments.     

Local and Systemic Complications after Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Different Ocular Diseases: A Five-Year Retrospective Study

Abstract

Purpose: To observe the frequency of complications in patients undergoing intravitreal anti-VEGF injections for different ocular diseases in a five-year period. Materials and Methods: Charts of patients receiving intravitreal anti-VEGF were retrospectively reviewed. Out of 1173 eyes, 762 were treated with bevacizumab, 382 with ranibizumab, and 29 with pegaptanib. Data recorded included demographic information, clinical findings, total injections received, and info about the onset of adverse effects. Results: 12.86% of the eyes treated with bevacizumab presented side-effects, while ratings in the ranibizumab and pegaptanib groups were 15.97% and 20.69%, respectively. Odds ratios calculated comparing incidences after each anti-VEGF are 0.78 (bevacizumab versus ranibizumab, p?=?0.152), 0.57 (bevacizumab versus pegaptanib, p?=?0.227), and 0.73 (ranibizumab versus pegaptanib, p?=?0.508). A total of 185 complications were detected (62.16% after bevacizumab). Ocular side-effects registered were 40 cases of sustained intraocular pression (IOP) elevation, one infectious uveitis, one retinal detachment, and one sub-retinal hemorrhage. Other cases were related to transient IOP elevation immediately after injection. Systemic complications registered were one case of nausea, one episode of chest pain with acute vision loss, and one case of acute blood hypertension. Conclusions: The majority of significant complications occurred in patients receiving multiple bevacizumab administrations. However, results may be affected by the difference in the utilization amount for each drug. AMD patients were the most represented, probably due to greater indication to treatment.     

Complications of intravitreal injections--own experience

PURPOSE: Authors present complications associated with intravitreal injection perfomed in Ophthalmic Clinic CMKP MATERIAL AND METHODS: retrospective study, between January 2006 and July 2009 we performed intravitreal injections with triamcinolone acetonide (Kenalog, 4 mg), ranibizumab (Lucentis, 0.5 mg), bevacizumab (Avastin, 1.25 mg) and pegaptanib (Macugen, 0.3 mg). We treated eyes with age-related macular degeneration, diabetic macular edema, after retinal venous occlusion, with uveitis, Irvine-Gass syndrome, idiopathic juxtafoveolar teleangiectasia and central serous retinopathy. RESULTS: 943 eyes received intravitreal injections. The most common ocular complication was subconjunctival hemorrhage which was seen in 36% cases. Temporary elevated intraocular pressure above 21 mmHg was noticed in 18 eyes (5%) after anti-VEGF agents injections and in 30 eyes (23.4%) after Kenalog injection. Anterior uveitis developed in sixteen cases (1.7%) from the Avastin (5 eyes) and Lucentis (3 eyes) group. Anterior-posterior inflammation occurred in 8 eyes (0.8%), including four eyes (0.4%) with sterile endophthalmitis (3 following bevacizumab and 1 following ranibizumab injection), one eye (0.1%) with pseudoendophthalmitis (after triamcinolone). There were three cases of suspected endophthalmitis (2 following bevacizumab and 1 following triamcinolone injection). The infectious endophthalmitis after triamcinolone injection was culture-proven and revealed Staphylococcus epidermidis. Cataract formation or progression was noted in 34 eyes totally. In Kenalog group progression of cataract was seen in 23.4% of eyes (30 cases) during 2-years of follow-up and in anti-VEGF agents group--in two cases (0.6%) and 2 cases of iatrogenic cataract. Three diabetic patients suffered systemic adverse events: one patient developed renal insufficiency, one patient developed cerebrovascular accidents and one suffered a myocardial infarction resulting in death. Conclusions: Intravitreal injections are associated with a low incidence of serious adverse events. The most common ocular complication was subconjunctival hemorrhage. There was one case of serious complication--the culture-proven infectious endophthalmitis after Kenalog injection. Cataract formation and increase of intraocular pressure were more often observed following intravitreal triamcinolone injection.     

