**4. Optical coherent tomography**

Systematic analysis of OCT at the initial visit provides insight into the severity and duration of the disease and guides the appropriate choice of treatment and regimen.

**The location, size and content of intra- and subretinal fluid collections**: **Cystic spaces exceeding 200μm** involving the outer nuclear layer (ONL) are seen in late stage of DME and have a worse impact on macular function than smaller cysts or cystoid formations occurring in inner retinal layers (**Figure 2b**). **Large cysts located in the perimacular area** tend to extend centrally with time (**Figure 3b** and **d**). Even though in the early phases the visual acuity is not severely deteriorated, in the presence of other risk factors treatment has to be initiated – these patients have excellent chances to retain good function without major fluctuations. Lack of retinal bridges between the cystic spaces in the inner and outer retina is a sign of long-standing severe disease and is associated with poor visual prognosis despite resolution of the fluid post treatment (**Figure 2d**). **Subfoveolar neurosensory detachment** is seen in cases with more severe edema and has been associated with more active inflammatory components of the disease (**Figure 1a**). These patients responded favorably in the pivotal clinical trials on anti-VEGF and dexamethasone treatment with significant functional gains. This type of edema has a tendency to recur in chronic cases with interrupted intravitreal treatment, deterioration of the systemic disease or after cataract surgery (**Figure 4**).

**Hyperreflective retinal foci** appear as small lesions with size less than 30μm with reflectivity similar to retinal nerve fiber layer and without back-shadowing over the underlying layers. They appear to represent subclinical lipoproteins that extravasate after breakdown of inner blood–retinal barrier, although there are suggestions that they might be activated microglial cell, and indicate chronicity and predominant inflammation in the eye. Increased number of the spots indicate tendency for recurrence of the edema and require close monitoring (**Figures 1c** and **7d**).

**Hard exudates** present in the OCT as hyperreflective intraretinal accumulations larger than 30 μm with back-shadowing. The deposits are thought to consist of lipoproteins and indicate advanced microvascular damage and chronicity. In severe cases they can form fibrotic lesions that are associated with visual decline, especially if located in or close to the macula (**Figure 5**) [11].

**Disorganization of retinal inner (DRIL) and outer layers within the central 1 mm retinal zone** may not be readily distinguishable if the edema is severe and

#### **Figure 2.**

*58 years old male, nephropathy, diabetic foot, CAD, PDR, recurrent macular edema, neovascularglaucoma after glaucoma drainage implant (Ahmed valve). a –OCTA total retina –broad areas of hypoperfusion, microaneurisms, enlarged distorted foveolar avascular zone; b -severe recurrence during Leukemoid reaction, HbA1c 11%, VA 20/200; c -one week after anti-VEGF injection, VA 20/70; d* − *3 months later -recurrence after treatment on Imatinib for 3 months, VA 20/100; e -one month after anti-VEGF injection, VA 20/50; f –recurrence during deteriorated foot ulcer, HbA1c 9% VA 20/150; g –one month after anti-VEGF intravitreal injection, VA 20/50; h –OCTA superficial plexus-decreased central perfusion by 54% in 6 months after 4 major recurrences; i –advanced OND pallor, macrocystsand atrophic areas in the macula, severe ischemia and NVE.*

#### **Figure 3.**

*60 years old female, 20 years of poorly controlled DM, arterial hypertension; multiple recurrences of perimacularedema, NPDR. a –One month after anti-VEGF injection, VA 20/20; b –treatment interrupted for 8 months, VA 20/30, 5 months after hysterectomy; c –one month later after anti-VEGF, VA 20/20; d, e–3 months later-new recurrent intraretinal edema progressing towards the macula, new ischemic areas, VA 20/30, f, g–one month after anti-VEGF injection and focal laser, persistent perimacular ischemia, VA 20/20.*

associated epiretinal membranes and hyperreflective lesions, especially if there are media opacities (**Figure 2**). It is becoming evident in the course of the treatment after regression of the edema and explains the low visual acuity and minimal vision gain. DRIL has been attributed to macular capillary non-perfusion, the size and erosion

