Fibrosis in neovascular age-related macular degeneration: A review of definitions based on clinical imaging

Bachmeier, Isabel; Armendariz, Beatriz Garcia; Yu, Siqing; Jäger, Ralf Josef; Ebneter, Andreas; Glittenberg, Carl; Pauleikhoff, Daniel; Sadda, Srinivas R; Chakravarthy, Usha; Fauser, Sascha

doi:10.1016/j.survophthal.2023.03.004

Cited by 7 publications

(4 citation statements)

References 107 publications

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“…Long-term adherence can be improved through specific case management modules, such as compliance checks at every appointment with a recall system if the patient is a no-show, as well as continuous situation-specific and personalized patient informa-(e.g., AMD-Netz; www.amd-netz.de) [10]. Since years or decades of therapy are likely to be in many cases [11,12], structured treatment programs may also be useful.…”

Section: Discussionmentioning

confidence: 99%

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Ist die exsudative neovaskuläre AMD eine chronische Erkrankung? Analyse von Langzeitverläufen unter einer Anti-VEGF-Therapie

Gunnemann,

Ziegler,

Book

et al. 2024

Klin Monbl Augenheilkd

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Hintergrund: Die Anti-VEGF-Therapie ist die Standardtherapie bei der exsudativen neovaskulären Altersabhängigen Makuladegeneration (nAMD), deren Ursache die Entwicklung einer makulären Neovaskularisation (MNV) mit assoziierter Flüssigkeitsexsudation ist. Die therapeutischen Strategien (T&E oder PRN) gingen von einer narbigen Transformation der MNV aus und Exit-Strategien wurden dementsprechend formuliert. Die vorliegende Studie untersucht als real-life Langzeitanalyse diese Hypothese. Patienten: 150 Augen von 97 Patienten wurden über ein mittleres follow-up von 5,1 Jahren (1-14 Jahre) nach Beginn einer Anti-VEGF-Therapie zwischen 2009-2017 kontinuierlich bis 2022 nachbeobachtet. Behandelt wurde nach PRN-Schema analog der IVAN-Studie mit Ranibizumab, Aflibercept oder Bevacizumab. Ausgewertet wurden Länge und Intensität der Therapie. Ergebnisse: Von den 150 Augen benötigten 119 Augen (79,3%) eine fortlaufende Anti-VEGF-Therapie, während bei 18 Augen (12,0%) die Therapie auf Grund einer Stabilisierung der Situation beendet werden konnte. Bei 13 Augen (8,7%) wurde die Therapie auf Grund einer Visusverschlechterung auf ein Sehvermögen <0,05 abgebrochen. Bei fortlaufender Therapie zeigte sich häufig eine lange Therapiedauer mit Therapieindikation beim letzten dokumentierten Arztbesuch, während eine Stabilisierung oft innerhalb der ersten 2 Behandlungsjahre erreicht wurde. Die Therapieintensität nahm vor allem nach 2013 mit Einführen der OCT-basierten Behandlungskriterien auf 7,7-8,0 Inj/Jahr zu. Die meisten Augen (74,8%) mit fortlaufender Therapie benötigten 6-9 Injektionen / Jahr auch noch in den letzten drei Behandlungsjahren. Schlussfolgerung: Die Tatsache, dass in der vorliegenden Studie erneut bei der Therapie der exsudativen nAMD bei einem Großteil der Patienten (ca. 80%) eine langfristige und intensive Therapienotwendigkeit beobachtet wurde, unterstützt die Einschätzung, dass die nAMD als eine chronische Erkrankung anzusehen ist. Daher erscheint eine proaktive Behandlungsstrategie mit konsequenter Therapie bei jeglichen Aktivitätszeichen sinnvoll. Insbesondere im Hinblick auf die Gefahr des irreversiblen Visusverlusts ist zudem die Langzeitadhärenz der Patienten für ein bestmögliches langfristiges Therapieergebnis entscheidend. Background: Anti-VEGF therapy is the standard treatment for exudative neovascular age-related macular degeneration (nAMD) caused by the development of macular neovascularization (MNV) with associated fluid exudation. The therapeutic strategies (T&E or PRN) assumed a scarring transformation of the MNV and exit strategies 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 follow-up 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 eyes (79.3%) required ongoing anti-VEGF therapy, while in 18 eyes (12.0%) therapy could be discontinued due to stabilization of the situation. In 13 eyes (8.7%), therapy was discontinued due to a deterioration in visual acuity to <0.05. With ongoing therapy, there was often a long duration of therapy with an indication for therapy at the last documented doctor's visit, while stabilization was often achieved within the first 2 years of treatment. The treatment intensity increased to 7.7-8.0 Inj/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 a long-term and intensive need for therapy was again in the majority of patients (approx. 80%) with exudative nAMD observed, 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.

