Einstein International Journal Organization(EIJO)

Abstract

Background: Diabetic macular edema (DME) is the leading cause of vision loss in working-age adults with diabetes mellitus. Optical coherence tomography (OCT) has emerged as an indispensable tool in DME assessment, providing high-resolution, non-invasive, cross-sectional imaging of retinal microstructure. However, the prognostic value of individual OCT biomarkers in determining visual outcomes remains incompletely characterized.

Aim: To conduct a systematic review of the evidence of OCT-derived biomarkers as predictors of best-corrected visual acuity (BCVA) and other visual outcomes in patients with DME.

Methods: PubMed/MEDLINE, Embase, and the Cochrane Library were systematically searched for cross-sectional and cohort studies published between January 2014 and December 2024. Studies reporting at least one quantitative OCT biomarker with concurrent best-corrected visual acuity (BCVA) measurement in patients with DME were eligible.  Due to substantial heterogeneity across studies, a narrative synthesis approach was adopted. Biomarkers evaluated included central macular thickness (CMT), disorganization of retinal layers (DRIL), ellipsoid zone (EZ) integrity, external limiting membrane (ELM) status, subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), choroidal thickness, and vitreomacular traction

Findings: Ten studies (n = 1,589 eyes) were included. DRIL demonstrated the strongest association with BCVA loss (r = 0.68–0.79; OR 4.2, 95% CI 2.8–6.3). EZ disruption and FAZ area enlargement were also potent predictors (AUC 0.81 and 0.83, respectively). CMT showed a moderate correlation (r = 0.42–0.61). SRF showed weak correlation with visual outcomes. HRF density was associated with adverse treatment prognosis.

Conclusion: OCT biomarkers, particularly DRIL, EZ disruption, and FAZ area, show consistent structural associations with visual outcomes in DME across observational studies and may serve as candidate prognostic markers pending prospective longitudinal validation. Systematic incorporation of these biomarkers into clinical evaluation may support more individualized therapeutic decision-making and improve patient prognostication, though stronger longitudinal evidence is needed before they can be considered established predictors.

Keywords: Diabetic Macular Edema, Optical Coherence Tomography, OCT Biomarkers, Visual Acuity, DRIL, Ellipsoid Zone, Central Macular Thickness, Hyperreflective Foci, Systematic Review.

1. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022; 183:109119.
2. Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580–1591.
3. Das A, McGuire PG, Rangasamy S. Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology. 2015;122(7):1375–1394.
4. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science. 1991;254(5035):1178–1181.
5. Schmidt-Erfurth U, Sadeghipour A, Gerendas BS, Waldstein SM, Bogunovic H. Artificial intelligence in retina. Prog Retin Eye Res. 2018;67:1–29.
6. Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45–50.
7. Vujosevic S, Aldington SJ, Silva P, et al. Screening for diabetic retinopathy: new perspectives and challenges. Lancet Diabetes Endocrinol. 2020;8(4):337–347.
8. Kim JH, Kim JW, Kim CG, Lee DW. Optical coherence tomography-based biomarkers as predictors of visual outcomes after intravitreal anti-VEGF injections for diabetic macular edema. J Ophthalmol. 2019;2019:4655432.
9. Das R, Spence G, Hogg RE, Stevenson M, Chakravarthy U. Disorganization of inner retina and outer retinal morphology in diabetic macular edema. JAMA Ophthalmol. 2018;136(2):202–208.
10. Radwan SH, Soliman AZ, Tokarev J, Zhang L, Van Kuijk FJ, Koozekanani DD. Association of disorganization of retinal inner layers with vision after resolution of center-involved diabetic macular edema. JAMA Ophthalmol. 2015;133(7):820–825.
11. Vujosevic S, Torresin T, Bini S, Convento E, Pilotto E, Parrozzani R, et al. Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema. Acta Ophthalmol. 2017;95(5):464–471.
12. Yilmaz I, Acar N, Altan C, Bayraktar S. Vitreomacular traction and subretinal fluid as predictors of visual outcomes in center-involving diabetic macular edema. Clin Ophthalmol. 2021;15:2453–2462.
13. Sun JK, Radwan SH, Soliman AZ, Lammer J, Lin MM, Prager SG, et al. Neural retinal disorganization as a robust marker of visual acuity in current and resolved diabetic macular edema. Diabetes. 2015;64(7):2560–2570.
14. Balaratnasingam C, Inoue M, Ahn S, McCann J, Dhrami-Gavazi E, Yannuzzi LA, et al. Visual acuity is correlated with the area of the foveal avascular zone in diabetic retinopathy and retinal vein occlusion. Ophthalmology. 2016;123(11):2352–2367.
15. Uji A, Murakami T, Nishijima K, Akagi T, Horii T, Arakawa N, et al. Association between hyperreflective foci in the outer retina, status of photoreceptor layer, and visual acuity in diabetic macular edema. Am J Ophthalmol. 2012;153(4):710–717.
16. Lopez J, Moreno C, Perez-Rojo G, Donate J. Choroidal thickness and subretinal fluid patterns in diabetic macular edema: implications for visual prognosis. Ophthalmic Res. 2023;66(1):45–53.
17. Borrelli E, Grosso D, Barresi C, Lari G, Sacconi R, Senni C, et al. Long-term visual outcomes and morphologic biomarkers of vision loss in eyes with diabetic macular edema treated with anti-VEGF therapy. Am J Ophthalmol. 2022;235:80–89.
18. Sun JK, Lin MM, Lammer J, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132(11):1309–1316.
19. Maheshwary AS, Oster SF, Yuson RM, Cheng L, Mojana F, Freeman WR. The association between percent disruption of the photoreceptor inner segment–outer segment junction and visual acuity in diabetic macular edema. Am J Ophthalmol. 2010;150(1):63–67.
20. Browning DJ, Glassman AR, Aiello LP, et al.; Diabetic Retinopathy Clinical Research Network. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology. 2007;114(3):525–536.
21. Wells JA, Glassman AR, Ayala AR, et al.; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193–1203. [DRCR Protocol T]
22. Maturi RK, Glassman AR, Liu D, et al.; DRCR Retina Network. Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema. JAMA Ophthalmol. 2018;136(1):29–38. [DRCR Protocol U]
23. Yang D, Tang Z, Ran A, et al. Assessment of parafoveal diabetic macular ischemia on optical coherence tomography angiography images to predict diabetic retinal disease progression and visual acuity deterioration. JAMA Ophthalmol. 2023;141(7):647–655.