Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results.

PURPOSE: To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial. PARTICIPANTS: Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy. METHODS: Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years). MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 44 and 48, weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters). RESULTS: The PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 44/48, 60/64 and 88/92 of -0.2 (95% confidence interval [CI], -1.8 to +1.3), +0.4 (95% CI, -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3), respectively. Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. The PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events of special interest (AESI) were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AESI reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab. CONCLUSIONS: The PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. The AESIs were generally manageable, with learnings continually implemented to minimize PDS-related AEs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate macular atrophy (MA) presence in the 24-month HARBOR study (NCT00891735) for neovascular age-related macular degeneration (AMD). DESIGN: Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. PARTICIPANTS: Evaluable subjects (N = 1095) with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD treated with ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN). METHODS: Fluorescein angiograms (FAs) and color fundus photographs at baseline and months 3, 12, and 24 were retrospectively graded by masked graders for MA: well-defined areas of depigmentation with increased choroidal vessel visibility, diameter ≥250 µm, corresponding to flat areas of well-demarcated staining on FA, excluding atrophy associated with retinal pigment epithelium tears. Atrophy immediately within, adjacent, and nonadjacent to CNV lesions was included. MAIN OUTCOME MEASURES: Macular atrophy incidence, best-corrected visual acuity (BCVA). RESULTS: At baseline, MA was detected in 11.2% (123/1095) of study eyes. At month 24, 29.4% (229/778) of eyes without baseline atrophy had detectable MA. Eyes with and without baseline MA had significant mean BCVA gains from baseline at month 24 (letters [95% confidence interval]: +6.7 [4.1-9.3]; +9.1 [8.0-10.2], respectively). Among eyes with and without MA at month 24, mean month 24 BCVA was 62.0 [60.3-63.7] and 64.7 [63.2-66.3] letters, respectively. Baseline risk factors for month 24 MA presence included intraretinal cysts (hazard ratio [HR], 2.45 [1.76-3.42]) and fellow eye atrophy (HR, 2.02 [1.42-2.87]); subretinal fluid was associated with a lower MA risk (HR, 0.50 [0.33-0.74]). Ranibizumab dose was not associated with MA development. Monthly versus PRN treatment trended toward an association with MA (HR, 1.29 [0.99-1.68]), but was not statistically significant. CONCLUSIONS: New MA was detected in 29% of study eyes after 24 months of treatment. Clinically significant BCVA gains were achieved with MA present over 24 months. Baseline subretinal fluid absence, intraretinal cyst presence, and fellow eye atrophy presence were associated with month 24 MA presence. With existing data, the benefits of ranibizumab for neovascular AMD outweighed the risk of MA development over 24 months in HARBOR, although outcomes >2 years were not evaluated.

Reducing oral flora contamination of intravitreal injections with face mask or silence.

PURPOSE: To provide experimental evidence to support or refute the proposition that the use of surgical face masks and/or avoidance of talking can decrease the dispersion of respiratory flora during an intravitreal injection. METHODS: Ten surgeons recited a 30-second standardized script with blood agar plates positioned 30 cm below their mouths. The plates were divided into 4 groups, with 10 plates per group. In Group 1, participants did not wear a face mask. In Group 2, participants wore a standard surgical mask. In Group 3, no mask was worn, but plates were pretreated with 5% povidone-iodine. In Group 4, no mask was worn, and participants remained silent for 30 seconds. The plates were then incubated at 37°C for 24 hours, and the number of colony-forming units (CFUs) was determined. RESULTS: Mean bacterial growth were as follows: Group 1, 8.6 CFUs per subject; Group 2, 1.1 CFUs per subject; Group 3, 0.1 CFUs per subject; and Group 4, 2.4 CFUs per subject. Differences between the groups were statistically significant (P < 0.05), with the exception of Group 2 versus Group 4 (P = 0.115). CONCLUSION: The use of a face mask and avoidance of talking each significantly decreased the dispersion of bacteria. Even without these interventions, plates pretreated with povidone-iodine demonstrated the least bacterial growth.

Hospitalized cardiovascular events in patients with diabetic macular edema.

