Daniel Pauleikhoff

Purpose: To characterize the choroidal morphology across a spectrum of participants affected by normal aging as well as age-related macular degeneration (AMD) using various metrics. Methods: Four cohorts were analyzed: healthy young ( n = 42), healthy elderly ( n = 19), iAMD ( n = 20), and treatment-naive nAMD eyes ( n = 79). Quantification of choroidal volume (CV) and choroidal vessel volume (VV) resulting in choroidal vascularity index (CVI) as well as mean choroidal thickness (CT), vessel thickness (VT) and foveal vessel area (FVA) and vessel count (FVC) were derived from spectral-domain optical coherence tomography using an artificial intelligence (AI)-based semantic segmentation model with manual validation. Cohort differences were statistically assessed. Results: All choroidal parameters were reduced in healthy elderly, iAMD and nAMD eyes compared with young controls. While most of these reduced choroidal measurements were largely similar between healthy elderly, iAMD and nAMD eyes, only CVI and FVA showed a specific reduction in nAMD eyes. Conclusions: This study demonstrates a decline in several choroidal parameters with age, which can be quantified using AI-based segmentations. While age-related reductions were comparable between elderly and iAMD eyes, a significantly higher reduction of the CVI and FVA was observed in eyes with nAMD which may indicate a more pronounced alteration of choroidal structure in this condition.

Purpose: To compare artificial intelligence (AI)-based annotations of hyperreflective material (HRM) and manual demarcation of macular neovascularization (MNV) on optical coherence tomography (OCT) volume scans in neovascular age-related macular degeneration (nAMD), and to assess the suitability of AI-driven OCT segmentation for longitudinal lesion monitoring. Methods: In this retrospective study, 42 eyes from 36 patients (21 f, 15 m; mean age baseline 76.6 y) with exudative nAMD were analyzed using longitudinal spectral-domain OCT data. Manual MNV demarcations on en-face OCT projections served as ground truth and were compared to AI-predicted HRM segmentations generated by a 3D nU-Net model on OCT scans. HRM and MNV lesion areas were quantified at multiple time points, and agreement between manual and AI-based measurements was evaluated using Pearson correlation, ordinary least squares regression and robust regression. Results: A highly similar mean lesion growth was observed when comparing HRM/MNV lesion sizes in longitudinal measurements. Point-by-point comparison revealed a strong overall correlation (r = 0.78) between AI-predicted and manually annotated HRM areas with increasing significance with longer follow-up. However, two aspects were responsible for some AI measurements being larger than manual measurements: At baseline, AI measurements included hyperreflective subretinal fluid as HRM, which was resorbed after three anti-VEGF injections, and during longer-term follow-up, manually annotated MNV areas were occasionally smaller than those derived from AI-based HRM segmentation due to the manual underestimation of very thin HRM. Conclusions: AI-based segmentation of HRM on OCT scans demonstrates strong overall agreement with manual MNV measurements, particularly on longitudinal assessments. Despite some AI-based overestimations occurring at baseline and some manual MNV underestimations during follow-up, measurements between both methods were highly comparable over time.

Growth of macular neovascularization (MNV) associated with development of complete retinal pigment epithelial and outer retina atrophy (cRORA) been observed in eyes neovascular age-related macular degeneration (nAMD) under effective anti-vascular endothelial growth factor (VEGF) therapy. We aimed to evaluate the influence of the presence of MNV on the sensitivity of the overlaying retina both in patients with or without cRORA and to generate hypotheses about their association. Pilot study on nAMD patients undergoing long-term anti-VEGF therapy that had also undergone microperimetry testing. Area of MNV and, if present, associated cRORA were identified on optical coherence tomography (OCT) volume scans and transposed onto en-face near-infrared images. Mesopic microperimetry performed at the same visit was then superimposed. Retinal sensitivity above the MNV and the surrounding retina were compared, excluding areas of cRORA. Twenty-six eyes (19 f, 7 m; age 79.3 ± 5.7 y; fu 4.0 ± 1.8 y; 7.4 ± 2.5 inj./y) were classified into a no cRORA (n = 11) and a cRORA group (n = 15). In the no cRORA group, mean retinal sensitivity above the MNV did not differ from the surrounding retina (20.9 ± 2.8 vs. 22.0 ± 2.4, p = 0.33), while in the cRORA group, a lower sensitivity above the MNV in comparison to the surrounding retina was observed (16.2 ± 3.4 vs. 19.9 ± 2.0, p = 0.001). In the absence of cRORA, retinal sensitivity above the MNV did not differ significantly from that of the surrounding retina. These results could indicate a possible nutritional function of the MNV to the overlying retina in cases where no cRORA is present.

