Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema.
BACKGROUND
Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. The retina at the macula thickens and this can cause gradual loss of central vision. Although grid or focal laser photocoagulation has been shown to reduce the risk of visual loss in DMO or clinically significant macular oedema (CSMO), vision is rarely improved. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) modalities has recently been proposed for improving vision in people with DMO. Anti-VEGF drugs are delivered by an injection in the vitreous cavity of the eye.


OBJECTIVE
This review aims to assess the effectiveness of anti-VEGF therapy for preserving or improving vision in people with DMO.


METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and Caribbean Literature on Health Sciences (LILACS). There were no language or date restrictions in the search for trials.The electronic databases were last searched on 16 April 2009.


METHODS
We included randomised controlled trials (RCTs) comparing any antiangiogenic drugs with an anti-VEGF mechanism of action compared to another treatment, sham treatment, or no treatment.


METHODS
Two authors independently extracted the data. The risk ratio (RR) of visual loss and visual gain of 3 or more lines was estimated at least six months after treatment.


RESULTS
We found four small studies that collected only short-term outcomes (24 to 36 weeks); three of which had more than two randomisation groups generating five types of comparisons overall. Only one comparison included more than one trial in the analysis. The short-term outcome was the mean change in LogMAR visual acuity. One study on 172 patients compared three doses of pegaptanib versus sham (about 5 injections on average) and another compared bevacizumab or bevacizumab plus triamcinolone with sham (multiple bevacizumab injections and a single triamcinolone injection in 101 patients, 115 eyes overall) in patients with CSMO that was refractory to photocoagulation. Bevacizumab or bevacizumab plus triamcinolone were also compared to photocoagulation in 129 patients with untreated CSMO (150 eyes, multiple injections needed in 24 patients). Although comparisons tended to favour antiangiogenic therapy, estimates did not reach statistical significance or, if they did, they were not robust to sensitivity analysis regarding missing data and potential bias related to single trial estimates. No difference could be demonstrated in one study on 26 patients comparing bevacizumab to triamcinolone (both administered with a single injection) and between bevacizumab and bevacizumab plus triamcinolone in two studies on 182 patients. All the studies in this review, except for the study on pegaptanib, were at risk of bias based on the assessment of six methodological quality items.There were no serious adverse effects in these short-term studies, except for one case of severe anterior uveitis in one eye treated with bevacizumab. No included study examined long-term adverse effects of antiangiogenic therapy.


CONCLUSIONS
There is not sufficient high quality evidence from large RCTs supporting the use of either single or multiple anti-VEGF intravitreal injections to treat DMO. Results from ongoing studies on several compounds should assess not only treatment efficacy but also, if a benefit is found, the number of injections needed for maintenance and long-term safety.
Parravano
Mariacristina
M
Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Via Livenza n 3, Rome, Italy, 00198.
Menchini
Francesca
F
Virgili
Gianni
G
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide / Q000627:therapeutic use; D000068258:Bevacizumab; D003930:Diabetic Retinopathy / Q000150:complications*; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014221:Triamcinolone / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; D014221:Triamcinolone; C495058:pegaptanib; D000068258:Bevacizumab