
==== Front
Invest Ophthalmol Vis Sci
Invest Ophthalmol Vis Sci
IOVS
Investigative Ophthalmology & Visual Science
0146-0404
1552-5783
The Association for Research in Vision and Ophthalmology

39226049
10.1167/iovs.65.11.2
IOVS-24-40137
Lens
Lens
Lens Power and Associated Factors in Nonhuman Primate Subjects: A Cross-sectional Study
Lens Power and Associated Factors in Nonhuman Primates
Zhu Yingting 1
Xie Rui 1
Zhang Qi 1
Zhang Yuan 1
Ye Guitong 1
Xu Liangzhi 2
Hou Simeng 3
Liu Wei 2
Huang Zhiwei 2
Wu Jian 3 4
Zhuo Yehong 1
1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
2 Guangzhou Huazhen Biosciences, Guangzhou, China
3 Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China
4 Henan Academy of Innovations in Medical Science, Henan, China
# Correspondence: Yehong Zhuo, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, No. 54 Xianlie South Road, Guangzhou 510060, China; zhuoyh@mail.sysu.edu.cn.
Jian Wu, Beijing Tongren Eye Center, Beijing Key Laboratory of Ophthalmology and Visual Sciences, No. 1 Dong Jiao Min Xiang Street, Dongcheng District, Beijing 100730, P.R. China; karena.wu@mail.ccmu.edu.cn.
* YZ, RX, and QZ contributed to the work equally and should be regarded as co-first authors.

03 9 2024
9 2024
65 11 223 7 2024
03 4 2024
Copyright 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Purpose

We aimed to examine the normative profile of crystalline lens power (LP) and its associations with ocular biometric parameters including age, axial length (AL), spherical equivalent refraction (SE), corneal radius (CR), lens thickness, anterior chamber depth, and AL/CR ratio among a cynomolgus monkey colony.

Methods

This population-based cross-sectional Non-human Primate Eye Study recruited middle-aged subjects in South China. All included macaques underwent a detailed ophthalmic examination. LP was calculated using the modified Bennett's formula, with biometry data from an autorefractometer and A-scan. SPSS version 25.0 was used for statistical analysis.

Results

A total of 301 macaques with an average age of 18.75 ± 2.95 years were collected in this study. The mean LP was 25.40 ± 2.96 D. Greater LP was independently associated with younger age, longer AL, and lower SE (P = 0.028, P = 0.025, and P = 0.034, respectively). LP showed a positive correlation with age, SE, CR, AL, lens thickness, and anterior chamber depth, whereas no correlation was observed between LP and AL/CR ratio.

Conclusions

Our results suggested the LP distribution in the nonhuman primate colony and indicated that AL and SE strongly influenced the rate of LP. Therefore, this study contributed to a deeper understanding of the relative significance of the LP on the optics of the crystalline lens study.

crystalline lens power
biometry
nonhuman primate
==== Body
pmcWith increasing prevalence, myopia has been regarded as a major concern to public health over the past decades,1 with the predictions that nearly 50% of the population will be myopic by 2050 worldwide.2,3 Patients with high myopia are prone to pathological changes in the fundus,1,4 which may lead to irreversible vision loss with a heavy financial burden.5 However, the etiology and pathogenesis of myopia were still not clear, which indicated that a full understanding of the disrupted balance with refractive status and the process of morphological changes in ocular components were essential.

Several studies have displayed that cornea refractive power (CP), refractive crystalline lens power (LP), and axial length (AL) were most correlated with the spherical equivalent refraction (SE).5–7 Meanwhile, as the rate of axial elongation outpaces the changes in LP, a myopic shift may occur and eventually develop into myopia.8,9 Although the significance of the LP and its changes in determining the final SE,8 little evidence is available on relevant mechanisms and effects. Previous studies have reported the LP ex vivo.10,11 They found that the total isolated lens refractive power decreased with age. However, in vitro measurements correspond with the maximally accommodated state, whereas in vivo measurements can be performed at various accommodative states. It is also not possible to determine the relation between the lens parameters measured in vitro and the actual accommodation response of the whole eye.

