Comparison of a single intravitreal injection of bevacizumab versus triamcinolone acetonide as primary treatment for diffuse diabetic macular oedema

Authors


Mauricio Maia, MD
Vision Institute
Rua Botucatu 822
São Paulo – SP 04023-062
Brazil
Tel: 55 11 50852020
Fax: 55 11 55734002
Email: maiamauricio@terra.com.br

Editor,

Retinal pharmacotherapy has been used either as a primary treatment or in combination with laser for diabetic macular oedema (DME). Diabetic Retinopathy Clinical Research Network (DRCR.net) first showed that laser photocoagulation is superior to intravitreal triamcinolone (IVT) after 1 year. More recently, the same group demonstrated that ranibizumab alone or in combination with laser may have better functional outcome than laser alone or IVT (Elman et al. 2010). However, looking at pseudophakic patients, the results were very similar with triamcinolone and ranibizumab (Elman et al. 2010). The goal of combo therapy is to provide a faster recovery using a pharmacological agent and a long-term effect of laser therapy requiring fewer injections. However, the ideal combination was not yet determined.

We conducted a retrospective, case–control study of eyes with diffuse DME treated in five institutions in Latin America from the Pan-American Collaborative Retina Study Group (PACORES) group.

We compared the short-term effects of a single intravitreal injection of bevacizumab (IVB) 1.25 mg/2.5 mg (70 eyes) versus triamcinolone (IVT) 4 mg (70 eyes) (Triancinolona, Ophthalmos, São Paulo, Brazil or Kenalog, Bristol-Squibb-Myers, Princeton, NJ, USA) in patients with diffuse DME. The dosage of IVB was left to the discretion of each investigator, and it did not correlate with the severity of DME.

Change in best-corrected visual acuity (BCVA) and reduction in central macular thickness (CMT) at 1, 3 and 6 months were used for comparison.

We enrolled 140 eyes, and there were no differences between the groups at baseline except for systemic hypertension (Table 1). After 6 months, both groups improved their BCVA and reduced their CMT compared to the baseline (Tables 2 and 3). There was no statistically significant difference on BCVA between the groups in all follow-up periods (p = 0.29). The analysis of CMT reduction showed no difference between both groups at the first month (p = 0.15). However, at month 3 and 6, the CMT reduction was greater in IVT than IVB (p < 0.01). There was no statistical difference between the two doses of bevacizumab or the two brands of triamcinolone with regard to BCVA and CMT measurements at all follow-up times (p = 0.38).

Table 1.   Baseline characteristics (n = 140).
 Treatment groups (%)p-value
TriamcinoloneBevacizumab
  1. * Pearson Chi-square’s; Student t-test.

  2. No. = number, SD = standard deviation, PDR = proliferative diabetic retinopathy, BCVA = best-corrected visual acuity, CMT = central macular thickness.

Number of eyes70 (50)70 (50)0.45*
Mean age ± SD56.24 ± 14.0960.68 ± 9.080.31
Gender
 Male36 (52)38 (55)0.74*
 Female34 (48)32 (45)
Systemic hypertension
 No34 (48)55 (79)<0.01*
 Yes36 (52)15 (21)
PDR
 No51 (73)44 (64)0.26*
 Yes19 (27)26 (36)
Mean BCVA (logMar) ± SD0.85 ± 0.220.78 ± 0.270.20
Mean CMT ± SD416 ± 69436 ± 1420.37
Table 2.   Comparison of best-corrected visual acuity measurements (logMAR) between the baseline and following visits for the triamcinolone and bevacizumab groups.
TimeTriamcinolonep-value*Bevacizumabp-value*
Mean ± SDMean ± SD
  1. * Repeated measurements analysis of variance (anova) from each visit comparing to the baseline; SD = standard deviation.

Baseline0.85 ± 0.22 0.78 ± 0.27 
1 month0.62 ± 0.21<0.010.55 ± 0.30<0.01
3 months0.60 ± 0.25<0.010.58 ± 0.30<0.01
6 months0.63 ± 0.26<0.010.60 ± 0.30<0.01
Table 3.   Comparison of central macular thickness measurements between the baseline and following visits for the triamcinolone and bevacizumab groups.
TimeTriamcinolonep-value*Bevacizumabp-value*
Mean ± SDMean ± SD
  1. * Repeated measurements analysis of variance (anova) from each visit comparing to the baseline; SD = standard deviation.

Baseline416 ± 69.00 436 ± 142.00 
1 month282 ± 52.00<0.01306 ± 108.68<0.01
3 months287 ± 57.16<0.01366 ± 140.16<0.01
6 months329 ± 96.72<0.01405 ± 139.450.15

We also examined the retreatment criteria according to the DRCR.net protocol(Elman et al. 2010). At 3 months, there was no statistically significant difference between the groups, which was found at 6 months. Forty-seven (67.14%) patients would be retreated in IVB group versus 37 (52.85%) in IVT group (p = 0.04).

Regarding safety issues, IVT group developed clinically controlled intraocular hypertension (>21 mmHg) in 23.3% which was not observed in the IVB group (p < 0.01). During the 6-month study period, no cataract progression was observed either in the IVT or in the IVB group.

Triamcinolone has been successfully used for DME treatment; however, the major concerns are the side-effects such as glaucoma and cataract (Maia et al. 2007). On the other hand, anti-VEGF agents are apparently safer even after longer follow-up periods, but with short-term effect, requiring more frequently injections (Arevalo et al. 2009). The clinical effect of a single IVT is comparable to three injections of bevacizumab (Kreutzer et al. 2010). The combination of both drugs, IVT 2 mg with IVB 1.25 mg, could also be an alternative with good results and less side-effects of the corticoid (Folgosa et al. 2010).

This short-term study suggests that both drugs could improve BCVA and CMT. However, a single injection of triamcinolone seems to be more effective to reduce CMT up to 6 months when compared with bevacizumab in DME. These results could be important to choose the best drug to be combined with laser photocoagulation.

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