Influence of Fluorescein Angiography on the Diagnosis and Management of Retinopathy of Prematurity

Abstract

Purpose: To examine the influence of fluorescein angiography (FA) on the diagnosis and management of retinopathy of prematurity (ROP).

Design: Prospective cohort study.

Participants: Nine recognized ROP experts (3 pediatric ophthalmologists and 6 retina specialists) interpreted 32 sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images from infants with ROP.

Methods: All experts independently reviewed the 32 image sets on a secure website and provided a diagnosis and management plan for the case presented, first based on color fundus photographs alone, and then based on color fundus photographs and corresponding FA images.

Main outcome measures: Sensitivity and specificity of the ROP diagnosis (zone, stage, plus disease, and category, i.e., no ROP, mild ROP, type 2 ROP, and ROP requiring treatment) were calculated using a consensus reference standard diagnosis, determined from the diagnosis of the color fundus photographs by 3 experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. The κ statistic was used to analyze the average intergrader agreement among experts for the diagnosis of zone, stage, plus disease, and category.

Results: Addition of FA to color fundus photography resulted in a significant improvement in sensitivity for diagnosis of stage 3 or worse disease (39.8% vs. 74.1%; P = 0.008), type 2 or worse ROP (69.4% vs. 86.8%; P = 0.013), and pre-plus or worse disease (50.5 vs. 62.6%; P = 0.031). There was a nonsignificant trend toward improved sensitivity for diagnosis of ROP requiring treatment (22.2% vs. 40.3%; P = 0.063). Using the κ statistic, addition of FA to color fundus photography significantly improved intergrader agreement for diagnosis of ROP requiring treatment. Addition of FA to color fundus photography did not affect intergrader agreement significantly for the diagnosis of stage, zone, or plus disease.

Conclusions: Compared with color fundus photography alone, FA may improve the sensitivity of diagnosis of ROP by experts, particularly for stage 3 disease. In addition, intergrader agreement for diagnosis of ROP requiring treatment may improve with FA interpretation.

Figure 1. Study Design Presented to Retinopathy of Prematurity (ROP) Experts to Determine ROP Diagnosis and Management Plan using Color Fundus Photography and Fluorescein Angiography (FA)

In the first part of this study, each expert completed 8 clinical cases in which he or she provided a diagnosis of zone, stage, plus, category, management, advanced posterior-ROP, and recommended clinical follow-up. In the second part of the study, experts were presented with the same 8 clinical cases, but were now provided with the corresponding FAs. For each clinical case, the experts were asked to provide a clinical diagnosis and management plan, but were not able to see their previous responses from the first part of the study.

Figure 2. Mean Distribution of Retinopathy of Prematurity (ROP) Diagnosis by 9 ROP Experts using Color Fundus Photographs Only versus Color Fundus Photographs with Corresponding Fluorescein Angiograms (FA)

Gray bars indicate diagnosis using color fundus photographs only and black bars indicate diagnosis using color fundus photographs and corresponding FAs (black bars). A, Distribution of responses for the 8 eyes with a consensus diagnosis of type 2-ROP. B, Distribution of responses for the 8 eyes with a consensus diagnosis of treatment-requiring ROP. C, Distribution of responses for the 12 eyes with a consensus diagnosis of stage 3. D, Distribution of responses for the 4 eyes with a consensus diagnosis of stage 2. E, Distribution of responses for the 8 eyes with a consensus diagnosis of zone I. ROP = Retinopathy of Prematurity; FA = Fluorescein Angiogram; TR-ROP = Treatment requiring ROP

Figure 3. Intergrader Agreement of Retinopathy of Prematurity (ROP) Diagnosis by 9 ROP Experts using Color Fundus Photographs only versus Color Fundus Photographs with Corresponding Fluorescein Angiograms (FA)

Intergrader agreement is measured as the unweighted kappa (κ) statistic for each expert as compared to all other experts. Each open circle represents the mean unweighted κ for a single expert. The closed circle is the value for the unweighted κ averaged across all experts, and the whiskers off the closed circles denote the 95% confidence interval for this mean. Significance is calculated using a nonparametric sign test that analyzes mean κ differences using color fundus photographs versus color fundus photographs with corresponding FAs. FA = Fluorescein Angiogram