To decrease the risks faced by human research, animal testing has become an indispensable bridge in the early exploratory research of medicine. Nonhuman primates play an important role in the study of eye diseases and visual function. Currently, nonhuman primates have been used widely as a refractive error and myopia model.10,12,13 In a prior study of 1148 macaques, we observed a higher prevalence of myopia compared with humans.14 The refractive characteristics and biometry parameters of cynomolgus monkeys resemble those of humans closely.15

At present, it is known that AL and diopter can be used as indicators to evaluate the progression of myopia and the prevention and control effect. Previous studies on refractive errors have paid more attention to these two indicators,16 but no studies have focused on the distribution and change characteristics of LP in nonhuman primates. Not the same as small animals, nonhuman primates have shown similarities in anatomy, physiology, and refractive adjustment close to humans, with the accommodation apparatus decreasing with age in adulthood as the human does.12,17,18 The lens parameters play a pivotal role in the refractive adjustment, although a full description of the accommodation is essential to establish the nonhuman primate myopia model for studies. The study of crystalline LP in macaques can lay a foundation for further research on the pathogenesis and prevention of myopia.

Because the LP of macaque in vivo has not been reported, and parameters in vivo are crucial for the study of refractive error in nonhuman primates, our study aimed to elucidate the distribution of lens parameters in nonhuman primate subjects. In addition, we sought to further investigate the characteristics of LP and to identify the associated factors.

Methods

Subjects

This cross-sectional study is a part of the Non-human Primate Eye Study, which on-site ocular examination of approximately 1000 macaques held in Guangdong Province, southeastern China. The Non-human Primate Eye Study was performed from 2021 to 2022 and aims to demonstrate the normative ocular parameters distribution in an nonhuman primate colony, displaying the characteristics of the naturally occurring ocular disease nonhuman primates. Furthermore, the study sought to assist in preclinical research to identify the etiology of human ocular disease. A detailed methodology description has been reported previously.14 Subjects included in this study were both male and female, had no other eye diseases except refractive errors, no systemic diseases, and could tolerate anesthesia well. All animal experiments complied with the National Institutes of Health Guide and the guidelines of the Association for Research of Vision and Ophthalmology for the Use of Animals in Ophthalmic and Vision Research. The Non-human Primate Eye Study was approved by the Ethical Committee of the Guangzhou Huazhen Biosciences Company (Ethics Number: 2020-168) and Zhongshan Ophthalmic Center (Permit Number: SYXK (YUE) 2018-0189).

Measurements and Calculations

Fieldwork was conducted by one ophthalmologist, two optometrists, two coordinators, and several veterinarians. All subjects were anesthetized by intramuscular injection of Zoletil (4 mg/kg body weight, Virbac) mixed with xylazine/ketamine 0.2 mg/kg (Sumianxin, Shengda Animal Medicine, Heilongjiang, China), and underwent all examinations. All subjects underwent a comprehensive ocular examination in 60 to 120 minutes according to the standardized protocols, including refractive status measurement using an autorefractor and keratometer (model FXR-710; Fario, Zhejiang, China), anterior chamber depth (ACD), lens thickness (LT), and AL using A-scan (model AL-4000; Tomey, Nagoya, Japan), intraocular pressure measured by Icare tonometer (Tonovet Plus; Icare, Helsinki, Finland), fundus photography examination after pupil dilation using a digital fundus scope (APS-BER Fundus Camera & FFA model, AITOMU), and peripapillary retinal nerve fiber layer thickness and macular retinal thickness measurements using optical coherence tomography (Heidelberg Engineering GmbH, Heidelberg, Germany).

Subjects’ demographics, including age and sex, were recorded properly, and heights and weights were measured by trained veterinarians. The body mass index was calculated as the weight in kilograms divided by the height in meters squared.

