Detailed Eligibility Criteria

Both Lucentis® and Avastin® are contraindicated in pregnancy, breastfeeding, children and adolescents. While it is highly unlikely that patients with nAMD will be pregnant or will have given birth recently (patients <50 years are ineligible and the average age at presentation of patients with nAMD is approximately 73 years), any woman who fulfils all other criteria for enrolment who has recently given birth and wishes to participate must discontinue breast-feeding during therapy and not breast feed for at least six months following the last dose Avastin®.

Avastin® and Lucentis® are contraindicated in those patients known to be hypersensitive to the active compound or excipients. Additionally, Avastin® is contraindicated in patients known to be hypersensitive to Chinese hamster ovary (CHO) cell products or other recombinant human or humanised antibodies. IVAN has been designed for participants with a confirmed diagnosis of CNV due to AMD and the study will only enrol patients 50 years or older. IVAN will not enrol children or adolescents in whom both Lucentis® and Avastin® are contraindicated.

Any woman of child-bearing potential (i.e. those not sterilised or postmenopausal) will be advised of the risk of foetal harm. Dosing in male subjects who have a pregnant or lactating female partner could also result in harm to the foetus or neonate. Therefore, male subjects with pregnant or lactating partners who are otherwise eligible and wish to participate should use a condom when engaging in sexual activity for the duration of the trial and for 3 months after the last dose.

Notwithstanding the above caveats, we propose to use eligibility criteria that are as inclusive as possible, to promote the applicability of the evidence obtained during the trial.

Inclusion criteria:

• Adults of either sex aged 50 years or older;
  
  
• Newly referred for the treatment of nAMD in the first or second eye;
  
  
• Corrected distance logMAR visual acuity (VAlogMAR) ≥25 letters read on a standard ETDRS chart at 1 metre;
  
  
• Any component of the neovascular lesion (CNV, blood, serous pigment epithelial detachment, elevated blocked fluorescence) involving the centre of the fovea.
  
  

If a fellow eye develops CNV from AMD, it will be treated with the optimum locally available treatment.

Exclusion criteria

• Age less than 50 years
  
  
• Corrected VAlogMAR <25 letters at 1 metre;
  
  
• Long standing CNV evidenced by the presence of fibrosis in excess of 50% of the total lesion;
  
  
• Greatest linear diameter >6000μm (equivalent to about 12 disc diameters);
  
  
• Argon laser treatment to the proposed study eye within the last 6 months;
  
  
• Presence of thick blood involving the centre of the fovea;
  
  
• Presence of other active ocular disease causing concurrent vision loss, e.g. diabetic retinopathy;
  
  
• Previous treatment with PDT or an anti-VEGF drug in the eye being considered for inclusion;
  
  
• Pregnant and or lactating women;
  
  
• Women with child bearing potential (i.e. not sterilised or not post menopausal) who are unwilling to use contraception;
  
  
• Men with a spouse or partner with child bearing potential unless the participant has agreed to use condoms.
  
  

A past medical history of cardiovascular disease or cardiovascular comorbidity, e.g. previous myocardial infarction or stroke, current angina, will not be an exclusion criterion. However, such factors will be documented carefully at the time of recruitment, and the potential benefits and harms of treatment discussed carefully with potential participants.