Estimated retinal ganglion cell counts in glaucomatous eyes with localized retinal nerve fiber layer defects

Abstract

Purpose: To estimate retinal ganglion cell (RGC) losses associated with visible glaucomatous localized retinal nerve fiber layer (RNFL) defects.

Design: Observational cross-sectional study.

Methods: A multicenter study of 198 normal eyes (138 subjects) and 66 glaucomatous eyes (55 subjects) recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All eyes underwent standard automated perimetry (SAP), spectral-domain optical coherence tomography, and fundus stereophotography within 6 months. Glaucomatous eyes were included if localized RNFL defects were detected by masked grading of stereophotographs. The number of RGCs in each sector of a structure-function map was estimated using a previously published model combining RGC estimates from SAP and spectral-domain optical coherence tomography. The estimated percentage loss of RGCs (combined structure-function index) was calculated.

Results: In glaucomatous eyes, there were 136 sectors with visible RNFL defects and 524 sectors without visible RNFL defects. The most common sectors with visible RNFL defects were inferior and inferotemporal sectors, followed by superior and supertemporal sectors. Eyes with visible RNFL defects had a mean estimated RGC count of 657,172 cells versus 968 883 cells in healthy eyes (P < .001). The average combined structure-function index in sectors with a visible RNFL defect (59 ± 21%) was significantly higher than in sectors without a visible RNFL defect in glaucomatous eyes (15 ± 29%; P < .001) and higher than in healthy eyes (1 ± 13%; P < .001).

Conclusions: Although visible localized RNFL defects often are considered an early sign of glaucoma, this study indicates that they are likely to be associated with large neuronal losses.

Trial registration: ClinicalTrials.gov NCT00221897 NCT00221923.

Figure 1

Illustration of the structure function map for the right eye used for sectorial estimation of retinal ganglion cell counts. The map divides the standard automated perimetry plot into 10 sectors (Left), with 10 corresponding optic disc sectors, each of 36-degrees.(Center) The location of the retinal nerve fiber layer defect was determined by fitting a 10-segment circle, corresponding to the 10 zones of the structure function map, to the optic disc photograph.(Right) In this example, the visible nerve fiber defect is in sector 8.

Figure 2

Histogram showing the distribution of estimated retinal ganglion cell loss (estimated using the combined structure function index (CSFI)) in sectors of glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects.

Figure 3

Box plot showing the distribution of estimated retinal ganglion cell loss (estimated using the combined structure function index (CSFI)) in all sectors of healthy eyes compared to the combined structure function index in sectors with visible localized retinal nerve fiber layer (RNFL) defects and the combined structure function index in sectors of glaucomatous eyes without visible localized RNFL defects.

Figure 4

Histogram showing the distribution of sectors with the greatest estimated retinal ganglion cell loss (estimated using the combined structure function index (CSFI)) for healthy eyes (Top) and glaucomatous eyes with a visible localized retinal nerve fiber (RNFL) defect.(Bottom)

Figure 5

Examples of 3 glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects. The optic disc photographs show the estimated retinal ganglion cell loss (estimated using the combined structure function index) in each of ten sectors of the structure function map.(Top row) The first example shows a visible RNFL defect inferior-temporal to the optic disc.(Top left) The estimated retinal ganglion cell loss in the two sectors corresponding to the defect is 57 to 68%. There is good agreement with the spectral domain optical coherence tomography RNFL thickness map, which shows RNFL loss in the inferior-temporal region (Center left) and with standard automated perimetry showing a superior arcuate defect.(Bottom left). The second example shows a RNFL defect associated with an estimated retinal ganglion cell loss of 81 to 85% (Top center) and the third example a RNFL defect associated with an estimated retinal ganglion cell loss of 21 to 35%.(Top right) The corresponding spectral domain optical coherence tomography (Center row) and standard automated perimetry (Bottom row) results for these eyes are also shown.

Figure 6

Example of an eye of a 70 year-old subject with a localized retinal nerve fiber (RNFL) defect visible on optic disc photography.(Left) The RNFL defect corresponded to two sectors of the structure function map with an estimated retinal ganglion cell loss of 42 to 48%.(Left) The estimated retinal ganglion cell loss in the other sectors is also shown.(Left) Spectral domain optical coherence tomography revealed localized thinning of the RNFL in the inferior-temporal region.(Top right and Bottom center) Despite high estimated retinal ganglion cell losses, standard automated perimetry global indices were within statistically normal limits.(Bottom right)