LP was calculated using Bennett's formula,6 with ACD, LT, AL, the refractive index of aqueous and vitreous humors (n = 4/3), the estimated parameters by the Gullstrand-Emsley eye model (c1 = 0.596 and c2 = −0.358), the SE at the corneal vertex (Scv), and the vitreous body depth (V). LP=-1000nSCV+CP1000n-ACD+c1LTSCV+CP+1000n-c2LT+VScv=SE1-0.014×SEV=AL-ACD-LT

The refraction data were divided into three categories according to international criteria19 (SE = sphere +1⁄2 cylinder): hyperopia (SE > 0.5 D), emmetropia (−0.5 D ≤ SE ≤ 0.5 D), myopia (SE < −0.5 D), and high myopia (SE < −5 D). In addition, the AL/CR ratio was defined as the AL divided by the mean CR of curvature. Anterior segment length (ASL) was defined as ACD plus LT.

Statistical Analyses

The IBM SPSS Statistics (version 25.0; IBM Corp., Armonk, NY, USA) was used for the statistical analysis. Continuous variables were expressed as means ± standard deviations and/or median. The correlations between CR, SE, AL, ACD, LT, ASL, AL/CR ratio, CP, and LP were assessed using Pearson's correlation coefficients. Mann–Whitney U test was used to analyze the difference between genders or age groups. Multiple comparisons were performed using one-way ANOVA or the Kruskal–Wallis test. Multiple linear regression analysis was performed after unitary linear regression to investigate the factors associated with LP. P values of less than 0.05 (two tailed) were considered statistically significant.

Results

General Characteristics

Of 307 nonhuman primate subjects, 301 (98.05%) had a full set of refractive data and with no diagnosed ocular diseases. Therefore, our study included 301 subjects, including 79 males (26.25%) and 222 females (73.75%), with a mean age of 18.75 ± 2.95 years (range, 5.23–26.52 years).

The mean SE was −1.55 ± 3.59 D (range, −20.56 D to 3.31 D), the mean ASL was 6.63 ± 0.45 mm (range, 5.74–11.90 mm), the mean AL/CR ratio was 3.30 ± 0.17 (range, 2.93–3.94), and the mean LP was 25.40 ± 2.96 D (range, 16.37–34.78 D). Table 1 presents detailed ocular characteristics. The LP exhibited the normal distribution, the distribution of spherical equivalent, and AL are shown in Figure 1.

Table 1. Ocular Biometry for Cynomolgus Macaque Monkeys

	Right Eye	Left Eye		
Variables	N	Value	N	Value	P Value*	
SE (D)						
 Median (interquartile range)	300	−0.33 (−2.04 to 0.71)	299	−0.38 (−2.4 to 0.56)	0.567	
AL (mm)						
 Median (interquartile range)	301	18.44 (18.10 to 18.97)	301	18.45 (18.11 to 18.97)	0.182	
ACD (mm)						
 Median (interquartile range)	301	3.23 (3.05 to 3.41)	301	3.23 (3.08 to 3.43)	0.266	
LT (mm)						
 Median (interquartile range)	300	3.33 (3.19 to 3.55)	301	3.34 (3.19 to 3.53)	0.379	
ASL (mm)						
 Median (interquartile range)	300	6.59 (6.4 to 6.82)	301	6.61 (6.40 to 6.84)	0.087	
AL/CR ratio						
 Median (interquartile range)	301	3.25 (3.17 to 3.38)	300	3.25 (3.18 to 3.38)	0.115	
CP (D)						
 Mean ± SD (range)	301	59.17 ± 2.28	300	59.28 ± 2.34	0.316	
		(51.67 to 66.08)		(51.54 to 68.4)		
LP (D)						
 Mean ± SD (range)	294	25.49 ± 3.27	292	25.33 ± 3.21	0.428	
		(16.50 to 36.48)		(15.27 to 34.52)		
CP, corneal power; CR, corneal radii; SE, spherical equivalent.

* P value between the right eye and left eye (Paired T test or Wilcoxon signed−rank test).

Figure 1. Distribution of LP, spherical equivalent, and AL of the right eye in Cynomolgus macaque monkeys. (a) Total distribution of LP. (b) Distribution of spherical equivalent in male and female monkeys. (c) Distribution of AL in male and female monkeys.

