Diabetic macular oedema: what to fear? How to treat?

F or some time, there has been an ongoing discussion regarding the optimal treatment for patients with diabetic macular oedema (DMO). Many years ago, the pivotal Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid laser photocoagulation could reduce visual loss by 50%, but that improved vision was often an unlikely event (Early Treatment Diabetic Retinopathy Study Research Group 1985). Since then, new treatment options have been made available, and in particular, treatment with vascular endothelial growth factor (VEGF) inhibitors may lead to a substantial improvement in visual acuity (Wells et al. 2016). However, the high number of anti-VEGF injections has often been a concern for the patients and for the healthcare system. It is well known that in DMO the production of VEGF is primarily driven by hypoxia (Stefansson 2001). With this in mind, the beneficial effect of focal/grid laser photocoagulation can be explained by the improved oxygen saturation in the retinal tissue (Stefansson 2006). The likely explanation for this is a combination of increased oxygen diffusion from the choroid through the laser scars, and a decreased retinal oxygen consumption caused by photoreceptor destruction. In other words, combining laser and anti-VEGF could target the problem from two sides: increase the oxygen saturation by laser as well as reduce the VEGF burden by intravitreal therapy. However, two points of concerns have been raised. Firstly, laser may be harmful for the patients due to the destructive nature of the treatment. In particular, creeping of laser scars over time may be a problem. Secondly, so far patients in combination therapy have not fared better than patients in anti-VEGF mono treatment (Mitchell et al. 2011). The recent paper in Acta Ophthalmologica, “Effects of focal/grid laser treatment on the central visual field in diabetic macular oedema: a 2-year follow-up study” (Tababat-Khani et al. 2016) adds a substantial contribution to the first point. The paper aimed to evaluate the long-term visual field impairment after focal/grid laser in DMO. In a two-year prospective study, 26 patients had focal/grid laser and standard automated perimetry of the central 10 degrees at baseline and follow-up. In general, visual fields were stable over time. Furthermore, the number of depressed points at followup did not correlate with the amount of laser effects nor the number of laser sessions. With the relatively long follow-up of the paper in mind, we now believe that visual field side-effects should be less of a concern. Regarding the second point, most studies using combination therapy have included a standard laser system. We believe that newer laser options may provide better results. In particular, navigated laser could be a viable option. Navigated laser combines imaging, laser planning and treatment in one computer-based device. In particular, it allows the treating physician to plan the treatment using a fluorescein angiography in order to target leaking microaneurysms. With a traditional laser, these may be hard to see and even harder to photocoagulate. Furthermore, the system includes eyetracking which allows safer treatment closer to the centre. Regarding accuracy, it has been demonstrated that navigated laser has a 92% microaneurysm hit rate as compared to 72% using a standard laser system (p < 0.01) (Kozak et al. 2011). Even more encouraging were the results from a 12-month, prospective study (Liegl et al. 2014). Sixty-six patients with DMO were selected to ranibizumab monotherapy or combination therapy with ranibizumab and navigated laser. In both groups, there was a loading phase with three monthly ranibizumab injections. Patients in the combination group then received navigated laser, and finally, both groups had additional ranibizumab injections pro re nata. At follow-up, the visual outcome was similar between the groups. However, patients in the combination group had fewer additional injections after the loading phase (0.9 versus 3.9, p < 0.001). In fact, as compared to 84% in the mono group, only 35% in the combination group needed additional injections after the loading phase (p < 0.001). Inspired by this, we believe that the choice of the optimal treatment for DMO is no longer a matter of either/or but rather both/and. With laser sideeffects being less of a concern, upcoming studies should address combination therapy, in particular using aflibercept that for many treating physicians has become the preferred choice of treatment.