Management of patients with diabetic macular oedema and good visual acuity: new findings from Protocol V

Abstract

As we observe a dramatic increase in diabetes prevalence worldwide, diabetes-associated eye complications are rapidly emerging as a global health issue that may threaten patients’ visual acuity [1]. Even though treatment of diabetic retinopathy (DR) can reduce the risk of visual loss by 60% [2], this disorder still remains the leading cause of blindness among working-age adults. Diabetic macular oedema (DMO) is a major cause of vision decrease in these patients and may occur at any stage of DR. In 1985, the Early Treatment Diabetic Retinopathy Study reported on the use of laser photocoagulation to treat DMO [3]. The latter trial enrolled 1122 patients with DMO and demonstrated that the laser treatment effects in a reduced risk of moderate vision loss. Until the introduction of intravitreal anti-vascular endothelial growth factor (VEGF) injections, laser had been thus considered as the treatment of choice for eyes with DMO. Since 2010, several evidences have suggested that anti-VEGF agents may be considered as an effective and safe treatment in eyes with DMO and impaired vision [4–8]. To simplify, anti-VEGF therapies demonstrated a better improvement in visual acuity in comparison with focal/grid laser therapy. Nonetheless, the anti-VEGF treatment was also displayed to produce an amelioration in DR severity [9], even without an enhancement in retinal perfusion [10]. Of note, in a number of cases the anti-VEGF treatment may be ineffective and in these cases a switch to other treatments, including intravitreal dexamethasone, was proved to be potentially effective, especially in presence of definite imaging biomarkers [11]. Thanks to the support of the National Eye Institute, National Institutes of Health, the Diabetic Retinopathy Clinical Research (DRCR) Retina Network has organized and realized different important clinical trials which delineated guidelines for patients with DMO. In detail, in a study on 854 eyes with DMO, they provided evidence that intravitreal ranibizumab is superior in gaining visual acuity, with 30% of eyes increasing by three lines of visual acuity and 50% increasing by two lines at 1 year [4]. Successively, the DRCR Retina Network compared the three available anti-VEGF drugs in 660 DMO eyes with moderate to severe visual impairment [12, 13]. The latter clinical trial demonstrated that all the three agents cause VA improvement from baseline to 1 and 2 years with a decreased number of injections in the second year [12, 13]. However, aflibercept was displayed to be more efficacious at improving vision at 1 year in eyes with severe visual impairment (20/50 to 20/320 Snellen equivalent) [12, 14]. Among these eyes with worse baseline visual acuity, aflibercept had superior visual outcomes at 2 years compared with bevacizumab, while superiority of aflibercept over ranibizumab, noted at 1 year, was no longer displayed [13, 14]. Limited data was however available on the most appropriate therapeutic approach for eyes with DMO and good visual acuity. This aspect is crucial, assuming that these patients represent a main portion of DR population [15]. Recently, the DRCR Retina Network investigators reported significant results from Protocol V which specifically sought to address this critical debate [16]. This study included patients with centre-involved DMO and good visual acuity (20/25 or better) who were divided into three arms: prompt laser photocoagulation, prompt aflibercept therapy, or observation. Furthermore, this trial allowed eyes randomized to observation or laser to receive aflibercept rescue if visual acuity decreased from baseline by ≥10 letters at one visit or by 5–9 letters at two following visits [16]. This study concluded that the proportion of eyes experiencing a reduction in visual acuity by five letters at 2 years was similar independently on the assigned group [16]. Moreover, data from this trial also demonstrated that prompt treatment with aflibercept does not cause a significant reduction in the risk of a five letter or more loss, as this * Giuseppe Querques [email protected]