BACKGROUND: Microvascular and macrovascular complications in diabetes stem from chronic hyperglycemia and are thought to have overlapping pathophysiology. The aim of this study was to investigate the incidence rate of hospitalized myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with diabetic macular edema (DME) compared with diabetic patients without retinal diseases. METHODS: This was a retrospective cohort study of a commercially insured population in an administrative claims database. DME subjects (n = 3519) and diabetes controls without retinal disease (n = 10557) were matched by age and gender. Healthcare claims were analyzed for the study period from 1 January 2002 to 31 December 2005. Incidence and adjusted rate ratios of hospitalized MI and CVA events were then calculated. RESULTS: The adjusted rate ratio for MI was 2.50 (95% CI: 1.83-3.41, p < 0.001) for DME versus diabetes controls. Predictors of MI events were heart disease, history of acute MI, and prior use of antiplatelet or anticoagulant drugs. The adjusted rate ratio for CVA was 1.98 (95% CI: 1.39-2.83, p < 0.001) for DME versus diabetes controls. Predictors of CVA events were cardiac arrhythmia, Charlson comorbidity scores, history of CVA, hyperlipidemia, and other cerebrovascular diseases. CONCLUSION: Event rates of MI or CVA were higher in patients with DME than in diabetes controls. This study is one of few with sufficient sample size to accurately estimate the relationship between DME and cardiovascular outcomes.

Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: The port delivery system (PDS) with ranibizumab has demonstrated noninferior and equivalent efficacy compared with monthly intravitreal injections of ranibizumab, an anti-vascular endothelial growth factor (VEGF) agent, in patients with neovascular age-related macular degeneration (nAMD), but evaluating patient preference is important to help inform clinical decision-making. Objective: Evaluate treatment satisfaction for ranibizumab delivered via PDS vs intravitreal injections as well as patient preference among those assigned to PDS. Design, Setting, and Participants: Archway was a phase 3 randomized active-comparator open-label clinical trial conducted at 78 sites in the US. Patients 50 years and older with nAMD diagnosed within 9 months of screening with a documented response to anti-VEGF therapy were included. Of 619 patients screened, 418 were enrolled; 415 were included in the primary analysis and 234 were included in the secondary exploratory analysis. The Archway study ran from September 12, 2019, through primary readout on May 22, 2020. Interventions: Patients were randomized 3:2 to PDS with ranibizumab, 100 mg/mL, with fixed refill exchanges every 24 weeks or intravitreal ranibizumab injections, 0.5 mg, every 4 weeks. Main Outcomes and Measures: Treatment satisfaction was measured using the Macular Disease Treatment Satisfaction Questionnaire in the PDS and intravitreal injection arms at week 40. Patient preference was assessed using the content-validated PDS Patient Preference Questionnaire (PPPQ), which measured the proportion of patients in the PDS arm with monthly monitoring who preferred treatment with the PDS at week 40 over previous intravitreal injections or concurrent fellow-eye injections. Both outcomes were exploratory end points. Results: The mean (SD) age of participants at baseline was 75.0 (7.9) years; 234 participants (59%) were women and 162 (41%) were men. At week 40, differences in overall treatment satisfaction scores were minimal for the PDS and intravitreal injection arms (mean, 68.0; 95% CI, 67.4-68.6; n = 237 and mean, 66.1; 95% CI, 64.9-67.3; n = 159, respectively; difference, 1.9; 95% CI, 0.7-3.1). A total of 234 of 248 patients (94.4%) in the PDS arm were included in the PPPQ analysis. At week 40, almost all patients in the PDS arm preferred treatment via PDS (218 of 234 [93.2%]) vs previous intravitreal injections (3 of 234 [1.3%]), including 172 of 234 (73.5%) with a very strong preference for the PDS. In patients who received concurrent fellow-eye injections (n = 78), 72 (92.3%) preferred the PDS. Conclusions and Relevance: Although PDS treatment was preferred by almost all patients assigned to PDS over previous intravitreal injections, both delivery methods have high treatment satisfaction. These findings provide further evidence for the PDS as a meaningful alternative treatment option for patients with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT03677934.

Sustained-release intravitreal liquid drug delivery using triamcinolone acetonide for cystoid macular edema in retinal vein occlusion.

