Ask a retina specialist how she treats patients with diabetic macular edema, and more than likely she will reply that she follows the DRCR.net Protocol I. Really? How many retina specialists know that to follow Protocol I, patients are seen not monthly but every 4 weeks for more than a year? Or that the first opportunity to not treat the patient with ranibizumab on an every-4-week basis was at week 16? Approximately 25% of patients met the criteria not to be treated at week 16; however, more than 90% of these patients recurred and had to be re-treated. How many retina specialists know that in Protocol I the first opportunity to not see the patient and thereby decrease the treatment burden of being seen on an every-4-week basis was after week 60? And the bottom line is that as important a study as Protocol I is, it is largely a hypothetical study and rarely, if ever, is it followed in clinical practice because it is simply not sustainable. Remember that patients with diabetic macular edema are often young patients in the workforce who are historically noncompliant.