Eye Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Neoplasm Metastasis

Myopia

Retinal Diseases

Neovascularization, Pathologic

Vision, Low

Myopia, Degenerative

Choroidal Neovascularization

Vision Disorders

Neoplastic Processes

Refractive Errors

Metaplasia

Choroid Diseases

Uveal Diseases

Sensation Disorders

Neurologic Manifestations

Antineoplastic Agents

All Drugs and Chemicals

Angiogenesis Inhibitors

Ranibizumab

Growth Inhibitors

Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection

All patients received a single initial intravitreal injection of ranibizumab 0.5 mg/0.05 ml as per Committee for Human Medicinal Products (CHMP)approval. Further injections might have been required when monitoring reveals disease activity. Disease activity, defined as reduced visual acuity and/or signs of lesion activity, was evaluated based on clinical examination (BCVA, fundus), and/or optical coherence tomography (OCT), and/or fluorescein angiography (FAG). Bilateral treatment was allowed provided at least 14 days of intercurrence.

Novartis Pharmaceuticals

The primary objective of the study was to investigate current criteria driving re-treatment in patients affected by Choroidal Neovascularization (CNV) secondary to Pathologic Myopia (PM) and experiencing a relapse of the disease after the first administration of ranibizumab.

A Study of the Criteria Establishing the Need for Re-treatment With Ranibizumab Upon Relapse in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia.

A 12-month, Open-label, Interventional, Multicentre Study to Investigate the Current Criteria Driving Re-treatment With Ranibizumab Upon Relapse in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Presence of active leakage on fluorescein angiography (FAG) was assessed at screening (14 to 3 days before baseline visit), month 2 and month 6. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of active leakage (Yes/No). For retreated patients, the presence/absence of active leakage was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Presence of macular edema from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of macular edema (Yes/No). For retreated patients, the presence/absence of macular edema was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Presence of cysts from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of cysts (Yes/No). For retreated patients, the presence/absence of cysts was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Presence of Intra-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of Intra-retinal fluid (Yes/No). For retreated patients, the presence/absence of Intra-retinal fluid was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Central subfield thickness (CSFT) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSFT versus previous visit. For retreated patients, the change in CSFT was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Central subfield volume (CSV) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSV versus previous visit. For retreated patients, the change in CSV was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Presence of sub-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. The regression model for sub-retinal fluid was not valid because "Yes" was reported in almost all subjects causing a quasi-complete separation of data points. \*NE = Not evaluable

Presence of clinically significant abnormalities was assessed at baseline, month 1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of clinically significant abnormalities (Yes/No). For retreated patients, the presence/absence of clinically significant abnormalities was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Improvement in BCVA \< 5 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA \< 5 letters (Yes/No) which was reported as Gain \>= 5 letters versus Gain \< 5 letters. For retreated patients, Gain \>= 5 letters and Gain \< 5 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Improvement in BCVA \< 10 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA \< 10 letters (Yes/No) which was reported as Gain \>= 10 letters versus Gain \< 10 letters. For retreated patients, Gain \>= 10 letters and Gain \< 10 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Changes from baseline in BCVA are described for the ETDRS parameter considering the following categories at each assessment: "no change" if the change was equal to 0 letter, "worsening" if change \< 0 letter , "improvement" if change \> 0 letter. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change from baseline in BCVA (improved/worsened/stable) which was reported as Improved versus no change and worsened versus no change. For retreated patients, this variable was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Change from baseline in BCVA (Best Corrected Visual Acuity) was Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score. Patients with a BCVA ETDRS letter score of 78 to 24 in the study eye were included; A higher score represents better functioning of the study eye. A positive change from baseline shows improvement.

Mean number of ranibizumab injection is reported as number of injections per patient.

Time to re-treatment, defined as time in months from the data of first dose of ranibizumab to the date of re-treatment, was evaluated.

Number of patients with any systemic AE, with serious systemic AE, with an ocular AE, with an ocular serious AE are reported

Patient quality of life was assessed by Impact of Vision Impairment (IVI) questionnaire. IVI is a 32-item instrument, either self- or interviewer-administered, developed to measure the impact of vision impairment on daily activities in five domains. The 32 items were divided into 5 domains as follows: Leisure and work (items 1 to 5), Social and consumer interaction (items 6 to 10 and items 23-24), Household and personal care (items 11 to 14 and items 20-21), Mobility (items 15 to 19 and item 22), Emotional reaction to vision loss (items 25 to 32). Responses to the IVI items were rated on a five-category Likert scale: not at all, 0; hardly at all, 1; a little, 2; a fair amount, 3; a lot, 4; and can't do because of eyesight, 5. Total score was an arithmetic average of the items rated between 0 (the best score) and 5 (the worst score). A negative change indicates improvement. Data was computed on items with non missing response

Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.

All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.

Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.

Ranibizumab: Treated Once

Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.

Ranibizumab: Re-treated Once

Total

Age, Continuous

Sex: Female, Male

Full Analysis Set (FAS): All subjects who received at least one dose of ranibizumab

Study Director

Screening: Active leakage, No

Screening: Active leakage, Yes

Screening: Active leakage, NE

Screening: Active leakage, Missing

Month 2: Active leakage, No

Month 2: Active leakage, Yes

Month 2: Active leakage, NE

Month 6: Active leakage, No

Month 6: Active leakage, Yes

Month 6: Active leakage, NE

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent fluorescein angiography at that time point.

Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage

Change at 6 month

Change at 12 month

Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. The study eyes of the patients belonging to the FAS were analyzed.

Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 6 and Month 12 on Study Eye

Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab

Mean Number of Ranibizumab Injection

Time to Re-treatment

Any systemic Adverse Event

Serious systemic Adverse Event

Ocular Adverse Event

Ocular serious adverse event

Safety Population: all subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.

Number of Patients Having Ocular and/or Systemic Adverse Event (AE)

Change at Month 2

Change at month 12

Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab with data at both timepoints.

Change in Patient Quality of Life From Baseline to Month 2 and Month 12

Screening: Macular Edema, No

Screening: Macular Edema, Yes

Screening: Macular Edema, NE

Month 2: Macular Edema, No

Month 2: Macular Edema, Yes

Month 2: Macular Edema, NE

Month 6: Macular Edema, No

Month 6: Macular Edema, Yes

Month 6: Macular Edema, NE

Month 12: Macular Edema, No

Month 12: Macular Edema, Yes

Month 12: Macular Edema, NE

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.

Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema

Screening: Cysts, No

Screening: Cysts, Yes

Screening: Cysts, NE

Month 2: Cysts, No

Month 2: Cysts, Yes

Month 2: Cysts, NE

Month 2: Cysts, Missing

Month 6: Cysts, No

Month 6: Cysts, Yes

Month 6: Cysts, NE

Month 12: Cysts, No

Month 12: Cysts, Yes

Month 12: Cysts, NE

Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts

Presence vs. absence of intra-retinal fluid.

Screening: Intra-retinal fluid, No

Screening: Intra-retinal fluid, Yes

Screening: Intra-retinal fluid, NE

Month 2: Intra-retinal fluid, No

Month 2: Intra-retinal fluid, Yes

Month 2: Intra-retinal fluid, NE

Month 6: Intra-retinal fluid, No

Month 6: Intra-retinal fluid, Yes

Month 6: Intra-retinal fluid, NE

Month 12: Intra-retinal fluid, No

Month 12: Intra-retinal fluid, Yes

Month 12: Intra-retinal fluid, NE

Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid

Change in Central subfield thickness vs previous visit.

Month 2 Vs. Screening : CSFT

Month 6 Vs. Month 2: CSFT

Month 12 Vs. Month 6: CSFT

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point and previous visit.

Change in Central Subfield Thickness (CSFT)

Change in Central subfield volume vs previous visit.

Month 2 Vs. Screening : CSV

Month 6 Vs. Month 2: CSV

Month 12 Vs. Month 6: CSV

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point and the previous visit.

Change in Central Subfield Volume (CSV)

Screening: Sub-retinal fluid, No

Screening: Sub-retinal fluid, Yes

Screening: Sub-retinal fluid, NE

Month 2: Sub-retinal fluid, No

Month 2: Sub-retinal fluid, Yes

Month 2: Sub-retinal fluid, NE

Month 6: Sub-retinal fluid, No

Month 6: Sub-retinal fluid, Yes

Month 6: Sub-retinal fluid, NE

Month 12: Sub-retinal fluid, No

Month 12: Sub-retinal fluid, Yes

Month 12: Sub-retinal fluid, NE

Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid

Presence vs. absence of clinically significant abnormalities.

Baseline: Clinically Significant Abnormal, No

Baseline: Clinically Significant Abnormal, Yes

Baseline: Clinically Significant Abnormal, Missing

Month 1: Clinically Significant Abnorma, No

Month 1: Clinically Significant Abnormal, Yes

Month 1: Clinically Significant Abnormal, Missing

Month 2: Clinically Significant Abnormal, No

Month 2: Clinically Significant Abnormal, Yes

Month 2:Clinically Significant Abnormal, Missing

Month 3: Clinically Significant Abnormal, No

Month 3: Clinically Significant Abnormal, Yes

Month 3: Clinically Significant Abnormal, Missing

Month 6: Clinically Significant Abnormal, No

Month 6: Clinically Significant Abnormal, Yes

Month 6: Clinically Significant Abnormal, Missing

Month 12: Clinically Significant Abnormal, No

Month 12: Clinically Significant Abnormal, Yes

Month 12: Clinically Significant Abnormal, Missing

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent ocular examination during that time point.

Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities

Gain \< 5 letters vs. Gain \>= 5 letters.

Month 1: Gain >= 5 letters

Month 1: Gain < 5 letters

Month 2: Gain >= 5 letters

Month 2: Gain < 5 letters

Month 3: Gain >= 5 letters

Month 3: Gain < 5 letters

Month 6: Gain >= 5 letters

Month 6: Gain < 5 letters

Month 12: Gain >= 5 letters

Month 12: Gain < 5 letters

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab with improvement in BCVA \< 5 letters from baseline at that time point.

Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters

Gain \< 10 letters vs. Gain \>= 10 letters.

Month 1: Gain >= 10 letters

Month 1: Gain < 10 letters

Month 2: Gain >= 10 letters

Month 2: Gain < 10 letters

Month 3: Gain >= 10 letters

Month 3: Gain < 10 letters

Month 6: Gain >= 10 letters

Month 6: Gain < 10 letters

Month 12: Gain >= 10 letters

Month 12: Gain < 10 letters

Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab with improvement in BCVA \< 10 letters from baseline to that time point.

Spots Global Cancer Trial Database for pathological myopia