Retinal and Choroidal Phenotypes Across Novel Subtypes of Type 2 Diabetes Mellitus.

Purpose: To investigate longitudinal changes in choroidal thickness (CT) and ganglion cell-inner plexiform layer thickness (GC-IPLT) across distinct phenotypes of type 2 diabetes mellitus (T2DM) patients.

Design: Prospective cohort study.

Methods: T2DM patients were categorized into 5 groups (SAID, SIDD, SIRD, MOD, and MARD) using K-means clustering based on β-cell function and insulin resistance. Swept-source optical coherence tomography measured baseline and 4-year follow-up CT and GC-IPLT. Linear mixed-effects models assessed absolute and relative changes in CT and GC-IPLT across subtypes.

Results: Over a median 4.11-year follow-up, CT and GC-IPLT decreased significantly across all groups. Choroidal thinning rates were most pronounced in SIDD (-6.5 ± 0.53 µm/year and -3.5 ± 0.24%/year) and SAID (-6.27 ± 0.8 µm/year and -3.19 ± 0.37%/year), while MARD showed the slowest thinning rates (-3.63 ± 0.34 µm/year and -1.98 ± 0.25%/year). SIRD exhibited the greatest GC-IPLT loss (-0.66 ± 0.05 µm/year and -0.91 ± 0.07%/year), with the least in SIDD (-0.36 ± 0.05 µm/year and -0.49 ± 0.07%/year), all statistically significant (all P < 0.001). Adjusted for confounding variables, SIDD and SAID groups showed faster CT thinning than MARD [-2.57 µm/year (95% CI: -4.16 to -0.97; P = 0.002) and -2.89 µm/year (95% CI: -4.12 to -1.66; P < 0.001), respectively]. GC-IPLT thinning was notably accelerated in SIRD versus MARD, but slowed in SIDD relative to MARD [differences of -0.16 µm/year (95% CI: -0.3 to -0.03; P = 0.015) and 0.15 µm/year (95% CI: 0.03 to 0.27; P = 0.015), respectively].

Conclusions: Microvascular damage in the choroid is associated with SIDD patients, whereas early signs of retinal neurodegeneration are evident in SIRD patients. All these changes may precede the onset of DR.