Influence of Refraction Parameters

Table 2 shows a comparison of distribution in ocular parameters under different refractive statuses. We divided all subjects into myopia, emmetropia, and hyperopia groups, the difference among each group mainly relied upon AL. Eyes with myopia had longer AL (19.08 ± 0.93 mm), greater AL/CR ratio (3.37 ± 0.16), and stronger CP (3.40 ± 0.17 mm) and LP (26.01 ± 3.64 D) than those with hyperopia and emmetropia (P < 0.001, P < 0.001, P < 0.001, and P = 0.034), whereas LT had no statistically significant differences between different refractive group (P = 0.172).

Table 2. Distribution of Ocular Biometry in Right Eyes of Cynomolgus Macaque Monkeys Under Different Refractive Status

	Myopia	Emmetropia	Hyperopia		
Variables	n	Mean ± SD (Range)	Median (IQR)	n	Mean ± SD (Range)	Median (IQR)	n	Mean ± SD (Range)	Median (IQR)	P Value*	
Age (years)	138	18.59 ± 3.57	18.99	68	18.78 ± 2.40	18.66	89	19.02 ± 2.19	19.15	0.611	
		(5.23 to 26.52)	(18.00 to 20.25)		(5.56 to 26.13)	(17.94 to 19.64)		(8.69 to 26.32)	(18.13 to 20.12)		
Weight (kg)	128	4.49 ± 1.26	4.09	65	4.48 ± 1.14	4.25	82	4.64 ± 1.22	4.19	0.646	
		(2.68 to 8.26)	(3.64 to 5.10)		(2.44 to 7.22)	(3.57 to 5.32)		(2.66 to 8.52)	(3.80 to 5.21)		
SE (D)	142	−4.12 ± 3.93	−2.67	68	0.02 ± 0.29	−0.04	90	1.41 ± 0.90	1.25	<0.001	
		(−23.21 to −0.5)	(−6.17 to −1.17)		(−0.46 to 0.50)	(−0.21 to 0.25)		(0.54 to 7.21)	(0.79 to 1.83)		
AL (mm)	142	19.08 ± 0.93	18.87	68	18.44 ± 0.51	18.33	90	18.45 ± 0.59	18.21	<0.001	
		(18.00 to 22.04)	(18.22 to 19.6)		(18.00 to 20.68)	(18.05 to 18.65)		(18.00 to 22.24)	(18.07 to 18.63)		
ACD (mm)	142	3.22 ± 0.28	3.20	68	3.21 ± 0.29	3.21	90	3.31 ± 0.32	3.28	0.029	
		(2.66 to 3.96)	(3.05 to 3.37)		(2.55 to 4.07)	(3.04 to 3.35)		(2.61 to 4.08)	(3.05 to 3.59)		
LT (mm)	142	3.36 ± 0.27	3.32	68	3.31 ± 0.27	3.29	89	3.39 ± 0.28	3.42	0.172	
		(2.86 to 4.30)	(3.19 to 3.58)		(2.73 to 4.20)	(3.12 to 3.42)		(2.83 to 4.10)	(3.20 to 3.60)		
ASL (mm)	142	6.58 ± 0.35	6.54	68	6.52 ± 0.33	6.50	89	6.71 ± 0.35	6.70	0.003	
		(5.97 to 7.74)	(6.38 to 6.76)		(5.54 to 7.24)	(6.33 to 6.74)		(6.09 to 7.53)	(6.52 to 6.98)		
AL/CR ratio	142	3.37 ± 0.16	3.36	68	3.25 ± 0.12	3.22	90	3.19 ± 0.13	3.17	<0.001	
		(3.06 to 3.92)	(3.24 to 3.47)		(3.01 to 3.75)	(3.17 to 3.30)		(2.94 to 3.82)	(3.13 to 3.25)		
CP (D)	142	59.59 ± 2.22	59.70	68	59.43 ± 1.98	59.34	90	58.31 ± 2.39	58.60	<0.001	
		(53.65 to 66.08)	(58.25 to 61.04)		(54.93 to 65.39)	(58.10 to 60.7)		(51.67 to 64.01)	(56.63 to 59.86)		
LP (D)	141	26.01 ± 3.64	25.87	66	25.02 ± 2.90	25.32	87	25.02 ± 2.77	25.20	0.034	
		(17.46 to 36.48)	(23.58 to 28.07)		(18.16 to 30.89)	(23.21 to 27.15)		(16.50 to 31.04)	(23.15 to 27.08)		
CP, corneal power; CR, corneal radii; IQR, Interquartile range; SE, spherical equivalent.