#### *High-Risk Diabetic Maculopathy: Features and Management DOI: http://dx.doi.org/10.5772/intechopen.99748*

#### **Figure 4.**

*57 years old female, DM for 25 years, sleeve gastrectomy, chronic cholecystitis, CAD, DME, PDR, secondary glaucoma. a –after 3 anti-VEGF injections and 1 OzurdexVA 20/60, cataract; b –deteriorated edema with subsensory fluid 14 days after phacemulsificationVA 20/60; c* − *14 days after anti-VEGF injection, VA 20/30; d – recurrent edema during CABG, subsensory fluid, hyperreflective foci VA 20/40; e –severe edema after pyocele and sepsis, VA 20/40; f –recurrence after stroke, VA 20/30; g* − *7 days after Ozurdex, VA 20/25; h –severe recurrence 3 months after the second Ozurdex, VA 20/40; j –rapid response to Iluvien, VA 20/25; k –microperimetry-decreased central retinal sensitivity, unstable central fixation; l -decreased central perfusion in the superficial plexus by 46% in 18 months; m –microcystic edema and hard exudates in the macula, stable PDR, visible Iluvien implant.*

#### **Figure 5.**

*70 years old female. Chronic macular edema, NPDR, chronic uveitis, secondary glaucoma for 12 years, poorly controlled diabetes, arterial hypertension, lost for follow up for 4 years. a –Three weeks after intensive topical steroids and antiglaucoma medications VA 20/250; b -after 4 anti-VEGF and focal laser –persistent macrocystic edema, regressing hard exudates, VA 20/50, c –OCTA –total retina-significant capillary dropout, enlarged irregular foveolar avascular zone; d –chronic edema, circinate hard exudates.*

of the foveolar avascular zone and has been correlated with increasing severity of the retinopathy, especially in patients with proliferative disease (**Figure 6**). The presence of DRIL can be associated with disorganized outer retinal layer disruption,

**Figure 6.**

*60-years old female, 20 years of poorly controlled diabetes. Phacoemulsification and vitrectomy, choroidal effusions. a -Severe DME, epiretinal membrane, DRIL one month after surgery; b* − *4 months later after 3 anti-VEGF injections –incomplete, unstable response; c* − *6 months later after 2 Ozurdex implants –residual perimacular degenerative fluid spaces; d –persistent macular edema, mild DRIL, epiretinal membrane, hard exudates and microaneurisms.*

specifically ellipsoid zone (EZ) and external limiting membrane (ELM). Moreover, Sun and colleagues have found that an increase in DRIL during 4months predicted a decline of visual acuity by one line [12].

OCT assessment of the **vitreomacular adhesions and traction** is indispensable in the choice of treatment. The presence of anterior–posterior traction is considered an indication for pars-plana vitrectomy in eyes with DME, however other OCT findings - greater retinal thickness, presence of subretinal fluid, lack of external limiting membrane integrity and disruption of the ellipsoid zone - have been associated with a poorer final absolute BCVA [10]. Macular edema in eyes with lamellar holes associated with tangential traction needs careful consideration – it often responds favorably to intravitreal treatment and may remain stable, however should be monitored closely in the presence of active PDR and may eventually require surgical management (**Figure 1**).

### **5. Optical coherent tomography angiography**

The contribution of OCTA in the assessment of high-risk DME is substantial. It will detect capillary dropout, microaneurisms and neovascularization in detailed 3-dimentional segments (**Figure 2a**) and provide quantitative estimates of the perfusion and vascular density by areas [13] (**Figure 4I**). A recent study demonstrated that although there was no significant difference in the superficial capillary plexus between anti-VEGF responders and poor responders, poor responders tended to show greater damage and more microaneurysms in the deep capillary plexus and a larger foveolar avascular zone (FAZ) area. The topographic location of the disrupted synaptic portion of the outer plexiform layer in SD OCT exactly corresponded to the nonflow area of the deep capillary plexus in OCTA [14]. The enlargement and irregularities of the FAZ have to be interpreted carefully in the presence of large central cysts as such findings could be associated with capillary displacement rather than ischemia, especially in eyes with retained inner and outer retinal morphology. OCTA assessment of patients with DME and neurosensory detachment demonstrated improvement in cysts area and perfusion density in the superficial and deep capillary plexus in response to treatment with Dexamethasone and ranibizumab [15]. Persistent microaneurisms and declining perfusion in the deep capillary plexus in another comparative work was associated with less vision gain and incomplete resolution of the edema after treatment with aflibercept [16].
