I have a patient in the NICU that I’ve been following for the past couple of weeks with ROP, so it’s given me the opportunity to review the ETROP results, the final results of which were published in 2004 by William V. Good on behalf of the ETROP Cooperative Group.
The CRYO-ROP trial had given us the “threshold” of treatment for ROP. Threshold was defined by the CRYO-ROP as at least five clock hours of contiguous, or eight cumulative clock hours of stage 3 ROP in zone I or II in the presence of plus disease. When I was a resident, a quick trick we were taught was to look at the posterior pole for plus disease. If there was no plus disease, no matter how extensive the ROP might be, you weren’t at threshold. And I still do this now, looking first at the posterior pole for plus disease, before heading off into the periphery to determine zones and stages.
The ETROP study came about because of a sense that treating some patients sooner than these threshold definitions could be beneficial, and in fact the ETROP proved it to be so, effectively changing the threshold for treatment. The most important change is that treatment can now be considered sooner without regard to the number of clock hours involved. The new criteria defined by ETROP are:
1. Zone I ROP with plus disease (doesn’t matter what stage)
2. Zone I ROP with stage 3 disease (don’t need plus disease)
3. Zone II ROP, stage 2 or 3, with plus disease.
These three criteria are defined as “Type I” ROP.
Treating these eyes instead of waiting for CRYO-ROP threshold criteria resulted in reduction in unfavorable visual acuity outcomes from 19.8% to 14.3%, and a reduction in unfavorable structural outcomes from 15.6% to 9.0% (both at 9 months). Bear in mind that these results are not comparing “treated” to “untreated”, but are comparing “treating earlier” to “waiting for CRYO-ROP threshold”. Treating these Type I eyes resulted in treatment on average 2 weeks earlier than waiting for CRYO-ROP threshold.
Looking at these numbers, there is a definite clinical benefit to treating earlier, but you can spin the numbers in a couple of ways. You can say that unfavorable visual acuity outcomes were reduced by 25% (from 19.8 down to 14.3%), but I think it’s more meaningful to look at the absolute percentage reduction, which is about 5%. A 5% decrease means that for every 20 eyes you treat early, you see a benefit in one of them. Not great, but given that you’re only changing the timing of the treatment in most cases, (66% of control eyes went on to need treatment by CRYO-ROP criteria anyway), it’s pretty good. The question though is, what risk was involved in treating these infants two weeks earlier? The study showed that there was a definite increase in morbidity in the early treatment group (but not mortality) — bradycardia, re-intubation, etc. How often did this occur? If you treat two patients early, one had a potentially serious systemic side effect. So, the decision regarding the timing of treatment is not so cut and dried as the study numbers might suggest. On the other hand, it does support treating ROP at “pre-threshold” levels, and that should be taken into account. Furthermore it points to the need to follow pre-threshold eyes more closely, and to be prepared to treat within 48 hours of reaching threshold.