Role of ranibizumab in management of macular degeneration

Age-related macular degeneration (AMD) is one of the most common causes of severe vision loss in the western world. Both animal and human studies have established that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of this process. Ranibizumab (Lucentis(TM) Genentech, South San Francisco, CA) is a monoclonal antibody fragment (Fab) directed toward all isoforms of VEGF-A that was specifically designed to target wet AMD. The human antibody fragment is produced by an E. coli expression system and has a molecular weight of 48kD allowing for excellent retinal penetration. The most common ocular complaints of patients receiving ranibizumab injections in randomized clinical trials were transient conjunctival hemorrhage, vitreous floaters, intraocular inflammation, increased intraocular pressure and eye pain. The rates of serious adverse events such as retinal detachment, cataract and endophthalmitis were similar to those that have been reported with other intravitreal injections and patients should always be treated under strict aseptic conditions to reduce this risk. There were no significant non-ocular events found during any study so far and the risk of thromboembolic events was less than 4% and not different than sham. The MARINA, ANCHOR and PIER studies validated the safety and efficacy of ranibizumab amongst a large population with different choroidal neovascular membrane lesion types against sham or standard of care treatment. These studies recommended monthly intravitreal ranibizumab for patients. However, the PIER study reported that an alternative dosing of every three months is acceptable but less effective than monthly injections.     

Comparison of bevacizumab and ranibizumab in age-related macular degeneration:a systematic review and meta-analysis

AIM: To compare the effectiveness and safety between bevacizumab and ranibizumab in the treatment of age-related macular degeneration (AMD) through a systematic review and meta-analysis.METHODS:We performed a comprehensive search of randomized controlled trials (RCTs), non-RCTs, case-control and cohort studies that compared bevacizumab and ranibizumab using PubMed and the Cochrane Library. After the related data were extracted by two investigators independently, pooled weighted mean differences (WMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects or a fixed-effects model.RESULTS:A total of four RCTs involving 1927 patients and eleven retrospective case series involving 2296 patients were included. For the primary outcomes, no significant differences were found between ranibizumab group and bevacizumab group in visual acuity (WMD:-0.04; 95%CI:-0.08 to 0.00; P=0.06), best corrected visual acuity (WMD:-0.05; 95%CI:-0.10 to 0.00; P=0.05), retina thickness (WMD:-4.69; 95%CI:-13.15 to 3.76; P=0.86) and foveal thickness (WMD:10.91; 95%CI:-14.73 to 36.56; P=0.40). The pooled analyses in the evaluation of safety showed that compared to bevacizumab, ranibizumab was associated with decreased risks of ocular inflammation (RR:0.45; 95% CI:0.23 to 0.89; P=0.02) and venous thrombotic events (RR:0.27; 95%CI:0.08 to 0.89; P=0.03). However, there were no significant differences observed in deaths (P=0.69) and arterial thromboembolic events (P=0.71) between the two groups.CONCLUSION:With equal clinical efficacy, ranibizumab was found to be associated with less adverse events compared to bevacizumab, indicating that ranibizumab might be a safer management.     

Bevacizumab and ranibizumab for neovascular age-related macular degeneration: a treatment approach based on individual patient needs

ObjectiveTo compare the efficacy of intravitreal bevacizumab and ranibizumab for the treatment of neovascular age-related macular degeneration using an as-needed treatment regimen.DesignRetrospective chart review.ParticipantsOne hundred and ninety two eyes of 184 patients.MethodsPatients received an initial treatment of 3 monthly intravitreal injections of ranibizumab or bevacizumab and retreatment is individually considered for each patient on the basis of optical coherence tomography, angiography, and clinical examination.ResultsFifty eyes treated with ranibizumab and 142 eyes treated with bevacizumab were included. The average age of the patients at baseline was 76.9 ± 8 years and 76.4 ± 8 years in the ranibizumab and bevacizumab group respectively. Mean visual acuity improved from 0.69 to 0.55 logMAR at 12 months in the ranibizumab group and from 0.70 to 0.67 logMAR in the bevacizumab group. At 12 months, 92% of eyes treated with ranibizumab had lost fewer than 0.3 logMAR, as compared with 83% in the bevacizumab group. The ranibizumab group received a mean of 4.92 injections, compared to 4.75 injections in the bevacizumab group over 12 months. After the first 3 injections, 20% of patients in the ranibizumab group and 26% in the bevacizumab group never needed another injection.ConclusionsAn approach based on clinical onset and choroidal neovascularization progression at angiography may provide benefit by reducing the number of intravitreal injections required.     

