You can use Tie::File for the deletion of the unwanted records.

use Tie::File;

...

tie my @ptt_records, q{Tie::File}, $ptt_file or die $!;

foreach my $k1 (keys %empty_geneids){
    @ptt_records = grep { ! /$k1/ } @ptt_records;
}

untie @ptt_records;
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Note that you don't need an intermediate file ($ptt_file2) with this technique.

Also, Tie::File uses a very small memory footprint which may be a bonus given you're working with biological data.