Figures (2)  Tables (4)

    • Figure 1. 

      Overall workflow of the cohort study. NDR, diabetic patients without retinopathy; DR, diabetic retinopathy patients.

    • Figure 2. 

      The box plot of the changes in macular ganglion cell layer–inner plexiform layer thickness over time with (a) axial length, (b) BCVA, (c) macular retinal thickness, and (d) macular GCIPL thickness. The Fast group included eyes whose rate of GCIPL thinning was greater than or equal to –1 μm/year; the Slow group included eyes with a rate slower than −1 μm/year. BCVA, best corrected visual acuity; logMAR, logarithm of the minimal angle of resolution; GCIPL, ganglion cell–inner plexiform layer.

    • Characteristic Included
      (n = 1,500)      		 Excluded
      (n = 623)      		 p-value
      Age (year) 64.83 (7.35) 64.19 (8.19) 0.069
      Female (%) 858 (57.20%) 359 (57.72%) 0.826
      Body mass index (kg/m2) 24.65 (9.54) 24.81 (3.62) 0.014
      Duration of diabetes (y) 8.93 (6.86) 8.46 (6.99) 0.080
      Diabetic retinopathy (%) 212 (14.13%) 126 (20.26%) < 0.001
      HbA1c (%) 7.03 (1.38) 7.26 (1.64) 0.015
      Systolic blood pressure (mmHg) 133.44 (18.56) 134.64 (18.96) 0.116
      Eye examination
      Axial length (mm) 23.37 (0.83) 23.37 (0.80) 0.859
      Spherical 1.05 (1.63) 1.01 (1.30) 0.131
      Intraocular pressure (mmHg) 15.77 (2.22) 15.86 (2.41) 0.439
      BCVA (logMAR) 0.16 (0.13) 0.19 (0.15) < 0.001
      Macular retinal thickness (μm) 246.82 (77.96) 255.10 (68.26) 0.283
      Macular GCIPL thickness (μm) 71.64 (5.27) 72.41 (7.42) 0.008
      Macular choroidal thickness (μm) 189.93 (73.34) 192.34 (75.16) 0.448
      Disc area (mm2) 2.10 (0.40) 2.08 (0.42) 0.605
      RNFL thickness (μm) 110.79 (13.97) 111.50 (14.25) 0.153
      Blood lipids
      Total cholesterol (mmol/L) 4.86 (1.07) 4.87 (1.09) 0.928
      Triglycerides (mmol/L) 2.32 (1.67) 2.54 (1.94) 0.019
      HDL-c (mmol/L) 1.30 (0.40) 1.25 (0.38) 0.004
      LDL-c (mmol/L) 3.05 (0.94) 3.07 (0.94) 0.851
      Renal function
      eGFR (mL/min/1.73 m2) 99.07 (18.44) 98.71 (20.59) 0.729
      Serum creatinine (mg/L) 71.57 (20.56) 72.98 (25.39) 0.790
      Serum uric acid (μmol/L) 370.09 (100.41) 370.16 (101.91) 0.032
      Microalbuminuria (mg/mL) 4.44 (25.42) 8.35 (48.98) < 0.001
      HbA1c, glycosylated hemoglobin; BCVA, best corrected visual acuity; logMAR, logarithm of the minimal angle of resolution; GCIPL, ganglion cell–inner plexiform layer; RNFL, retinal nerve fiber layer; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. Data are presented as the mean and standard deviation, or counts and percentages. Data in bold indicate statistically significant differences (p < 0.05).

      Table 1. 

      Baseline characteristics of included and excluded participants.

