Assessing assumptions of a combined structure-function index

PURPOSE: Medeiros et al. developed a combined structure-function index for glaucoma by combining two ganglion cell models developed by Harwerth et al. The current study assessed assumptions of the Medeiros combined structure-function index by evaluating whether the two Harwerth models gave similar distributions of ganglion cells in an independent dataset. METHODS: The Harwerth models were applied to our previously published data for retinal nerve fibre layer (RNFL) thickness (Stratus OCT 3.4) and visual field sensitivities (24-2 SITA Standard) from one eye each of 51 patients with glaucoma and 62 age-similar control subjects free of eye disease. RNFL thicknesses and perimetric sensitivities were converted to ganglion cell numbers using the Harwerth model for perimetry and the Harwerth model for RNFL. These two estimates of ganglion cell number were compared for the inferior temporal (IT) and superior temporal (ST) sectors of the optic disc and the corresponding visual field locations. Comparisons were made with 14 visual field locations per sector (including a point in the macula for the inferior temporal sector) and with 13 locations (no point in the macula). Data for controls and patients were analysed separately, comparing mean values for RNFL perimetry models. Bonferroni correction was applied to control for repeated tests of significance. The difference between mean values for the RNFL and perimetry models was quantified by equating the means for controls through reduction of the assumed axon diameter used by the RNFL model. RESULTS: For the control group, the Harwerth RNFL model yielded smaller mean number of retinal ganglion cells than the Harwerth perimetry model, 23–47% lower (t > 13, p < 0.0001). This corresponded to mean axon diameters from 0.48 to 0.69 μm, with the smallest axons when the 14th location in the macula was included. With these new axon diameters, estimates of ganglion cell numbers for patients were still lower than for the RNFL model, by 19–28% (t > 6.5, p < 0.0001). CONCLUSIONS: The Harwerth RNFL model consistently gave lower ganglion cell numbers than the Harwerth perimetry model, and this discordance persisted in patients even after reducing assumed axon diameter for controls. This finding contradicts the assumptions of the Medeiros structure-function index.