Flavoprotein Fluorescence Correlation with Visual Acuity Response in Patients Receiving Anti-VEGF Injection for Diabetic Macular Edema.

Jorge S Andrade Romo,Michael Jansen,Kevin Liu,Matthew G Field,Daniel Kim,Giselle Lynch,Victor M Elner,Richard B Rosen

doi:10.1155/2018/3567306

Abstract

Anti-VEGF treatment of diabetic macular edema (DME) complicating diabetic retinopathy (DR) has greatly improved structural and visual outcomes for patients with diabetes mellitus. However, up to 50% of patients are either nonresponsive or refractory to anti-VEGF treatment (no improvement in BCVA or central macular thickness (CMT)). It is believed that factors such as mitochondrial structural and functional damage, due to oxidative stress, are partially responsible for this lack of improvement. Flavoprotein fluorescence (FPF) has been shown to be a sensitive marker of mitochondrial function and has been found to correlate with the degree of diabetic retinopathy. FPF may also provide additional information regarding therapeutic response of patients receiving anti-VEGF treatment for DME. Eight patients with DR and DME with clinically significant DME (CSDME) who underwent anti-VEGF (bevacizumab) treatment were imaged before injection and at follow-up visit using FPF in addition to standard color fundus photography and OCT CMT. A strong correlation r = 0.98 (p = 0.000015) between the FPF decrease and the BCVA improvement was observed; BCVA improved as FPF values decreased. Notably, in the same patients, the correlation between OCT CMT decrease and BCVA improvement (r = 0.688) was not found to be significant (p = 0.13). These findings suggest that FPF can detect improvement in metabolic function preceding structural improvement and even with small changes in edema. Additionally, FPF may be supplementary to current diagnostic methods for earlier detection of therapeutic response to anti-VEGF treatment in patients with DME.

Highlights

Diabetic macular edema (DME), complicating advanced diabetic retinopathy (DR), may result in severe visual morbidity
Statistical analyses were performed on 8 subjects (6 men and 2 women; mean age 58 years, range 40–73), all of whom had type 2 DM and DME complicating proliferative diabetic retinopathy (PDR) (5 eyes) and severe nonproliferative diabetic retinopathy (NPDR) (3 eyes)
Significant clinically significant diabetic macular edema (CSDME) was present in all 8 patients based on Early Treatment Diabetic Retinopathy Study (ETDRS) criteria

Summary

Introduction

Diabetic macular edema (DME), complicating advanced diabetic retinopathy (DR), may result in severe visual morbidity. Current primary therapy for DME is aimed at stabilizing damage, leaking blood vessels by administration of antivascular endothelial growth factor (VEGF) agents into the vitreous when clinically significant diabetic macular edema (CSDME) is present. The variability in DME responses to anti-VEGF therapy suggests that DME is the result of multiple factors underlying the pathogenesis of DR. Anti-VEGF agents may stabilize vascular leakage and reduce edema but may not address other factors which contribute to CSDME or adversely impact best corrected visual acuity (BCVA), the most important endpoint for DME treatment. Recent large, multicenter studies have shown that the best antiVEGF treatments improve diabetic retinopathy severity scores (DRSS), but do not result in statistically significant

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