* P value between three refractive groups (one−way ANOVA or Kruskal-Wallis test).

The results of subjects in each AL category are presented in Table 3, which shows that in comparison with the AL group, LP was greater in the AL > 19 mm group than the 18<AL ≤ 19 mm group in all subjects (P = 0.025). Because males have shown a similar trend in different AL groups (P = 0.008), the LP was greater in the shorter eyes (AL ≤ 18 mm) and smaller in the longer eyes (18 mm < AL ≤ 19 mm). In addition, the negative correlation between AL/CR ratio with LP (y = 53.66 − 8.58 × x [R2 = 0.178]; male: y = 47.69 − 6.67 × x [R2 = 0.139]; female: y = 56.04 − 9.33 × x [R2 = 0.191]) and SE (y = 49.68 − 15.56 × x [R2 = 0.482]; male: y = 53.42 − 16.86 × x [R2 = 0.515]; female: y = 48.35 − 15.11 × x [R2 = 0.476]) was displayed in Figure 2.

Table 3. Distribution of LP in Right Eyes Stratified by Refractive Status and AL for Both Sexes

		LP, D			
	N (% Male)	Total	Males	Females	P Value*	SE, D	
Total	76 (25.85%)	25.40	25.94	25.31	0.213	−0.38	
		(23.31 to 27.45)	(24.09 to 27.55)	(23.15 to 27.45)		(−2.33 to 0.71)	
Age (years)							
 ≤18	25 (31.65%)	26.15	27.36	25.14	0.006	−0.50	
		(24.13 to 28.03)	(25.67 to 29.30)	(23.23 to 27.70)		(−2.75 to 0.63)	
 >18	47 (22.38%)	25.31	24.89	25.35	0.422	−0.29	
		(23.01 to 27.08)	(23.00 to 26.81)	(23.01 to 27.43)		(−2.07 to 0.75)	
  P value†		0.028	<0.001	0.738			
Refractive status							
 Hyperopia	87 (25.29%)	25.20	26.02	25.00	0.209	1.25	
		(23.15 to 27.08)	(24.17 to 27.41)	(22.92 to 27.06)		(0.79 to 1.72)	
 Emmetropia	66 (18.18%)	25.32	25.31	25.32	0.738	−0.04	
		(23.21 to 27.15)	(22.09 to 27.04)	(23.28 to 27.43)		(−0.21 to 0.25)	
 Mild myopia	79 (32.91%)	26.09	26.59	26.04	0.055	−1.25	
		(23.88 to 28.13)	(23.75 to 29.7)	(23.69 to 27.79)		(−1.88 to −0.79)	
 Moderate myopia	18 (27.78%)	24.69	26.10	24.13	0.664	−4.44	
		(22.34 to 27.53)	(22.84 to 26.59)	(22.33 to 30.06)		(−4.81 to −3.39)	
 High myopia	44 (25.00%)	25.33	24.89	25.72	0.270	−8.21	
		(23.64 to 28.25)	(24.45 to 26.60)	(23.18 to 30.38)		(−10.19 to −6.17)	
  P value†		0.113	0.259	0.115			
AL (mm)							
 ≤18	9 (11.11%)	26.66	27.06	26.30	0.796	0.42	
		(24.82 to 28.31)		(24.58 to 28.79)		(−1.13 to 1.10)	
 18 < AL ≤ 19	211 (24.64%)	25.94	26.62	25.77	0.023	0.00	
		(23.79 to 27.82)	(24.90 to 28.49)	(23.36 to 27.70)		(−0.96 to 0.92)	
 >19	74 (30.08%)	24.39	24.45	24.24	0.479	−5.21	
		(22.27 to 25.90)	(22.89 to 25.55)	(22.20 to 26.02)		(−8.53 to −1.72)	
 P value†		0.025	0.008	0.322			
Data are presented as medians (interquartile range).

