Prospective Longitudinal Evaluation of Nascent Geographic Atrophy in Age-Related Macular Degeneration

Wu, Zhichao; Luu, Chi D; Hodgson, Lauren; Caruso, Emily; Tindill, Nicole; Aung, Khin Zaw; McGuinness, Myra; Makeyeva, Galina; Chen, Fred K.; Chakravarthy, Usha; Arnold, Jennifer; Heriot, Wilson; Durkin, Shane R.; Guymer, Robyn H.

doi:10.1016/j.oret.2019.12.011

Cited by 61 publications

(60 citation statements)

References 12 publications

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“…This could be expected since hypertransmission arises as an immediate consequence of tissue loss, whereas nGA is detected after subsidence of inner retinal tissue and the appearance of the hypereflective wedge-shaped band, which arise as a consequence (not as a primary cause) of a certain amount of tissue loss. Besides, like other authors [ 23 ], here, we demonstrate that nGA is a predictor for GA providing supportive evidence of the potential value of nGA as a surrogate endpoint in future intervention trials for the early stages of AMD.…”

Section: Discussionsupporting

confidence: 90%

Early Detection of Incipient Retinal Pigment Epithelium Atrophy Overlying Drusen with Fundus Autofluorescence vs. Spectral Domain Optical Coherence Tomography

Rodríguez

Biarnés

Coco‐Martín

et al. 2020

Journal of Ophthalmology

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Purpose. This study aims to find out which tool, fundus autofluorescence (FAF) or spectral domain optical coherence tomography (SD-OCT), is more sensitive in detecting retinal pigment epithelium (RPE) demise overlying drusen and can, therefore, help predict geographic atrophy (GA) appearance in Age-Related Macular Degeneration (AMD). Methods. A single-site, retrospective, observational, longitudinal study was conducted. Patients with intermediate AMD (iAMD) (large (>125 μm) or intermediate (63–125 μm) drusen with hyper/hypopigmentation) with a minimum follow-up of 18 months were included. Drusen with overlying incipient RPE atrophy were identified on SD-OCT defined as choroidal hypertransmission or nascent geographic atrophy (nGA). These selected drusen were, then, traced backwards in time to determine if incipient RPE atrophy overlying drusen was observed on FAF (well-demarcated region of absence of autofluorescence) before, simultaneously, or after having detected the first signs of incipient RPE atrophy on SD-OCT. The number of drusen in which signs of incipient RPE atrophy was detected earlier using FAF or SD-OCT was compared. The time elapsed from the identification with the more sensitive method to the other was recorded and analyzed. Results. One hundred and thirty-three drusen in 22 eyes of 22 patients were included. Of these, 112 (84.2%) drusen showed choroidal hypertransmission and 21(15.8%) nGA. Early signs of atrophy overlying drusen were found simultaneously on SD-OCT and FAF in 52 cases (39.1%, 95% CI 30.8–47.9%), earliest on FAF in 51 (38.3%, 95% CI 30.0–47.2%) and first on SD-OCT in 30 (22.6%, 95% CI 15.8–30.6%; p<0.05). Statistically significant differences were found between both techniques (p=0.005), with FAF detecting it earlier than SD-OCT. When RPE atrophy was found first on FAF, the median time to diagnosis with SD-OCT was 6.6 months (95% CI 5.5 to 8.6), while if detection occurred earlier on SD-OCT, the median time until identification with FAF was 12.6 months (95% CI 6.0 to 23.4; p=0.0003). Conclusions. In iAMD cases in which early atrophy overlying drusen is not detected simultaneously in FAF and SD-OCT, FAF was significantly more sensitive. Nevertheless, a multimodal approach is recommended and required to evaluate these patients.