Efficacy of intravitreal bevacizumab after unresponsive treatment with intravitreal ranibizumab

Objective: To evaluate visual outcomes of eyes with choroidal neovascular membrane secondary to age-related macular degeneration that were initially treated with intravitreal ranibizumab then switched to intravitreal bevacizumab due to treatment failure.Design: Retrospective chart review.Participants: Fifty eyes of 50 patients presenting to the Barnes Retina Institute.Methods: Patients unresponsive to treatment with intravitreal ranibizumab were switched to intravitreal bevacizumab. Main outcome measures included number of intravitreal injections, visual acuity (VA), and resolution of leakage. Mean follow-up was 6 months after the final intravitreal bevacizumab injection. On average, each patient received 3.5 ranibizumab injections and 2.5 bevacizumab injections. Each patient received an average of 6 injections.Results: Resolution of leakage on fluorescein angiography and optical coherence tomography was achieved in 44 eyes (88%). Initial VA ranged from 20/30 to counting fingers (CF) (median VA 20/125). Final VA ranged from 20/20 to CF (median VA 20/100). Change in VA varied from loss of 2 lines to gain of 4 lines, but overall, remained stable (average gain 0.3 lines). Eighteen eyes (36%) had afinal VA of ≥ 20/50 and 18 eyes (36%) had a final VA of ≤ 20/200.Conclusions: Treatment with intravitreal bevacizumab may be effective, as measured by visual and anatomic criteria, in patients who are unresponsive to treatment with intravitreal ranibizumab.     

Effects of an Intravitreal Bevacizumab Injection Combined With Panretinal Photocoagulation on High-Risk Proliferative Diabetic Retinopathy

Purpose

To investigate the short-term effects of panretinal photocoagulation (PRP) combined with an intravitreal injection of Avastin® (bevacizumab) as an adjuvant to high-risk proliferative diabetic retinopathy (PDR).

Methods

The data was collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. One eye was treated with only PRP (PRP only group) and the fellow eye of same patient was treated with both PRP and intravitreal bevacizumab injection (Adjuvant group). Best corrected visual acuity (BCVA), IOP (intraocular pressure), and new vessel (NV) size in fluorescein angiography were recorded immediately and at the six-week follow-up visit. Adverse events associated with intravitreal injection were investigated.

Results

Of 12 patients with high-risk PDR, five were male and seven were female. There were no statistically significant BCVA or IOP changes after treatment in either group (p=0.916, 0.888). The reduction of NV size was found in both groups, but NV size in the adjuvant group showed a greater decrease than that of the PRP only group (p=0.038). Three patients had adverse events after intravitreal injection. Two patients had mild anterior uveitis and one patient had a serious complication of branched retinal artery obstruction (BRAO).

Conclusions

Intravitreal bevacizumab injection with PRP resulted in marked regression of neovascularization compared with PRP alone. One serious side effect, BRAO, was noted in this study. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.     

