Ann: Security Class Reinstatement to Quotation- OPTOB, page-616

Think others like PigRace are better equipped to answer.

The question about letters on the same line is valid if we are thinking about just ourselves or one patient can read one, two, or all five letters on a given line, they’re still recognizing letters of the same size.
As you said, the real test of visual improvement for an individual is whether they can read letters on the next line down (5 letters) or ideally the next one after that (10 letters)

In my experience letter recognition isn’t uniform; some letters (e.g., V, E, K) may be easier to distinguish than others, like O, C and Q, which share similar shapes. The scientific methodology behind BCVA (Best Corrected Visual Acuity) accounts for this by focusing on statistical averages across a large sample rather than individuals. Personally, when I take an eye test, I find the marginal line easy enough to read with certain letters like V and E, but much harder to distinguish Os from Cs, oddly even if I can make out some letters on the smaller line below.

For an individual patient (n=1), I'd expect that most who respond well to treatment will be able to read one or two smaller lines on the eye chart—especially considering that the combined treatment (excluding RAP) showed a life changing 14-letter gain in the Phase 2b trials.

Zoom out to a statistically significant sample, say n=996 individuals, the individual results will be all over the place. Some will see a huge improvement—gaining 14 letters (three lines or more), going from 20/40 to 20/30 or even 20/30 to 20/20—while others might see little to no change or, in some cases, even a decline. The goal in Phase 3 clinical trials is move the average in a clinically meaningful way across entire treatment arm or sub group. Ideally, we’re aiming for an average improvement of 3.3 letters or more, and if we hit 5+ letters, that’s blockbuster territory.