Spontaneous Refractive Error, Ocular Biometry and Age Related Lens Changes in a Population of Geriatric Rhesus Macaques

Spontaneous Refractive Error, Ocular Biometry and Age Related Lens Changes in a Population of Geriatric Rhesus Macaques | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Spontaneous Refractive Error, Ocular Biometry and Age Related Lens Changes in a Population of Geriatric Rhesus Macaques Jonathon M. Ross, Karolina Roszak, Ana Ripolles-Garcia, Glenn Yiu, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5010162/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 6 You are reading this latest preprint version Abstract Purpose The purpose of this investigation was to determine refractive error, ocular biometry and age-related lens changes in a population of geriatric rhesus macaques ( Macaca mulatta ) from the California National Primate Research Center (CNPRC). Methods Ophthalmic examination was performed in 182 rhesus macaques \(\:\ge\:\) 19 years of age using a cross-sectional study design, including streak retinoscopy, anterior segment tomography, A-scan ultrasound biometry and handheld slit lamp biomicroscopy. Results Median spherical equivalent refractive error was + 0.75 D with an interquartile range (IQR) of 0 to 1 D. Most eyes were hyperopic (n = 102, 55%) or emmetropic (n = 68, 36%); myopic eyes were least common (n = 17, 10%). Anisometropia was present in 13 subjects (14%). Mean (± SD) corneal curvature was 52.6 ± 2.6 D (n = 79). Mean (± SD) axial globe length was 20.2 ± 1.5 mm, anterior chamber depth was 3.7 ± 0.4 mm, lens thickness was 4.1 ± 0.4 mm, and vitreous chamber depth was 12.2 ± 1.0 mm (n = 86). Median (IQR) nuclear sclerosis grade (n = 99, 96%) assessed with the lens opacities classification system II was 1 (1–2). Conclusion Low hyperopia is the most common refractive error in the geriatric rhesus macaque population at CNPRC. This study provides reference values for an isolated geriatric rhesus macaque population and broadens our understanding of refractive error and lens opacities in geriatric rhesus macaques which may serve as a model for studying novel therapeutics for presbyopia and cataract. Biological sciences/Zoology Health sciences/Anatomy Biological sciences/Developmental biology/Ageing refractive error ocular biometry nuclear sclerosis geriatric rhesus macaques cataract Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Highlights Low hyperopia is the most common refractive error in geriatric rhesus macaques (46%). Myopia is the least common refractive error in geriatric rhesus macaques (10%). Nuclear sclerosis is common (96%) in geriatric rhesus macaques while advanced stage cataracts are rare (2%). 1. Introduction Non-human primates (NHPs) have proven to be useful models for studying the human visual system. 1 The genus Macaca is the most widely utilized NHP model and shares >90% DNA sequence similarity to humans with comparable ocular size, structure and function. 2 Rhesus macaques ( Macaca mulatta ) have a lifespan of ~27 years in captivity while aging at a rate nearly 3 times that of humans. 3,4 In general, this species reaches adulthood (i.e. sexual maturity) by 5 years and is considered geriatric after 19 years. 5 Rhesus macaques demonstrate age-related ocular changes similar to humans, including development of cataracts. 5,6 Analysis of spontaneous changes in the geriatric rhesus macaque population may provide better understanding of the natural progression of aging in the human visual system. Rhesus macaques raised in research facilities are often the subjects of translational investigations. Due to their similarities with humans, this species has proven to be invaluable for understanding refractive development and ocular changes observed in humans. However, to appreciate the full implication of the findings from studies in rhesus macaques a complete longitudinal observation (birth to geriatric) is necessary. To date, there have been few studies reported in the literature on refractive error in the geriatric rhesus macaque population. ( Table 1 ). Thus, it is important to establish refractive error and ocular biometry characteristics across the lifespan of this species, particularly geriatric rhesus macaques. Mean refractive error distribution changes with age. 7,8 Previous investigations have determined refractive status and anterior segment biometrics in rhesus monkey populations from birth to adulthood. 9-11 Longitudinal studies in rhesus macaques from infancy to adulthood have reported measures of ocular biometry, including corneal curvature, endothelial cell density, axial length (AL), anterior and vitreous chamber depth (ACD and VCD, respectively) and lens thickness (LT). 