November 2018
Volume 59, Issue 13
Open Access
Letters to the Editor  |   November 2018
Letter to the Editor: Challenges to the Common Clinical Paradigm for Diagnosis of Glaucomatous Damage With OCT and Visual Fields
Author Affiliations & Notes
  • Dennis C. Mock
    David Geffen UCLA School of Medicine, Los Angeles, California, United States.
Investigative Ophthalmology & Visual Science November 2018, Vol.59, 5522-5523. doi:10.1167/iovs.18-25563
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      Dennis C. Mock; Letter to the Editor: Challenges to the Common Clinical Paradigm for Diagnosis of Glaucomatous Damage With OCT and Visual Fields. Invest. Ophthalmol. Vis. Sci. 2018;59(13):5522-5523. doi: 10.1167/iovs.18-25563.

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      © ARVO (1962-2015); The Authors (2016-present)

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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: 
 
\(\def\upalpha{\unicode[Times]{x3B1}}\)\(\def\upbeta{\unicode[Times]{x3B2}}\)\(\def\upgamma{\unicode[Times]{x3B3}}\)\(\def\updelta{\unicode[Times]{x3B4}}\)\(\def\upvarepsilon{\unicode[Times]{x3B5}}\)\(\def\upzeta{\unicode[Times]{x3B6}}\)\(\def\upeta{\unicode[Times]{x3B7}}\)\(\def\uptheta{\unicode[Times]{x3B8}}\)\(\def\upiota{\unicode[Times]{x3B9}}\)\(\def\upkappa{\unicode[Times]{x3BA}}\)\(\def\uplambda{\unicode[Times]{x3BB}}\)\(\def\upmu{\unicode[Times]{x3BC}}\)\(\def\upnu{\unicode[Times]{x3BD}}\)\(\def\upxi{\unicode[Times]{x3BE}}\)\(\def\upomicron{\unicode[Times]{x3BF}}\)\(\def\uppi{\unicode[Times]{x3C0}}\)\(\def\uprho{\unicode[Times]{x3C1}}\)\(\def\upsigma{\unicode[Times]{x3C3}}\)\(\def\uptau{\unicode[Times]{x3C4}}\)\(\def\upupsilon{\unicode[Times]{x3C5}}\)\(\def\upphi{\unicode[Times]{x3C6}}\)\(\def\upchi{\unicode[Times]{x3C7}}\)\(\def\uppsy{\unicode[Times]{x3C8}}\)\(\def\upomega{\unicode[Times]{x3C9}}\)\(\def\bialpha{\boldsymbol{\alpha}}\)\(\def\bibeta{\boldsymbol{\beta}}\)\(\def\bigamma{\boldsymbol{\gamma}}\)\(\def\bidelta{\boldsymbol{\delta}}\)\(\def\bivarepsilon{\boldsymbol{\varepsilon}}\)\(\def\bizeta{\boldsymbol{\zeta}}\)\(\def\bieta{\boldsymbol{\eta}}\)\(\def\bitheta{\boldsymbol{\theta}}\)\(\def\biiota{\boldsymbol{\iota}}\)\(\def\bikappa{\boldsymbol{\kappa}}\)\(\def\bilambda{\boldsymbol{\lambda}}\)\(\def\bimu{\boldsymbol{\mu}}\)\(\def\binu{\boldsymbol{\nu}}\)\(\def\bixi{\boldsymbol{\xi}}\)\(\def\biomicron{\boldsymbol{\micron}}\)\(\def\bipi{\boldsymbol{\pi}}\)\(\def\birho{\boldsymbol{\rho}}\)\(\def\bisigma{\boldsymbol{\sigma}}\)\(\def\bitau{\boldsymbol{\tau}}\)\(\def\biupsilon{\boldsymbol{\upsilon}}\)\(\def\biphi{\boldsymbol{\phi}}\)\(\def\bichi{\boldsymbol{\chi}}\)\(\def\bipsy{\boldsymbol{\psy}}\)\(\def\biomega{\boldsymbol{\omega}}\)\(\def\bupalpha{\unicode[Times]{x1D6C2}}\)\(\def\bupbeta{\unicode[Times]{x1D6C3}}\)\(\def\bupgamma{\unicode[Times]{x1D6C4}}\)\(\def\bupdelta{\unicode[Times]{x1D6C5}}\)\(\def\bupepsilon{\unicode[Times]{x1D6C6}}\)\(\def\bupvarepsilon{\unicode[Times]{x1D6DC}}\)\(\def\bupzeta{\unicode[Times]{x1D6C7}}\)\(\def\bupeta{\unicode[Times]{x1D6C8}}\)\(\def\buptheta{\unicode[Times]{x1D6C9}}\)\(\def\bupiota{\unicode[Times]{x1D6CA}}\)\(\def\bupkappa{\unicode[Times]{x1D6CB}}\)\(\def\buplambda{\unicode[Times]{x1D6CC}}\)\(\def\bupmu{\unicode[Times]{x1D6CD}}\)\(\def\bupnu{\unicode[Times]{x1D6CE}}\)\(\def\bupxi{\unicode[Times]{x1D6CF}}\)\(\def\bupomicron{\unicode[Times]{x1D6D0}}\)\(\def\buppi{\unicode[Times]{x1D6D1}}\)\(\def\buprho{\unicode[Times]{x1D6D2}}\)\(\def\bupsigma{\unicode[Times]{x1D6D4}}\)\(\def\buptau{\unicode[Times]{x1D6D5}}\)\(\def\bupupsilon{\unicode[Times]{x1D6D6}}\)\(\def\bupphi{\unicode[Times]{x1D6D7}}\)\(\def\bupchi{\unicode[Times]{x1D6D8}}\)\(\def\buppsy{\unicode[Times]{x1D6D9}}\)\(\def\bupomega{\unicode[Times]{x1D6DA}}\)\(\def\bupvartheta{\unicode[Times]{x1D6DD}}\)\(\def\bGamma{\bf{\Gamma}}\)\(\def\bDelta{\bf{\Delta}}\)\(\def\bTheta{\bf{\Theta}}\)\(\def\bLambda{\bf{\Lambda}}\)\(\def\bXi{\bf{\Xi}}\)\(\def\bPi{\bf{\Pi}}\)\(\def\bSigma{\bf{\Sigma}}\)\(\def\bUpsilon{\bf{\Upsilon}}\)\(\def\bPhi{\bf{\Phi}}\)\(\def\bPsi{\bf{\Psi}}\)\(\def\bOmega{\bf{\Omega}}\)\(\def\iGamma{\unicode[Times]{x1D6E4}}\)\(\def\iDelta{\unicode[Times]{x1D6E5}}\)\(\def\iTheta{\unicode[Times]{x1D6E9}}\)\(\def\iLambda{\unicode[Times]{x1D6EC}}\)\(\def\iXi{\unicode[Times]{x1D6EF}}\)\(\def\iPi{\unicode[Times]{x1D6F1}}\)\(\def\iSigma{\unicode[Times]{x1D6F4}}\)\(\def\iUpsilon{\unicode[Times]{x1D6F6}}\)\(\def\iPhi{\unicode[Times]{x1D6F7}}\)\(\def\iPsi{\unicode[Times]{x1D6F9}}\)\(\def\iOmega{\unicode[Times]{x1D6FA}}\)\(\def\biGamma{\unicode[Times]{x1D71E}}\)\(\def\biDelta{\unicode[Times]{x1D71F}}\)\(\def\biTheta{\unicode[Times]{x1D723}}\)\(\def\biLambda{\unicode[Times]{x1D726}}\)\(\def\biXi{\unicode[Times]{x1D729}}\)\(\def\biPi{\unicode[Times]{x1D72B}}\)\(\def\biSigma{\unicode[Times]{x1D72E}}\)\(\def\biUpsilon{\unicode[Times]{x1D730}}\)\(\def\biPhi{\unicode[Times]{x1D731}}\)\(\def\biPsi{\unicode[Times]{x1D733}}\)\(\def\biOmega{\unicode[Times]{x1D734}}\)\begin{equation}\rm Luminance_{({1 \over \it L})} = 10^{\Delta \it L(\it dB) \over 10} \propto RGC\ count\ where\ \Delta L(\rm dB) = 10 \times log_{10}\left ({\it L_{ref} \over {\it L - L_{bkgd}}} \right)\end{equation}
 
