Reproducibility and age-related changes of ocular parametric measurements in rabbits

Abstract

Background: The rabbit is a common animal model for ophthalmic research, especially corneal research. Ocular structures grow rapidly during the early stages of life. It is unclear when the rabbit cornea becomes mature and stabilized. We investigated the changes of keratometry, refractive state and central corneal thickness (CCT) with age. In addition, we studied the intra- and inter-observer reproducibility of anterior chamber depth (ACD) and anterior chamber width (ACW) measurements in rabbits using anterior segment-optical coherence tomography (AS-OCT).

Results: The growth of New Zealand White rabbits (n = 16) were monitored from age 1 to 12 months old. Corneal keratometric and refractive values were obtained using an autorefractor/keratometer, and CCT was measured using an AS-OCT. Keratometry and CCT changed rapidly from 1 to 7 months and appeared to be stabilizing after 8 months. The reduction of corneal curvature was approximately 1.36 diopter (D)/month from age 1 to 7 months, but the change decelerated to 0.30 D/month from age 8 to 12 months. An increase of 10 μm/month in CCT was observed from age 1 to 7 months, but the gain was reduced to less than 1 μm/month from age 8 to 12 months. There was a hyperopic shift over the span of 12 months, albeit the increase in spherical equivalent was slow and gradual. Rabbits of random age were then selected for 2 repeated ACD and ACW measurements by 2 independent and masked observers. Bland-Altman plots revealed a good agreement of ACD and ACW measurements inter- and intra-observer and the ranges of 95% limit of agreement were acceptable from a clinical perspective.

Conclusions: Corneal keratometry, spherical equivalent refraction and CCT changed significantly during the first few months of life of rabbits. Young rabbits have been used in a large number of eye research studies. In certain settings, the ocular parametric changes are an important aspect to note as they may alter the findings made in a rabbit experimental model. In this study, we have also demonstrated for the first time a good between observer reproducibility of measurements of ocular parameters in an animal model by using an AS-OCT.

Figure 1

Anterior segment OCT image of the anterior chamber in a rabbit eye. Anterior chamber depth (ACD) was measured from the posterior surface of the center of the cornea to the apex of the crystalline lens. Anterior chamber width (ACW) was measured from the scleral spurs in the nasal and temporal quadrants of the eye.

Figure 2

Age-related changes in body weight (A), corneal curvature (B), refractive state (C) and central corneal thickness (D). Error bars represent standard deviation of the mean value.

Figure 3

Bland-Altman plots for observer 1 and observer 2 comparing measurements of anterior chamber depth (A) and anterior chamber width (B). The horizontal lines represent the mean and 95% limit of agreement (LoA).

Figure 4

Bland-Altman plots showing intra-observer agreement on measurements of anterior chamber depth (ACD) and anterior chamber width (ACW). (A) Repeated ACD measurements made by observer 1. (B) Repeated ACW measurements made by observer 1. (C) Repeated ACD measurements made by observer 2. (D) Repeated ACW measurements made by observer 2. The horizontal lines represent the mean and 95% limit of agreement (LoA).