Vascular Analysis of Type 1, 2, and 3 Macular Neovascularization in Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Angiography Shows New Insights into Differences of Pathologic Vasculature and May Lead to a More Personalized Understanding

Abstract

Background: The clinical appearance of macular neovascularization (MNV) in age-related macular degeneration (nAMD) varies widely, but so far, this has had no relevance in terms of therapeutic approaches or prognosis. Therefore, our purpose was to investigate if and which differences exist in the vascular architecture of MNV and to quantify them. Methods: In 90 patients with newly diagnosed nAMD, MNV was identified by means of optical coherence tomography angiography (OCTA), and automated quantitative vascular analysis was carried out. The analyzed vascular parameters were area, flow, fractal dimension (FD), total vascular length (sumL), number of vascular nodes (numN), flow, and average vessel caliber (avgW). The current classification of MNVs divides them according to their localization into type 1 (grown from the choroid below the RPE), type 2 (grown from the choroid through RPE), and type 3 (grown from the retina toward the RPE). We compared the analyzed vascular parameters of each of the three MNV types. Kruskal–Wallis test was applied, Dunn test was performed for post hoc analysis, and for pairwise comparison, p-values were adjusted using Bonferroni comparison. Results: Regarding the MNV area, there was no significant difference between types 1 and 2, but type 3 was significantly smaller than types 1 and 2 (p < 0.00001). For FD, types 1 and 2 did not differ significantly, but again, type 3 was lower than type 1 and 2 (p < 0.00001). The numN were significantly higher in types 1 and 3 than in 2 (p < 0.005), but not between types 1 and 3. No significant differences were found between MNV types for flow. As for sumL, types 1 and 2 did not differ significantly, but type 3 was significantly lower than types 1 and 2 (p < 0.00001). For avgW, there was no significant difference between types 1 and 2 or between types 2 and 3, but type 3 was significantly larger than type 1 (p < 0.05). Conclusions OCTA yields detailed information on the vascular morphology of MNV in patients with nAMD and is able to show differences among types 1, 2, and 3. Especially comparing types 1 and 2 with type 3 reveals significant differences in area, FD, sumL, and numN. One explanation could be the similar pathogenesis of types 1 and 2 with their origin in the choroid and their growth towards the retinal pigment epithelium (RPE), whereas type 3 originates in the deep capillary plexus. Between types 1 and 2, however, only the numN differ significantly, which could be due to the fact that type 1 spreads horizontally below the RPE and, thus, display more vascular branching, while type 2 grows more vertically through the RPE and under the neurosensory retina. Detailed information about the pathologic vasculature is important for proper monitoring of the disease and to assess the efficacy of medication, especially with regard to new substances. This should be taken into consideration in future studies.

The Choroidal Vascularity Index Versus Optical Coherence Tomography Angiography in the Evaluation of the Choroid with a Focus on Age-Related Macular Degeneration

“…The exudative form is characterized by the growth of neo-formed vessels. Based on the origin of these vessels, macular neovascularization (MNV) is distinguished into three types: MNV type I, when the vessels originate from the CC and grow under the RPE; MNV type II, when the vessels grow between the RPE and the neuroepithelium; and MNV type III, when the vessels originate grow in neuroepithelium and deepen and anastomose with the choroid [ 75 ]. In addition to these types, exudative AMD also includes polypoidal choroid vasculopathy (PCV), characterized by subretinal polypoidal vascular lesions associated with a serous detachment of the RPE, particularly common in African Americans and Asian populations [ 76 ].…”

The Architecture of Macular Neovascularizations Predicts Treatment Responses to Anti-VEGF Therapy in Neovascular AMD

“…The described characteristics of the OCT images predominantly represented secondary effects of MNV, such as SRF/IRF, RPE alterations, PED, atrophy, hyperreflective foci, subretinal hyperreflective material, and changes in retinal thickness [ 28 ]. OCTA provides new detailed information on the vascular architecture of MNV, enabling more precise delineation of the various MNV types [ 17 , 18 ]. Schranz et al also described the vascular architecture of MNV in detail in a study and investigated at initial diagnosis and after one month (after single anti-VEGF administration) whether the MNV morphology or its change due to therapy allows conclusions to be made about the fluid distribution [ 34 ].…”

“…A further advantage of OCTA over FA is that the vessels can be viewed segment-wise and in three dimensions, with the vascular structure portrayed in detail [ 16 ]. This permits objective mathematical description of MNV and shows previously unseen differences in patterns of disease [ 17 , 18 , 19 ]. It would be desirable to have a biomarker before the start of anti-VEGF-therapy that predicts the response to therapy in order to enable optimal patient education and individual therapy.…”

Association between Polymorphisms in CFH, ARMS2, CFI, and C3 Genes and Response to Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration

“…The nAMD is characterized by macular neovascularization (MNV)—an invasion of vascular and associated tissues into the outer retina, subretinal space, or sub-retinal pigment epithelium (sub-RPE) space in varying combinations, leading to the accumulation of subretinal fluid (SRF) and intraretinal fluid (IRF) and RPE detachment (PED) [ 1 ]. The current classification of MNVs divides them according to their localization into type 1 (grown from the choroid below the RPE), type 2 (grown from the choroid through RPE), and type 3 (grown from the retina toward the RPE) [ 5 ]. At present, optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow-up of nAMD patients [ 6 ].…”