Table 1.
Characterization of metabolomics studies of retinal neovascularization events.
| References | Comparison | Age | Male% | Source/Race | Biofluid | Technique Employed | Evaluation Standard |
|---|---|---|---|---|---|---|---|
| ROP | |||||||
| Yang (2020) | ROP patients (n = 40) | GA (31.20 ± 4.62 weeks) | 37.50 | China | Blood | UPLC-MS/MS | OPLS-DA (VIP > 1) & t-tests (p < 0.05) & Wilcoxon (p < 0.05) |
| controls (n = 41) | GA (30.96 ± 4.17 weeks) | 73.17 | |||||
| Nilsson (2021) | 47 ROP cases | Sweden | Serum | LC-MS | Repeated measures data (Spline function) | ||
| cord blood and at postnatal days 1, 7, 14, and 28, and at postmenstrual weeks 32, 36, and 40 | |||||||
| Zhou (2021) | ROP patients (n = 58) | 29.09 ± 2.23 (weeks) | 58.62 | China | Plasma | HPLC-MS/MS | Mann-Whitney U test (p < 0.05) |
| controls (n = 25) | 31.29 ± 2.33 (weeks) | 52.00 | |||||
| Zhou (2020) | ROP patients (n = 38) | GA (29.28 ± 2.42) | 55.26 | China | Plasma | UHPLC-MS | OPLS-DA (VIP >1) and t-test (p < 0.05/0.05 < p < 0.1) |
| controls (n = 24) | 30.61 ± 2.75 | 56.52 | |||||
| Ozcan (2020) | ROP patients (n = 26) | GA (28.5 ± 2.7) | Turkey | Plasma | LCMS/MS | Mann-Whitney-U test (p < 0.05) | |
| controls (n = 29) | 31.52 ± 2.6 | ||||||
| AMD | |||||||
| Mitchell (2018) | NVAMD patients (n = 100) | 79.2 | 35.00 | America | Plasma | LC-MS and LC-MS/MS | Nested feature selection |
| controls (n =192) | 71.9 | 36.00 | |||||
| Luo (2017) | NVAMD patients (n = 20) | 66.20 ± 11.51 | 55.00 | China | Plasma | UPLC-QTOF MS | PLS-DA (VIP > 1) & t-test (p < 0.05 or 0.05 < p < 0.1) |
| controls (n = 20) | 64.70 ± 11.60 | 55.00 | |||||
| Osborn (2013) | NVAMD patients (n = 26) | 76.0 ± 5.7 | Caucasian | Plasma | LC-FTMS | Multiple testing | |
| controls (n = 19) | 76.4 ± 4.8 | ||||||
| Li (2016) | PCV (n = 21) | 60.7 ± 9.4 | 62.00 | China | Serum | UPLC-MS | OPLS (VIP > 1), t-test (p < 0.05) |
| controls (n = 19) | 64.8 ± 9.2 | 53.00 | |||||
| Barca (2020) | NVAMD patients (n = 40) | 81.1 | 39.00 | France | Plasma | LC MS | t-test (p < 0.05) |
| controls (n =40) | 81.8 | 41.00 | |||||
| Liu (2020) | AMD (n =88), PCV (n = 102), PM (n = 57) | 69.84 ± 8.47 (AMD), 66.06 ± 11.42 (PCV), 55.32 ± 14.49 (PM) | 66.28 (AMD), 71.57 (PCV), 28.07 (PM) |
China | Serum | GC-TOF-MS | OPLS-DA (VIP > 1.0), t-test (p < 0.05), and FC > 1.2 or <0.8 |
| controls (n = 81) | 65.83 ± 11.94 | 35.80 | |||||
| Han (2020) | nAMD patients (n =26) | 74.12 | 53.85 | China | AH | UHPLC-MS/MS | OPLS-DA (VIP > 1) & one-way variance (p < 0.05) |
| Cataract patients without AMD (n = 20) | 69.6 | 65.00 | |||||
| Deng (2021) | 127 nAMD (CNV + PCV) | 71.1 ± 8.4 | 61.00 | China | Plasma | UHPLC-MS | PLS-DA (VIP ≥ 1), FC ≥ 2 and FC ≤ 0.5, p < 0.05 |
| controls (n = 50) | 68.5 ± 9.0 | 61.00 | |||||
| Lambert (2020) | nAMD (n = 72) | 38.89 | European | Serum | NMR | one-way ANOVA | |
| controls (n = 50) | 74.96 (6.24) | 48.00 | |||||
| PDR | |||||||
