Abstract
Purpose:
Confidence in knowledge of biometric dimensions of the ocular chambers and structures is essential in pharmacokinetic/dynamic modeling and preclinical development of therapeutic compounds and devices. Furthermore, knowledge of comparative biometric values between animal models and humans can impact dosing methods, concentration delivered, and techniques employed in nonclinical studies. Consideration of comparative differences also improves accuracy in prediction of human safety risk. Our objective was to summarize available normative data for the human and six common animal models - mouse, rat, rabbit, dog, pig, and non-human primate (NHP).
Methods:
References citing normative ocular biometric values in all seven species were collected by searching online publication databases, textbooks, and journals available to the authors. Biometric parameters researched included: axial globe length (AGL), anterior chamber depth (ACD), axial lens diameter (ALD), vitreous chamber depth (VCD), and vitreous chamber volume (VCV). Available data were assembled and evaluated. For scarce or unavailable values, additional data was generated to establish normative values. All data are presented as mean ± SD.
Results:
Reported values were obtained using both in vivo and ex vivo techniques as well as calculation and/or estimation. Parameters with values of higher intraspecies variability (>25% coefficient of variation) included: ACD in the mouse (0.50 ± 0.17); ALD in the rat and rabbit (3.55 ± 1.08 and 6.18 ± 1.88 mm, respectively); VCD in the mouse and NHP (0.61 ± 0.16 and 8.72 ± 3.58 mm, respectively); and VCV in the mouse, rat, dog, and NHP (0.01 ± 0.01, 0.03 ± 0.02, 2.63 ± 0.81, and 2.20 ± 0.89 ml, respectively). Relative to other laboratory species, fewer values were reported for AGL in the rat; ACD in the rat, rabbit, pig, and NHP; VCD in the rabbit, pig, and NHP; and VCV in the rat, dog, and NHP.
Conclusions:
Reliable normative ocular biometric values are critical for use of animal models in eye research and preclinical ocular drug and device development. This review summarizes published data, highlighting parameters of greater variability and identifying data gaps for species commonly used in the development of new therapeutics.