Performance of confocal scanning laser tomograph Topographic Change Analysis (TCA) for assessing glaucomatous progression

Abstract

Purpose: To determine the sensitivity and specificity of confocal scanning laser ophthalmoscope's Topographic Change Analysis (TCA; Heidelberg Retina Tomograph [HRT]; Heidelberg Engineering, Heidelberg, Germany) parameters for discriminating between progressing glaucomatous and stable healthy eyes.

Methods: The 0.90, 0.95, and 0.99 specificity cutoffs for various (n=70) TCA parameters were developed by using 1000 permuted topographic series derived from HRT images of 18 healthy eyes from Moorfields Eye Hospital, imaged at least four times. The cutoffs were then applied to topographic series from 36 eyes with known glaucomatous progression (by optic disc stereophotograph assessment and/or standard automated perimetry guided progression analysis, [GPA]) and 21 healthy eyes from the University of California, San Diego (UCSD) Diagnostic Innovations in Glaucoma Study (DIGS), all imaged at least four times, to determine TCA sensitivity and specificity. Cutoffs also were applied to 210 DIGS patients' eyes imaged at least four times with no evidence of progression (nonprogressed) by stereophotography or GPA.

Results: The TCA parameter providing the best sensitivity/specificity tradeoff using the 0.90, 0.95, and 0.99 cutoffs was the largest clustered superpixel area within the optic disc margin (CAREA(disc) mm(2)). Sensitivities/specificities for classifying progressing (by stereophotography and/or GPA) and healthy eyes were 0.778/0.809, 0.639/0.857, and 0.611/1.00, respectively. In nonprogressing eyes, specificities were 0.464, 0.570, and 0.647 (i.e., lower than in the healthy eyes). In addition, TCA parameter measurements of nonprogressing eyes were similar to those of progressing eyes.

Conclusions: TCA parameters can discriminate between progressing and longitudinally observed healthy eyes. Low specificity in apparently nonprogressing patients' eyes suggests early progression detection using TCA.

Figure 1

Sensitivities, specificities, and cutoffs for TCA parameters at 0.99, 0.95, and 0.90 specificity cutoffs (determined using permuted longitudinal data with 1000 permutations) for largest area superpixel clusters. Only pixels with depth change from baseline ≥ 50 μm were considered outside normal limits. Although HRT measurements are generally expressed in millimeters, the cutoff values are expressed in micrometers, to prevent rounding to zero in some cases.

Figure 2

Sensitivities, specificities, and cutoffs for TCA parameters at 0.99, 0.95, and 0.90 specificity cutoffs (determined using permuted longitudinal data with 1000 permutations) for largest area superpixel clusters. Only pixels with depth change from baseline ≥ 100 μm were considered outside normal limits.

Figure 3

Sensitivities, specificities and cutoffs for TCA parameters at 0.99, 0.95, and 0.90 specificity cutoffs (determined using permuted longitudinal data with 1000 permutations) for largest area superpixel clusters. Only pixels with depth change from baseline ≥ 200 μm were considered outside normal limits.

Figure 4

Examples of agreement for detecting progression among TCA analysis, stereophotography assessment and SAP GPA. (A) An example of a true-positive TCA result. This eye progressed by stereophotograph assessment, SAP GPA and TCA CAREA^disc (using the 0.90 specificity cutoff of ≥0.036 mm²). Inferior rim thinning was apparent in both the TCA image (CAREA^disc = 0.252 mm²) and the stereophotograph pair. This change is reflected in significant superior hemifield change measured by GPA. (B) An example of a false-negative TCA result. This eye progressed by stereophotograph assessment and SAP GPA, but not by TCA. Inferior rim thinning is apparent in the stereophotograph pair and reflected in significant superior hemifield change by GPA. However, the TCA image shows little clustered change (CAREA^disc = 0.011 mm²). (C) A “false-positive” TCA result. This eye showed very significant cup enlargement by TCA (CAREA^disc = 0.819 mm²) but showed no change by stereophotography or SAP GPA.