Intraocular pressure changes after repeated intravitreal antivascular endothelial growth factor injections in patients with neovascular age-related macular degeneration with or without glaucoma

PurposeTo investigate the long-term effects of multiple intravitreal injections on intraocular pressure (IOP) in patients with exudative age-related macular degeneration, and to determine whether this is related to a pre-existing diagnosis of glaucoma.MethodsA retrospective study was carried out on 209 eyes in 173 patients with neovascular age-related macular degeneration who received at least three intravitreal injections of bevacizumab or ranibizumab, or both, from January 2006 to December 2012 at Shin Kong Wu Ho-Su Memorial Hospital. Sequential changes in IOP following the intravitreal injections were documented and the incidence and characteristics of the patients diagnosed with glaucoma were recorded and analyzed.ResultsTwo hundred and nine eyes in 173 patients were included in this study. The mean number of injections was 10.1 (range 3–23). No significant change was found in IOP (p = 0.41, paired t test) and none of the patients experienced delayed ocular hypertension during the treatment course. No correlation was found between differences in IOP and the number of injections (correlation coefficient −0.086) and no significant change in IOP was found in patients with or without glaucoma (p = 0.42 and 0.37, respectively, paired t test). In addition, the use of drugs to lower IOP did not increase with repeated intravitreal injections in patients with glaucoma [single drug, 24 (63.2%) patients; two drugs 14 (36.8%) patients].ConclusionRepeated intravitreal antivascular endothelial growth factor injections of bevacizumab or ranibizumab, or both, did not increase the risk of increasing IOP in patients with exudative age-related macular degeneration, with or without glaucoma.     

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.     

Bevacizumab versus ranibizumab for neovascular age-related macular degeneration:a Meta-analysis

AIM: To systematically compare the efficacy and safety of off-label bevacizumab versus licensed ranibizumab intravitreal injections as well as monthly regimen versus pro re nata [PRN (as needed)] regimen in the treatment of neovascular age-related macular degeneration (nAMD). METHODS: Relevant publications were identified through automatically retrieve of database and manually retrieving. The methodological quality of studies included was assessed using the Jadad score and the risk-of-bias assessment. The efficacy estimates were measured by the weight mean difference (WMD) for the improvement of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) reduction. The safety estimates were measured by odds ratios (OR) for adverse events rates. Statistical analysis was conducted by Revman 5.2.7. RESULTS: Seven studies were included in the Meta-analysis. There were no statistically significant differences between bevacizumab and ranibizumab in BCVA at 1 and 2y (P=0.37, P=0.18, respectively), However, both drugs has better BCVA given monthly than given as needed at 1 and 2y (P<0.05). The results demonstrated the mean decrease in CRT was less in bevacizumab group than ranibizumab group at 1y (P<0.05), while the difference was not significant at 2y (P=0.24). Treatment monthly gained much more decrease in CRT at 1 and 2y (P<0.005). There were no differences between drugs in the rates of death, arterial thrombotic events and venous thrombotic events (P=0.41, P=0.55, P=0.10, respectively), while the rates of medical dictionary for regulatory activities (MedDAR) system organ class events and ≥1 systemic serious adverse events were higher in bevacizumab group than ranibizumab group (P<0.05). But the incidences of death, arterial thrombotic events, venous thrombotic events, MedDAR system organ class events as well as ≥1 systemic serious adverse events were not statistically different between both treatment regimens of monthly and as needed (P=0.14, P=0.76, P=0.73, P=0.12, P=0.11, respectively). CONCLUSION: Bevacizumab was equivalent to ranibizumab for BCVA, however bevacizumab tended to gain less decrease in CRT and had higher rates of serious adverse events. Compared with treatment as needed, treatment monthly showed superior efficacy in BCVA improvement and CRT reduction, while the rates of adverse events were similar in the two dosing regimens.     

Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome,using combined intravitreal injection of bevacizumab and triamcinolone acetate

The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.     

