Well, if this is in a tight loop, then you might gain a bit by not building a scope each time through the loop:

expensive_function($str_a , $str_b) unless ($letter eq substr $str_b,0
+,1);
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IOW, get rid of the curlies. I'd be curious to find out if this really has any significant effect...

Or even...

expensive_function($str_a , $_)
    unless ($letter eq substr $_,0,1)
        for @list;
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... if we are free to play with $_ (otherwise predeclaring $str_b will work too).