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.36 
Figure 1
 
Here are two specific progression changes in the light sensitivity (dB) that correspond to the same amount of RGC or proportional to 200 luminance units per time period (e.g., t1 to t2 and t2 to t3). Note the rate of progression (dB per unit time) corresponds to the initial level MD (dB) with an increasing deviation between the two rates of progression, though representing the same decrease in RGC count per time.
Figure 1
 
Here are two specific progression changes in the light sensitivity (dB) that correspond to the same amount of RGC or proportional to 200 luminance units per time period (e.g., t1 to t2 and t2 to t3). Note the rate of progression (dB per unit time) corresponds to the initial level MD (dB) with an increasing deviation between the two rates of progression, though representing the same decrease in RGC count per time.
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 
Figure 2
 
Here are two specific linear progression changes in MD (dB) that represent an equal change in ΔRGC from two different regions of the Garway-Heath map.
Figure 2
 
Here are two specific linear progression changes in MD (dB) that represent an equal change in ΔRGC from two different regions of the Garway-Heath map.
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. 
References
Hood DC, De Moraes CG. Challenges to the common clinical paradigm for diagnosis of glaucomatous damage with OCT and visual fields. Invest Ophthalmol Vis Sci. 2018; 59: 788–791.
Harwerth RS, Wheat JL, Fredette MJ, Anderson DR. Linking structure and function in glaucoma. Prog Retin Eye Res. 2010; 29: 249–271.
Malik R, Swanson WH, Garway-Heath DF. ‘Structure-function relationship’ in glaucoma: past thinking and current concepts. Clin Exp Ophthalmol. 2012; 40: 369–380.
Caprioli J, Mock D, Bitrian E, et al. A method to measure and predict rates of regional visual field decay in glaucoma. Invest Ophthalmol Vis Sci. 2011; 52: 4765–4773.
Saunders LJ, Medeiros FA, Weinreb RN, Zangwill LM. What rates of glaucoma progression are clinically significant? Expert Rev Ophthalmol. 2016; 11: 227–234.
Price DA, Swanson WH, Horner DG. Using perimetric data to estimate ganglion cell loss for detecting progression of glaucoma: a comparison of models. Ophthalmic Physiol Opt. 2017; 37: 409–419.
Heijl A, Lindgren G, Olsson J. Normal variability of static perimetric threshold values across the central vision. Arch Ophthamol. 1987; 105: 1544–1549.
Marin-Franch I, Swanson WH. The visualFields package: a tool for analysis and visualization of visual fields. J Vis. 2013: 13 (4): 10.
Figure 1
 
Here are two specific progression changes in the light sensitivity (dB) that correspond to the same amount of RGC or proportional to 200 luminance units per time period (e.g., t1 to t2 and t2 to t3). Note the rate of progression (dB per unit time) corresponds to the initial level MD (dB) with an increasing deviation between the two rates of progression, though representing the same decrease in RGC count per time.
Figure 1
 
Here are two specific progression changes in the light sensitivity (dB) that correspond to the same amount of RGC or proportional to 200 luminance units per time period (e.g., t1 to t2 and t2 to t3). Note the rate of progression (dB per unit time) corresponds to the initial level MD (dB) with an increasing deviation between the two rates of progression, though representing the same decrease in RGC count per time.
Figure 2
 
Here are two specific linear progression changes in MD (dB) that represent an equal change in ΔRGC from two different regions of the Garway-Heath map.
Figure 2
 
Here are two specific linear progression changes in MD (dB) that represent an equal change in ΔRGC from two different regions of the Garway-Heath map.
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