12-19 The incidence of cataract in rhesus macaques has also been investigated. 6 Uno and colleagues reported that 20% of postmortem rhesus macaque eyes (n=175) had cataract at 20 – 22 years of age with significant increases after 26 years of age; although standardized grading was not performed. 6 By contrast, a lack of lens haze, cloudiness or age-related cataract was documented by Denlinger and coauthors in adult rhesus macaques, 20 with only one primate being affected by a rosette shaped cataract of suspected traumatic etiology. Despite detailed categorization of visual and ocular characteristics in young and adult rhesus macaques, there remains limited reports among the geriatric population in this species. The California National Primate Research Center (CNPRC) maintains a population of rhesus macaques ≥19 years of age so that aging studies can be conducted. Thus, a dataset comprised of geriatric refractive and ocular characteristics in rhesus macaques at CNPRC will provide reliable reference for future investigations involving anterior segment anatomy and physiology and provide completeness to existing datasets on the natural progression of changes. Thhe purpose of this investigation was to determine refractive error, ocular biometry and age-related lens changes in the eyes of geriatric (≥19 years of age) rhesus macaques using a cross-sectional study design. 2. Method 2.1. Subjects : All the animals in this investigation were rhesus macaques ( Macaca mulatta ) born and maintained at the CNPRC. The CNPRC is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. Guidelines of the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research were followed. All aspects of this study were in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Ophthalmic examinations were performed according to a protocol approved by the University of California Davis Institutional Animal Care and Use Committee. Phenotypic data was collected from rhesus macaques previously evaluated for drusenoid lesions. 21 Some of the macaques in the present study were included in previous studies by Lin and coauthors 5 (n=67) and Casanova and colleagues (n=52). 19 The indoor animals experienced a 12:12 light-dark cycle, with light levels in the facility varying from 70 to 930 lux depending on the area. The free-range animals were housed in large outdoor enclosures with shaded and unshaded areas and were exposed to light levels as high as 10,000 lux on a clear, sunny day. All animals were transferred to the procedure room for evaluation, where light levels ranged from 700 to 1670 lux. The animals were classified as “Mostly indoor” or “Mostly outdoor” if they spent more than 50% of their lifespan in either environment before their refractive error was measured. In addition, the same classification was recorded for the first 6 years of life to capture the initial phase of eye growth. 11 All measurements were obtained within a 6-hour period (8 a.m. to 2 p.m.), during which diurnal variations are expected to be minimal and consistent across animals. Consequently, no evaluation of diurnal variation in ocular parameters was conducted. Comprehensive ophthalmic examination was performed on sedated animals in the supine position under pharmacologic mydriasis and cycloplegia. Sedation was achieved by intramuscular injection of ketamine hydrochloride (5–30 mg/kg), dexmedetomidine (7.5–15 µg/kg) and/or midazolam (0.10 mg/kg). Topical tropicamide 1% (Akorn Inc., Lake Forest, IL, USA), phenylephrine 2.5% (Paragon BioTeck Inc., Portland, OR, USA) and cyclopentolate 2% (Alcon Laboratories Inc., Fort Worth, TX, USA) were instilled for mydriasis and cycloplegia. Animals were monitored by a trained ophthalmic technician and veterinarian throughout the experiment. 2.2 Refractive error : Objective streak retinoscopy was performed by veterinarians with training in ophthalmology using a handheld retinoscope (Welch-Allyn Inc., New York, NY, USA) to determine the refractive status of each eye under cycloplegic conditions. The power and axis of major and minor meridians were measured. Spherical equivalent refractive error was calculated; spherical equivalent refractive error = spherical power (diopters, D) + (cylinder power [D] / 2). Eyes were categorized based on their refractive error into groups defined by the American Optometric Association. 22,23 Eyes with a refractive error ranging -0.50 to +0.50 D were classified as emmetropic. Those with values between +0.75 D to +2.00 D, +2.25 D to +5.00 D, and greater than +5.00 D were categorized as low, moderate, and high hyperopia, respectively. Eyes with values between -0.75 D to -2.75 D, -3.00 D to -6.00 D, and those exceeding -6.00 D were grouped as low, moderate, and high myopia respectively. Any animal with a refractive discrepancy of 1.00 D or more between their eyes was identified as having anisometropia. 