Real-world clinical insights and aqueous humor biomarker analysis of diabetic macular edema subtypes classified by OCT following intravitreal injections

Abstract

Purpose: This study aimed to observe the morphological changes and visual outcomes in diabetic macular edema (DME) subtypes based on optical coherence tomography classification following intravitreal injection.

Methods: Ninety-four eyes from seventy-eight patients were enrolled between July 1, 2018, and June 30, 2023. Best-corrected visual acuity (BCVA), central subfield thickness, and morphological changes were examined at each follow-up visit. Aqueous humor samples were obtained before intravitreal injection of anti-vascular endothelial growth factor or cataract surgery. The inflammatory cytokine profile in the aqueous humor of each DME subtype was analyzed to explore potential contributions.

Results: The BCVA in the diffuse retinal thickening group was significantly improved at the last follow-up (p = 0.006), but no significant change in central subfield thickness was observed. Conversely, the BCVA in the cystoid macular edema and serous retinal detachment groups did not significantly improve, although a significant reduction in central subfield thickness was observed in both groups at the final follow-up (both p < 0.05). Principal component analysis of proteomic data revealed clear segregation between samples from patients with different DME subtypes and those from the control group. 59 proteins were found to be significantly regulated in the diffuse retinal thickening group compared to those in the control group. Of these, 10 proteins were upregulated, whereas 49 were downregulated. In the cystoid macular edema group, 30 proteins were significantly regulated, with 8 proteins upregulated and 22 downregulated. In the serous retinal detachment group, 87 proteins showed significant changes: 24 exhibited increased expression and 63 decreased expression.

Conclusions: The diffuse retinal thickening subtype showed a better response and cystoid macular edema was the most common morphological subtype of DME after intravitreal injection treatment in real-world clinical observations. The variations in protein expression of aqueous humor suggested distinct pathological mechanisms for each DME subtype, laying the groundwork for more targeted treatment strategies.

Keywords: Cystoid macular edema; Diabetic macular edema; Diffuse retinal thickening; Intravitreal injection; Optical coherence tomography; Serous retinal detachment.

Fig. 1

Design, inclusion and exclusion criteria, and analysis of the study

Fig. 2

Classification of diabetic macular edema as (A) diffuse retinal thickening, (B) cystoid macular edema, and (C) serous retinal detachment subtypes

Fig. 3

Principal component analysis indicated that samples from patients with diabetic macular edema could nearly be separated from control samples based on their proteomic profiles

Fig. 4

Volcano plots (A, E, I), bioinformatic analyses of significantly regulated proteins (B, C, F, G, J, K), and string clustering analysis of regulated proteins (D, H, L)