Functional assessment of diabetic macular edema using flicker electroretinography

Diabetes mellitus is a major public health challenge worldwide, and diabetic macular edema (DME) remains the most common cause of visual impairment among diabetic individuals. DME results from chronic hyperglycemia-induced breakdown of the inner blood-retinal barrier. Loss of pericytes, capillary leakage, and accumulation of intraretinal fluid contribute to macular thickening.[1] Alongside vascular dysfunction, diabetes also induces early neuronal dysfunction, especially affecting cone-mediated pathways, which may precede or accompany structural alterations.[2] This explains why visual acuity does not always correlate with macular thickness. While optical coherence tomography (OCT) offers excellent structural assessment in DME, it does not reflect retinal function. Electroretinography (ERG), particularly the 30 Hz flicker protocol, offers a rapid, objective assessment of cone pathway integrity and can detect functional delay in retinal responses. Previous studies using multifocal ERG (mfERG) and mydriasis-free handheld ERG have documented functional alterations in diabetic retinopathy. However, only a few studies have evaluated how these ERG parameters relate to OCT-derived macular status in DME. In our cross-sectional observational study, we evaluated 60 eyes of 34 diabetic patients, divided into DME (n = 30) and no-DME (n = 30) groups. Using the handheld RETeval™ system, we evaluated 30 Hz flicker amplitude and implicit time at 16 and 32 Td-s stimuli and correlated these parameters with best-corrected visual acuity (BCVA) and central macular thickness (CMT) on spectral-domain OCT (SD-OCT). Our study demonstrated a significant reduction in amplitudes and prolongation of implicit times among eyes with DME compared to those without DME. Furthermore, in the DME group, amplitudes showed a negative correlation with both CMT and logMAR BCVA, while implicit times showed a positive correlation with these parameters. These findings indicate that functional retinal impairment parallels structural changes and visual reduction in DME. Key flicker ERG and multifocal ERG studies in diabetic eyes are summarized in Table 1. While mfERG-based research has demonstrated correlations between functional parameters, CMT and BCVA, handheld flicker ERG studies have generally focused on change in ERG parameters with increasing diabetic retinopathy severity rather than specifically comparing DME versus no-DME eyes or evaluating simultaneous correlations with CMT and BCVA. The present study specifically demonstrates that handheld, nonmydriatic, 30 Hz flicker ERG shows significant differences in amplitude and implicit time between eyes with and without DME and establishes a structure–function relationship, wherein reduced amplitude and prolonged implicit times parallel increasing macular thickness and worsening visual acuity. While not intended as a replacement for OCT, handheld flicker ERG may complement structural assessment by providing additional functional information in eyes with DME.Table 1: Comparative review of literature evaluating ERG parameters in diabetic retinopathy and diabetic macular edemaIn summary, our findings reinforce the concept that DME is not solely a structural disorder but also involves significant neurofunctional compromise. Incorporating handheld flicker ERG with OCT may offer a more holistic evaluation of diabetic macular edema and enhance functional assessment in routine practice.