Reevaluating the definition of intraretinal microvascular abnormalities and neovascularization elsewhere in diabetic retinopathy using optical coherence tomography and fluorescein angiography

Abstract

Purpose: To evaluate the agreement between clinical examination, spectral-domain ocular coherence tomography (SD OCT), and fluorescein angiography (FA) in diagnosing intraretinal microvascular abnormality (IRMA) and neovascularization elsewhere (NVE) and define the SD OCT features that differentiate NVEs from IRMAs.

Design: Retrospective study.

Methods: Data were collected from 23 lesions from 8 diabetic patients, seen from July 2012 through October 2013 at Moorfields Eye Hospital, United Kingdom. Main outcomes were SD OCT features and FA leakage of IRMA and neovascular complex. The agreement between 3 evaluations was analyzed by Fleiss' kappa.

Results: The following 5 SD OCT features significantly differentiated IRMAs from NVEs: (1) hyperreflective dots in superficial inner retina (P = .002); (2) the outpouching of internal limiting membrane (ILM) (P = .004); (3) the breach of ILM (P = .004); (4) the breach of posterior hyaloid (P = .0005); (5) hyperreflective dots in vitreous (P = .008). The agreement was moderate between 3 evaluations (κ = 0.48, P = 7.11 × 10(-5)) but substantial between clinical and SD OCT evaluation (κ = 0.72, P = .00055). There was no significant agreement between OCT evaluation and FA leakage (κ = 0.249, P = .232).

Conclusions: SD OCT will be a valuable adjunct in evaluating IRMA and NVE, since it can verify the histopathologic correlate. SD OCT provides subtle anatomic insights and may be more accurate than clinical examination or leakage on FA, our current method of diagnosing this important endpoint, which has implications in future trial design for proliferative diabetic retinopathy prevention.

Conflict of interest statement

THE AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

FIGURE 1

Spectral-domain optical coherence tomography characteristics found in intraretinal microvascular abnormalities and/or neovascularization elsewhere in diabetic retinopathy. The top row illustrates different characteristics of intraretinal microvascular abnormalities on spectral-domain optical coherence tomography and the bottom row shows those of neovascularization elsewhere. (Top left) There are hyperreflective dots (arrow) in the inner retina without breach of the internal limiting membrane (ILM). (Top middle) There is an outpouching of the ILM without disruption of the layer (arrow). The contour of the ILM remains smooth. (Top right) There are 2 areas of ILM breach (arrows) without the breach of posterior hyaloid or further growth into the core vitreous. The posterior hyaloid membrane is placed over 2 lesions. (Bottom left) There is a breach of posterior hyaloid and the lesion grows into the core vitreous. (Bottom middle) The lesion shows multiple breaches of posterior hyaloid and linear growth along the horizontal plane of the vitreous cortex. (Bottom right) There are multiple hyperreflective dots in the vitreous near the neovascularization elsewhere lesion (arrow).

FIGURE 2

Discrepancy between clinical grading and spectral-domain optical coherence tomography (SD OCT) imaging in defining intraretinal microvascular abnormality vs neovascularization elsewhere in diabetic retinopathy. (Top left) A red-free photograph of clinically defined intraretinal microvascular abnormality (IRMA). (Top right) Even though this lesion is diagnosed as IRMA based on clinical grading, the same lesion on SD OCT shows disruption of the internal limiting membrane and growth into the posterior hyaloid. Thus, this is defined as neovascularization elsewhere on SD OCT. (Bottom) The lesion shows no leakage on the mid (Bottom left) or late (Bottom right) phase on fluorescein angiography.

FIGURE 3

Leakage on fluorescein angiography and spectral-domain optical coherence tomography (SD OCT) imaging of clinically defined intraretinal microvascular abnormalities (IRMAs) in diabetic retinopathy. (Top left) A red-free photograph of 3 clinically defined IRMAs shown with arrow, arrowhead, and asterisk. (Top middle) Fluorescein angiography shows early hyperfluorescence of 3 IRMAs. (Top right) Fluorescein angiography shows diffuse late leakage, including from 3 IRMAs, despite the commonly accepted idea that “IRMAs do not leak.” (Bottom) All 3 lesions were defined as IRMAs on SD OCT, supporting the clinical diagnosis. (Bottom left) SD OCT of IRMA indicated with arrow reveals multiple outpouchings of the internal limiting membrane (ILM). (Bottom middle) SD OCT of IRMA lesion indicated with arrowhead shows hyperreflective dots in the inner retina. (Bottom right) SD OCT of IRMA lesion marked with asterisk shows hyperreflective dots in inner retina and slight outpouching of the ILM.

FIGURE 4

Temporal progression of intraretinal microvascular abnormality (IRMA) to neovascularization elsewhere (NVE) of a single lesion in diabetic retinopathy over a 14-month period. (First row, left) Infrared image shows an IRMA. (First row, right) Concurrent spectral-domain optical coherence tomography (SD OCT) shows slight outpouching of the internal limiting membrane (ILM) with hyperreflective dots in the inner retina. (Second row, left) Infrared image taken 4 months after image in first row. (Second row, right) On concurrent SD OCT image, there is more distinctive outpouching of the ILM without disruption. (Third row, left) Infrared image taken 5 months after image in second row. (Third row, right) The area of outpouching is larger without disruption of the ILM. (Fourth row, left) Infrared image taken 5 months after image in third row shows fine vessels characteristic of neovascularization. (Fourth row, right) SD OCT image shows evidence of NVE with a breach of the ILM and growth into the posterior hyaloid.