2.3 Ocular biometry : Anterior segment tomography (Pentacam High-Resolution Tomographer, Oculus, Wetzlar, Germany) was performed to measure corneal curvature and anterior chamber (AC) properties, including ACV and ACD. Corneal astigmatism was calculated from corneal curvature measurements. Against-the-rule astigmatism was defined when the cornea was steeper along the horizontal meridian than the vertical one. A-scan ultrasound biometry (Sonomed Pacscan Plus, Escalon, Wayne, PA, USA) was performed to measure ACD (corneal endothelium to anterior capsule of crystalline lens), crystalline LT (anterior capsule to posterior capsule of crystalline lens), VCD (posterior capsule of crystalline lens to inner limiting membrane of retina) and AL (corneal epithelium to inner limiting membrane of retina) as previously described. 4 Specifically, a 10 MHz A-scan probe was perpendicularly placed over the central cornea with a coupling gel (Goniosoft, OcuSoft Inc., Richmond, TX, USA) following topical anesthesia with proparacaine (Bausch & Lomb, Tampa, FL, USA). Five A-scan recordings were obtained on the manual freeze mode when all the required echoes with sufficient height were present and averaged for each eye. 2.4 Ophthalmic examination, including crystalline lens grading: All macaques underwent a comprehensive ophthalmic examination, including slit-lamp biomicroscopy, indirect ophthalmoscopy (Heine Optotechnik, Gilching, Germany) with a set of condensing lenses of different diopters and intraocular pressure measurement using rebound tonometry (TonoVet; Icare, Vantaa, Finland). Subjects with substantial posterior segment pathology were excluded from this study. Handheld slit lamp biomicroscopy was performed (SL-17, Kowa Optics, CA, USA) by a physician ophthalmologist and a veterinarian with expertise in ophthalmology. Crystalline lens changes including type, location and size of cataracts were documented using the semiquantitative preclinical ocular toxicology scoring (SPOTS) system; 24 lenticular sclerosis was graded (nuclear sclerosis grade, NS-grade) using a clinically accepted (0 – 4) grading scale ( Supplementary Figure S1 ), lens opacities classification system II (LOCS II). 25 In addition, anterior segment tomography was performed using the Pentacam High-Resolution Tomographer (Oculus, Wetzlar, Germany) to measure the nuclear sclerosis density (Pentacam Nucleus Staging, NS-Pentacam) using a 0–5 grading scale ( Supplementary Figure S2 ). 2.5 Statistical analysis : Parametric data was presented as mean ± SD and nonparametric data as median and interquartile range (IQR). To calculate agreement between ACD measures with Pentacam vs. A-scan ultrasound and between, NS-grade vs. NS-Pentacam, a concordance correlation coefficient (CCC) and bias were calculated using values obtained from the same eye. For the CCC, the results were interpreted as previously described, with values of greater than +0.75 indicating good agreement, values between +0.40 and +0.75 indicating moderate agreement, values of less than +0.40 indicating poor agreement and negative values of the same magnitudes, indicating disagreement. 19,26,27 Normality was determined by the Shapiro-Wilk test. For normally distributed data, paired t-tests were used (ACD measures with Pentacam versus A-scan ultrasound values) while for comparisons with non-normal data (NS-Grade versus NS-Pentacam), Wilcoxon signed-rank test was used. Bland-Altman linear regression was used to evaluated agreement between anterior chamber depth measurements with Pentacam (ACD Pentacam) and A-scan ultrasound (ACD A-scan) and simple lienear regression was used to investigate associations with the different parameters. Each rhesus macaque was treated as a random effect and all other variables were considered fixed effects. A Chi-square test was used to evaluate whether the indoor/outdoor environment across the entire lifespan influenced refractive error type (emmetropia, myopia, hyperopia). A P value of <0.05 was considered statistically significant; GraphPad Prism v9 (GraphPad Software Inc., La Jolla, CA, USA) was used for all analyses. Generalized Estimating Equations (GEE) were used to account for inter-eye correlations when appropriate using R software. 3. Results 3.1 Animals Both eyes of 182 geriatric rhesus macaques from the CNPRC were evaluated with a mean age of 22.2±2.5 (19.1 – 30.5) years. Geriatric status was defined as 19 years of age (human equivalence of approximately 57 years), 4 with human age equivalence estimated at a 1:3 ratio. 