PURPOSE: To investigate side effects seen with this formulation and to search for evidence of effectiveness after a single intravitreal injection of IBI-20089 in eyes with cystoid macular edema (CME) secondary to retinal vein occlusion. DESIGN: Prospective, phase 1 clinical trial. PARTICIPANTS: Ten patients with chronic CME resulting from retinal vein occlusion. METHODS: Patients received a single intravitreal injection of IBI-20089 using a sequential dose escalation schedule. Each cohort consisted of 5 patients who received the intravitreal injection of the sustained liquid drug delivery system containing either 6.9 mg (25 µl) triamcinolone acetonide (TA; cohort 1) or 13.8 mg (50 µl) TA (cohort 2). At each study visit, best-corrected visual acuity testing, slit-lamp biomicroscopy, IOP measurement, dilated ophthalmoscopy, fundus photography and optical coherence tomography (OCT) were performed. Patients also underwent laboratory testing and physical examinations to monitor for any systemic adverse events. MAIN OUTCOME MEASURES: Optical coherence tomography central subfield thickness, ocular and systemic adverse events. RESULTS: In cohort 1, mean baseline OCT central subfield thickness (CST) was 477 µm and decreased to 369 µm at day 1 (P<0.06), 387 µm at day 30 (P = 0.18), and 251 µm at day 360 (P = 0.46). In cohort 2, mean baseline OCT CST was 518 µm and decreased to 404 µm at day 1 (P = 0.134), 289 µm at day 30 (P = 0.003), 207 µm at day180 (P = 0.004), and 278 µm at day 360 (P = 0.009). Related adverse events included elevation of IOP in 3 patients, in 2 because of neovascular glaucoma (not related to study drug) and in 1 who required a glaucoma tube shunt. CONCLUSIONS: A single intravitreal injection of IBI-20089 resulted in a controlled and sustained delivery of a TA. Side effects included elevated IOP in 3 eyes, 2 of which had neovascular glaucoma.

Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration?

PURPOSE: To determine whether presence of macular hemorrhage on dilated fundus examination (DFE) or fundus photography influences vision outcomes with OCT-guided pro re nata (PRN) ranibizumab retreatment in patients with neovascular age-related macular degeneration (nAMD), we investigated whether hemorrhage without OCT-detectable fluid impacted vision outcomes. DESIGN: Post hoc analysis of prospectively collected data from the 24-month pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvascular age-related macular degeneration (HARBOR) trial (ClinicalTrials.gov identifier, NCT00891735). PARTICIPANTS: This post hoc analysis examined 1097 patients from the intention-to-treat population of HARBOR. METHODS: Dilated fundus examination and fundus photography were evaluated for hemorrhage, and spectral-domain (SD) OCT images from HARBOR participants were analyzed for macular fluid secondary to macular neovascularization. Agreement between methods was determined for each time point. Visual outcomes were evaluated for 82 patients with evidence of hemorrhage on DFE or fundus photography at 3 months and no evidence of SD-exudative activity requiring retreatment at month 3. MAIN OUTCOME MEASURES: Pooled data from the intention-to-treat population of HARBOR were analyzed for hemorrhage on DFE or fundus photography and exudative activity on SD OCT. A subgroup of PRN patients were analyzed for best-corrected visual acuity gains at 24 months. RESULTS: Most study eyes (89% [973/1095]) showed macular hemorrhages at baseline, declining to 31% (319/1042) at month 3 and stabilizing at 11% (111/989) by month 6 of follow-up. After baseline, exudative activity was detected on SD-OCT in more than 89% of eyes when hemorrhage was present on DFE or fundus photography. Patients not requiring a month 3 PRN ranibizumab injection achieved similar visual gains over 24 months, regardless of month 3 hemorrhage presence versus absence: 9.4 and 8.7 Early Treatment Diabetic Retinopathy Study letter scores, respectively (P = 0.74). CONCLUSIONS: After 3 initial ranibizumab injections, SD-OCT detected nAMD activity in 89% of eyes when hemorrhage was present on fundus photography. Ranibizumab retreatment guided by monthly SD-OCT achieved similar vision gains with or without injection when hemorrhage was present without OCT-detectable fluid. This suggests that macular hemorrhages without OCT-detectable macular fluid may not require treatment and DFE may not be needed at every visit. These conclusions should be confirmed in a prospective randomized trial before firm recommendations regarding clinical practice can be made.

