Hyperreflective Foci and Specks Are Associated with Delayed Rod-Mediated Dark Adaptation in Nonneovascular Age-Related Macular Degeneration

Echols, Benjamin S.; Clark, Mark E.; Swain, Thomas A.; Chen, Ling; Kar, Deepayan; Zhang, Yuhua; Sloan, Kenneth R.; McGwin, Gerald; Singireddy, Ramya; Mays, Christian; Kilpatrick, David; Crosson, Jason N.; Owsley, Cynthia; Curcio, Christine A.

doi:10.1016/j.oret.2020.05.001

Cited by 41 publications

(36 citation statements)

References 46 publications

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“…Similarly to composite end points, a variety of single outcomes have been associated with progression to late-stage disease [3,36,[51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Schaal et al [65] have published a comprehensive review of anatomical end points in nonexudative AMD.…”

Section: Discussionmentioning

confidence: 99%

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions

et al. 2020

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The slow progression of early AMD stages to advanced AMD requires the use of surrogate endpoints in clinical trials. The use of combined endpoints may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite endpoints as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite endpoints used in early/intermediate AMD studies published during the last 10 years. A total of 673 articles of interest were identified. After reviewing abstracts and applicable full-text articles, 33 articles were eligible and thus included in the qualitative synthesis. The main composite endpoint categories were: Combined structural and functional endpoints, combined structural endpoints, combined functional endpoints and combined multi-categorical endpoints. The majority of the studies included binary composite endpoints. There was a lack of sensitivity analyses of different endpoints against accepted outcomes (i.e. progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined endpoints in clinical studies of early stages of AMD exists and no surrogate endpoints have been accepted for AMD progression.

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Section: Discussionmentioning

confidence: 99%

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions

et al. 2020

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“…Two reviewers (JJG and MH), masked to the lifetimes, marked hyperautofluorescent areas in FAF (SSC or LSC) and graded them according to OCT and CFP features: OCT was checked for the presence of drusen or drusenoid PED (smallest diameter > 350 µm 42 ), thickening of the RPE-BL band, and the presence or absence of HRF anterior to the ellipsoid zone. 43 CFP was checked for the presence or absence of hyperpigmentation. This way, we found three lesion entities consistent with the cellular-level model described above: (i) a thickened RPE-BL band atop drusenoid PED with no hyperpigmentation in CFP, (ii) hyperpigmentation associated with thickened RPE-BL but no HRF, and (iii) HRF independent from the thickness of the underlying RPE-BL.…”

Section: Methodsmentioning

confidence: 99%

Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

Hammer

Jakob-Girbig

Schwanengel

et al. 2021

Preprint

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Purpose: To observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO). Methods: Multimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization) (mean age: 74.2+/-7.0 years). Twenty-three eyes were followed for 28.3+/-18.3 months. Seven eyes had a second follow up after 46.6+/-9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, and migrated RPE, seen as hyperreflective foci (HRF) on OCT, were identified. Fluorescence lifetimes in two spectral channels (SSC: 500-560 nm, LSC: 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO. Results: As hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256+/-49 ps (SSC) and 336+/-35 ps (LSC) and an ESIR of 0.552+/-0.079. For hyperpigmentation, these values were 317+/-68 ps (p<0.001), 377+/-56 ps (p<0.001), and 0.609+/-0.081 (p=0.001), respectively, and for HRF 337+/-79 ps (p<0.001), 414+/-50 ps (p<0.001), and 0.654+/-0.075 (p<0.001). Conclusions: In the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.

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“…The debris can be located at the external limiting membrane, external nuclear layer and the plexiform layer. They are biomarkers of poor prognosis, because they reveal that Muller Cells are losing their structure and will collapse [30].…”

Section: Hyperreflective Focimentioning

confidence: 99%

OCT Biomarkers for AMD

Quirino-Makarczyk¹,

Ugarte²

2022

Recent Advances and New Perspectives in Managing Macular Degeneration

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Age-related Macular Degeneration (AMD) is an acquired retina disease that can potentially cause significant central visual impairment. Optical coherence tomography (OCT) applied to the study of retinal pathologies has revolutionized the understanding and management of AMD, especially with the technology of full-depth imaging (FDI) Spectral Domain (SD) OCT. With the increasing amount of data from several important studies using SD-OCT and OCT-angiography (OCT-A) we can now better classify and more accurately decode AMD. The purpose of this chapter is to describe the most important AMD biomarkers recently discovered using SD OCT. Understanding AMD phenotype is very important to define prognosis and individualized forms of treatment and follow up. Biomarkers on OCT have been crucial for a better understanding of AMD.

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Hyperreflective Foci and Specks Are Associated with Delayed Rod-Mediated Dark Adaptation in Nonneovascular Age-Related Macular Degeneration

Cited by 41 publications

References 46 publications

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions

Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

OCT Biomarkers for AMD

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