Ranibizumab治疗湿性年龄相关性黄斑变性的安全性分析

湿性年龄相关性黄斑变性（AMD）的主要病理改变为脉络膜新生血管（CNV）的形成,血管内皮生长因子（VEGF）水平的升高是其重要的发病机制之一。Ranibizumab是一种重组人源化抗VEGF单克隆抗体片段,能够抑制新生血管形成,玻璃体腔内注射ranibizumab治疗湿性AMD的疗效已得到多项临床研究的证实。此外,玻璃体腔内注射ranibizumab的耐受性良好,眼内与全身不良反应的风险未显著增加。其主要眼内不良事件为眼部炎症和一过性眼压升高,但发生率较低。主要的严重眼内不良事件的发生率〈4％。Ranibizumab应用后心脑血管意外的发生风险无显著增加,采取在每月随访监测的基础上降低注射频率的方法可能得到最佳的风险获益比。就近年来湿性AMD患者应用ranibizumab治疗的临床试验为基础,从循证医学角度讨论其玻璃体腔内注射的安全性。     

Submacular haemorrhage after intravitreal bevacizumab compared with intravitreal ranibizumab in large occult choroidal neovascularization

Background: Submacular haemorrhage may occur following intravitreal bevacizumab injection for large occult choroidal neovascularization (CNV) in age‐related macular degeneration (AMD). We report the occurrence of submacular haemorrhage following intravitreal ranibizumab compared with intravitreal bevacizumab for large occult CNV in AMD. Methods: Retrospective, comparative evaluation of two interventional case series. Evaluation of consecutive patients with occult CNV ≥ 15 mm² treated with intravitreal bevacizumab (n = 14) and intravitreal ranibizumab (n = 22) over a 2‐year period within a single institution. Postoperative submacular haemorrhage, Early Treatment Diabetic Retinopathy Study‐derived visual acuity, preoperative blood pressure and anticoagulant use were noted. The two groups were compared using Fisher's exact test. Results: The mean surface area of occult CNV at presentation was 20.9 ± 5.4 mm² in the bevacizumab group and 24.0 ± 11.0 mm² in the ranibizumab group. Fresh submacular haemorrhage was seen in 4 out of 14 patients following bevacizumab compared with 0 out of 22 patients following ranibizumab (P = 0.017, odds ratio = 19.29). Mean preoperative blood pressures were very similar between the groups. 28.6% of patients in the bevacizumab group were on oral anticoagulants compared with 31.8% in the ranibizumab group. None of the patients who developed postoperative haemorrhage were on anticoagulants. Conclusions: Acute submacular haemorrhages appear to be a significant adverse event following intravitreal bevacizumab in occult CNV ≥ 15 mm². Intravitreal ranibizumab appears to have a significantly lower incidence of postoperative submacular haemorrhage in occult CNV ≥ 15 mm². Larger studies are required to identify the most appropriate agent for the treatment of large occult CNV.     

Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): year 2 results

PURPOSE: To assess the efficacy and adverse-events profile of combined treatment with ranibizumab and verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration. DESIGN: Two-year, multicenter, randomized, single-masked, controlled study. METHODS: Patients received monthly intravitreal injections of ranibizumab 0.5 mg (n = 106) or sham injections (n = 56). All patients received PDT on day zero, then quarterly as needed. Efficacy assessment included changes in visual acuity (VA) and lesion characteristics and PDT frequency. Adverse events were summarized by incidence and severity. RESULTS: At month 24, 88% of ranibizumab + PDT patients had lost <15 letters from baseline VA (vs 75% for PDT alone), 25% had gained >or=15 letters (vs 7% for PDT alone), and the two treatment arms differed by 12.4 letters in mean VA change (P < .05 for all between-group differences). The VA benefit of adding ranibizumab to PDT in year one persisted through year two. On average, ranibizumab + PDT patients exhibited less lesion growth and greater reduction of CNV leakage and subretinal fluid accumulation, and required fewer PDT retreatments, than PDT-alone patients (mean = 0.4 vs 3.0 PDT retreatments). Endophthalmitis and serious intraocular inflammation occurred, respectively, in 2.9% and 12.4% of ranibizumab + PDT patients and 0% of PDT-alone patients. Incidences of serious nonocular adverse events were similar in the two treatment groups. CONCLUSIONS: Through two years, ranibizumab + PDT was more effective than PDT alone and had a low rate of associated adverse events.     