SE, spherical equivalent.

* P value between males and females (Mann−Whitney U test).

† P value between different age, refractive status, and different AL groups (Mann−Whitney U test or One way ANOVA).

Figure 2. The relationship of LP or spherical equivalent to AL/CR ratio. (a) The LP decreases with the AL/CR ratio increase. (b) The spherical equivalent decreases with the AL/CR ratio increase.

Influence of Age and Sex

The age distribution is presented in Table 4. LP of older subjects was lower (25.24 ± 3.29 D vs. 26.16 ± 3.15 D; P = 0.033), whereas the LT and ASL were higher (3.41 ± 0.27 mm vs. 3.23 ± 0.23 mm [P < 0.001]; 6.64 ± 0.36 mm vs. 6.53 ± 0.33 mm [P = 0.021]). As can be seen from Table 4, the LP of older males was smaller (24.89 D vs. 27.36 D; P < 0.001), whereas the LP of females showed no significant statistical difference between the two age groups (P = 0.738). There was no significant difference in LP between different refractive statuses, and neither between males and females in further analysis of each group. When the subjects were divided into three groups by AL, the LP of the males of the second group (18 mm < AL ≤ 19 mm) was larger than that of the females (26.62 mm vs. 25.77 mm; P = 0.023).

Table 4. Distribution of Ocular Biometry in Right Eyes of Cynomolgus Macaque Monkeys Under Two Age Groups

		Age (Years)			
		≤18		>18			
Variables	N	Mean ± SD (Range)	Median (Interquartile Range)	N	Mean ± SD (Range)	Median (Interquartile Range)	P Value*	P Value†	
Weight (kg)	65	4.28 ± 1.11	4.04	206	4.58 ± 1.22	4.20	0.077	0.094	
		(2.44 to 7.18)	(3.40 to 5.11)		(2.66 to 8.52)	(3.70 to 5.20)			
SE (D)	79	−1.72 ± 3.57	−0.42	216	−1.45 ± 3.82	−0.29	0.582	0.408	
		(−13.25 to 2.13)	(−1.96 to 0.65)		(−23.21 to 7.21)	(−2.17 to 0.71)			
AL (mm)	80	18.72 ± 0.87	18.27	216	18.77 ± 0.84	18.48	0.694	0.367	
		(18.00 to 22.12)	(18.07 to 18.88)		(18.00 to 22.24)	(18.14 to 19.03)			
ACD (mm)	80	3.29 ± 0.31	3.27	216	3.23 ± 0.29	3.22	0.088	0.117	
		(2.71 to 4.07)	(3.07 to 3.52)		(2.55 to 4.08)	(3.04 to 3.38)			
LT (mm)	80	3.23 ± 0.23	3.22	215	3.41 ± 0.27	3.37	<0.001	<0.001	
		(2.83 to 4.10)	(3.09 to 3.36)		(2.73 to 4.30)	(3.21 to 3.6)			
ASL (mm)	80	6.53 ± 0.33	6.48	215	6.64 ± 0.36	6.60	0.021	0.006	
		(6.02 to 7.54)	(6.28 to 6.79)		(5.54 to 7.74)	(6.43 to 6.83)			
AL / CR ratio	80	3.28 ± 0.18	3.21	216	3.30 ± 0.16	3.26	0.444	0.111	
		(2.97 to 3.85)	(3.14 to 3.40)		(2.94 to 3.92)	(3.19 to 3.38)			
CP (D)	80	59.05 ± 2.16	59.21	216	59.24 ± 2.32	59.11	0.524	0.307	
		(54.57 to 66.08)	(57.91 to 60.57)		(51.67 to 65.39)	(58.00 to 60.89)			
LP (D)	79	26.16 ± 3.15	26.15	210	25.24 ± 3.29	25.31	0.033	0.028	
		(18.41 to 34.80)	(24.13 to 28.03)		(16.50 to 36.48)	(23.01 to 27.08)			
CP, corneal power; CR, corneal radii; SE, spherical equivalent.