28,29 Consistent with the demographics of the CNPRC breeding colony, 140 females and 42 males were included. 3.2. Cycloplegic streak retinoscopy Objective cycloplegic streak retinoscopy was used to determine refractive error in 187 eyes of 95 rhesus macaques. Females were overrepresented in the population evaluated (28 males vs 67 females), reflecting the colony proportions. The mean refractive error spherical equivalence was +0.7±1.7 D. Astigmatism was detected in 7 of the 187 eyes evaluated (3.7%). Of these, two eyes exhibited 1.50D of astigmatism, while the remaining five eyes showed ≤0.50 D. In 3 eyes the presence of advanced cataracts prevented streak retinoscopy (see Supplementary Figure S3 ). Most geriatric rhesus macaque eyes were hyperopic (n=102, 55%) with emmetropic eyes also commonly observed (n=68, 36%); myopes were least common (n=17, 10%) ( Figure 1A, Table 2 ). Both sexes were included in all the refractive error groups ( Figure 1B ) and the refractive error was not significantly different in older macaques ( P = 0.81, Figure 1C ). Anisometropia was observed in 13 rhesus macaques (14%) with nine (69%) qualifying as amblyogenic anisometropia (> 1.00 D hyperopia or > 3.00 D myopia). 30 Of the 95 rhesus macaques that underwent streak retinoscopy, only 3 (3.16%) were housed indoors before the age of 6. Of these, 2 had hyperopia and 1 had myopia. Due to the small sample size, statistical analysis could not be performed for this group. However, when comparing the environmental conditions over the entire lifespan of the animals, no significant associations between the indoor/outdoor environment and refractive error were found ( P = 0.6929). 3.3. Corneal curvature and AC properties evaluation with Pentacam High-Resolution Tomographer and A-scan ultrasound biometry A Pentacam High-Resolution Tomographer was used to measure corneal curvature and AC properties in 158 eyes of 91 rhesus macaques (75 females and 16 males). Corneal curvature was 52.6 ± 2.6 D (range: 43.0–61.8 D) and against-the-rule (ATR) corneal astigmatism was 1.6 ± 1.3 D x 099 ± 47.3 (range: 0–7.4 D); ACV and ACD were 136 ± 17 mm 3 (range: 102–180 mm 3 ) and 3.34 ± 0.3 mm (range: 2.5–4.0 mm), respectively. Ocular biometry measurements were also assessed via A-scan ultrasound biometry in 338 eyes of 171 rhesus macaques (134 females and 37 males). AL was 20.2 ± 1.5 mm (range: 17.5–28.7 mm), ACD was 3.7 ± 0.4 mm (range: 2.2–5.4 mm), LT was 4.1 ± 0.4 mm (range: 2.5–6.5 mm) and VCD was 12.2 ± 1.0 mm (range: 9.3–17.7 mm). Table 2 presents Pentacam keratometry values and A-scan measurements of anterior and posterior ocular segments across refractive error categories in geriatric rhesus macaques. 3.3.1 Differences in ACD measured via Pentacam tomography versus A-scan ultrasound Differences in ACD measured via tomography (ACD Pentacam) versus A-scan ultrasound (ACD A-scan) are represented in Figure 2 . Bias of ACD Pentacam versus ACD A-scan was equal at -0.3 and a significantly negative slope was identified indicating that Pentacam consistently underestimates the ACD ( P <0.001). The CCC of 0.2 demonstrated poor agreement between the two techniques and a Wilcoxon test demonstrated a statistically significant difference in ACD between the two measurements (Pentacam = 3.4±0.3 mm; A-scan = 3.7±0.4 mm, P <0.0001). 3.4 Slit lamp biomicroscopy findings in the lens With slit lamp biomicroscopy, 191 of 195 (98%) eyes of 99 macaques had nuclear sclerosis. Median NS-grade was 1 (1–2) and 47 eyes (24%) had a grade >2 ( Figure 3A ). Four eyes had no nuclear sclerosis (grade 0), two eyes had a complete cataract, and one eye had a resorbing cataract (Figure 4A) . Punctate cataracts were most frequently observed (45 of 198 eyes, 23%) followed by incipient and incomplete cataracts (22 and 12 of 198 eyes, 11% vs. 6%). Cataracts were most frequently located in the anterior and posterior cortex (37 and 28 of 198 eyes, 19% vs. 14%) (Figure 4B). Median NS-Pentacam, as calculated by anterior segment tomography via the Pentacam in 136 eyes of 75 primates was 0 with an interquartile range of 0 to 0, with only 18 eyes having score >0 (13%). Nuclear sclerosis grade vs. NS-Pentacam were compared in Figure 3A-B . Bias of NS-grade versus NS-Pentacam was identified at 1.4 with a significant negative slope ( P =0.3) and poor correlation (CCC=0.2); a Wilcoxon test confirmed statistically significant differences between the two measurement types ( P <0.0001) suggesting that the Pentacam Nucleus Staging significantly underestimates the degree of nuclear sclerosis when compared to the gold standard slit lamp grading of nuclear sclerosis. As expected, a significant increase in NS-Grade and NS-Pentacam scores with age (19.1–30.5 years) was observed using simple linear regression ( P =0.0004 and P =2.3E-11, respectively). 