| Sumarriva (2019) | PDR patients (n = 34) | 55.7 ± 10.9 | 65.60 | America | Plasma | LC-MS | PLS-DA (VIP ≥ 2) |
| NPDR patients (n = 49) | 59.4 ± 11.3 | 61.40 | |||||
| Haines (2018) | PDR (n = 9) | 41 ± 10 | America | Vitreous | UHPLC-MS | ANOVA, t-test (p < 0.05) | |
| rhegmatogenous RD (n = 25), and controls (n = 8) | 68 ± 6 (controls); 62 ± 10 (rhegmatogenous RD) |
||||||
| Zhu (2019) | PDR (n = 21) | 49 (46–56.5) | 42.86 | China | Plasma | UPLC Q-TOF-MS | t-test (p < 10−5), AUC ≥ 0.95 & PLS-DA (VIP > 1) |
| NDR (duration ≥ 10y) (n = 21) | 55 (50–58) | 42.86 | |||||
| Wang (2019) | PDR (n = 28) (Vitreous); PDR (n = 23) (AH) | 49.61 (26–65) | 42.86 | China | Vitreous & AH | GC-TOF-MS | OPLS-DA (VIP > 1), Mann-Whitney U test (p < 0.05) |
| non-diabetic patients with MH (n = 22) (Vitreous); non-diabetic patients with cataract (n = 25) (AH) | 53.95 (32–71) | 36.36 | |||||
| Paris (2015) | PDR (n = 20) | Tokyo | Vitreous | HILIC & RPLC QTOF-MS | Welch’s t test (p < 0.01, FC > 2) | ||
| controls (n = 31) | |||||||
| Barba (2010) | PDR (n = 22) | Spain | Vitreous | NMR | |||
| non-diabetic patients with MH (n = 22) | |||||||
| ABHARY (2009) | no diabetic retinopathy (n = 330) | Australia | Serum | LC-MS | Hierarchical multiple regression (p < 0.05) | ||
| PDR (n = 101) | |||||||
| Tomita (2020) | PDR (n = 43) | 58.1 ± 13.6 | 77.1 | Tokyo | Vitreous | UHPLC-MS | t-test (FDR < 0.05) |
| controls (n = 21) | 69.4 ± 7.0 | 42.1 | |||||
| Lin (2020) | PDR (n = 31) | America | Vitreous | LC/MS/MS | t-test (p < 0.05) | ||
| controls (n = 13) | |||||||
| Yun (2020) | PDR (n = 51) | 62.60 (11.60) | 60.2 | Korea | Serum | LC-MS | Logistic regression analysis |
| NPDR (n = 123) | 61.18 (11.87) | 50.29 | |||||
| Ye (2021) | PDR (n = 45) | 59.9 ± 11.3 | 55.56 | China | Fecal | UPLC-MS | PLS-DA (VIP > 1), p < 0.05, |log2(FC)| > 1 |
| diabetic patients without DR (n = 90) | 60.9 ± 9.9 | 55.56 | |||||
| Wang (2022) | PDR (n = 88) (Plasma); PDR (n = 51) (Vitreous) | 55.3 ± 9.7 (Plasma); 54.9 ± 9.2 (Vitreous) | 51.80 | China | Plasma & Vitreous | UPLC-MS/MS | FDR < 0.05, OPLS-DA (VIP > 1.0), FC > 1.2 or <0.83 and multivariate analysis |
| nondiabetic controls (n = 51) (Plasma); nondiabetic controls(n = 23) (Vitreous) | 67.0 ± 8.1 (Plasma); 67.1 ± 8.8 (Vitreous) | 36.49 | |||||
ROP = retinopathy of prematurity; nAMD = Neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy; PDR = proliferative diabetic retinopathy; NPDR = non-proliferative diabetic retinopathy; RD = retinal detachment; MH = macular hole; GA = gestational age; AH = aqueous humor; LC = Liquid Chromatogram; MS = mass spectrometry; UPLC = Ultra Performance Liquid Chromatography; GC = gas chromatography; TOF = time of flight; Q-TOF = Quadrupole-Time of Flight; OPLS-DA = orthogonal projections to latent structures discriminant analysis; PLS-DA = partial least squares discriminant analysis; ANOVA = one-way analysis of variance; FC = fold change; VIP = variable importance in projection; FDR = false discovery rate.