* P value between two age groups (Student's t test).

† P value between two age groups (Mann−Whitney U test).

Factors Associated With LP

LP positively correlated with CR (r = 0.342; P < 0.001), LT (r = 0.247; P < 0.001), and ASL (r = 0.064; P = 0.278), using Pearson's correlation coefficients, whereas it correlated negatively with SE (r = −0.167; P = 0.004), AL (r = −0.176; P = 0.003), ACD (r = −0.148; P = 0.011), AL/CR ratio (r = −0.421; P < 0.001), and CP (r = −0.352; P < 0.001) (Supplementary Fig. S1). According to the results of unitary linear regression, the significantly correlated independent variables are included in the multiple regression analysis model. Table 5 demonstrated that LP was significantly related to age (P = 0.053), SE (b = −1.676; P < 0.001), CR (b = 1.140; P < 0.001), AL (b = −1.721; P < 0.001), LT (b = 0.167; P < 0.001), and ACD (b = 0.258; P < 0.001).

Table 5. Relationship Between Refractive LP and Ocular Parameters in Right Eyes

	Refractive LP	
	Simple Liner Regression Analysis	Multiple Liner Regression Analysis	
Variables	Standard β	P Value	Standard β	95% CI	P Value	
Age	−0.243	<0.001			0.053	
Weight	0.046	0.451				
SE	−0.167	0.004	−1.676	−1.52 to −1.46	<0.001	
CR	0.342	<0.001	1.140	16.52 to 17.26	<0.001	
AL	−0.176	0.003	−1.721	−7.30 to −7.00	<0.001	
ACD	−0.148	0.011	0.258	2.65 to 3.10	<0.001	
LT	0.247	<0.001	0.167	1.825 to 2.288	<0.001	
CI, confidence interval; CR, corneal radii.

Discussion

Nonhuman primate experimental animal models are used increasingly in ophthalmology research, especially in studies related to refractive errors, because the nonhuman primate visual system (including the structure of the eye) is highly similar to that of humans. To design and carry out preclinical studies more reasonably, it is important to establish standardized data and fully understand the biological structure of the eyes of nonhuman primates. Most previous studies of refractive errors in nonhuman primates have focused on AL and refractive power,16 although lens refractive power has rarely been systematically reported.

To our knowledge, this study is the first to investigate the characteristics of LP and the associated factors in nonhuman primate colonies. The results indicated that there was a significant difference in LP between young and old subjects, although the LP differences were also associated with AL, CR, ACD, and LT. In addition, more evident associations of LP with AL were shown in the emmetropia than in the myopia, irrespective of age.

Our results demonstrated that the mean LP for a healthy cynomolgus macaque colony was 25.40 ± 2.96 D, which was similar compared with the age-matched population-based human study.9,20 Meanwhile, there were no significant differences in eye- and sex-specific characteristics in this case. In contrast with our findings, population-based studies demonstrated that women had greater LP than men,21,22 the possible explanation being that women have a thicker lens with a shorter AL. Thus, further study in the distribution of LP between human and monkey groups is still required.

In our study, we sought to demonstrate a correlation between LP and age; therefore, we divided all subjects into young and old age groups, with the borderline at 18 years of age. We found that the LP exhibited a decreasing trend in aging subjects, which is consistent with previous studies.12,23,24 It is understood widely that CP and diameter are stable after the age of 2 to 3 years,25,26 AL increases in the age of minors, and the AL/CR ratio is likely to be stable during teenage years. Then, the decrease rate exhibited a monotonous decrease in LP of approximately 0.58 D each year in a monkey colony.12 This finding may be due to the increasing prevalence of cycloplegic hyperopia over middle age years, with the hyperopic changes driven by LP loss and shown related to decreased LP in older subjects.20 The similarities in the lens characteristics validate the use of nonhuman primate as a model for investigating human lens accommodation and presbyopia.