    • Variable Univariate model
      β (95% CI) †p-value
      Age, per 10-year increase 0.004 (−0.089, 0.098) 0.923
      Male versus female −0.078 (−0.217, 0.061) 0.269
      Body mass index, per 1-SD increase −0.007 (−0.076, 0.062) 0.848
      Duration of diabetes, per 1-year increase −0.004 (−0.014, 0.007) 0.463
      Systolic blood pressure, per 1-SD increase −0.047 (−0.116, 0.021) 0.177
      Eye examination, per 1-SD increase
      Axial length −0.176 (−0.244, -0.108) < 0.001
      Spherical 0.068 (−0.001, 0.136) 0.054
      Intraocular pressure −0.091 (−0.159, –0.022) 0.010
      BCVA (logMAR) −0.202 (−0.270, –0.133) < 0.001
      Macular retinal thickness −0.231 (−0.298, –0.163) < 0.001
      Macular GCIPL thickness −0.343 (−0.410, –0.277) < 0.001
      Macular choroidal thickness 0.005 (−0.064, 0.074) 0.889
      Disc area 0.079 (−0.079, 0.163) 0.067
      RNFL thickness −0.005 (−0.075, 0.064) 0.880
      HbA1c, per 1-SD increase
      Baseline 0.029 (−0.039, 0.098) 0.403
      Mean −0.038 (−0.106, 0.031) 0.283
      Peak −0.062 (−0.130, 0.007) 0.078
      Fluctuation −0.085 (−0.153, -0.016) 0.016
      Range −0.091 (−0.160, -0.022) 0.009
      Blood lipid, per 1-SD increase
      Total cholesterol 0.027 (−0.041, 0.096) 0.434
      Triglycerides −0.019 (−0.087, 0.050) 0.597
      HDL-c −0.022 (−0.091, 0.047) 0.537
      LDL-c −0.014 (−0.083, 0.055) 0.689
      Renal function, per 1-SD increase
      eGFR −0.082 (−0.151, -0.013) 0.019
      Serum creatinine 0.057 (−0.012, 0.126) 0.104
      Serum uric acid 0.031 (−0.038, 0.100) 0.378
      Microalbuminuria −0.086 (−0.155, 0.017) 0.015
      DM, diabetes mellitus; CI, confidence interval; SD, standard deviation; BCVA, best corrected visual acuity; logMAR, logarithm of the minimal angle of resolution; GCIPL, ganglion cell inner plexiform layer; RNFL, retinal nerve fiber layer; HbA1c, glycosylated hemoglobin; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. †p-values are from the univariate linear regression analysis. Variables with p < 0.01 remained statistically significant after Benjamini–Hochberg false discovery rate correction (q < 0.05). Data in bold indicate statistically significant differences (p < 0.05).

      Table 2. 

      Clinical characteristics factors contributing to the change in GCIPL thickness over time in DM participants as determined by univariate linear regression analysis.

    • Variable Multivariate model
      β (95% CI) p-value
      Duration of diabetes, per 1-year increase −0.003 (−0.013, 0.007) 0.582
      Eye examination, per 1-SD increase
      Axial length −0.187 (−0.255, −0.120) < 0.001
      Intraocular pressure −0.064 (−0.132, 0.004) 0.066
      BCVA (logMAR) −0.201 (−0.271, −0.130) < 0.001
      Macular retinal thickness −0.126 (−0.198, −0.054) 0.001
      Macular GCIPL thickness −0.305 (−0.376, −0.235) < 0.001
      HbA1c, per 1-SD increase
      Fluctuation 0.187 (−0.311, 0.684) 0.462
      Range −0.237 (−0.735, 0.262) 0.351
      Renal function, per 1-SD increase
      eGFR −0.057 (−0.128, 0.014) 0.118
      Microalbuminuria −0.069 (−0.136, −0.002) 0.045
      DM, diabetic retinopathy; CI, confidence interval; SD, standard deviation; BCVA, best corrected visual acuity; HbA1c, glycosylated hemoglobin; logMAR, logarithm of the minimal angle of resolution; GCIPL, ganglion cell–inner plexiform layer; eGFR, estimated glomerular filtration rate. Data in bold indicate statistically significant differences (p < 0.05).

      Table 3. 

      Clinical characteristics factors contributing to the changes in GCIPL thickness over time in DM participants as determined by multivariate linear regression analysis.

