Is Exudative Neovascular AMD a Chronic Disease? Analysis of Long-term Progression under Anti-VEGF Therapy. / Ist die exsudative neovaskuläre AMD eine chronische Erkrankung? Analyse von Langzeitverläufen unter einer Anti-VEGF-Therapie.

BACKGROUND: Anti-VEGF therapy is the standard treatment for exudative neovascular age-related macular degeneration (nAMD) caused by the development of macular neovascularisation (MNV) with associated fluid exudation. The therapeutic strategies (T&E or PRN) assumed a scarring transformation of the MNV and exit strategies and were formulated accordingly. The present study investigates this hypothesis as a real-life long-term analysis. PATIENTS: 150 eyes of 97 patients were continuously followed up over a mean period of 5.1 years (1 - 14 years) after initiation of anti-VEGF therapy between 2009 - 2017 until 2022. Treatment was based on the PRN regimen analogous to the IVAN study with ranibizumab, aflibercept or bevacizumab. The length and intensity of therapy were evaluated. RESULTS: Of these 150 eyes, 119 (79.3%) required ongoing anti-VEGF therapy, while in 18 eyes (12.0%) therapy could be discontinued due to stabilisation of the situation. In 13 eyes (8.7%), therapy was discontinued due to deterioration in visual acuity to < 0.05. With ongoing therapy, therapy was often protracted, with an indication for therapy at the last documented doctor's visit, while stabilisation was often achieved within the first 2 years of treatment. The treatment intensity increased to 7.7 - 8.0 injections/year, especially after 2013, with the introduction of OCT-based treatment criteria. Most eyes (74.8%) with ongoing therapy required 6 - 9 injections/year even in the last three years of treatment. CONCLUSION: The fact that in the present study there is a long-term and intensive need for therapy in the majority of patients (approx. 80%) with exudative nAMD, supports the assessment that nAMD should be regarded as a chronic disease. Therefore, a proactive treatment strategy with consistent therapy at any sign of lesion activity might be recommended. Particularly in view of the risk of irreversible loss of vision, long term adherence of patients is also crucial for the best possible long term therapeutic outcome.

Analysis of the Vascular Morphology of the Fibrotic Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography. / Analyse der Gefäßmorphologie der fibrosierten choroidalen Neovaskularisation bei neovaskulärer altersabhängiger Makuladegeneration mittels optischer Kohärenztomografie-Angiografie.

PURPOSE: Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA). METHODS: In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruch's membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images. RESULTS: Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006). CONCLUSION: In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.

Microvascular Density Analysis of Patients with Inactive Systemic Lupus Erythematosus-A Two-Year Follow-Up Optical Coherence Tomography Angiography Study.

Background/Objectives: This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence tomography angiography (OCT-A). Methods: Twenty-four eyes of 24 patients with inactive SLE under hydroxychloroquine (HCQ) therapy were included. The OCT-A data (mainly vessel density (VD) and foveal avascular zone (FAZ) data of the superficial and of the deep capillary plexus (SCP, DCP) and the choriocapillaris (CC)) were analyzed and compared between the baseline examination (t0) and 2 years later (t1). Results: At t1, VD in the whole en face SCP and in the CC was notably reduced compared to t0 (SCP: p = 0.001, CC: p = 0.013). VD in the DCP, CRT and FAZ area showed no difference at t1 compared to t0 (DCP: p = 0.128, FAZ: p = 0.332, CRT fovea: p = 0.296). Correlation analysis between the increase in cumulative doses of HCQ between t0 and t1 and the VD of the whole en face SCP did not show any correlation (Spearman r = 0.062 (95% CI -0.367; 0.477). Conclusions: SLE patients demonstrated a decrease in the retinal VD of the SCP and CC over a 2-year period. There was no correlation with the change in cumulative doses of HCQ. These results suggest an ongoing effect of the disease on the retinal and choriocapillary microcirculation.

[Influence of CNV vascular morphology in exudative age-related macular degeneration on development of visual acuity and need for anti-VEGF therapy after 1 year]. / Einfluss der CNV-Gefäßmorphologie bei exsudativer altersabhängiger Makuladegeneration auf die Visusentwicklung und den Anti-VEGF-Therapiebedarf nach 1 Jahr.

