Nonlinear Mixed Effects Modeling of Electroretinography (ERG) b-wave Latency for Whole Eye Transplantation

Abstract

Purpose :
The goal was to estimate the difference in ERG b-wave latency for transplanted eyes vs the fellow/naive eye.

Methods :
6 rats were studied. Right eyes were transplanted. At 12 week timepoint, rats were dark-adapted in a dark box overnight. Animals were anaesthetized and were prepared for ERG recording in a light-sealed room. Recording electrodes gently contacted the corneal surface of eyes. A subdermal needle electrode served as common reference while another subdermal needle electrode was inserted at the base of the left leg. A Ganzfield delivered light stimuli with various stimulus strengths following different programmed dark adaption and light adaption protocols. Log b-wave latency responses were sigmoidal, so a nononlinear mixed effects model was used. R environment for statistical computing was used. 4 parameter logistic function was used to fit the b-wave log latency as a function of log light intensity with parameters: 1) A – asymptote as light intensity goes to -infinity, 2) B - asymptote as light intensity goes to +infinity, 3) X_mid – inflection point for light intensity, and 4) S – scale = difference between X_mid and light intensity where response is 75% of distance from A to B asymptotes. Larger S = shallower slope. Fixed effects were A, B, X_mid, and S for the left/naive eye and their differences with right eyes. Random effects (RE) were included for rats for X_mid (σ_rat) and for eyes for B (σ_eye). Fixed effects (FE) describe typical effect while REs describe rat/eye-specific effects.

Results :
There were no consistent detectable OD ERG responses for rat 1. Model results shown in Table 1. Left half of table shows FE estimates in log space. Where possible, FE values were converted to original scale and shown on right half of table. Bottom part of table shows RE estimates and residual standard error. Compared to left/naive eyes, sigmoidal curve for transplanted right eyes had 1) similar asymptote A, 2) lower asymptote B, 3) higher inflection point X_mid, and 4) lower scale S. Difference in inflection points was statistically significant (0.0810, P<0.0001). FE + RE are shown in Figure 1.

Conclusions :
The b-wave latency showed clear sigmoidal patterns for transplanted and left eyes. For transplanted/right eyes, however, the decrease in latency occured later and bottomed out at a lower level than for the naive/left eye. Rate of decrease was greater for the transplanted/right eyes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.