3.4Evolving Algorithms

e

Fig. 3.31 Color (a) and red-free (b) photographs showing vasogenic macular edema, characterized by increased retinal thickness, cluster of lipids, microaneurysms, intraretinal hemorrhages, and cotton wool spots. (c, d) FA early (c) and late (d) frames revealing breakdown of the bloodretinal barrier. (e) OCT discloses increased retinal thickness, with intraretinal cysts and hard exudates

vasogenic form is characterized by retinal thickness associated with leaking aneurisms and hard exudates (Fig. 3.31). In vasogenic DME, laser photocoagulation, according to the ETDRS recommendations, has been proposed as the first-choice treatment option. If DME resolution is achieved, a 6-month follow-up, including BCVA and OCT examination, should be considered. In case of nonresponder DME after laser therapy, anti-VEGF or steroid injections should be offered to the patient as a second-choice option. In non-vasogenic DME, characterized by retinal thickness with a reduced number of microaneurysms and vascular abnormalities, intravitreal injections of anti-VEGF or steroids are the first-line treatment. In case of DME well responding to the injections, laser photocoagulation is the additional therapeutic approach proposed to maximize and extend the benefits. In case of the

d

h

Fig. 3.32 (a–d) Diffuse diabetic macular edema, with multiple microaneurysms and hemorrhages and few hard exudates (a, b) and severe fluorescein leakage with a “petalloid” pattern (c), reflecting the fluid accumulation in the cystoid spaces (d). (e–h) Refractory diabetic macular edema, after grid macular laser and three monthly intravitreal injections of ranibizumab; a persistence of fluorescein leakage (f, g) and increased retinal thickness is visible (h), associated to clusters of hard exudates in red-free image (e)

absence of response to the treatment, steroid injections are suggested as a rescue treatment offer (Fig. 3.32). In the third form, tractional DME associated with epiretinal membrane or vitreomacular adherence, vitreoretinal surgery is considered as the gold standard. Intravitreal injections of steroid and anti-VEGF could be proposed as an additional procedure after surgery to achieve more benefits.

An expert panel that reviewed the recent literature on ranibizumab has formulated in 2011 further evidence-based recommendations for the treatment of DME [131]. The authors suggested IVR as a validated treatment for clinically significant

d

Fig. 3.33 (a) Red-free photograph displays an exudative plaque of hard exudates centered in the macular area, multiple hemorrhages, and microaneurysms. (b, c) FA early (b) and late (c) frames show multiple leaking microaneurysms, areas of retinal non-perfusion, and a diffuse breakdown of the blood-retinal barrier. (d) EDI OCT scan, passing through the plaque of hard exudates, reveals increased retinal thickness only in the inter papillo-macular area, while in the macula hard exudates, atrophic changes, and gliosis are clearly visible, associated to a diffuse reduced choroidal thickness. The green lines are part of the OCT scan examination

the past from the majority of the published clinical studies, possibly because there is limited evidence of the benefits of the therapy in such cases. Furthermore, in case of mixed pathologies, it is hard to explicate which is the degree of ischemia responsible to the vision loss, and thus incomplete conclusion could be drawn. The reduced number of papers on the topic and the clinical practice suggested a limited functional recovery expected from each type of experimented therapy in such dramatic condition. Moreover, there is supporting evidence that anti-VEGF treatment seemed rarely to further compromise the amount of retinal circulation [141].

Nevertheless, few case reports describing the development or the progression of macular ischemia after anti-VEGF treatment have been published [142–144]. The hypothetic mechanism underlying this severe complication is still unknown. It is possible that anti-VEGF (and in particular bevacizumab) could affect the vascular integrity, which is already compromised by the preexistent diabetic retinopathy and by a systemic vascular insufficiency. In a recent paper, analyzing 33 patients treated with 3 monthly IVB, an asymptomatic increase of the foveal avascular zone after treatment has been reported. In two of these cases, an increase of 50 % or more has been noted even in the absence of vision deterioration and recording a reduction of CRT.

c

f

Fig. 3.34 (a–c) Severe diabetic macular edema with massive lipid exudation (a, b) throughout the posterior pole and extensive intraretinal fluid on OCT (c). (d–f) Two years after grid laser photocoagulation, the reabsorption of the hard exudates (a) and intraretinal fluid is clearly seen, associated to the comparison of large subretinal fibrosis (arrow) which did not allow the visual acuity recovery

c

d

Fig. 3.35 (a, b) FA early (a) and late (b) frames show enlargement of foveal avascular zone, localized areas of retinal non-perfusion, and diffuse macular leakage. (c, d) OCT diagonal (c) and vertical (d) scans reveal diabetic macular edema, characterized by subretinal detachment and intraretinal fluid

Therefore, even if there is limited evidence, it is possible that anti-VEGF injection could affect the foveal vascular integrity and induct or aggravate macular ischemia.

Thus, some authors warned that patients with chronic DME and coexisting macular ischemia, requiring multiple injections of anti-VEGF, should be treated with caution to prevent the damage of the fragile fine foveal network of capillaries.

Summary 3.8

Patient-centered therapeutic algorithms should be considered in order to achieve satisfactory management of the DME. Factors predicting a better response to the treatment have been reported, including younger age, a good controlled systemic condition, and a better baseline functional and anatomical ocular condition, such as visual acuity, retinal thickness, and photoreceptor’s integrity. A validated treatment for DME associated to macular ischemia is still lacking.