In their recent Perspective, Hood and De Moraes assess the clinical diagnosis for the progression of glaucoma by readdressing the common clinical paradigm (CCP) for the disease.
1 They state specific challenges for measuring functional changes with visual field perimetry (VF) and structural changes with optical coherence tomography (OCT) for integration with the clinical information.
As a supplement to the recommendations suggested by the authors, here are some technical points to recall when examining and comparing data units for the structure/function measurements.
The light sensitivity is generally accepted to be proportional to the corresponding underlying quantity of retinal ganglion cells (RGC).
2,3 Therefore, a causal, local relationship exists when comparing the unnormalized light sensitivity, which is linear in apostilbs (asb, 1/L) or nonlinear as ratios in decibels (dB), to the RGC count, as the following definition formula indicates:
For example, a decrease in VF sensitivity of approximately 3 dB corresponds to a 50% drop of the luminance or light intensity in lambert units (1/L). However, one should note that any decrease in VF sensitivity in dB corresponds to a varying decrease in amount of the RBC count depending on the present count levels. Similarly, any rate decrease in RGC count per time corresponds to a varying decrease in the VF sensitivity rate in dB depending on the present light sensitivity levels at a particular test point location (
Fig. 1). Various studies may have addressed these issues by showing that the differing rates of VF progression, possibly nonlinear in dB units compared to
ΔRGC, are based on the measured retinal nerve fiber layer (RNFL) thickness which relates to the ganglion cell density.
3–6
Furthermore, from the physical meaning of light sensitivity, measurements in 1/L and dB units are considered base quantities. The numerical values of base quantities are said to be scale invariant, which means that though the numerical values change with the base units (i.e., 1/L to dB), the physical attribute of luminance remains unchanged. However, formulas such as the total and mean deviation (TD, MD in the 24-2 perimetric field), whether used locally or globally as summary statistics, make use of database quantities such as normal light sensitivity (generally in dB) per VF test location for different age groups. These formulas are considered derived quantities since their derivations cannot be directly scaled numerically to any of the unnormalized light sensitivity units without considering the biased, predetermined normal values. Therefore, a model specifying the light sensitivity in dB or 1/L to RGC count values may be sensitive to normal baseline differences in specific test locations.
Finally, the MD is a weighted average summation of all test locations composed of the differences of the measured light sensitivities to the normal values in a database (i.e., total deviation). The weights are applied locally, not globally, and a change in MD corresponds to a vast number of combinations from the light sensitivity changes in the VF regions. As shown in
Figure 2, by simply isolating the VF change to two separate areas of the Garway-Heath map, the linear progressions representing the same change in unnormalized light sensitivity light (i.e., equal
ΔRGC at the same starting dB level), but from different VF regions, have different MD trajectories.
7,8
Therefore, for any comparison of structure/function measurements, one should account for how the physical units are being used and specify what the data inferences from the results of the clinical models represent.