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. 2023 Jul 21;13(14):2444. doi: 10.3390/diagnostics13142444

Table 1.

Studies on early optical coherence tomography biomarkers linked with age-related macular degeneration (continuation of the table on pages 5–7).

Author Year Number of Patients/Eyes Included Biomarker Characteristics of Biomarker Description Correlation with AMD Method The Role of Biomarker in Clinical Practice
Hilely et al. [24] 2021 45 eyes Drusen height Quantitative biomarker The height of the drusen causing reduced choroidal perfusion might lead to RPE 1 pump failure An early sign of atrophy on OCT 2 imaging OCT 2 Predictor
Au et al. [25] 2022 155 eyes Drusen height Quantitative biomarker Drusen height, more so than drusen GHD 3, is correlated with the presence of OCT 1 predictors of atrophy Early biomarker for targeting early intervention to prevent atrophy and vision loss OCT 2 Predictor
Abdelfattah et al. [26] 2016 89
patients
Drusen volume Quantitative biomarker Quantifying drusen volume through OCT 2 could be a promising biomarker for identifying patients at higher risk of developing MNV 4 Important predictor for the development of advanced AMD 5 at 12 and 24 months of follow-up in the fellow eye OCT 2 Predictor
Lamin et al. [27] 2019 248 patients Drusen volume Quantitative
biomarker
Increase in the overall amount of drusen measured through optical coherence tomography before neovascular AMD 5 development A useful method for detecting early signs of neovascular AMD 5 in those at risk for the disease OCT 2 Predictor
Amissah-Arthur et al. [19] 2012 749 patients RPE 1 changes Qualitative
biomarker
Abnormalities in the RPE 1 without any visible alterations in the outer neural retina Possible to diagnose conversion to a wet form of AMD 5 in the fellow eye by looking for small changes in RPE 1 contours/elevation OCT 2 Predictor
Nagai et al. [13] 2020 30 eyes PROS 6 Quantitative biomarker The length of the PROS 6 where the visual pigment is concentrated Potential sensitive biomarker for the degeneration of photoreceptors OCT 2 Risk factor
Jaffe et al.
(CAM Report 5) [28]
2021 Not available Intraretinal hyperreflective foci, focal RPE 1 thickening, and choroidal hypertransmission Qualitative
biomarker
Early signs of RPE 1 damage and disturbance that may lead to geographic atrophy Predictors of atrophy OCT 2 Predictor
Harada et al. [10] 2022 24 eyes CCFA 7 ratio Quantitative biomarker Percentage of choriocapillaris slab area to analyzed area from OCTA 8 images Smaller CCFA 7 ratio in AMD high-risk fellow eyes than in control eyes, indicating decline in choriocapillaris flow OCTA 8 Risk factor
Trinh et al. [29] 2019 63 eyes GCL 9 thickness Quantitative biomarker Reduction in GCL 9 thickness in AMD eyes Structural loss in the early stages of AMD may be linked to retinal vascular alterations OCT 2/OCTA 8 Predictor
Trinh et al. [29] 2019 63 eyes Vascular density in the superficial capillary plexus (SCP) 10 Quantitative biomarker As different OCTA 8 modalities utilize different scanning techniques and definitions to automatically separate the retinal vasculature from the scan, differences between OCTA 8 studies may be device-related Substantial reduction in the SCP’s 10 vascular density in AMD patients; however, vascular density in DCP 11 was not significantly decreased OCTA 8 Risk factor
Lamin et al. [14] 2020 51 eyes Drusen load Quantitative biomarker Comparison of drusen load between the two types of CNV 12 Significant rise in the area and volume of drusen during the 12 months preceding the onset of occult CNV 12 OCT 2 Risk factor
Lamin et al. [14] 2020 51 eyes Retinal layer volumes Quantitative biomarker Comparison of retinal layer volumes between CNV 12 types Decrease in ONL 13 volume and increase in outer plexiform layer volume in eyes with occult CNV 12 OCT 2 Risk factor
