17 As mentioned above, AURA and many other real-world practice studies show that the vision gains seen in tightly controlled clinical trials are not transferrable to clinical practice. A United Kingdom study of approximately 93,000 Lucentis injections reviewed EMRs of thousands of patients treated outside the context of clinical trials. On average, patients received a median of 5, 4, and 4 injections of Lucentis over years one, two and three, respectively. The study found that although patients showed early improvement, they regressed, on average, to pretreatment levels by the end of year two with continued deterioration below their starting visual acuity by year three, as shown in the chart below. Figure: Mean visual acuity (VA), as measured by letter score, over time comparing patients with follow-up of at least 1, 2 or 3 years. More importantly, with many patients losing vision, during the study follow-up many patients experienced new sight impairment (29.6%, 41%, 48.7% and 53.7% in years one, two, three and four, respectively) and even new cases of blindness (5.1%, 8.6%, 12% and 15.6% in years one through four, respectively). In the United States, an EMR study of 7,650 eyes treated with Lucentis and EYLEA outside of the clinical trial setting showed that these therapies improved patients’ visual acuity less in practice than they do in clinical trials. Further, by the end of the first year of treatment, patients’ average visual acuity had deteriorated below their pretreatment levels. Figure: Mean change in visual acuity (VA) letter score at 3, 6 and 12 months in the first year of treatment. VA was lower at 12 months than at the beginning of treatment. LogMar VA Letters (ETDRS) Time (weeks) 0 52 104 156 0.3 0.5 0.7 0.9 70 65 60 55 50 45 40 3-year follow up: 4 Median Number of Injections 1 year follow up: 5 2-year follow up: 4 Follow-up (Month) Lucentis Eylea Unadjusted mean change from baseline in VA letter score 0 3 6 12 1.24 0.71 -0.30 -0.19 1.01 1.52 4 3 2 1 0 -1 -2 -3 -4 Month 12 p=0.67 Mean (+SD) injections through Month 12 Lucentis: 6.7 (2.5) Eylea: 7.0 (2.4)