A Simplified Model of Activation and Deactivation of Human Rod Phototransduction-An Electroretinographic Study.

Purpose: To test the hypothesis that a simple model having properties consistent with activation and deactivation in the rod approximates the whole time course of the photoresponse. Methods: Routinely, an exponential of the form f = α·(1 - exp(-(τ·(t - teff)s-1))), with amplitude α, rate constant τ (often scaled by intensity), irreducible delay teff, and time exponent s-1, is fit to the early period of the flash electroretinogram. Notably, s (an integer) represents the three integrating stages in the rod amplification cascade (rhodopsin isomerization, transducin activation, and cGMP hydrolysis). The time course of the photoresponse to a 0.17 cd·s·m-2 conditioning flash (CF) was determined in 21 healthy eyes by presenting the CF plus a bright probe flash (PF) in tandem, separated by interstimulus intervals (ISIs) of 0.01 to 1.4 seconds, and calculating the proportion of the PF a-wave suppressed by the CF at each ISI. To test if similar kinetics describe deactivation, difference of exponential (DoE) functions with common α and teff parameters, respective rate constants for the initiation (I) and quenching (Q) phases of the response, and specified values of s (sI, sQ), were compared to the photoresponse time course. Results: As hypothesized, the optimal values of sI and sQ were 3 and 2, respectively. Mean ± SD α was 0.80 ± 0.066, I was 7700 ± 2400 m2·cd-1·s-3, and Q was 1.4 ± 0.47 s-1. Overall, r2 was 0.93. Conclusions: A method, including a DoE model with just three free parameters (α, I, Q), that robustly captures the magnitude and time-constants of the complete rod response, was produced. Only two steps integrate to quench the rod photoresponse.

The Development of Retinal Function and Refractive Error in Children With Retinopathy of Prematurity.

Purpose: The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10 degrees but not 30 degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE). Methods: We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2 degree diameter, 50 ms, blue (λ < 510 nm) flashes at 10 degrees and 30 degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13). We also tested Term-born (n = 28) controls. To determine the age at half-maximal sensitivity (Agehalf) for each group and eccentricity, we fit DATs to logistic growth curves. We obtained VA and SE for Preterm subjects and evaluated the course of threshold development at 10 degrees and 30 degrees for significant association with VA and SE predicted at age 10 years. Results: DAT development at 10 degrees was significantly delayed in ROP (Mild and Severe); ROP did not significantly alter DAT development at 30 degrees. At age 10 years, among Preterm subjects, both VA and SE were significantly associated with group (None,Mild, and Severe). SE was predicted by the course of DAT development at 30 degrees. VA was not associated with the course of DAT development at 10 degrees. Conclusions: At 10 degrees, ROP-whether mild or severe-is associated with significant delays in DAT development, evidence that the late-maturing central retina is vulnerable to ROP. The association of 30 degree threshold and myopia are evidence that more peripheral retina is important to refractive development.

Longitudinal Change of Refractive Error in Retinopathy of Prematurity Treated With Intravitreal Bevacizumab or Laser Photocoagulation.

PURPOSE: To compare progression of myopia and refractive error in former premature infants with retinopathy of prematurity (ROP) treated using intravitreal bevacizumab (IVB) or laser. DESIGN: Retrospective clinical cohort study. METHODS: We identified premature infants with ROP treated using IVB from 2011 to 2020 and compared their longitudinal cycloplegic refraction data to that of infants with ROP treated using laser during the same timeframe. A subset of infants treated using IVB also underwent additional treatment using laser. We included cycloplegic refractions from 789 cumulative visits over a median 3.2 years. We used a linear mixed-effects model with a log decay function to evaluate how refraction changed with age after treatment. RESULTS: In aggregate, the model estimated a significant (P < .001) trend in refraction-from slight hyperopia to relatively more myopic states. However, progression in laser-treated eyes was significantly (P < .001) more rapid, regardless of treatment with IVB. The number of laser spots resulted in increased myopic progression by approximately 0.16 diopters per 100 laser spots. Both ROP stage and zone had a significant effect on myopic progression, with more severe disease resulting in faster myopic progression. Random effects, including individual subject variation with nested variance for left and right eye, accounted for 86.4% of the remaining variance not explained by age and treatment. CONCLUSIONS: Laser treatment for severe ROP increases the trend to severe myopia. In our sample, IVB did not affect myopic progression but did substantially reduce the amount of consequent laser required to treat ROP. The effect of laser persists after accounting for differences in ROP stage and zone.