Menteş et al. [30] 2019 27 eyes Drusen load Quantitative biomarker Comparison of drusen load between the two types of CNV 12 Significant rise in the area and volume of drusen during the 12 months preceding the onset of occult CNV 12 OCT 2 Risk factor
Shi et al. [31] 2019 100 eyes DLS 14 Qualitative
biomarker
Identification of type 1 MNV in eyes with nonexudative AMD DLS 14 has good predictive values for identifying type 1 MNV 2 OCT 2 Predictor
Oliveira Dias et al. [32] 2018 160 patients Subclinical neovascularization Qualitative
biomarker
Neovascularization was not visible on clinical exam, but detected on OCT 2 imaging Increased risk of exudation in eyes with subclinical MNV 4 compared to eyes without detectable MNV 4 OCTA 8 Risk factor
Nassisi et al. [33] 2019 501 eyes IHRF 15, hRF 16, DLs 14, SDD 17, and Drusen volume Qualitative
biomarkers (except drusen volume—quantitative biomarker)
Various features visible on OCT imaging IHRF 15, hRF 16 within a drusen-like lesion, and SDD 17 were significantly associated with an increased risk of progression to late AMD 5. SDD 17 is strongly associated with the development of GA 18 and type 3 MNV 4. Drusen volume was not significantly associated with the development of MNV 4 OCT 2 Risk factors
Kang et al. [34] 2022 70 eyes Chorioretinal thickness, RPE 1 degenerative features, and SDDs 17 Chorioretinal thickness—quantitative biomarker; RPE 1 degenerative features and SDDs 17—qualitative biomarkers The thickness of the retina and choroid in eyes with RPE 1 degeneration is comparatively reduced to those without this degeneration Early AMD 5 eyes with SDDs 17 are prone to overall chorioretinal degeneration. Fellow eyes with neovascular AMD 5 showed greater proportions of RPE 1 degeneration and a thicker retina and choroid OCT 2 Risk factor
Kwak et al. [35] 2021 93 eyes CVI 19 Quantitative biomarker Lower CVI 19 values in unaffected fellow eyes may be associated with possible subclinical disease Significant correlation between the incidence of fellow eye type 3 neovascularization and the presence of large soft drusen, reticular pseudodrusen, and lower choroidal vascularity index CVI 19 values OCT 2 Risk factor
Toprak et al. [36] 2017 47 eyes RPE 1 and EZ 20 reflectivity Qualitative
biomarker
Lower reflectivities suggest early photoreceptor damage Non-neovascular AMD patients have significantly lower reflectivities compared to healthy controls. OCT 2 Predictor
Schick et al. [21] 2015 104 patients Macular drusen Quantitative biomarker More than 20 drusen in non-affected eyes indicate potential biomarkers for more severe progression of the disease Prevalence of more than 20 macular drusen is more prevalent in non-affected eyes of individuals with early onset of unilateral neovascular AMD 5 OCT 2 Risk factor
RPD 21 Qualitative
biomarker
Prevalence increases with age and is more common in the late-onset CNV 12 group; link with neovascular AMD 5 RPDs 21 were more commonly observed in the late-onset CNV 12 group than in the no-CNV 12 group. Predictor

1 RPE—retinal pigment epithelium; 2 OCT—optical coherence tomography; 3 GHD—greatest horizontal diameter; 4 MNV—macular neovascularization; 5 AMD—age-related macular degeneration; 6 PROS—photoreceptor outer segment; 7 CCFA—choriocapillaris flow area; 8 OCTA—optical coherence tomography angiography; 9 GCL—ganglion cell layer; 10 SCP—superficial capillary plexus; 11 DCP deep capillary plexus; 12 CNV—choroidal neovascularization; 13 ONL—outer nuclear layer; 14 DLs—drusenoid lesions; 15 IHRF—intraretinal hyperreflective foci; 16 hRF—hyporeflective foci; 17 SDDs—subretinal drusenoid deposits; 18 GA—geographic atrophy; 19 CVI—choroidal vascularity index; 20 EZ—ellipsoid zone; and 21 RPD—reticular pseudodrusen.