This retrospective, real-life cohort was analyzed to detect the frequency of different HRM evolution patterns and their correlation with MNV types, morphol

Purpose: Growth of macular neovascularization (MNV) associated with the development of macular atrophy in some eyes has been observed in neovascular age-related macular degeneration (nAMD) under effective anti-vascular endothelial growth factor (VEGF) therapy. We aimed to evaluate the influence of growing MNV and macular atrophy development on the sensitivity of the overlaying retina. Methods: Prospective pilot study on nAMD patients undergoing long-term anti-VEGF therapy (IVAN treatment strategy) that had also undergone microperimetry testing. MNV extension and, if present, associated macular atrophy defined as complete retinal pigment epithelial and outer retina atrophy (cRORA) were identified on OCT volume scans and transposed onto en-face NIR images. Mesopic microperimetry performed at the same visit was superimposed. Retinal sensitivity above the MNV and the surrounding retina was compared, excluding areas of cRORA. Results: 26 eyes (19 f, 7 m; age 79.3 ± 5.7 y; fu 4.0 ± 1.8 y; 7.4 ± 2.5 inj./y) were classified into “no cRORA” group (n=11) and “cRORA” group (n=15). In the “no cRORA” group, BCVA was significantly higher, and mean retinal sensitivity above the MNV did not differ from the surrounding retina (20.9 ± 2.8 vs. 22.0 ± 2.4, p=.33), while in the “cRORA” group, a lower sensitivity above the MNV was observed (16.2 ± 3.4 vs 19.9 ± 2.0, p=.001). Conclusion: In the absence of cRORA, retinal sensitivity above the MNV did not differ significantly from that of the surrounding retina. These results support the hypothesis that MNV itself may not be detrimental if cRORA can be prevented.

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 doctorʼs 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.

Purpose: To analyze the morphological changes of macular neovascularization (MNV) in exudative neovascular age-related macular degeneration under long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy in a retrospective cohort study. Methods and patients: We evaluated 143 nAMD eyes of 94 patients (31 male, 63 female; initial age 55–97 y, mean age 75.9 ± 7.5 y), who started anti-VEGF therapy (IVAN pro re nata (PRN) protocol) between 2009–2018 and received ongoing therapy until the last recorded visit (mean follow-up 5.3 ± 2.9 y, range 1–14 y). The mean total number of injections was 33.3 ± 19.8 with 7.0 ± 2.3 injections/year. MNV size and, if present, associated complete retinal pigment epithelium (RPE) and outer retina atrophy (cRORA) size were measured on optical coherence tomography (OCT) volume scans at the initial visit and for each year of follow-up. MNV and cRORA were identified on B-scans and their respective borders were manually transposed onto the en-face near infrared image and measured in mm². Results: MNV enlarged through follow-up, with a mean growth rate of 1.24 mm² / year. The mean growth in MNV size was independent of initial MNV size, age, gender, MNV subtypes or number of injections per year. Nevertheless, a great interindividual variation in size and growth was observed. cRORA developed in association with increasing MNV size and its incidence increased linearly over follow-up. cRORA lesions also showed continuous growth by a rate of 1.22 mm² / year. Conclusions: Despite frequent long-term anti-VEGF therapy, we observed ongoing MNV growth. This is consistent with the concept that the development of MNV may be a physiological biological repair mechanism to preserve RPE and photoreceptor function, provided hyperpermeability and fluid exudation are controlled. Whether recurring low VEGF levels or other factors are responsible for MNV growth remains controversial.