Applying the CONSORT and STROBE statements to evaluate the reporting quality of neovascular age-related macular degeneration studies.

PURPOSE: To evaluate the quality of reporting in the neovascular age-related macular degeneration (nvAMD) literature by applying the Consolidated Standards for Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement writing standards. DESIGN: CONSORT and STROBE impact analysis; literature review. PARTICIPANTS: Phase III randomized controlled trials (RCTs) of verteporfin photodynamic therapy, pegaptanib, and ranibizumab, and interventional case studies of bevacizumab for nvAMD. METHODS: A literature search identified eligible articles published before October 31, 2007. We assessed the report quality of Phase III RCTs using the CONSORT statement and case series publications using the STROBE statement, both with indicators relevant to nvAMD. MAIN OUTCOME MEASURES: Presence or absence of CONSORT or STROBE statement indicators. RESULTS: Seven publications of Phase III RCTs and 29 publications on bevacizumab interventional case studies for nvAMD met our inclusion criteria. Of 37 possible CONSORT writing guideline items, the mean report quality for RCTs was 30.6 (83%), with a range from 23 to 35 (65%-95%). Of 35 possible STROBE writing guideline items, the mean report quality grade for intravitreal bevacizumab case series was 23 (70%), with a range from 16 to 31 (46%-94%). Among the bevacizumab studies, more than 90% reported scientific background, drug dose and administration, baseline characteristics, unadjusted results, and adverse events. Fewer than 20% reported study size calculations, handling of missing data, or a discussion of bias. CONCLUSIONS: Since the adoption of the CONSORT standards by Ophthalmology and other journals in 1996, the reporting quality for RCTs has further improved among this cohort of nvAMD articles. On the other hand, no reporting standards for case series have existed until the recent publication of the STROBE statement. In this first application of the STROBE standards to ophthalmology, we found that the small interventional studies in our series had an average reporting score lower than the RCTs, but also that some individual scores were higher than the RCTs. This outcome demonstrates that good, useful articles can be written about small studies. Although not a direct measure of the quality of a study, good reporting allows a reader to assess the validity and applicability of the study's findings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Advances in the treatment of diabetic retinopathy.

As the diabetes epidemic in the United States continues to worsen, so too does the prevalence of diabetic retinopathy (DR). DR is divided broadly into nonproliferative and proliferative stages, with or without vision-threatening macular edema. Progression to proliferative DR is associated with vision loss that is often irreparable, and a rapid decline in health-related quality of life. Vascular endothelial growth factor (VEGF)-A is upregulated in the diabetic eye, and has been identified as a key driver of DR pathogenesis. With this perspective, we review the published phase III clinical trial data of anti-VEGF therapies approved for the treatment of DR in the United States. Using the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale, in which an improvement of ≥2 steps is considered clinically significant, approximately one-third of patients with DR and macular edema experience this level of improvement after 1 year of treatment with either ranibizumab or aflibercept. The rates of clinically significant DR improvement with ranibizumab could be twice that in the subgroup of patients with moderately severe or severe nonproliferative DR and macular edema. These clinical trial data indicate that intraocular inhibition of VEGF is a rational approach for the management of DR.

