I use a hash for the options whose keys are option letters and whose values can be either a scalar for a single or empty value or an array reference for multiple values, e.g.:

use Getopt::Std;
my %opt;
getopt('abc',\%opt);
Multivalued(\%opt);

#...

sub Multivalued { # convert lists to array refs.
    my $href = shift;
    while( my ($k, $v ) = each %$href ) {
        my @anon = split /\,/, $v or next;
        $href -> { $k } = \@anon;
    }
}
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And to iterate the combinations of the arrays, see Math::Combinatorics.

Update: and if you have to support protected commas in quotes, instead of just splitting, parse with something like Text::Csv::Simple