*3.4.3.2 Management of diabetic macular edema associated with proliferative diabetic retinopathy*

In patients with noncenter-involved DME associated with PDR, a focal laser is a good option to be used to treat the DME [119].

If the PDR is presented with center-involved DME, anti-VEGF therapy is recommended, it will improve the DME and cause regression of the neovascularization, then, PRP can be applied. Both ranibizumab and aflibercept were equally effective in improving visual acuity and reducing CRT in eyes with DME and PDR after 2 years; however, the number of microaneurysms, supplementary laser PRP and micropulse laser sessions were higher in the Ranibizumab group [120].

#### *3.4.3.3 Surgical management of DME*

Currently, the indication of pars plana vitrectomy (PPV) in eyes with DME is the presence of vitreomacular traction or the persistence of macular edema following intensive intravitreal injection with anti-VEGF or steroids [121, 122].

The performance of internal limiting membrane (ILM) peeling is, however, a matter of controversy. Complications from ILM peeling in cases of DME when the *Diabetic Macular Edema, Clinicopathologic and Keys for Management DOI: http://dx.doi.org/10.5772/intechopen.112974*

retinal architecture is disorganized and weakened by a longstanding and chronic DME, such as rupturing intraretinal cystoid spaces, might be expected. In one study, the functional results as regards improvement of VA did not differ whether the ILM was peeled or not [122].

As regards the preoperative OCT findings, it was found that eyes with neurosensory detachment had the best postoperative VA improvement following PPV, while eyes with sponge-like diffuse retinal thickening (SDRT) did not show any VA improvement following PPV [123].

Although from the theoretical point of view, PPV reduces VEGF and other DMEpromoting cytokine concentration in the premacular area [124] and increases oxygen supply to the ischemic retina further suppressing VEGF production with consequent reduction of DME, yet there is no universal agreement in the performance of PPV for cases of DME without traction [125, 126].

Results of clinical trials appear controversial [121–123]. Although a limited improvement of function and a short-term improvement in macular thickness reduction following surgery were reported by some authors [121, 127], others demonstrated a significant benefit [128, 129].

#### *3.4.3.4 Cataract extraction in the presence of DME*

It is usually recommended to give anti-VEGF 1–2 weeks before cataract extraction to stabilize DME prior to surgery. A less preferred option is to give the anti-VEGF during the surgery [130, 131].

#### **3.5 Newer advances to solve the unmet needs in the management of DME**

#### 1.Predictive medicine:

This subset of medicine detects the occurrence of a disease before its manifestations appear in an individual, as per population-based cross-sectional studies linked to clinical data. People at risk can therefore have personalized treatment plans with better treatment outcomes [132, 133].

2.Solving the problems of delayed diagnosis, referral and screening


3.Reducing the burden of monthly anti-VEGF injections

A Ranibizumab port delivery system, which is a sustained delivery refillable implant, is described in ongoing studies for approval. It can be implanted over the pars plana without sutures. It is now in phase II trial (LADDER, ClinicalTrials.gov identifier: NCT02510794) [135].

4.Overcoming the poor response to anti-VEGFs:

Newer pathway drugs are recently under investigation for the treatment of DME (**Table 3**).


**Table 3.**

*Recently, pathway drugs under investigation are used for the treatment of DME.*

*Diabetic Macular Edema, Clinicopathologic and Keys for Management DOI: http://dx.doi.org/10.5772/intechopen.112974*