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Section: Discussionmentioning

confidence: 99%

“…jahrzehntelange Therapie oft notwendig ist [11,12], sind zudem strukturierte Behandlungsprogramme eventuell sinnvoll.…”

Section: Behandlungsintensität Während Der Letzten 3 Jahre Der Studie...unclassified

Ist die exsudative neovaskuläre AMD eine chronische Erkrankung? Analyse von Langzeitverläufen unter einer Anti-VEGF-Therapie

Gunnemann,

Ziegler,

Book

et al. 2024

Klin Monbl Augenheilkd

Self Cite

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“…Additionally, the type of anti-VEGF agents varied between patients and also over time in individual patients and was not taken into account in our study, which could also impact MNV growth. Since patients did not have annual angiographic examinations or color fundus photographs, differentiation of MNV parts with more fibrotic transformation or presumed capillary growth was not possible [36]. Strengths of our study include the very long follow-up duration, a highly standardized grading performed by one, experienced retina specialist, the study of real-word patients rather than those from a controlled trial, and cRORA grading on OCT rather than on fundus photograph as performed in some earlier reports.…”

Section: Plos Onementioning

confidence: 99%

Morphological changes of macular neovascularization during long-term anti-VEGF-therapy in neovascular age-related macular degeneration

Pauleikhoff,

Gunnemann,

Ziegler

et al. 2023

PLoS ONE

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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.

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“…Furthermore, while there is plenty of data evaluating visual acuity in eyes with retinal fibrosis there is a lack of data considering focal retinal sensitivity to our knowledge [24][25][26]. Aggravating, there is a lack of uniformity considering the definition of retinal fibrosis and the ideal imaging method [27].…”

Section: Introductionmentioning

confidence: 99%

Structure-Function Correlation of Retinal Fibrosis in Eyes with Neovascular Age-Related Macular Degeneration

Schranz,

Sacu,

Reiter

et al. 2024

JCM

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Purpose: To assess retinal function in areas of presumed fibrosis due to neovascular age-related macular degeneration (nAMD), using multimodal imaging and structure-function correlation. Design: Cross-sectional observational study. Methods: 30 eyes of 30 consecutive patients with nAMD with a minimum history of one year of anti-vascular endothelial growth factor therapy were included. Each patient underwent microperimetry (MP), color fundus photography (CFP), standard spectral-domain-based OCT (SD-OCT), and polarization sensitive-OCT (PS-OCT) imaging. PS-OCT technology can depict retinal fibrosis based on its birefringence. CFP, SD-OCT, and PS-OCT were evaluated independently for the presence of fibrosis at the corresponding MP stimuli locations. MP results and morphologic findings in CFP, SD-OCT, and PS-OCT were co-registered and analyzed using mixed linear models. Results: In total, 1350 MP locations were evaluated to assess the functional impact of fibrosis according to a standardized protocol. The estimated means of retinal areas with signs of fibrosis were 12.60 db (95% confidence interval: 10.44–14.76) in CFP, 11.60 db (95% COI: 8.84–14.36) in OCT, and 11.02 db (95% COI 8.10–13.94) in PS-OCT. Areas evaluated as subretinal fibrosis in three (7.2 db) or two (10.1 db) modalities were significantly correlated with a lower retinal sensitivity than a subretinal fibrosis observed in only one (15.3 db) or none (23.3 db) modality (p < 0.001). Conclusions: CFP, SD-OCT and PS-OCT are all suited to detect areas of reduced retinal sensitivity related to fibrosis, however, a multimodal imaging approach provides higher accuracy in the identification of areas with low sensitivity in MP (i.e., impaired retinal function), and thereby improves the detection rate of subretinal fibrosis in nAMD.

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Fibrosis in neovascular age-related macular degeneration: A review of definitions based on clinical imaging

Cited by 7 publications

References 107 publications

Ist die exsudative neovaskuläre AMD eine chronische Erkrankung? Analyse von Langzeitverläufen unter einer Anti-VEGF-Therapie

Ist die exsudative neovaskuläre AMD eine chronische Erkrankung? Analyse von Langzeitverläufen unter einer Anti-VEGF-Therapie

Morphological changes of macular neovascularization during long-term anti-VEGF-therapy in neovascular age-related macular degeneration

Structure-Function Correlation of Retinal Fibrosis in Eyes with Neovascular Age-Related Macular Degeneration

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