3.5 Refractive status and ocular non measurements Biometric parameters were analyzed across the different refractive error categories to gain further insights into the underlying causes of these refractive states. We observed that the ACD was significantly shallower in older myopes and emmetropes ( P =0.02 in both; Figure 5A ), likely due to age-related lens thickening in these groups ( P =0.002 and P =0.008, respectively; Figure 5B ). By contrast, VCD ( Figure 5C ) and AL ( Figure 5D ) did not significantly change across all refractive error groups in older macaques, consistent with the expectation that globe growth has ceased at this stage. Myopes had significantly deeper ACD (3.77±0.59) when compared to emmetropes (3.59±0.26; P =0.008) and hyperopes (3.66±0.40; P =0.012, Figure 5E 1 ). There were no significant differences between LT between the refractive error groups ( Figure 5E 2 ). Myopes also had significantly deeper VCD (12.59±0.69) when compared to emmetropes (11.90±0.68; P =0.003) and hyperopes (11.91±0.71, P =0.001; Suppl. Figure 5E 3 ). Similarly, myopes had significantly longer AL (20.55±0.83) when compared to emmetropes (19.77±0.72; P <0.001) and hyperopes (19.77±0.69, P <0.001; Figure 5E 4 ). 4. Discussion Herein, we report refractive error, ocular biometry characteristics and age-related lens changes in a large geriatric rhesus macaque population at the CNPRC. While refractive error has been previously reported in immature and adult rhesus macaques 31,32 , our study measured refractive error and lens changes in a large population of rhesus macaques ≥19 years of age. We determined that low hyperopia and emmetropia were the most common refractive states in this geriatric population consistent with previously shown hyperopic emmetropization in adolescent macaques with an average refractive value of +2.00 D. 33 In the present study, myopia was less common (n=17, 10%) in geriatric rhesus macaques with high myopia being the least common refractive error (n=1, 1%). Indeed, Tzu-Ni Sin and colleagues described this non-human primate model of myopic foveoschisis amongst a cohort of 40 myopic rhesus macaques with AL >21 mm (age 7.3–29.0 years old) at the CNPRC. 34 We note that cycloplegic retinoscopy may overestimate the degree of hyperopia in this population versus psychophysical methods. 35 Nevertheless, the predominance of low refractive error is expected in rhesus macaques given their lifestyle. Limited near activity and outdoor living likely reduce the stimulus for myopia progression and subsequently also reduces the risk of myopia-related ocular health complications, including retinal detachment. 36-39 While there is no direct evidence linking indoor housing to refractive errors in rhesus macaques, existing studies suggest that environmental factors, particularly lighting conditions, may influence refractive error development. 40 Exposure to natural outdoor light has been shown to reduce the risk of myopia in rhesus macaques, with those housed under dim light conditions more likely to develop refractive errors. 41,42 Therefore, in our study, the low number of animals housed indoor in the first six years of life (3.16%) likely contributed to the generally low incidence of refractive errors observed in our colony. Given the low prevalence of myopia in rhesus macaques, further understanding of the mechanisms that lead to this may provide valuable insights into the underlying factors causing the progression of nearsightedness in human patients. Further studies involving a broader sample size and varying housing conditions will be crucial in understanding how early environmental factors, including light exposure, affect refractive error development in rhesus macaques. In the present study, anisometropia (≥1.00 D) was present in 14% of the geriatric rhesus macaques that were refracted. The prevalence of anisometropia in the human population varies widely depending on inclusion criteria, but can generally be estimated at ~19%. 43 In the current study, a notable proportion of rhesus macaques had a degree of anisometropia that if present in early life could have put them at potential risk for amblyopia. However, the purview of this study was limited, and we were unable to determine if this amblyogenic anisometropia was present early in life among our population.The best estimate of amblyopia among humans is 2% with anisometropic and strabismic amblyopia accounting for 90% of all amblyopic cases. 30,44 Interestingly, no rhesus macaques included in this investigation demonstrated frank signs of large angle strabismus during clinical examination, whereas strabismus in the human population is estimated to be between 2–5%. 