Long-term Retinal Morphology and Functional Associations in Treated Neovascular Age-Related Macular Degeneration

Evans, R. J.; Reeves, Barnaby C; Harding, Simon; Madhusudhan, Savita; Lotery, Andrew; Downes, Susan M.; Balaskas, Konstantinos; Bailey, Clare; Foss, Alexander; Ghanchi, Faruque; Yang, Yit; Phillips, Dawn; Rogers, Chris; Muldrew, Alyson; Hamill, Barbra; Chakravarthy, Usha

doi:10.1016/j.oret.2022.03.010

Cited by 7 publications

(11 citation statements)

References 28 publications

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“…In the long-term, a stabilization of both function and uid distribution can be achieved by different treatment strategies such as the IVAN, CATT, or Treat-and-Extent (T&E) scheme, as shown by previous reports. [2][3][4][5][6] As has been described in other studies, 7 we also observed that even under effective anti-VEGF treatment with regard to uid control, MNV growth during follow-up can be observed when using the IVAN PRN treatment strategy. 8 A similar growth was observed in type 1 MNV without associated exudation and negative visual effects, which was hence termed "quiescent" MNV (also referred to as "nonexudative nAMD").…”

Section: Introductionsupporting

confidence: 66%

“…The aim of the present pilot study was to investigate retinal function above the MNV under long-term anti-VEGF therapy using microperimetry. Because macular atrophy, de ned as complete RPE and outer retina atrophy (cRORA) according to the Consensus De nition for Atrophy Associated with Age-Related Macular Degeneration (CAM), 13 was shown to develop under therapy in several long-term studies [2][3][4]6,[14][15][16][17] and may in uence function, the presence and loacation of cRORA was also assessed.…”

Section: Introductionmentioning

confidence: 99%

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Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration

Pauleikhoff,

Ziegler

et al. 2024

Preprint

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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.

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Section: Introductionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration

Pauleikhoff,

Ziegler

et al. 2024

Preprint

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“…Long-term findings in eyes treated with anti-VEGF therapy for exudative neovascular AMD often included macular atrophy affecting photoreceptors and the retinal pigment epithelium. In the IVAN trial, an average of 6.18 years after anti-VEGF treatment initiation, macular atrophy was observed in 89.5% of eyes . In the SEVEN-UP cohort study, after an average of 7.3 years, macular atrophy was detected in 98% of eyes and decreased visual acuity was significantly correlated with increased area of macular atrophy ( P < .001) …”

Section: Discussion and Observationsmentioning

confidence: 97%

Age-Related Macular Degeneration

Fleckenstein,

Schmitz-Valckenberg,

Chakravarthy

2024

JAMA

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ImportanceAge-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040.ObservationsOlder age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti–vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment.Conclusions and RelevanceThe prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

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“…The drugs used were ranibizumab, aflibercept or beva-cizumabadministered alternately in numerous eyes (selected according to the assessment of the treating physician). For organizational reasons, the PRN treatment plan was consistently used throughout the treatment period, analogous to the IVAN study [3]. Accordingly, after saturation with 3 injections, a further series of 3 injections was given if there were signs of MNV activity at the monthly check-ups; this is in line with the opinions of the Professional Association of German Ophthalmologists (BVA), the German Ophthalmological Society (DOG), and the Retinological Society (RG) [2].…”

Section: Methodsmentioning

confidence: 99%

“…wurde konsequent während der ganzen Behandlungszeit das PRN-Behandlungsschema analog der IVAN-Studie verwendet [3]. Bei diesem erfolgt nach der Aufsättigung mit 3…”

Section: Accepted Manuscriptunclassified

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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Long-term Retinal Morphology and Functional Associations in Treated Neovascular Age-Related Macular Degeneration

Cited by 7 publications

References 28 publications

Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration

Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration

Age-Related Macular Degeneration

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

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