The Systemic Safety of Ranibizumab in Patients 85 Years and Older with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: Ranibizumab safety is well established for treatment of neovascular age-related macular degeneration (nAMD), but less is known about the risk of systemic serious adverse events (SAEs), specifically among patients with heightened baseline risk due to age (≥85 years). This analysis examines whether patients ≥85 years of age versus those <85 years experience an increased risk of key systemic SAEs during intravitreal ranibizumab treatment for nAMD. DESIGN: Retrospective, pooled analysis of safety data from 5 phase III/IIIb multicenter randomized clinical trials in patients with nAMD: ANCHOR, MARINA, PIER, SAILOR, and HARBOR. PARTICIPANTS: Patients with nAMD receiving ranibizumab (n = 4347) or control (sham/verteporfin photodynamic therapy, n = 441) treatment included in the safety-evaluable set of the 5 trials. METHODS: The incidence of nonocular SAEs was analyzed stratified by age (<85 years [n = 3795] vs ≥85 years [n = 993]), treatment (control, ranibizumab 0.3 mg, ranibizumab 0.5 mg, ranibizumab 2.0 mg), and injection frequency (monthly, as needed [PRN]). MAIN OUTCOME MEASURES: Incidence of key systemic SAEs, defined as total nonocular SAEs, deaths, cardiovascular events, cerebrovascular (CBV) events, and Antiplatelet Trialists' Collaboration events. RESULTS: The MARINA and ANCHOR trials had greater rates of key SAEs for patients ≥85 years versus those <85 years. Ranibizumab exposure did not increase the risk of most SAEs in elderly patients; for CBV events and death, the effect of ranibizumab versus control treatment for age ≥85 years was not interpretable due to small number of events (CBV: n = 2, 2, 5 for control, ranibizumab 0.3 mg, and ranibizumab 0.5 mg, respectively; death: n = 2, 4, 5, respectively). Across all 5 trials, an increased risk was found for age ≥85 years versus <85 years for the marketed dose of ranibizumab 0.5 mg. In the HARBOR trial, increased rates of key SAEs (excluding total nonocular SAEs) for age ≥85 years versus <85 years were observed with monthly dosing but not with PRN dosing; event rates were similar for 2.0 mg versus 0.5 mg. CONCLUSIONS: Consistent with general trends, the risk of key systemic SAEs was associated with age ≥85 years versus <85 years, but not with ranibizumab drug exposure. The difference between monthly versus PRN was inconclusive. There was no evidence of a dose effect. Interpretation of this retrospective analysis is limited because it was not prospectively powered for statistically definitive conclusions.

Ranibizumab Induces Regression of Diabetic Retinopathy in Most Patients at High Risk of Progression to Proliferative Diabetic Retinopathy.

PURPOSE: To evaluate diabetic retinopathy (DR) outcomes with ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA) treatment in patients with DR and diabetic macular edema (DME) at high risk of progression to proliferative disease. DESIGN: Post hoc analysis of the phase 3 RIDE (ClinicalTrials.gov identifier, NCT00473382) and RISE (ClinicalTrials.gov identifier, NCT00473330) clinical trials of ranibizumab for the treatment of DME. PARTICIPANTS: Seven hundred forty-six patients with baseline fundus photographs and randomized for treatment. METHODS: Diabetic retinopathy outcomes were assessed through month 36 by baseline DR severity level. Diabetic retinopathy severity was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). MAIN OUTCOME MEASURES: Two-step or more or 3-step or more improvement or worsening on the ETDRS DRSS and time to new proliferative event (composite end point). RESULTS: At baseline, most patients were distributed evenly among mild or moderate nonproliferative DR (NPDR; ETDRS DRSS, 35/43), moderately severe or severe NPDR (ETDRS DRSS, 47/53), and proliferative DR (ETDRS DRSS, 60-75; 28.8%, 33.2%, and 31.1%, respectively). At month 24, rates of 2-step or more improvement with ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham treatment were highest among patients with baseline DR levels 47/53 (78.4%, 81.1%, and 11.6%, respectively) compared with patients with baseline DR levels 35/43 (10.3%, 15.8%, and 1.4%, respectively) or 60 through 75 without panretinal photocoagulation (31.0%, 36.4%, and 6.7%, respectively; all ranibizumab vs. sham comparisons, P < 0.05). In patients with baseline DR levels 47/53, ranibizumab treatment reduced the probability of patients experiencing a new proliferative event at month 36 by 3 times compared with sham treatment (12.4% and 11.9% vs. 35.2% for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham, respectively). In patients with baseline DR levels 47/53 who achieved 2-step or more DR improvement, improvements were independent of all assessed baseline characteristics (P > 0.4). CONCLUSIONS: Ranibizumab treatment resulted in DR improvements in all 3 baseline DR severity subsets examined. The greatest benefits in DR improvement occurred in patients with baseline moderately severe to severe NPDR (DR levels 47/53). Diabetic retinopathy improvements were rapid, clinically meaningful, and sustained through month 36.

