Søren Leer Blindbæk

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside

The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes.

Venous loops: a benign feature of diabetic retinopathy or cause for concern?

ducibility of assessment data. Med Educ 38: 1006–1012. Gupta RR & Lam WC (2006): Medical students’ self-confidence in performing direct ophthalmoscopy in clinical training. Can J Ophthalmol 41: 169–174. Thomsen AS, Subhi Y, Kiilgaard JF, la Cour M & Konge L (2015): Update on simulation-based surgical training and assessment in ophthalmology: a systematic review. Ophthalmology 122: 1111–1130. Wu GT, Kang JM, Bidwell AE, Gray JP & Mirza RG (2014): The use and evaluation of an inexpensive eye model in direct ophthalmoscopy training. JAO 7: e21– e25.

Changes in retinal oxygen saturation after intravitreal aflibercept in patients with diabetic macular edema.

Abstracts will be available online on 25 May 2017.

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.

Predictive value of retinal venous loops in the screening for proliferative diabetic retinopathy

© 2016 Wichtig Publishing visual acuity (VA) was 53.9, 59.1, and 55.6 letters, and central retinal thickness (CRT) was 414.8, 370.4, and 430.1 μm, respectively. At 1 year, in T1, T2, and T3, the mean VA improved by 4.4, 1.9, and 4.6 letters, accompanied by a reduction in mean CRT of 57.7, 34.0, and 92.9 μm, respectively. The VA improvements in T1 were similar to T3 at 1 year but with a lower mean number of injections (T1, 3.7; T3, 4.7) and visits (T1, 6.4; T3, 8.4). In treatment-naïve patients at 1 year, VA outcomes stratified by baseline VA of <23, ≥23 to <39, ≥39 to <60, ≥60 to <74, and ≥74 letters were 11.8, 15.0, 6.2, 1.7, and -2.4 letters, with a mean of 2.3, 2.8, 3.7, 4.1, and 4.0 injections, respectively. The rate of ocular and nonocular serious adverse events reported was 0.38% and 4.86%, respectively. Conclusions: Prior Ranibizumab-treated patients showed higher VA and lower CRT at baseline versus treatment-naïve patients. VA improved over one year irrespective of previous treatment status. Ranibizumab 0.5 mg showed substantial improvements in VA in treatment-naïve patients with low baseline VA in a real-world scenario.

Reply: Prophylactic treatment of retinal breaks

Editor, W e read with great interest the article by Blindbæk & Grauslund (2015) on the prophylactic treatment of retinal breaks. It was concluded that follow-up after symptomatic posterior vitreous detachment (PVD) is only necessary in cases of incomplete retinal examination and there is no unequivocal conclusion regarding prophylactic treatment for asymptomatic retinal break. While we do not want to do unnecessary followup and overtreat asymptomatic retinal breaks, we also do not want to undertreat those lesions that are at risk of developing into clinical retinal detachment. Among the many risk factors, high myopia (> -6 dioptres) may be an important one. For example, patients with high myopia are more prone to developing retinal break and retinal detachment when compared with patients in the idiopathic group (Fan et al. 1999; Goh et al. 2015). Similarly, retinal breaks in patients with high myopia may behave differently from retinal breaks in individuals with emmetropia. In Blindbaek & Grauslund’s study, this important factor has not been taken into consideration (Blindbaek & Grauslund 2015). The eyes with high myopia are at higher risk of developing into rhegmatogenous retinal detachment (RRD) for a number of reasons (Semeraro et al. 2014): (1) a weak attachment between the neurosensory retina and the retinal pigment epithelium in the elongation of the vitreous chamber, especially posterior staphyloma. (2) The vitreous and retinal shear stresses in the enlargement and elongation of the vitreous chamber are increased by the movement of the eye, which may cause high myopic eyes more prone to develop posterior vitreous detachment and retinal detachment. (3) The pumping efficiency of the retinal pigment epithelium in high myopic eyes may also alter by the chorioretinal atrophy, thus influencing the strength of adhesion and leading to further weakening of mechanical attachments and the promotion of retinal detachment. In a population-based incidence study in Beijing (Li & Beijing Rhegmatogenous Retinal Detachment Study 2003), 57.1% patients with bilateral RRD and 32.4% patients with unilateral RRD were high myopic patients. In cases of rhegmatogenous retinal detachment managed in our hospital, over 30% of patients had high myopia (D. Lam, unpublished data). Furthermore, the cost-effectiveness of laser barrier treatment for retinal breaks may be lower than that of regular examinations, especially for patients who may not be able to attend regular follow-up. In conclusion, further studies about the role of high myopia in prophylactic laser treatment for asymptomatic break seem warranted. Before results are available, we may want to have a lower threshold to treat asymptomatic retinal breaks in eyes that also have high myopia.