State of the art management of diabetic macular edema

Table 1 Summary of the studies using intravitreal Bevacizumab for treatment of diabetic macular edema

Ref.	Purpose	Study design	Out comes measures	IVBdose	Interval of injection	Naive or refractory/DME	Duration of study	Number of eyes	Treatment regimen	Results
Soheilian et al[61]	IVB or IVB, IVT or MPC	Randomized clinical trial	BCVA, CMT	1.25 mg	-				(1) 1.25 mg IVB; (2) IVB/ IVT/ 1.25 mg IVB and 2 mg IVT; and (3) MPC	Group B and C had a greater reduction in CMT at 3 wk and 1 line better median VA over 12 wk there were no significant differences between group B and C. Combining MPC with IVB resulted in no apparent short term benefit
Soheilian et al[62]	IVB or IVB/ IVT or MPC	Randomized clinical trial	BCVA, CMT	1.25 mg	12 wk	Naïve	24 wk	150 eye	(1) 1.25 mg IVB; (2) IVB/ IVT 1.25 mg IVB and 2 mg IVT; and (3) MPC	The significant treatment effect on VA was demonstrated in the IVB group at all follow- up visits and in the IVB/ IVT group at 6 and 12 wk. CMT Changes were not significant among the groups in all visits
Soheilian et al[63]	the same as above	randomized clinical trial	BCVA, CMT	1.25 mg	12 wk	Naïve	2 yr	150 eyes	The same as above	The significant superiority of VA improvement in the IVB group, which had been noted at month 6, did not sustain thereafter up to 24 mo, and the difference among the groups was not significant at all visits. The reduction of CMT was more in the IVB group in relation to the other two treatment groups however, the difference among the groups was not significant at any of the follow-up visits
DRCR.Net[64]	IVB for DME	Randomized phase 2 clinical trial	CMT, BCVA	1.25 mg 2.5 mg	6 wk	Naive	24 wk	121	(1) Foal MPC12 or (2) 1.25 mg IVB at base line and 6 wk; (3) 2.5 mg IVB6 at baseline and 6 wk or (4) 1.25 mg at baseline; and (5) 1.25 mg IVB at base line and 6 wk + MPC at 3 wk	The significant treatment effect on VA was demonstrated at both 6 and 12 wk in the IVB group and only at 6 wk in the IVB/IVT group. Significant CMT reduction was observed in eyes in the IVB and IVB/ IVT groups only up to 6 wk, however, CMT changes were not significant in the groups
Marey et al[65]	IVB or IVB/ IVT for DME	Randomized clinical trial	VA and CMT	1.23 mg		Naïve	12 wk	90	(1) IVB; (2) IVB and IVT (4 mg); and (3) IVT	There was significant improvement in the VA in the three study groups at week 6 and 12. Comparing the visual acuity results at 6 wk between the 3 study groups there was no significant difference and also between each pair of the three study groups; however at week 12, there was high significant difference (P = 0.004) and between each pair there was high significant difference between IVT and IVB/ IVT groups (P = 0.001), significant difference between groups IVT and IVB and no significant difference between group IVB/ IVT and IVB. Comparing the CMT showed the same results
Lim et al[66]	IVB or IVB/ IVT or IVT	Randomized 3arm clinical trial	BCVA, CMT	1.25 mg	6 wk	Naïve	12 mo	111 eyes	IVB group, two IVB injections with 6 wk intervals; IVB / IVT (2 mg IVT + 1.25 mg IVB); 2 mg IVT	The IVB/ IVT group and IVT group showed better visual acuity and reduced CMT at 6 wk and 3 mo. However, no significant difference in VA and CMT was observed between 3 groups. No significant differences in VA or CMT were observed between the IVB/ IVT and IVT group during the follow- up
Ahmadieh et al[67]	IVB or IVB/T for refractory DME	Randomized clinical trial (Placebo- Controlled)	CMT BCVA	1.25 mg	6 wk	Refractory	24 wk	115 eyes	(1) three injection of 1.25 mg IVB at 6 wk intervals; (2) IVT (2 mg) followed by two injections of IVB at 6 wk intervals; and (3) sham injection	CMT was reduced significantly in both IVB and IVB/ IVT groups. Significant improvement of BCVA was seen in both IVB and IVB/ IVT groups. No significant differences were detected in the changes of CMT and BCVA between the IVB and IVB/IVT groups
BOLT study[68]	IVB or MPC for DME	Randomized clinical trial	BCVA	1.25 mg	6 wk	Refractory /DME	12 mo	80 eyes	IVB MPC	The mean ETDRS BCVA at 12 mo was 61.3 ± 10.4 in the IVB group and 50.0 ± 16.6 in the MPC group. The IVB group gained a median of 8 ETDRS letters, whereas the MPC group lost a median of 0.5 ETDR letters. At 12 mo, CMT decreased from 507 ± 145 μm at baseline to 378 ± 134 μm (P < 0.001) in the IVB group, whereas it decreased to a lesser extent in the MPC group, from 481 ± 121 μm to 413 ±135 μm (P = 0.02)

IVB: Intravitreal bevacizumab; IVP: Intravitreal pegaptanib; IVR: Intravitreal ranibizumab; IVT: Intravitreal triamcinolone; IVTL: Intravitreal triamcinolone plus laser; IVVTE: Intravitreal VEGF Trap Eye; DME: Diabetic macular edema; BCVA: Best corrected visual acuity; CMT: Central macular thickness.