Evaluation of Spectral Domain OCT Changes Following Anti-VEGF Therapy in Diabetic Macular Edema

Abstract

Background:

Diabetic macular edema (DME) is a leading cause of visual impairment in diabetic retinopathy. Spectral-domain optical coherence tomography (SD-OCT) enables high-resolution assessment of retinal microstructural changes. Antivascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for DME; however, anatomical and functional outcomes vary. This study evaluates SD-OCT morphological changes following anti-VEGF therapy and their correlation with visual outcomes.

Materials and Methods:

A prospective observational study was conducted on 100 eyes of 92 DME patients at a tertiary care center. All patients received three monthly intravitreal injections of bevacizumab (1.25 mg/0.05 ml). Baseline and post-treatment evaluations included best-corrected visual acuity (BCVA) and SD-OCT imaging. OCT biomarkers such as central macular thickness (CMT), cystoid macular edema (CME), subretinal fluid (SRF), disorganization of retinal inner layers (DRIL), ellipsoid zone (EZ) disruption, external limiting membrane (ELM) status, and hyperreflective foci (HRF) were assessed.

Results:

Post-treatment analysis showed significant reduction in CMT and resolution of CME and SRF in many cases. Partial restoration of EZ and ELM, as well as decreased HRF and DRIL, were associated with improved BCVA. Central-involving DME and EZ disruption were significantly associated with poorer outcomes.

Conclusion:

Anti-VEGF therapy leads to measurable anatomical improvements on SD-OCT in DME. Specific OCT biomarkers can aid in predicting visual response and guiding management.

INTRODUCTION

Diabetic macular edema (DME), a major cause of vision loss in diabetic retinopathy, results from retinal vascular leakage and fluid accumulation.[1] Anti-VEGF agents are the primary treatment, significantly improving best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both clinical trials and real-world settings.[2,3]

Spectral-domain OCT (SD-OCT) enables detailed assessment of retinal biomarkers such as cystoid spaces, DRIL, ELM and EZ integrity, subretinal fluid, and hyperreflective foci (HRF).[1] These features have shown measurable improvement after anti-VEGF therapy, correlating with better visual and anatomical outcomes.[1]

Recent studies also highlight therapy-induced changes in choroidal thickness and retinal perfusion, with notable reductions in choroidal thickness after 6 months and alterations in microvascular architecture detectable on OCT angiography.[3,4]

However, integration of SD-OCT biomarkers with quantitative vascular parameters remains limited. This study aims to assess SD-OCT changes post anti-VEGF therapy in DME to better understand their prognostic relevance.

MATERIAL AND METHODS

This prospective observational study was conducted from September 2022 to May 2024 in the Department of Ophthalmology of an Indian medical college, involving 100 eyes from 92 patients with central-involving diabetic macular edema (DME) and central macular thickness (CMT) >250 µm. Patients with other retinal diseases, prior anti-VEGF treatment, recent laser therapy, or systemic illnesses were excluded.

All patients underwent detailed ocular and systemic evaluation, including BCVA, intraocular pressure, slit-lamp examination, and dilated fundus assessment. SD-OCT (Cirrus HD-OCT, Zeiss) was used to assess CMT, macular volume, DME morphology, and biomarkers such as ellipsoid zone (EZ) integrity, disorganization of the retinal inner layers (DRIL), external limiting membrane (ELM) status, and hyperreflective foci (HRF).

Each patient received three monthly intravitreal bevacizumab (1.25 mg/0.05 mL) injections. Post-treatment BCVA and OCT assessments were performed one month after the final injection. A visual gain of ≥0.3 LogMAR and CMT reduction ≥100 µm were considered significant. Data were analyzed using SPSS v23 with a significance threshold of P < 0.05.

RESULTS

The study comprised 100 eyes from 92 patients, with a mean age of 58.53 ± 9.61 years. Most participants were aged 60-69 years (38%), followed by 50-59 years (35%). Men constituted 71% of the study population, showing significant gender distribution (P < 0.0001).

OCT imaging revealed typical DME patterns. Cystoid spaces with retinal thickening and foveal contour loss were observed pretreatment, which resolved after anti-VEGF therapy [Figure 1]. Subretinal fluid was present initially and showed marked reduction post-treatment [Figure 2]. Restoration of the ellipsoid zone and external limiting membrane was noted after therapy in eyes with initial disruption [Figure 3].

Figure 1.

OCT showing hyporeflective spaces within the retina, macular thickening, and loss of foveal depression suggestive of cystoid spaces; above-before treatment, below-after treatment

Figure 2.

OCT showing hypo reflective area above the RPE suggestive of sub retinal fluid (SRF); Above-Prior to treatment, Below-After treatment

Figure 3.

OCT showing intraretinal cavitation and disruption of ellipsoid zone and external limiting membrane; Above-Prior to treatment, Below-After treatment-OCT showing intraretinal cavitation with intact ellipsoid zone and external limiting membrane

These OCT changes suggest favorable anatomical responses to anti-VEGF therapy in DME.

DISCUSSION

In this study, SD-OCT revealed significant morphological improvements in DME after anti-VEGF therapy, particularly with respect to cystoid spaces, SRF, DRIL, EZ/ELM integrity, and HRF. These findings align with previous evidence showing reductions in intraretinal cysts and restoration of photoreceptor integrity.[5] Hyperreflective foci reduction and partial reconstitution of ELM/EZ were associated with visual acuity gains, especially in cases with baseline SRF—echoing prior observations that HRF count correlates negatively with final photoreceptor integrity and vision.[6]

Choroidal changes observed in our cohort, while not quantified, suggest anatomical responsiveness post anti-VEGF therapy. This aligns with studies reporting significant reductions in subfoveal choroidal thickness (SFCT) over six months,[7] though some real-world data indicate nonsignificant changes at 2 years.[8] These inconsistencies may reflect interindividual variability in choroidal response influenced by baseline choroidal thickness, treatment regimen, and treatment duration.

Emerging biomarkers such as the choroidal vascularity index (CVI) have demonstrated more consistency than SFCT in monitoring choroidal health. Although baseline SFCT did not predict treatment response, longitudinal CVI changes may better reflect therapy effectiveness. This aligns with recent findings suggesting CVI as a stable and reliable biomarker, less affected by systemic factors than SFCT.[9]

Limitations include a single-arm design and reliance on qualitative OCT analysis without quantification of choroidal metrics or CVI. A stratified analysis based on baseline choroidal thickness or CVI could elucidate predictive biomarkers. Integration of OCT angiography (OCTA) would further clarify microvascular changes following therapy.

CONCLUSION

Anti-VEGF therapy produces consistent SD-OCT improvements in retinal structure and HRF reduction, supporting its role in DME management. Future studies incorporating quantitative choroidal and OCTA biomarkers such as CVI may enhance prediction of therapeutic response and long-term visual prognosis.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.