A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (LUCERNE)
- Conditions
- Wet Macular Degeneration
- Interventions
- Registration Number
- NCT03823300
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with neovascular age-related macular degeneration (nAMD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 658
- Treatment-naïve choroidal neovascularization (CNV) secondary to age-related macular degeneration (nAMD) in the study eye
- Ability to comply with the study protocol, in the investigator's judgment
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive measures that result in failure rate <1% per year during the treatment period and for at least 3 months after the final dose of study treatment
- Other protocol-specified inclusion criteria may apply
- Uncontrolled blood pressure, defined as systolic blood pressure >180 millimeters of mercury (mmHg) and/or diastolic blood pressure >100 mmHg while a patient is at rest on Day 1
- Pregnancy or breastfeeding, or intention to become pregnant during the study
- CNV due to causes other than AMD in the study eye
- Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye
- Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study
- Uncontrolled glaucoma in the study eye
- Any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities in the study eye
- Prior IVT administration of faricimab in either eye
- History of idiopathic or autoimmune-associated uveitis in either eye
- Active ocular inflammation or suspected or active ocular or periocular infection in either eye
- Other protocol-specified exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Faricimab Faricimab - Arm A: Faricimab Sham Procedure - Arm B: Aflibercept Aflibercept - Arm B: Aflibercept Sham Procedure -
- Primary Outcome Measures
Name Time Method Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48 From Baseline through Week 48 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (\<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% CI is a rounding of 95.03% CI.
- Secondary Outcome Measures
Name Time Method Change From Baseline in BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (\<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% CI is a rounding of 95.03% CI.
Percentage of Participants Gaining ≥0 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60 Baseline, average of Weeks 52, 56, and 60 BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48 Baseline, average of Weeks 40, 44, and 48 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60 From Baseline through Week 60 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (\<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% CI is a rounding of 95.03% CI.
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48 Baseline, average of Weeks 40, 44, and 48 BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Gaining ≥5 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted percentage of participants avoiding a loss of letters in BCVA from baseline was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48 Baseline, average of Weeks 40, 44, and 48 BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112 Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of intraretinal and subretinal fluid were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 112 Baseline and Week 112 The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Gaining ≥10 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60 Baseline, average of Weeks 52, 56, and 60 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48 Baseline, average of Weeks 40, 44, and 48 BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Number of Study Drug Injections Received in the Study Eye Through Week 48 From Baseline through Week 48 Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 40, 44, and 48 From Baseline through Week 48 Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group iteraction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (\<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With Absence of Intraretinal Cysts in the Study Eye Over Time Up to 112 weeks Percentage of Participants Avoiding a Loss of ≥10 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted percentage of participants avoiding a loss of letters in BCVA from baseline was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals Among Those Completing Week 60 Week 60 Percentages are based on the number of participants randomized to the faricimab arm who have not discontinued the study at Week 60. The treatment interval at a given visit is defined as the treatment interval decision followed at that visit. The 95% confidence interval (CI) is a rounding of 95.03% CI.
Number of Study Drug Injections Received in the Study Eye Through Week 60 From Baseline through Week 60 Number of Study Drug Injections Received in the Study Eye Through Week 108 From Baseline through Week 108 Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 52, 56, and 60 From Baseline through Week 60 Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (\<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112 Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of subretinal fluid were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Avoiding a Loss of ≥5 Letters From the Baseline BCVA in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted percentage of participants avoiding a loss of letters in BCVA from baseline was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48 Baseline, average of Weeks 40, 44, and 48 BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\<69 letters vs. ≥69 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\<69 letters vs. ≥69 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals Among Those Completing Week 48 Week 48 Percentages are based on the number of participants randomized to the faricimab arm who have not discontinued the study at Week 48. The treatment interval at a given visit is defined as the treatment interval decision followed at that visit. The 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals Among Those Completing Week 112 Weeks 108 and 112 Percentages are based on the number of participants randomized to the faricimab arm who have not discontinued the study at Week 112. Treatment interval at a given visit is defined as the treatment interval decision followed at that visit. Treatment interval at Week 112 is calculated using data recorded at Week 108. The 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112 Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 millimetre \[mm\]). The weighted estimates of the percentage of participants with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With Absence of Pigment Epithelial Detachment in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112 Pigment epithelial detachment was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of pigment epithelial detachment were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and \<33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Percentage of Participants With at Least One Non-Ocular Adverse Event From first dose of study drug through end of study (up to 112 weeks) This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 48 Baseline and Week 48 The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112 Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (\<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.03% CI.
Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 48 Baseline and Week 48 The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Plasma Concentration of Faricimab Over Time Pre-dose at Baseline, Weeks 4, 16, 20, 48, 76, and 112 Faricimab concentration in plasma was determined using a validated immunoassay method.
Percentage of Participants With at Least One Adverse Event From first dose of study drug through end of study (up to 112 weeks) This analysis of adverse events (AEs) includes both ocular and non-ocular (systemic) AEs. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. AEs of special interest included the following: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 112 Baseline and Week 112 The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye From first dose of study drug through end of study (up to 112 weeks) This analysis of adverse events (AEs) only includes ocular AEs, which are categorized as having occurred either in the study eye or the fellow eye. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Percentage of Participants Who Tested Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Pre-dose at Baseline, Weeks 4, 20, 48, 76, and 112 Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The percentage of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period.
Trial Locations
- Locations (138)
Centro Oftalmológico Dr. Charles S.A.
🇦🇷Capital Federal, Argentina
Hospital de Sao Joao; Servico de Oftalmologia
🇵🇹Porto, Portugal
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Cumberland Valley Retina PC
🇺🇸Hagerstown, Maryland, United States
Midwest Retina
🇺🇸Dublin, Ohio, United States
Retina Consultants of Houston
🇺🇸The Woodlands, Texas, United States
Sydney Eye Hospital
🇦🇺Sydney, New South Wales, Australia
Sydney Retina Clinic and Day Surgery
🇦🇺Sydney, New South Wales, Australia
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Retina Assoc of Cleveland Inc
🇺🇸Cleveland, Ohio, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
Island Retina
🇺🇸Shirley, New York, United States
The Second Affiliated Hospital of Harbin Medical University; ophthalmology department
🇨🇳Harbin, China
The Affiliated Eye Hospital of Nanjing Medical University
🇨🇳Nanjing City, China
Centres Ophtalmologique St Exupéry; Ophtalmologie
🇫🇷St Cyr Sur Loire, France
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
"Intersec Research and Technology Complex Eye Microsurgery n a Fyodorov Novosibirsk Branch
🇷🇺Novosibirsk, Russian Federation
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Clinic de Barcelona; Consultas Externas Oftalmologia
🇪🇸Barcelona, Spain
Hospital Universitario Rio Hortega; Servicio de Oftalmologia
🇪🇸Valladolid, Spain
Taipei Veterans General Hospital; Ophthalmology
🇨🇳Taipei, Taiwan
Gazi University Faculty of Medicine; Department Of Ophthalmology
🇹🇷Ankara, Turkey
Organizacion Medica de Investigacion
🇦🇷San Nicolás, Argentina
The Lions Eye Institute
🇦🇺Nedlands, Western Australia, Australia
Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States
Retina Associates of Utah
🇺🇸Salt Lake City, Utah, United States
Sjællands Universitetshospital, Roskilde; Øjenafdelingen
🇩🇰Roskilde, Denmark
ASST FATEBENEFRATELLI SACCO; Oculistica (Sacco)
🇮🇹Milano, Lombardia, Italy
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
Retinal Consultants Med Group
🇺🇸Sacramento, California, United States
Retina Care Specialists
🇺🇸Palm Beach Gardens, Florida, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
Colorado Retina Associates, PC
