Fig. 3.27 (a, b) Tractional diabetic macular edema, persistent after grid laser photocoagulation. (c, d) Three months after vitrectomy, with removal of the epiretinal membrane and internal limiting membrane peeling, a complete resolution of retinal thickness is noticeable

3.3.3Pars Plana Vitrectomy

Even if the exact role in the pathogenesis of DME is not completely understood, the vitreous and the vitreoretinal junctions are currently considered as active modulators, leading to vascular increased permeability [113, 114]. Hypothesized pathogenic mechanisms included excessive glycation of vitreal collagen, accumulation of vasoactive factors in the premacular vitreous, and migration of cells to the posterior hyaloid, inducing vitreomacular traction and increased vascular permeability. Thus, the vitreomacular traction and the increased levels of permeability-related molecules in the vitreous gel (like growth factors and cytokines) are considered as contributing elements to the development and progression of DME.

Several investigations showed that posterior vitreous detachment played a protective role in the formation of DME, and patients with this condition are less likely to develop DME [115–117]. In 1992, Lewis has first proposed the role of PPV for the management of diffuse DME associated with a thickened and taut premacular posterior hyaloid [114]. Based on these results, pars plana vitrectomy (PPV), including the removal of the posterior hyaloid, has been considered as a validated therapy in such cases of persistent and diffuse DME, refractory to previous other treatments [114– 118]. Currently, the efficacy of PPV has been successfully reported in both cases of DME associated or not to visible posterior hyaloid traction and macular traction.

Some reports suggested that PPV could improve the diffusion of fluid from the retina and transport of oxygen in non-perfused areas [119, 120]. Major adverse

Fig. 3.28 (a, b) Severe tractional diabetic macular edema, associated to a diffuse breakdown of the blood-retinal barrier and a wide increase in retinal thickness. (c, d) Six month later, after vitrectomy with vitreomacular traction removal and peeling of the internal limiting membrane and grid laser photocoagulation, a complete resolution of macular edema is clearly visible

events related to the surgery are cataract formation and progression; IOP increase, retinal detachment, endophthalmitis, vitreous, and choroidal hemorrhage are also uncommon complications.

Recent papers showed that the removal of the internal limiting membrane (ILM) provided additional benefits in preventing the recurrence of the epiretinal membrane (ERM) (Fig. 3.27). The ILM could possibly act as a scaffold promoting the formation of the ERM, and its peeling leads to better anatomical and functional results [121, 122]. Nevertheless, this issue is still controversial and some authors suggested a possible toxicity on the photoreceptors and Muller cells related to the ILM peeling [123, 124].

The effectiveness of PPV in the treatment of DME and vitreomacular traction has been assessed in a prospective cohort study of 1 year of duration [125]. During surgery, additional procedures have been performed including ERM and ILM peeling, panretinal photocoagulation, and steroid injection.

At 6 months, median CRT was reduced by 160 μm; 43 % of patients showed a CRT inferior to 250 μm, and 68 % of subjects gained a 50 % decrease in CRT. An improvement in BCVA of ten or more letters was seen in 38 % of patients, while a deterioration of ten or more letters was reported in 22 % of subjects. At the final follow-up, retinal thickness decreased in most eyes.

Even if the role of PPV is still under investigation, the results of these and more studies suggested a meaningful benefit in terms of BCVA recovery and CRT reduction (Fig. 3.28).

c

d

Fig. 3.29 (a–c) Refractory diabetic macular edema, despite previous laser treatment, associated to vitreomacular traction (BCVA 20/400). (d) Resolution of macular edema and improvement of visual acuity (BCVA 20/100) after spontaneous release of the vitreomacular forces

Enzymatic vitreolysis is an innovative procedure that has been engineered to achieve a posterior vitreous detachment (PVD) and to improve the retinal oxygenation. Enzymes that may have some potential in achieving a PVD include hyaluronidase, chondroitinase, dispase, and plasmin [126]. Intravitreal hyaluronidase (Vitrase, ISTA Pharmaceuticals, Irvine, CA, USA) has been analyzed for the treatment of vitreous hemorrhage secondary to different pathologies, including PDR [127, 128]. Autologous plasmin, obtained by incubation of patient-derived purified plasminogen with streptokinase, has been studied alone or adjuvant to PPV in the treatment of DME [129, 130]. Some of the patients showed a spontaneous induction of PVD (Fig. 3.29) even if in other cases intravitreal plasmin seemed to be insufficient to obtain a complete resolution of the vitreomacular traction.