Summary 2.5

The international recommendations suggested an annual dilated fundus examination for diabetic children and adults by an eye-care professional. During pregnancy, diabetic women should undergo biomicroscopy every 3 months if the DR is absent, or every month in case of DR.

2.4.2Laser Photocoagulation

The Diabetic Retinopathy Study (DRS) published the results of the first randomized, multicenter clinical trial assessing the effects of photocoagulation compared to observation on 1,742 diabetic patients with severe NPDR or PDR [107]. Patients included had 20/100 or better in each eye and were treated randomly in one eye with both direct and scatter photocoagulation. In high-risk PDR, the results showed that scatter photocoagulation reduced by 50 % the risk of severe visual loss (defined as visual acuity <5/200 at two or more consecutively visits), and the reported rates were 26 and 11 % in the treated and control groups, respectively, by 2 years [41]. These rates were significantly lower in the eyes affected by severe NPDR. Visual field defects, visual acuity decrease of 1 line, reduced dark adaptation, and difficulties on night driving were reported. The results of this large trial did not clearly demonstrate if photocoagulation could be beneficial for patients with earlier stages of the disease, such as severe NPDR.

The Early Treatment Diabetic Retinopathy Study (ETDRS) investigated if early photocoagulation was effective for the treatment of DR [108]; 3,711 patients with mild NPDR to early PDR, with visual acuity of 20/200 or better, were randomly assigned to photocoagulation (scatter or focal) or observation. The results showed that early scatter photocoagulation leads to small reduction in the risk of severe visual loss in early treated eyes: at 5 years, the incidence rates were 2.6 and 3.7 % in treated and untreated groups, respectively [14]. In mild to moderate NPDR, the rates of progression were even lower. Thus, the benefits derived from early photocoagulation were not sufficient to compensate the secondary side effects and laser photocoagulation was not indicated for mild to moderate NPDR. Nevertheless, in case of very severe NPDR or early PDR, the benefits compared to the side effects were more favorable to suggest performing scatter photocoagulation before the incoming of high-risk PDR. An additional analysis of the data provided by the ETDRS study showed that early scatter photocoagulation was effective in decreasing the risk of severe visual loss especially in older, type 2, diabetic patients with severe NPDR or early PDR [109].

Today it is possible to associate laser therapy with intravitreal injections of antiangiogenic drugs in patients which show presence of macular edema. The possibility of a combined therapy is an important tool, and it is useful in a selected group of diabetic patients (Figs. 2.29, 2.30, and 2.31).

m

Fig. 2.29 (a–c) Panretinal FA image (a), OCT picture (b), and map of retinal thickness (c) of the right eye at baseline in a 22-year-old female with a long-lasting poor-controlled IDDM (HbA1c: 11,5 %); BCVA was 7/10. FA image (a) shows a diffuse BRB (blood-retinal barrier) breakdown and OCT picture (b) reveals the presence of a clinically significant macular edema. (d–f) One month after 1st intravitreal injection of ranibizumab and a better glycometabolic control, the retina showed an anatomical improvement with restoration of BRB integrity (FA image, d), regression of macular edema (OCT scan, e), and normalization of CRT (central macular thickness, in map f). BCVA was now 10/10. (g–i) After 3 months, there was a recurrence of sectoral macular edema, visible in the late phase of FA image (g) as a BRB breakdown and in the OCT scan (h) as a presence of intraretinal fluid. CRT remains <300 μm in the map (i). HbA1c reduced to 9.5 %. No further intravitreal injections were performed, and the patient went on with a better control of the systemic disease. (j–l) Thirty-six months later, the HbA1c turned out to be 7.4 %; biomicroscopic color photo (j), red-free image (k), and last follow-up OCT scan (l) show a complete regression of previous lesions. BCVA was finally stabilized to 10/10

l

Fig. 2.29 (continued)

Fig. 2.30 Panretinal FA image of a young diabetic patient with a severe NPDR at baseline (a), which shows severe peripheral ischemia and a diffuse BRB (blood-retinal barrier) breakdown, suggesting the presence of clinical significant macular edema. (b) Combined therapy with PRP (panretinal laser photocoagulation) and IV (intravitreal) injection of bevacizumab helped to control transition from severe NPDR to high-risk PDR, but nevertheless neovascularization of the optic disk occurred

Summary 2.6

The ETDRS revealed that early scatter photocoagulation is not indicated for eyes with mild to moderate NPDR. In case of very severe NPDR or early PDR, scatter photocoagulation is suggested before the incoming of high-risk PDR, especially in older patients with type 2 diabetes.

Fig. 2.31 Panretinal FA image and OCT scan of the left eye of a 22-year-old female with IDDM since age 4 and a history of inadequate glycemic control (HbA1c: 10.8 %). At baseline, BCVA was 4/10. FA image (a) shows the presence of diffuse retinal ischemia and the OCT scan reveals the presence of central cystoid macular edema. (b–d) One month after PRP (panretinal laser photocoagulation) and 1st IV (intravitreal) injection of ranibizumab, the patient showed a still poor metabolic control, but BCVA was 6/10 and the OCT scan (d) reveals the regression of macular edema. (e, f) After 6 months, the level of systemic control was still inadequate (HbA1c 10.3 %) and BCVA decreased to 3/10. The FA image (e) shows the breakdown of the BRB (blood-retinal barrier) in the posterior pole, and the OCT scan (f) reveals the recurrence of cystoid macular edema. (g, h) Finally 42 months later, after a combined therapy (PRP, other 3 IV ranibizumab, “grid” laser, cataract extraction + position of intraocular lens in posterior chamber) and an improvement in the glycometabolic control (HbA1c: 7.6 %), the patient gained at a final BCVA of 4/10. FA image (g) shows the results of laser therapy and a reduction of BRB breakdown, and the OCT scan (h) reveals the absence of macular edema