    • Variable NDR DR
      β (95% CI) p-value β (95% CI) †p-value
      Age, per 10-year increase 0.002 (−0.098, 0.104) 0.955 −0.011 (−0.033, 0.011) 0.334
      Male versus female −0.114 (−0.260, 0.032) 0.127 −0.034 (−0.405, 0.337) 0.856
      Body mass index 0.001 (−0.071, 0.074) 0.969 −0.131 (−0.316, 0.055) 0.167
      Duration of diabetes −0.014 (−0.026, −0.003) 0.012 0.039 (0.014, 0.064) 0.003
      Systolic blood pressure −0.070 (−0.143, 0.002) 0.055 0.068 (−0.117, 0.253) 0.471
      Eye examination Axial length −0.164 (−0.235, 0.092) < 0.001 −0.325 (−0.508, −0.141) 0.001
      Spherical 0.087 (0.015, 0.159) 0.018 0.031 (−0.159, 0.221) 0.750
      Intraocular pressure −0.056 (−0.128, 0.017) 0.131 −0.072 (−0.266, 0.121) 0.463
      BCVA (logMAR) −0.298 (−0.368, −0.228) < 0.001 −0.080 (−0.276, 0.116) 0.422
      Retinal thickness −0.238 (−0.309, −0.167) < 0.001 −0.293 (−0.476, −0.110) 0.002
      GCIPL thickness −0.327 (−0.397, −0.257) < 0.001 −0.269 (−0.452, −0.086) 0.004
      Choroidal thickness 0.014 (−0.059, 0.086) 0.714 −0.038 (−0.220, 0.145) 0.686
      Disc area 0.068 (−0.013, 0.149) 0.100 0.204 (−0.108, 0.517) 0.197
      RNFL thickness 0.006 (−0.066, 0.079) 0.863 −0.025 (−0.211, 0.160) 0.787
      HbA1c Baseline −0.043 (−0.115, 0.029) 0.241 0.403 (0.227, 0.580) < 0.001
      Mean −0.129 (−0.201, −0.058) < 0.001 0.449 (0.275, 0.624) < 0.001
      Peak −0.154 (−0.226, −0.083) < 0.001 0.461 (0.288, 0.634) < 0.001
      Fluctuation −0.144 (−0.216, −0.073) < 0.001 0.306 (0.128, 0.484) 0.001
      Range −0.148 (−0.219, −0.076) < 0.001 0.284 (0.106, 0.462) 0.002
      Blood lipid Total cholesterol 0.011 (−0.061, 0.083) 0.769 0.072 (−0.111, 0.254) 0.439
      Triglycerides −0.016 (−0.089, 0.056) 0.658 0.060 (−0.124, 0.244) 0.519
      HDL-c −0.025 (−0.098, 0.047) 0.490 −0.084 (−0.288, 0.119) 0.415
      LDL-c −0.038 (−0.110, 0.034) 0.299 0.048 (−0.136, 0.232) 0.609
      Renal function eGFR −0.037 (−0.110, 0.035) 0.310 −0.072 (−0.263, 0.119) 0.458
      Serum creatinine 0.007 (−0.065, 0.080) 0.840 0.090 (−0.098, 0.279) 0.347
      Serum uric acid 0.009 (−0.064, 0.081) 0.813 0.081 (−0.104, 0.265) 0.390
      Microalbuminuria −0.135 (−0.207, −0.063) < 0.001 0.177 (−0.076, 0.430) 0.169
      NDR, diabetic patients without retinopathy; DR, diabetic patients; CI, confidence interval; SD, standard deviation; BCVA, best corrected visual acuity; logMAR, logarithm of the minimal angle of resolution; GCIPL, ganglion cell–inner plexiform layer; RNFL, retinal nerve fiber layer; HbA1c, glycosylated hemoglobin; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. †p-values are from the univariate linear regression analysis. Within each subgroup (NDR and DR), all variables with p < 0.05 remained statistically significant after Benjamini–Hochberg false discovery rate correction (q < 0.05). Data in bold indicate statistically significant differences (p < 0.05).

      Table 4. 

      Clinical characteristics factors contributing to the rate of thinning of the macular ganglion cell–inner plexiform layer over time in NDR and DR participants as determined by univariate linear regression analysis.