The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide

AIM: Off-label intravitreal injections of bevacizumab (Avastin) have been given for the treatment of neovascular and exudative ocular diseases since May 2005. Since then, the use of intravitreal bevacizumab has spread worldwide, but the drug-related adverse events associated with its use have been reported only in a few retrospective reviews. The International Intravitreal Bevacizumab Safety Survey was initiated to gather timely information regarding adverse events from doctors around the world via the internet. METHODS: An internet-based survey was designed to identify adverse events associated with intravitreal bevacizumab treatment. The survey web address was disseminated to the international vitreoretinal community via email. Rates of adverse events were calculated from participant responses. RESULTS: 70 centres from 12 countries reported on 7113 injections given to 5228 patients. Doctor-reported adverse events included corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation or uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal haemorrhage, retinal pigment epithelium tears, blood pressure elevation, transient ischaemic attack, cerebrovascular accident and death. None of the adverse event rates exceeded 0.21%. CONCLUSION: Intravitreal bevacizumab is being used globally for ocular diseases. Self-reporting of adverse events after intravitreal bevacizumab injections did not show an increased rate of potential drug-related ocular or systemic events. These short-term results suggest that intravitreal bevacizumab seems to be safe.     

Sustained ocular hypertension following intravitreal injections of 0.5 mg/0.05 ml ranibizumab

To report three cases with sustained ocular hypertension following intravitreal injections of 0.5 mg/0.05 ml ranibizumab and to underline the importance of monitoring intraocular pressure (IOP) following intravitreal injections of ranibizumab (Lucentis). Three patients were found to have high IOP after intravitreal injections of 0.5 mg/0.05 ml ranibizumab. IOP was elevated after the second ranibizumab injection in patients 1 and 2, and after the third injection in patient 3. The increase in IOP was sustained, requiring treatment with anti-glaucoma eye drops in all patients, the addition of systemic carbonic anhydrase inhibitor in one patient, and the application of selective laser trabeculoplasty (SLT) in another patient. None of the patients had a previous history of glaucoma or ocular hypertension. Sustained ocular hypertension may occur after intravitreal injections of 0.5 mg/0.05 ml ranibizumab. Although the precise mechanism of the pressure rise is unknown, three eyes in our series were controlled with topical or oral medication and one with SLT. The necessity of IOP monitoring is strongly emphasized after intravitreal injections of 0.5 mg/0.05 ml ranibizumab.     

Comparison of outcomes after switching treatment from intravitreal bevacizumab to ranibizumab in neovascular age-related macular degeneration

ObjectiveTo compare visual acuity and central retinal thickness in patients initially treated with bevacizumab (Avastin) and switched to ranibizumab (Lucentis) for neovascular age-related macular degeneration (AMD).DesignA retrospective chart review.ParticipantsThis study included 87 eyes from 80 patients over the age of 65 with neovascular AMD.MethodsPatients were initially treated with bevacizumab injections every 6 weeks and then switched to ranibizumab every 4 weeks when it became publicly funded by the Ontario government. Outcomes include comparison of visual acuity and central retinal thickness after bevacizumab treatment, and after switching to ranibizumab.ResultsVisual acuity improved significantly versus initial baseline values following a treatment course of 3 or more injections of bevacizumab (0.58 logMar, SD = 0.30 vs 0.73 logMar, SD = 0.41; p = 0.0007). Patients then showed a further significant improvement in visual acuity after switching and receiving a course of ranibizumab (0.51 logMar, SD = 0.32) (p = 0.0122). Mean central retinal thickness as measured by optical coherence tomography significantly decreased after a course of bevacizumab (p = 0.0158), and a further decrease was noted after a subsequent course of ranibizumab (p < 0.0001).ConclusionsThere was a significant improvement in visual acuity and central retinal thickness in patients with neovascular AMD initially treated with bevacizumab. When these patients were uniformly switched to ranibizumab there was a further significant improvement in visual acuity and a reduction of retinal thickness. It appears that ranibizumab can maintain, or improve the effect achieved after an initial course of bevacizumab.