**3. The role of OCT + OCT-A in nAMD**

#### **3.1 Specific OCT biomarkers**

Several OCT-based biomarkers, including the central subfoveal thickness (CSFT), the presence of intraretinal cysts (IRCs) or fluid (IRF), subretinal fluid (SRF), and sub-RPE fluid or pigment epithelial detachment (PED), were found to be associated with baseline visual acuity and response to the anti-VEGF treatment (**Figure 1**). One of the main goals in the management of nAMD has been the removal of fluid in the macular compartments [26]. The clinical significance of fluid depends on its location where it plays a major role in determining the long term success of the treatment and its presence should be recorded at baseline, according to the guidelines from the Vision Academy. Fluid segments should be assesed individually and fluid status evaluated after loading phase and throughout the course of treatment [29, 30].

The introduction of OCT into everyday clinical practice allowed a new classification of CNV according to its location, complementing fluorescein angiography (FA) and indocyanin green angiography (ICGA) [31]. In OCT, type 1 CNV, located between Bruch membrane (BM) and RPE, corresponds to PED, often accompanied

**Figure 1.** *OCT biomarkers.*

by subretinal fluid and in later stages of disease by IRC [32]. Type 2 CNV presents as subretinal hyperreflective material (SHRM) and shows concomitant IRF and SRF [33]. SHRM may be composed of exudative fluid, fibrin, blood, or scarring and its characteristics may change during treatment period [34]. According to CATT study, SHRM was present in 77% of treatment-naive eyes at baseline with the prevalence decreasing to 58% at week 4 after treatment and further to 46% after 2 years [35]. It is hypothesized to be caused probably by a dehydration and condensation of the active CNV component [36, 37].

IRC overlying PED, accompanied by SRF, are typical features commonly present in retinal angiomatous proliferation (RAP), classified as type 3 CNV by Freund et al. [38]. Mature type 3 lesions, associated with serous PEDs, are highly responsive to anti-VEGF therapy [39]. However, the development of GA has frequently been described in association with treatment of RAP lesions [40].

#### *3.1.1 Central subfoveal thickness*

The greatest importance of CSFT was actually in the research because it was used as a criterion for continued treatment in trials of various drugs and treatment protocols. If the reduction in CSFT after injection is less than 25%, this is considered a criterion for reinjection [41, 42].

Value of CSFT depends mostly on the amount of retinal fluid in the different retinal compartments, so in most cases a higher CSFT is also a sign of a worse VA. If the cause of CSFT is mostly retinal fluid, it will be reduced by treatment with anti-VEGF factors, and VA in this case will be better or not get worse. Recently there was an observation that there is a direct correlation between vision, fluid, the amount of fluid, and fluctuations in CST [28]. A new option is to look at what effect a drug has on fluctuations in CST, which may prove to be extremely important in identifying patients at risk for closer monitoring and more aggressive therapy.

The presence of an epiretinal membrane (ERM) and the accumulation of drusenoid or fibrous material may also be responsible for a higher CSFT. In this case, the prognosis for CSFT reduction with anti-VEGF treatment is usually poor [28, 41].

A certain percentage of subjects in clinical trials as well as patients in clinical practice developed geographic atrophy (GA) after treatment with anti-VEGF factors. Risk factors for such development include the presence of foveal fluid and monthly dosing of injections. In the CATT study, approximately 38% of subjects developed GA after 5 years, mainly those receiving ranibizumab rather than aflibercept. In the case of GA development, a lower CSFT will also mean a significantly lower VA [7, 43].

#### *3.1.2 Intraretinal fluid*

Intraretinal fluid appears as round or oval hyporeflective spaces – cysts, but may also present as diffuse thickening of the neurosensory retina [1]. Intraretinal cysts (IRCs) are OCT biomarkers for various retinal diseases such as nAMD, diabetic macular edema, central retinal vein occlusion, and uveitic macular edema.

Since IRCs often differ in their shape and size, and also in their response to anti-VEGF therapy, some authors have divided them into exudative and degenerative. The criteria taken into account were the size of the cyst, its shape, and the possible alteration of the continuity of the RPE below the cyst. Degenerative cysts were described as smaller than 125 μm, usually square in shape and with RPE alterations below the cyst itself, while exudative cysts are more often ovoid and larger [41, 44, 45]. Intraretinal fluid usually results from active fluid exudation, but the

#### *Anti-VEGF Treatment and Optical Coherence Tomography Biomarkers in Wet Age-Related… DOI: http://dx.doi.org/10.5772/intechopen.97689*

degenerative cysts may orginate from passive fluid accumulation due to atrophy of neurosensory elements [1]. Exudative cysts had better initial response to 3 loading monthly injections of anti-VEGF treatment whereas degenerative cysts had lower response to the therapy, persisted for a longer time and were associated with lower VA after treatment [44–47].
