Is Avastin the new laser for diabetic macular edema?

19 11 2009

In the June 2009 issue of Ophthalmology Soheilian et al, out of Tehran, published an important paper comparing intravitreal bevacizumab (IVB) alone or in combination with triamcinolone (+IVTA) to macular photocoagulation for treatment of diabetic macular edema.  They randomized a total of 150 eyes with clinically significant macular edema (CSME) into three treatment groups, and followed them for up to 36 weeks (which is about 9 months).   If CSME persisted at 12 week (3 mo) intervals, the eye were retreated with the same intervention.  Their study showed that intravitreal bevacizumab yielded better visual acuity results at 36 weeks than did laser treatment.  Specifically, vision improved by > 2 Snellen lines of acuity in 37% of the IVB group, 25% of the IVB+IVTA group, and 15% of the laser group.  On the other hand, retreatment was required in 28%, 20% and 6% of the three groups respectively.  IVB improves vision more, but needs to be used more often.

One of the things that the study did not do, was differentiate the patients with CSME into those with cystic edema and those with non-cystic edema.  My hunch is that we would find that in the group with cystic edema, the difference between the effectiveness in bevacizumab and laser would be even greater.  Will bevacizumab become a replacement for laser in treating CSME?  It’s too soon to say.  My hope is that the Sohelian et al will continue to follow these patients and report on results as they reach the 1 year and 2 year marks.

In clinical practice, this paper seems to support what many of us are currently doing:  using bevacizumab as first line treatment for diabetic macular edema to decrease the edema and improve the vision, and following it up with laser treatment for long term control.  I’d like to see a study that looks at this situation.  I use the sequential approach with greatest success in patients with massive or cystic macular edema.

Here is the abstract:

Ophthalmology. 2009 Jun;116(6):1142-50. Epub 2009 Apr 19.

Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.

Soheilian MRamezani AObudi ABijanzadeh BSalehipour MYaseri MAhmadieh HDehghan MHAzarmina MMoradian SPeyman GA.

Ophthalmology Department, Labbafinejad Medical Center, Shaheed Beheshti Medical University, Tehran, Iran.

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME). DESIGN: Randomized 3-arm clinical trial. PARTICIPANTS: A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.

METHODS: The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (VA) at week 24.

RESULTS: VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.

CONCLUSIONS: Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.

Bevacizumab speeds resolution of vitreous hemorrhage

27 10 2009

A study in the September 2009 issue of Retina by Huang et al. out of Taiwan is titled “Intravitreal Bevacizumab and Panretinal Photocoagulation for Proliferative Diabetic Retinopathy Associated with Vitreous Hemorrhage.”  In this important study, they took 40 patients with vitreous hemorrhage (VH) too dense to treat with PRP, and if the VH  did not clear within two weeks, they treated them with bevacizumab (Avastin).  If the VH did not clear, they treated again in 4-6 weeks.  If the VH heme had not cleared by 12 weeks, they performed a pars plana vitrectomy (PPV).  They compared this to a group of 40 patients who did not receive bevacizumab.  When the vitreous was clear enough in either group, they received PRP.

The results showed that patients receiving bevacizumab cleared anywhere from 2-20 weeks (avg 12 weeks), whereas the patients who did not receive bevacizumab required 6-30 weeks (avg 18 weeks) to clear.  Only 10% of those receiving bevacizumab required PPV, whereas 40% of those who did not receive the drug required PPV.

So, clearly, intravitreal bevacizumab is helpful in the initial treatment of VH from proliferative diabetic retinopathy.  It improves the rate of resolution of VH, and decreases the need for surgery.  Two points were of interest to me.  Neither was specifically studied in the paper, but the authors raise the issues in their study design .  First, they remind us that bevacizumab can induce a fibrous response (“Avastin crunch”) and lead to tractional retinal detachments, and so they excluded patients whose ultrasounds showed the presence of tractional detachments or fibrous responses.  They repeated the B-scans as they followed the injected patients to watch for tractional detachments.  Second, they chose 4-6 weeks as the interval for re-injection of bevacizumab. They based this on two previous papers.  One by Jorge et al. which showed that peak regression of NV in diabetic retinopathy occured at 6 weeks, and that by 12 weeks, leakage had resumed; and the other by Arevalo et al. which showed that regression of NV could occur as quickly as 7-15 days after injection of bevacizumab.

Pearls to take away:  Inject bevacizumab for dense vitreous hemorrhages, get a baseline B-scan and follow the B-scans after injection for tractional detachments, and consider re-injections at 4-6 weeks.

Steroid Implants for Diabetic Macular Edema

26 10 2009

A presentation yesterday at the American Academy of Ophthalmology caught my interest.  There are two sustained-release steroid implants that are injectable, making it possible to use these within the office setting.  The two that I’m watching are the Alimera Iluvien fluocinolone acetonide resevoir implant, which contains half the drug as the Retisert implant to decrease the side-effects seen with Retisert.  It’s implantable with a 25-gauge needle and floats in the vitreous.  The phase 3 clinical trial results for DME may be out by the end of this year.

The other product is Allergan’s Ozurdex (called Posurdex everywhere except in the US).  It’s also an injectible implant that floats in the vitreous through a 22 gauge system, but contains dexamethasone.  It has been FDA approved as of June 2009 for persistent macular edema due to vein occlusion.  The phase 2 trials reported at the AAO meeting involving DME patients showed “35 percent of eyes receiving 700 micrograms improved 10 letters or more by Day 90, compared with 24 percent of those receiving 350 micrograms, and 13 percent in the observation group.”  (from Academy Live email from the AAO)

I like the Alimera product because it is implantable through a 25 gauge system.  The 22 gauge system required to implant the Allergan product is likely to require sutures more frequently to close to wound.  However, the advantage of the Allergan product is that it is completely biodegradable, whereas the Alimera product leaves behind the core which contained the drug.  This floats around in the vitreous, presumably forever.