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Section: Discussionsupporting

confidence: 90%

Early Detection of Incipient Retinal Pigment Epithelium Atrophy Overlying Drusen with Fundus Autofluorescence vs. Spectral Domain Optical Coherence Tomography

Rodríguez

Biarnés

Coco‐Martín

et al. 2020

Journal of Ophthalmology

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“…We recently determined that among individuals with bilateral large drusen that developed nGA, there was a 78‐fold increased rate of progression to GA as compared to eyes that did not develop nGA when followed over 3 years 12 . This was a similar finding to a previous study that demonstrated that eyes with nGA at baseline had a 56‐fold increased risk of developing GA over an average follow‐up period of 9 years 13 …”

Section: Multimodal Imaging: Reveals More Than Meets the Eyesupporting

confidence: 74%

Age‐related macular degeneration (AMD): More than meets the eye. The role of multimodal imaging in today's management of AMD—A review

Guymer

2020

Clinical Exper Ophthalmology

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Multimodal imaging (MMI) allows a more granular grading of age-related macular degeneration (AMD) disease severity, with many novel risk factors having been recently identified. With this imaging information, we are better able to counsel our patients with more accurate and individualized progression scenarios. MMI also allows identification of anatomical features that increase our understanding of disease processes involved in progression to late AMD. Treatment protocols for neovascular AMD (nAMD) depend largely on the optical coherence tomography (OCT) appearance to determine disease activity, which allows us to individualize treatment. In geographic atrophy (GA), new intervention trials require the ability to define the extent of GA, so that GA growth rate can be determined. This is achieved through fundus autofluorescence (FAF) imaging, which allows greater accuracy of border identification, as well as revealing FAF patterns predictive of growth rates. As we strive to bring interventions earlier in the disease course, OCT imaging provides an ability to identify the first signs of atrophy, which may serve as novel surrogate biomarkers for GA, thereby facilitating trials. In the future, the use of artificial intelligence (AI) to automatically identify relevant features on MMI could further enhance our ability to determine disease severity, predict progression and assist in identifying disease activity parameters to support clinical decision making when treating nAMD. Newer developments may allow frequent, remote capturing of images, reducing clinic visits, detecting progression and monitoring neovascular activity in-between clinic visits. Being aware of these new imaging insights in AMD, greatly enhance our clinical management of AMD.

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“…A previous study demonstrated that eyes detected as having nGA at baseline were associated with a 56-fold increased risk of developing GA over an average follow-up period of 9 years [16]. More recently, we demonstrated that amongst individuals with bilateral large drusen that developed nGA as detected on 6-monthly follow-up intervals for 3 years, there was a 78-fold increased rate of progression to GA as compared to eyes that did not develop nGA [17]. In this cohort, the probability of a person with bilateral large drusen developing nGA in either eye over a 36-month period was 24%, being substantially higher than a 13% probability of developing GA alone.…”

Section: Onset Of Atrophic Amdmentioning

confidence: 49%

Can the Onset of Atrophic Age-Related Macular Degeneration Be an Acceptable Endpoint for Preventative Trials?

Guymer

2020

Ophthalmologica

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The slowly progressive nature of age-related macular degeneration (AMD) means that establishing the efficacy of novel preventative treatments aiming to slow progression of disease, remains challenging, and where earlier endpoints are needed to improve their feasibility. This review examines whether the onset of atrophic AMD, as seen as anatomical signs on optical coherence tomography termed nascent geographic atrophy, could act as a useful surrogate endpoint for early intervention trials.

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Prospective Longitudinal Evaluation of Nascent Geographic Atrophy in Age-Related Macular Degeneration

Cited by 61 publications

References 12 publications

Early Detection of Incipient Retinal Pigment Epithelium Atrophy Overlying Drusen with Fundus Autofluorescence vs. Spectral Domain Optical Coherence Tomography

Early Detection of Incipient Retinal Pigment Epithelium Atrophy Overlying Drusen with Fundus Autofluorescence vs. Spectral Domain Optical Coherence Tomography

Age‐related macular degeneration (AMD): More than meets the eye. The role of multimodal imaging in today's management of AMD—A review

Can the Onset of Atrophic Age-Related Macular Degeneration Be an Acceptable Endpoint for Preventative Trials?

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