🇺🇸Lakewood, Colorado, United States
Orange County Retina Med Group
🇺🇸Santa Ana, California, United States
Retina Group of Florida
🇺🇸Fort Lauderdale, Florida, United States
Southern Vitreoretinal Assoc
🇺🇸Tallahassee, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Retina Associates of Florida, LLC
🇺🇸Tampa, Florida, United States
Georgia Retina PC
🇺🇸Marietta, Georgia, United States
Retina Consultants of Hawaii
🇺🇸'Aiea, Hawaii, United States
Prairie Retina Center
🇺🇸Springfield, Illinois, United States
University Retina and Macula Associates, PC
🇺🇸Oak Forest, Illinois, United States
Raj K. Maturi, MD PC
🇺🇸Indianapolis, Indiana, United States
Maine Eye Center
🇺🇸Portland, Maine, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Retina Specialists
🇺🇸DeSoto, Texas, United States
VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
🇺🇸Edina, Minnesota, United States
The Ohio State University Havener Eye Institute
🇺🇸Columbus, Ohio, United States
Mid Atlantic Retina - Wills Eye Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Palmetto Retina Center
🇺🇸West Columbia, South Carolina, United States
Southeastern Retina Associates Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Retina Res Institute of Texas
🇺🇸Abilene, Texas, United States
Retina Center of Texas
🇺🇸Southlake, Texas, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Austin Clinical Research LLC
🇺🇸Austin, Texas, United States
Strategic Clinical Research Group, LLC
🇺🇸Willow Park, Texas, United States
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Wagner Macula & Retina Center
🇺🇸Norfolk, Virginia, United States
Retina Center Northwest
🇺🇸Silverdale, Washington, United States
Oftalmos
🇦🇷Capital Federal, Argentina
Fundacion Zambrano
🇦🇷Caba, Argentina
Grupo Laser Vision
🇦🇷Rosario, Argentina
Buenos Aires Mácula
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Oftar
🇦🇷Mendoza, Argentina
Eyeclinic Albury Wodonga
🇦🇺Albury, New South Wales, Australia
Marsden Eye Research Centre
🇦🇺Parramatta, New South Wales, Australia
Centre For Eye Research Australia
🇦🇺East Melbourne, Victoria, Australia
Strathfield Retina Clinic
🇦🇺Strathfield, New South Wales, Australia
Sydney West Retina
🇦🇺Westmead, New South Wales, Australia
Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie
🇦🇹Wien, Austria
Hospital de Olhos de Aparecida - HOA
🇧🇷Aparecida de Goiania, GO, Brazil
LKH-Univ.Klinikum Graz; Universitäts-Augenklinik
🇦🇹Graz, Austria
Retina Specialists Victoria
🇦🇺Rowville, Victoria, Australia
Pentagram Eye Hospital (Medical Center "Pentagram")
🇧🇬Sofia, Bulgaria
Specialized Hospital for Active Treatment of Eye Diseases Zora
🇧🇬Sofia, Bulgaria
Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia
🇧🇷Sao Paulo, SP, Brazil
Peking Union Medical College Hospital
🇨🇳Beijing City, China
Beijing Friendship Hospital
🇨🇳Beijing, China
Beijing Tongren Hospital
🇨🇳Beijing, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Southwest Hospital , Third Military Medical University; Ophthalmology
🇨🇳Chongqing City, China
The Second Hospital of Jilin University; ophthalmology department
🇨🇳Changchun City, China
Daping Hospital of Third Military Medical University
🇨🇳Chongqing, China
Zhongshan Ophthalmic Center, Sun Yat-sen University
🇨🇳Guangzhou City, China
Shanghai First People's Hospital
🇨🇳Shanghai, China
Centre Odeon; Exploration Ophtalmologique
🇫🇷Paris, France
He Eye Specialist Shenyang Hospital
🇨🇳Shenyang City, China
Tianjin Eye Hospital
🇨🇳Tianjin City, China
CHU Nantes - Hôtel Dieu; Ophthalmology
