The outcomes of 91 treatment-naïve eyes of 91 DME patients treated with IVR were retrospectively analyzed in this study. The clinical and biochemical characteristics of all patients are summarized in Table 1.
Table 1. Baseline characteristics of 91 DME patients.
Characteristic
|
|
Age (years)
| 54 [47 – 61]
|
Male sex (%)
| 57 (62.6)
|
SBP (mmHg)
| 135 [121 – 147]
|
DBP (mmHg)
| 83 [72 – 90]
|
HbA1c (%)
| 7.24 ± 1.56
|
TC (mmol/L)
| 5.06 ± 1.21
|
TG (mmol/L)
| 1.52 [0.94 – 2.03]
|
HDL (mmol/L)
| 1.15 [0.90 – 1.42]
|
LDL (mmol/L)
| 2.73 [2.24 – 3.39]
|
Scr
| 86.90 [62.70 – 117.00]
|
BUN
| 6.00 [5.10 – 8.30]
|
Mean BCVA (letter score)
| 45.99 ± 12.74
|
Mean CRT (μm)
| 484.65 ± 113.08
|
WBC (×109/L)
| 5.93 [4.88 – 7.48]
|
Neutrophils (×109/L)
| 3.51 [2.73 – 4.84]
|
Monocytes (×109/L)
| 0.40 [0.30 – 0.48]
|
Platelets (×109/L)
| 186.00 [140.00 – 237.00]
|
Lymphocytes (×109/L)
| 1.62 [1.29 – 1.90]
|
NLR
| 2.27 [1.72 – 2.93]
|
MLR
| 0.24 [0.18 – 0.30]
|
PLR
| 114.37 [86.02 – 146.74]
|
Data are expressed as mean (SD), median (inter-quartile range), or percentage.
SBP systolic blood pressure, DBP diastolic blood pressure, WBC white blood cell, HbA1c Hemoglobin A1c, TC total cholesterol, TG triglycerides, HDL high-density lipoprotein cholesterol, LDL low-density lipoprotein cholesterol, Scr serum creatinine, BUN blood urea nitrogen, BCVA best-corrected visual acuity, CRT central retinal thickness, WBC white blood cell, NLR neutrophil-to-lymphocyte ratio, MLR monocyte-to-lymphocyte ratio, PLR platelet-to-lymphocyte ratio.
To identify factors that determine the therapeutic response to IVR at 24 weeks, correlations of changes in either BCVA or CRT between baseline and week 24 as well as baseline characteristics in individual patients were evaluated, as summarized in Table 2. Baseline BCVA, neutrophils, NLR, MLR, and PLR were negatively correlated with the changes in BCVA at 24 weeks compared with the baseline, while baseline CRT and lymphocytes were positively correlated with the changes in BCVA at 24 weeks compared with the baseline. No correlation was found between baseline clinical factors and changes in CRT at 24 weeks compared with the baseline.
Table 2. Association between baseline clinical factors and changes in either BCVA or CRT at week 24.
| Change in BCVA
| | Change in CRT
|
| Correlation coefficient
| P value
| Correlation coefficient
| P value
|
Age
| -0.063
| 0.555
| -0.013
| 0.903
|
SBP
| 0.018
| 0.864
| -0.146
| 0.166
|
DBP
| -0.012
| 0.913
| -0.018
| 0.867
|
HbA1c
| 0.021
| 0.845
| 0.138
| 0.191
|
TC
| 0.027
| 0.800
| 0.148
| 0.161
|
TG
| 0.027
| 0.797
| 0.044
| 0.681
|
HDL
| -0.072
| 0.499
| 0.016
| 0.880
|
LDL
| -0.085
| 0.426
| 0.078
| 0.462
|
Scr
| 0.157
| 0.137
| -0.006
| 0.953
|
BUN
| 0.054
| 0.610
| -0.089
| 0.401
|
Baseline BCVA
| -0.305
| 0.003
| 0.046
| 0.662
|
Baseline CRT
| 0.275
| 0.008
| 0.170
| 0.107
|
WBC
| -0.166
| 0.115
| -0.037
| 0.729
|
Neutrophils
| -0.383
| <0.001
| 0.061
| 0.564
|
Monocytes
| -0.074
| 0.486
| 0.031
| 0.770
|
Platelets
| -0.024
| 0.819
| 0.017
| 0.871
|
Lymphocytes
| 0.399
| <0.001
| -0.062
| 0.559
|
NLR
| -0.660
| <0.001
| 0.130
| 0.218
|
MLR
| -0.392
| <0.001
| 0.058
| 0.585
|
PLR
| -0.335
| 0.001
| 0.045
| 0.670
|
SBP systolic blood pressure, DBP diastolic blood pressure, WBC white blood cell, HbA1c Hemoglobin A1c, TC total cholesterol, TG triglycerides, HDL high-density lipoprotein cholesterol, LDL low-density lipoprotein cholesterol, Scr serum creatinine, BUN blood urea nitrogen, BCVA best-corrected visual acuity, CRT central retinal thickness, WBC white blood cell, NLR neutrophil-to-lymphocyte ratio, MLR monocyte-to-lymphocyte ratio, PLR platelet-to-lymphocyte ratio.