BACKGROUND: The aim of this pilot study was to investigate vascular morphological characteristics of choroidal neovascularization (CNV) at the time of the initial diagnosis of exudative age-related macular degeneration (nAMD), which enable a prognosis for the development of visual acuity and the necessity for treatment in the first year. METHODS: In 57 patients with the initial diagnosis of nAMD, CNV was detected by optical coherence tomography angiography (OCT-A) and an automated quantitative vessel analysis was performed with respect to area, total vessel length, flow value and average vessel caliber of the CNV. After 12 months patients were divided into 2 groups based on visual acuity (visual loss vs. visual gain) and necessity of anti-VEGF therapy (<7 intravitreal injections, IVOM vs. ≥7 IVOM). RESULTS: The mean CNV area was 0.95 mm2 ± 1.07 mm2 (group visual loss 1.56 mm2 ± 1.54 mm2; group visual gain 0.65 mm2 ± 0.53 mm2; p = 0.002/<7 IVOM 1.05 mm2 ± 1.40 mm2; ≥7 IVOM 0.98 mm2 ± 0.94 mm2, p = 0.60). The average total vessel length of the CNV was 9.84 mm ± 11.35 mm (visual loss 16.00 mm ± 16.58 mm; visual gain 6.74 mm ± 5.42 mm; p < 0.003/<7 IVOM 11.21 mm ± 15.10; ≥7 IVOM 9.90 mm ± 9.68 mm; p = 0.68). The mean flow value of the CNV was 0.40 ± 0.06 (visual loss 0.37 ± 0.04; visual gain 0.41 ± 0.07; p = 0.004/<7 IVOM 0.42 ± 0.08; ≥7 IVOM 0.38 ± 0.06; p = 0.02). The average vessel caliber was 28.86 µm ± 2.93 µm (visual loss 28.39 µm ± 2.97 mm; visual gain 29.32 µm ± 3.05 µm; p = 0.24/<7 IVOM 30.26 µm ± 3.49 µm; ≥7 IVOM 28.23 µm ± 2.25 µm; p = 0.02). CONCLUSION: The results show that a mathematical quantification of the CNV in nAMD is possible using OCT­A. This analysis confirmed again that the size of the CNV (area and total vessel length) is decisive for the prognosis of visual acuity. It also shows that a larger flow value as a sign of a well-differentiated CNV is associated with a better functional prognosis. The number of IVOMs required, however, depends primarily on the composition of the CNV (flow value and vascular caliber). More precise imaging and larger examination cohorts could possibly reveal further relevant biomarkers.

[Fibrovascular transformation of CNV in nAMD after long-term anti-VEGF therapy : Methodological evaluation of quantifying morphological changes]. / Die fibrovaskuläre Umwandlung der CNV bei nAMD unter lang andauernder Anti-VEGF-Therapie : Methodenevaluation zur Quantifizierung morphologischer Veränderungen.

BACKGROUND: Under long-term anti-VEGF therapy neovascular age-related macular degeneration (nAMD) may result in fibrovascular transformation of choroidal neovascularization (CNV). So far there is a lack of definitions on how a differentiated quantification of the associated morphological changes can best be carried out. This pilot study aimed to define the most appropriate imaging modalities. PATIENTS AND METHODS: In 56 eyes with fibrotic CNV after at least 2 years of anti-VEGF therapy and at least 12 intravitreal anti-VEGF injections, the following imaging modalities were investigated with respect to the delimitation of vascular and fibrous portions of CNV as well as associated atrophy of retinal pigment epithelium (RPE) and disruption of the ellipsoid zone (EZ): multicolor imaging (MC), fundus autofluorescence (FAF), fluorescein angiography (FA) and indocyanine green angiography (ICGA), spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). RESULTS: The vascular portion of fibrotic CNV was best visualized by OCTA, the fibrous portion by SD-OCT. The RPE atrophy was best delimitated by FAF, but differentiation was also possible by MC and ICGA. Disruption of the EZ could be delineated by SD-OCT b­scan. CONCLUSION: The use of MC is suitable for visualization of RPE atrophy and the fibrous portion of fibrotic CNV and FAF is suitable for differentiation of RPE atrophy. The SD-OCT can be used to quantify the fibrous portion of CNV; the EZ interruption is delimitable in the b­scan but not in the transverse structure-scan. The vascular part can best be detected by OCTA.

Morphologic analysis of macular neovascularizations by OCT angiography-Technical limitations in the comparison of 3×3mm and 6×6mm images.

BACKGROUND: The aim of this study was to ascertain whether there are relevant differences between the vascular morphology of macular neovascularizations (MNV) in 3×3mm and 6×6mm images, produced by optical coherence tomography angiography (OCTA). METHODS: MNV of 49 patients were automated quantitative analysed, measuring area, flow, the fractal dimension, average vessel length, vascular density, and average vessel caliber. These parameters were compared between the 3×3mm and the 6×6mm images. RESULTS: A strong linear association was found between the 3×3mm and the 6×6mm images. While area, flow, and FD of the MNV were very similar, the 3×3mm images showed significantly lower average total vessel length, greater vascular density, and lower average vessel caliber. CONCLUSION: In quantitative analysis of the morphologic parameters of MNV in 3×3mm and 6×6mm images, the structures are not directly equivalent in the two sizes of scan. The images must be evaluated on an individual basis.