An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration.

PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study. METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab. RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary. CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.

A systematic evaluation of payback of publicly funded health and health services research in Hong Kong.

BACKGROUND: The Health and Health Services Research Fund (HHSRF) is dedicated to support research related to all aspects of health and health services in Hong Kong. We evaluated the fund's outcomes and explored factors associated with the translation of research findings to changes in health policy and provider behaviour. METHODS: A locally suitable questionnaire was developed based on the "payback" evaluation framework and was sent to principal investigators of the completed research projects supported by the fund since 1993. Research "payback" in six outcome areas was surveyed, namely knowledge production, use of research in the research system, use of research project findings in health system policy/decision making, application of the research findings through changed behaviour, factors influencing the utilization of research, and health/health service/economic benefits. RESULTS: Principal investigators of 178 of 205 (87%) completed research projects returned the questionnaire. Investigators reported research publications in 86.5% (mean = 5.4 publications per project), career advancement 34.3%, acquisition of higher qualifications 38.2%, use of results in policy making 35.4%, changed behaviour in light of findings 49.4%, evidence of health service benefit 42.1% and generated subsequent research in 44.9% of the projects. Payback outcomes were positively associated with the amount of funding awarded. Multivariate analysis found participation of investigators in policy committees and liaison with potential users were significantly associated with reported health service benefit (odds ratio [OR]participation = 2.86, 95% confidence interval [CI] 1.28-6.40; ORliaison = 2.03, 95% CI 1.05-3.91), policy and decision-making (ORparticipation = 10.53, 95% CI 4.13-26.81; ORliaison = 2.52, 95% CI 1.20-5.28), and change in behavior (ORparticipation = 3.67, 95% CI 1.53-8.81). CONCLUSION: The HHSRF has produced substantial outcomes and compared favourably with similar health research funds in other developed economies. Further studies are needed to better understand the factors and pathways associated with the translation of research findings into practice.

Hypopyon and pseudoendophthalmitis associated with chronic vitreous hemorrhage.

Infectious endophthalmitis is an uncommon but potentially devastating eye disease. Although the presence of a hypopyon is considered one of the hallmark clinical signs of infectious endophthalmitis, hypopyon associated with non-infectious causes may occur. Two patients with hypopyon and pseudoendophthalmitis secondary to chronic vitreous hemorrhage are described. In both cases, the hypopyon improved without the use of intravitreal antibiotics.

Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion.

To determine whether bevacizumab could improve visual acuity and optical coherence tomography outcomes in a patient with macular edema from central retinal vein occlusion, an intravitreal injection of bevacizumab (1.0 mg) was given. Prior intravitreal injections of triamcinolone acetonide resulted in vision improvement but worsening cataract and borderline glaucoma. Within 1 week of the bevacizumab injection, visual acuity improved from 20/200 to 20/50 and optical coherence tomography revealed resolution of the cystic maculopathy. The improvements were maintained for at least 4 weeks. Intravitreal injections of bevacizumab may provide another treatment option for patients with macular edema from vein occlusions.

Microwave-superheated Vics Vapo Rub: an ocular public health danger.

PURPOSE: To report a case of a microwave-oven superheated petroleum-based liquid causing severe chemical and thermal ocular burns treated successfully with amniotic membrane transplantation. DESIGN: Observational case report. METHODS: Retrospective review of clinical case. RESULTS: A 77-year-old woman sustained a severe combined chemical and thermal burn from microwave-heated Vicks Vapo-Rub requiring amniotic membrane transplant, with subsequent development of phacomorphic glaucoma, requiring cataract extraction, and bullous keratopathy, requiring penetrating keratoplasty. CONCLUSIONS: As microwave oven use becomes more commonplace, the risk of superheating liquids becomes an increasingly significant ocular danger. Continued efforts to educate the public about safe microwave use is necessary. Additionally, amniotic membrane transplantation was found to be effective in managing a combined chemical and thermal ocular burn.