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. masoud_soheilian@yahoo.com

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.





SCORE (not!): Air-ball for IVTA in BRVO

7 11 2009

The one-year results of the SCORE study were published in September.  The studies (two really, one comparing standard of care vs. intravitreal triamcinolone (IVTA) injections in central retinal vein occlusion (CRVO), and the other in branch retinal vein occlusion (BRVO).  Here I’ll discuss the results in the BRVO study.  Standard of care for BRVO with macular edema is laser.  The study compared visual results for patients with BRVO who received either laser, IVTA 1 mg or IVTA 4 mg.  The results showed no significant difference if visual outcome among the three groups.  Vision improved by 3 lines or more in 29%, 26% and 27% respectively.  Because IVTA carries the risk of increased IOP and cataract, the study recommends that laser treatment remain standard of care for treating macular edema in BRVO.  It’s interesting that in the SCORE CRVO study, IVTA proved to be more effective than standard care (observation), whereas in the BRVO study, standard care (laser) proved to be more effective than IVTA.  Here’s the abstract.

Arch Ophthalmol. 2009 Sep;127(9):1115-28.
A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6.
Scott IU, Ip MS, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, Chan CK, Gonzalez VH, Singerman LJ, Tolentino M; SCORE Study Research Group.

OBJECTIVE: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with standard care (grid photocoagulation in eyes without dense macular hemorrhage and deferral of photocoagulation until hemorrhage clears in eyes with dense macular hemorrhage) for eyes with vision loss associated with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: Multicenter, randomized clinical trial of 411 participants. Main Outcome Measure Gain in visual acuity letter score of 15 or more from baseline to month 12.

RESULTS: Twenty-nine percent, 26%, and 27% of participants achieved the primary outcome in the standard care, 1-mg, and 4-mg groups, respectively. None of the pairwise comparisons between the 3 groups was statistically significant at month 12. The rates of elevated intraocular pressure and cataract were similar for the standard care and 1-mg groups, but higher in the 4-mg group.

CONCLUSIONS: There was no difference identified in visual acuity at 12 months for the standard care group compared with the triamcinolone groups; however, rates of adverse events (particularly elevated intraocular pressure and cataract) were highest in the 4-mg group. Application to Clinical Practice Grid photocoagulation as applied in the SCORE Study remains the standard care for patients with vision loss associated with macular edema secondary to BRVO who have characteristics similar to participants in the SCORE-BRVO trial. Grid photocoagulation should remain the benchmark against which other treatments are compared in clinical trials for eyes with vision loss associated with macular edema secondary to BRVO.





SCORE! A win for IVTA in CRVO

7 11 2009

The one-year results of the SCORE study were published in September.  The studies (two really, one comparing standard of care vs. intravitreal triamcinolone (IVTA) injections in central retinal vein occlusion (CRVO), and the other in branch retinal vein occlusion (BRVO).  Here I’ll discuss the results in the CRVO study.  Standard of care for CRVO with macular edema is observation.  No effective treatment has been available, to reduce the macular edema and improve vision.  The SCORE study has shown that IVTA at a 1 mg dose is indeed effective at improving vision in CRVO with macular edema.  How effective?  Those who were in the observation group had a 7% rate of improvement in vision, whereas those in the IVTA group had 26% improvement in vision.  Although this is nearly a five-fold increase in the rate of improvement, it bears mentioning that nearly 3/4 of patients who did receive IVTA did not gain the levels of vision defined as the endpoint of the study.  The study compared 1 mg and 4 mg doses of preservative free triamcinolone, and found that the success rate was essentially the same (27% and 26% respectively), but that the higher dose had increased risk of cataracts and IOP.  271 patients were enrolled in the study.

Bottom line:  A single 1 mg dose of IVTA results in 26% of patients with CRVO and ME gaining 3 or more lines of vision, vs. 7% with observation.  The shortcoming of the data is that we only have 1 year results.  Time will tell whether the improvement will hold.

Here are links to the NIH/NEI press release, the article on Medscape.  The abstract is below.

http://www.nei.nih.gov/news/pressreleases/091409a.asp

http://www.medscape.com/viewarticle/709517

Arch Ophthalmol. 2009 Sep;127(9):1101-14.
A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5.
Ip MS, Scott IU, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, Singerman LJ, Tolentino M, Chan CK, Gonzalez VH; SCORE Study Research Group.
OBJECTIVE: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO).

METHODS: Multicenter, randomized, clinical trial of 271 participants. MAIN OUTCOME MEASURE: Gain in visual acuity letter score of 15 or more from baseline to month 12.

RESULTS: Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.8-14.1; P = .001) and 5.0 times greater in 4-mg group than the observation group (OR, 5.0; 95% CI, 1.8-14.4; P = .001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P = .97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group.

CONCLUSIONS: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial.