Bevacizumab helpful in BRVO

7 12 2009

The SCORE study showed that intravitreal triamcinolone was no more helpful than standard therapy (macular laser) in improving vision in patients with branch retinal vein occlusions (BRVO), and thus the SCORE study concluded to continue using standard therapy to treat BRVO.  The question is, might another agent, say a VEGF inhibitor like bevacizumab (Avastin) be helpful in treating BRVO?

We get some indirect answers in a study published in the November/December issue of Retina.  The study (Comparison of two doses of intravitereal bevacizumab as primary treatment for macular edema secondary to branch retinal vein occlusion:  results of the pan american collaborative retina study group at 24 months) by Wu et al and the Pan-American Collaborative Retina Study Group was a retrtospective multicenter study looking at results from 63 eyes treated with two different doses of bevacizumab:  1.25 mg and 2.5 mg.  Other studies had shown benefit in visual acuity and central macular thickness (CMT) with bevacizumab in BRVO, and the authors wondered if an increased dose may improve the visual outcome or decrease the frequency of injections.  Patients with macular edema were given bevacizumab at one of the two doses (depending on the center they visited) and were examined on a monthly basis.  OCT’s were performed at months 1, 3, 6, 12 and 24.  If at any time the OCT measured CMT > 250 microns, they were classified as “recurrent” or “persistent” macular edema, and were re-injected.  Re-injections were also given if visual acuity decreased by more than 5 letters (1 line).

Their study found that there was no additional benefit from the higher dose, and that both groups experienced improved vision and decreased CMT.  The results showed that on average, CMT improved from about 450 mic at the first visit, to 250 mic at 3 months, and ended up at the 240 mic range at 24 months.  Furthermore, the mean time for repeat injections was in the 10-13 week range.

But is this better than laser?  Well, the study doesn’t directly look at this question, but it does state that among its small sample size of 63 eyes, of those receiving 1.25 mg, 68% experienced improvement in vision by 3 or more lines of vision (72% in the 2.5 mg group).  That’s pretty significant percentage of improved vision.  You’ll recall that the SCORE Study patients had improved vision in the 26-29% range for IVTA and laser.  So bevacizumab seems to give better results than laser for BRVO.  I realize I’m mixing studies — not really a meta-analysis (maybe a “mini”-analysis), and clearly this needs to be studied further.  But the authors seem to lay out a reasonable approach for treating BRVO with bevacizumab, and their results seem to be significantly better than best results we have available with laser or IVTA.  Check vision monthly, and if worse by 5 letters, treat with bevacizumab;  check OCT at 3, 6 12 and 24 mo, and if CMT > 250 treat with bevacizumab.  Expect about 70% to improve 3 or more lines of vision.

Early Treatment for Retinopathy of Prematurity (ETROP)

2 12 2009

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.