The correlation between age, SBP, DBP, TG, HDL, LDL, Scr, BUN, WBC, neutrophils, monocytes, platelets, lymphocytes, NLR, MLR, PLR and BCVA change were analyzed by Spearman’s correlation analysis, while HbA1c, TC, baseline BCVA, baseline CRT were analyzed by Pearson’s correlation analysis.
Univariate linear regression was used to analyze factors that were significantly associated with changes in BCVA based on correlation analysis in all patients (Table 3). Baseline BCVA, baseline CRT, lymphocytes, neutrophils, NLR, MLR, and PLR were independently associated with changes in BCVA at week 24. Multivariate analysis revealed that baseline BCVA (B = –0.081, p = 0.003) and NLR (B = –1.884, p < 0.001) were the only significant predictors of changes in BCVA in DME patients treated with IVR. Interestingly, only NLR was a significant factor associated with the changes in BCVA, while the other two inflammatory predictors (MLR and PLR) were no significant factors. Thus, correlations between changes in BCVA at 24 weeks and baseline in different NLR groups were further evaluated. The group with NLR < 2.27 showed a greater improvement in the BCVA letter score than the group with NLR > 2.27 at 8, 12, 16, 20, and 24 weeks (p = 0.004, <0.001, <0.001, <0.001, and <0.001, respectively; Figure 1). However, no significant difference between the two groups was found at four weeks.
Table 3. Univariate and multivariate linear regression analyses for predicting BCVA changes in DME patients treated with IVR.
| B
| SE
| β
| T
| P value
|
Univariate linear regression
|
Baseline BCVA
| -0.105
| 0.033
| -0.319
| -3.177
| 0.002
|
Baseline CRT
| 0.010
| 0.004
| 0.280
| 2.753
| 0.007
|
Lymphocytes
| 3.049
| 0.812
| 0.370
| 3.756
| <0.001
|
Neutrophils
| -0.983
| 0.237
| -0.403
| -4.151
| <0.001
|
NLR
| -1.986
| 0.276
| -0.607
| -7.202
| <0.001
|
MLR
| -15.471
| 3.929
| -0.385
| -3.938
| <0.001
|
PLR
| -0.035
| 0.009
| -0.387
| -3.955
| <0.001
|
Multivariate linear regression
|
Baseline BCVA
| -0.081
| 0.027
| -0.246
| -3.027
| 0.003
|
NLR
| -1.884
| 0.266
| -0.576
| -7.079
| <0.001
|
SE standard error; BCVA best-corrected visual acuity; CRT central retinal thickness; NLR neutrophil-to-lymphocyte ratio; MLR monocyte-to-lymphocyte ratio; PLR platelet-to-lymphocyte ratio.
In multivariate linear regression using stepwise procedure, baseline BCVA and NLR were significant factors, whereas baseline CRT, lymphocytes, neutrophils, MLR, and PLR were excluded to decide final linear model.
Fig. 1. Mean changes in BCVA after intravitreal ranibizumab injection with respect to the baseline and at each follow-up in the two groups. Bars indicate 95% confidence intervals. NLR neutrophil-to-lymphocyte ratio; BCVA best-corrected visual acuity.