A comparison of LPs among different refractive groups also displayed an interesting finding in this study. Several studies have confirmed the associations of LP with SE and AL, irrespective of different age stages.22,27,28 Our results also revealed a significant difference between the refraction groups in AL, CR, and LP; the highest and lowest LP was seen in the myopia and hyperopia groups, respectively. The available evidence suggests that, before the onset of myopia, the AL growth rates began to go faster, most likely affected by myopia risk factors; these macaques live in confined spaces, keeping them in a state of short distance use of eyes and less time spent outdoors for quite long periods of time.29 In the beginning, the high AL growth rate would balance the increasing LP loss rate, as was postulated by Mutti et al.30 The lens seems to reach a physiological limit, causing a sudden deceleration in LP loss. Meanwhile, a longer AL combined with the rapid change in LP loss, leads to the SE shift with the onset of myopia. Then, the myopic defocus slows the AL elongation rate. The coeffect of changes explains why myopes have lower LP than emmetropic eyes in children and adults.21,31

The results of simple linear and multiple regression analyses confirmed a negative correlation between SE, AL, and LP. The decrease in the LP with the increasing SE may have a positive effect on the maintenance of emmetropia and prevent the process of myopia.28 We also found a significant and positive correlation between LP and LT. The LP changes seem to be secondary to the modification in LT, as in the results presented by Hashemi et al.,27 where LT decreased with age and the slope of the decrease became flat after the teenager stage. This finding has been confirmed in other studies as well.9,23

Some strengths of this study include a large sample size in the nonhuman primate colony, with comprehensive ocular examination and relevant parameters. The results of this study are not only of great significance to our understanding of the visual system, but also provide valuable information for us to understand the physiological mechanism of the eye of nonhuman primate, In addition, it provided important data support and research clues for exploring the refractive LP of human, the pathogenesis of refractive errors, and the development of prevention and control measures.

There were several potential limitations of our study. We included middle- to old-age macaques with a short age span; future studies may include more adolescents to analyze the age-related changes in LP characteristics. This was a cross-sectional study and failed to examine the process of myopia and the relationships between LP and other parameters. Additionally, previous error analysis shows that the measurement accuracy of LP calculated according to Bennett's method is approximately ±1 D.32 The task of determining macaques' constants (such as the coefficient c) accurately proves to be both arduous and financially intensive; thus, we have had to rely on estimations rather than definitive measurements. When conditions permit in the future, the macaque's parameters will be quantified accurately.

In conclusion, the findings of the current study have demonstrated the normal range of LP in nonhuman primate colony and contributed to a deeper understanding of the role and relative importance of the LP on the optics of the crystalline lens, this result fills gaps in this field. Moreover, this study implies the AL and SE strongly influenced the rate of LP, which indicates the mechanism further needs to be clarified.

Supplementary Material

Supplement 1

Acknowledgments

Supported by the National Key R&D Project of China (2020YFA0112701); the National Natural Science Foundation of China (82171057); Science and Technology Program of Guangzhou, China (Science and Technology Program of Guangzhou, China (202206080005); Major Science and Technology Project of Zhongshan City (2022A1007).

Author Contribution Statements: Conception and design: YTZ, RX, JW, YHZ. Acquisition of data: YTZ, RX, QZ. Conducting the experiment: YZ, GTY, LZX, SMH, WL, ZWH. Analysis and interpretation of data: YTZ, RX. Drafting and critically revising the article: JW, YHZ. All of the authors have read and approved the final manuscript.

The data supporting this study's findings are available from the corresponding author upon reasonable request.

Disclosure: Y. Zhu, None; R. Xie, None; Q. Zhang, None; Y. Zhang, None; G. Ye, None; L. Xu, None; S. Hou, None; W. Liu, None; Z. Huang, None; J. Wu, None; Y. Zhuo, None
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