Diagnosing Persistent Hypertransmission Defects on En Face OCT Imaging of Age-Related Macular Degeneration

PURPOSE: A training exercise was performed to study the ability of graders to reliably identify precursor lesions to geographic atrophy (GA), known as persistent choroidal hyper-transmission defects (hyperTDs), using en face optical coherence tomography (OCT) images from eyes with non-exudative age-related macular degeneration (AMD). DESIGN: Intergrader agreement study PARTICIPANTS: Eleven graders participated in this exercise. METHODS: Formal training on how to identify persistent hyperTDs on en face OCT images was provided to the graders. Persistent hyperTDs were defined as bright lesions having a greatest linear dimension (GLD) of at least 250 μm. Training consisted of a tutorial session followed by the grading of three pretest exercises, each consisting of three cases. After all the graders scored 100% on the pretest exercises, they performed a final exercise consisting of 30 en face OCT images from 29 eyes with non-exudative AMD containing 107 hyperTDs that each grader needed to evaluate. The cases contained a variety of AMD-related atrophic lesions. MAIN OUTCOME MEASURES: The sensitivity, positive predictive value (PPV), and modified accuracy were assessed for each grader. RESULTS: A total of 1177 hyperTDs from 30 en face OCT images were reviewed by the graders. The mean sensitivity, PPV, and modified accuracy for all the graders were calculated to be 99.0%, 99.2%, and 98.2%, respectively. There was a 97% agreement observed between all the graders (AC(1) = 0.97). Internal graders from the Bascom Palmer Eye Institute (BPEI) had a slightly higher agreement compared with the external graders (AC(1) = 0.98 vs. 0.96). The hyperTDs most often incorrectly identified included the following features: (1) hyperTDs containing a hypo-transmission defect (hypoTD) core, (2) single hyperTDs that were incorrectly graded as two separate lesions, and (3) hyperTDs with a borderline GLD that was close to 250 μm. CONCLUSION: The accurate detection of persistent hyperTDs on en face OCT images by graders demonstrates the feasibility of using this OCT biomarker to identify disease progression in eyes with non-exudative AMD, especially when used as a clinical trial endpoint in studies designed to test new therapies that may slow disease progression from intermediate AMD (iAMD) to GA.