METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed.
RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 μm. The greatest mean CRT change was observed in the self-paid group, with -92.6 μm.
CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.
METHODS: Assessment of neovascular age-related macular degeneration patients with or without PCV after 12 months of ranibizumab treatment during the LUMINOUS study. Outcome measures were visual acuity and central retinal thickness changes from baseline and the rate of ocular adverse events.
RESULTS: At baseline, 572 and 5,644 patients were diagnosed with and without PCV, respectively. The mean visual acuity gain from baseline at Month 12 in the PCV and non-PCV groups was +5.0 and +3.0 letters, respectively; these gains were achieved with a mean of 4.4 and 5.1 ranibizumab injections. Eighty percent of PCV patients and 72.2% of non-PCV patients who had baseline visual acuity ≥73 letters maintained this level of vision at Month 12; 20.6% and 17.9% of patients with baseline visual acuity <73 letters achieved visual acuity ≥73 letters in these groups. Greater reductions in central retinal thickness from baseline were also observed for the PCV group versus the non-PCV group. The rate of serious ocular adverse events was 0.7% (PCV group) and 0.9% (non-PCV group).
CONCLUSION: LUMINOUS confirms the effectiveness and safety of ranibizumab in treatment-naive patients with PCV.
METHODS: This 5-year, prospective, multicenter, observational, study enrolled 30,138 patients across all approved ranibizumab indications from outpatient ophthalmology clinics. 297 consenting patients (≥18 years) with mCNV who were treatment-naïve or prior-treated with ranibizumab or other ocular treatments were enrolled, and treated with ranibizumab according to the local product label. The main outcomes are visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters or equivalent), adverse events during the study, and treatment exposure over 1 year. Results are presented by prior treatment status of the study eye and injection frequency.
RESULTS: Of the 297 mCNV patients recruited in the study, 108 were treatment-naïve and 175 were prior ranibizumab-treated. At baseline, the mean age of patients was 57.6 years, and 59.0 years and 80.6% and 65.7% were female in the treatment-naïve and prior ranibizumab-treated groups, respectively. Most were Caucasian (treatment-naïve, 88.9%; prior ranibizumab-treated, 86.9%). The mean (±standard deviation [SD]) VA letter changes to 1 year were +9.7 (±17.99) from 49.5 (±20.51) and +1.5 (±13.15) from 58.5 (±19.79) and these were achieved with a mean (SD) of 3.0 (±1.58) and 2.6 (±2.33) injections in the treatment-naïve and prior ranibizumab-treated groups, respectively. Presented by injection frequencies 1-2, 3-4 and ≥5 injections in Year 1, the mean (SD) VA changes were +15.0 (±14.70), +7.7 (±19.91) and -0.7 (±16.05) in treatment-naïve patients and +1.5 (±14.57), +3.1 (±11.53) and -3.6 (±11.97) in prior ranibizumab-treated patients, respectively. The safety profile was comparable with previous ranibizumab studies.
CONCLUSIONS: Ranibizumab treatment for mCNV showed robust VA gains in treatment-naïve patients and VA maintenance in prior ranibizumab-treated patients in a clinical practice setting, consisting mainly of Caucasians. No new safety signals were observed during the study.
DESIGN: Prospective cross-sectional study.
METHODS: Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV.
RESULTS: CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean area under the receiver operating characteristic curve (AUC) was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P < 0.001, P < 0.001 and P = 0.005, respectively).
CONCLUSIONS: There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.
Objective: To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.
Design, Setting, and Participants: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.
Interventions: Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.
Main Outcomes and Measures: Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.
Results: Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P
METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region.
RESULTS: Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable.
CONCLUSIONS: T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients.
METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators.
RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01).
CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.
METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II.
RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042).
CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.