🇫🇷Nantes, France
Eye Hospital, Wenzhou Medical University
🇨🇳Wenzhou City, China
Wuxi No.2 People's Hospital
🇨🇳Wuxi, China
Rigshospitalet Glostrup; Afdeling for Øjensygdomme, Center for Forskning
🇩🇰Glostrup, Denmark
Chi De Creteil; Ophtalmologie
🇫🇷Creteil, France
Hopital de la croix rousse; Ophtalmologie
🇫🇷Lyon cedex, France
Centre Paradis Monticelli; Ophtalmologie
🇫🇷Marseille, France
Pole Vision Val d'Ouest; Ophtalmologie
🇫🇷Ecully, France
Hopital Lariboisiere; Ophtalmologie
🇫🇷Paris, France
Centre Ophtalmologique; Imagerie et laser
🇫🇷Paris, France
Universitätsklinikum Köln; Augenklinik
🇩🇪Köln, Germany
Augenabteilung am St. Franziskus-Hospital
🇩🇪Münster, Germany
Universitätkslinikum Düsseldorf, Augenklinik; Klinik fürAugenheilkunde
🇩🇪Düsseldorf, Germany
Universitätsklinikum Münster; Augenheilkunde
🇩🇪Münster, Germany
Queen Mary Hospital; Department of Ophthalmology
🇭🇰Hong Kong, Hong Kong
Bajcsy-Zsilinszky Hospital
🇭🇺Budapest, Hungary
Magyar Honvedseg Egeszsegugyi Kozpont; Szemészeti Osztály
🇭🇺Budapest, Hungary
Szegedi Tudományegyetem ÁOK; Department of Ophtalmology
🇭🇺Szeged, Hungary
UNIVERSITA' DEGLI STUDI DI GENOVA - Di.N.O.G.;CLINICA OCULISTICA
🇮🇹Genova, Liguria, Italy
Fondazione Ptv Policlinico Tor Vergata Di Roma;U.O.S.D. Patologie Renitiche
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliero-Universitaria Careggi; S.O.D. Oculistica
🇮🇹Firenze, Toscana, Italy
Nuovo Ospedale S. Chiara - A.O.U.P Presidio Ospedaliero di Cisanello; U.O. Oculistica Universitaria
🇮🇹Pisa, Toscana, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
A.O. Universitaria S. Maria Della Misericordia Di Udine; Clinica Oculistica
🇮🇹Udine, Veneto, Italy
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Nune Eye Hospital; Ophthalmology
🇰🇷Seoul, Korea, Republic of
Asan Medical Center.
🇰🇷Seoul, Korea, Republic of
Optimum Profesorskie Centrum Okulistyki
🇵🇱Gdańsk, Poland
OFTALMIKA Sp. z o.o
🇵🇱Bydgoszcz, Poland
Hospital de Braga; Servico de Oftalmologia
🇵🇹Braga, Portugal
Caminomed
🇵🇱Tarnowskie Góry, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie Oddział Kliniczny Okulistyki i Onkologii Okulistycznej
🇵🇱Krakow, Poland
Centro Hospitalar E Universitário de Coimbra EPE - Serviço Oftalmologia; Serviço Oftalmologia
🇵🇹Coimbra, Portugal
Intersec Research and Technology Complex "Eye Microsurgery" n.a. S.N. Fyodorov; Cheboksary Branch
🇷🇺Cheboksary, Marij EL, Russian Federation
"Intersec. Research and Technology Complex "Eye Microsurgery" n a Fyodorov Irkutsk branch
🇷🇺Irkutsk, Russian Federation
National University Hospital; Ophthalmology Department
🇸🇬Singapore, Singapore
1 Saint-Petersburg St. Med. University named after academician I.P.Pavlov; Chair of ophathalmology
🇷🇺Saint Petersburg, Russian Federation
Singapore Eye Research Institute
🇸🇬Singapore, Singapore
Instituto Oftalmologico Fernandez Vega; Servicio de oftalmologia
🇪🇸Oviedo, Asturias, Spain
Institut de la Macula i la retina
🇪🇸Barcelona, Spain
Changhua Christian Hospital; Department of Ophthalmology
🇨🇳Changhua, Taiwan
Hospital Universitario Miguel Servet; Servicio de Oftalmologia
🇪🇸Zaragoza, Spain
Hacettepe University Medical Faculty; Department of Ophthalmology
🇹🇷Ankara, Turkey
Chang Gung Medical Foundation - Linkou; Ophthalmology
🇨🇳Taoyuan, Taiwan
Ankara University Medical Faculty; Department of Ophthalmology
🇹🇷Ankara, Turkey
Ege University Medical Faculty; Department of Ophthalmology
🇹🇷Izmir, Turkey
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hong Kong Eye Hospital; CUHK Eye Centre
🇭🇰Mongkok, Hong Kong