45 Possibly due to presence of darker scleral pigmentation in rhesus macaques creates more challenges in diagnosing strabismus in this species and anisometropia may be the more common risk factor for amblyopia in the rhesus macaque population. A future survey of spontaneous anisometropia and possible amblyopia among normal young rhesus macaques will be important for understanding the mechanism of disease in humans. In addition, the seemingly low prevalence of strabismus in this population warrants further investigation. Furthermore, it will be important to assess amblyopia, with a particular focus on evaluating the role of high bilateral isometropia in the development of amblyopia in this animal model. The quality of life in geriatric primates with amblyopia may further decrease as they develop presbyopia, leading to discomfort and visual impairment. Unfortunately, presbyopia was not evaluated in current study, but it would be an important future investigation topic in geriatric rhesus macaques. Corneal tomography confirmed that rhesus macaques have significantly steeper mean corneal curvature (52.6 ± 2.6 D) versus humans (43.8 ± 1.4 D). 46 ATR corneal astigmatism is known to increase with age in humans. 47 Our study confirmed an elevated incidence of ATR corneal astigmatism (1.6 ± 1.3 D) in this geriatric rhesus macaque population. Subjects with corneal astigmatism >2.00 D was approximately 30% and >3.00 D was approximately 15%. Conversely, the low presence of irregular astigmatism (despite steep mean corneal curvature) and minimal corneal pathological findings during anterior segment evaluation is suggestive of a low frequency of corneal dystrophy, including keratoconus, in this population. Future studies should utilize corneal topography to better understand the incidence of anterior and posterior corneal irregularity in this species to confirm its potential as a model for elucidating the mechanisms associated with corneal dystrophies. Anterior and posterior biometry measurements in geriatric rhesus macaques are similar to those of geriatric humans. 48,49 As previously reported by our group, in our study ACD (3.7 ± 0.4 mm versus 2.5, range: 2.5 – 2.5 mm 48 , respectively) was greater while LT (4.1 ± 0.4 mm versus 4.5, range: 4.4 – 4.5 mm, 48 respectively) and VCD (12.2 ± 1.0 mm versus 15.6, range: 15.5 – 15.6, 48 respectively) was lower in geriatric rhesus macaques compared to humans. 48,49 Relative to AL, the ratio of ACD:LT:VCD is ~1:1:3 in geriatric rhesus macaques and ~1:2:6 in humans 60–64 years of age. 48,50 Our study also confirmed poor agreement between ACD measurements obtained with two different methods, A-scan ultrasound and the Pentacam High-Resolution Tomographer. Future studies utilizing the ACD measurement should consider the variability of this measure between instruments during study design. In addition, an equivalent validation process should be performed for the corneal curvature and AC parameters obtained with the Pentacam. Although previous studies, including those from our group and others, have reported ocular biometric measurements in rhesus macaques, this study is the first to categorize these parameters by refractive error. 5,33 This approach offers a more comprehensive understanding of the relationship between biometric alterations and refractive changes, thereby advancing the characterization of aging in rhesus macaques. In our rhesus macaque population, we confirmed that myopic individuals exhibit significantly longer ACD, VCD and AL than emmetropes and hyperopes, consistent with an axial component to their refractive error. In all refractive error groups, LT was higher in older individuals, as it has been described to occur with age in this species. 5,33 However, we did not observe statistically significant differences in biometric parameters between hyperopic and emmetropic individuals. Based on these findings, we hypothesize that the nature of refractive error in this animal model is mixed—primarily axial in myopes, whereas hyperopia may be driven by refractive components, as their biometric measurements alone do not fully account for the observed refractive error. It is important to note that determining the precise nature of hyperopia was beyond the scope of this study, and future investigations should consider collecting additional data to further elucidate the underlying mechanisms. In this study, 24% of rhesus macaque eyes had nuclear sclerosis that would visually impair humans (≥ 3 grade); 2% of eyes assessed had grade 4 nuclear sclerosis. In our population, we observed a lower occurrence of cataract than anticipated (41%) with the most frequently observed type being punctate cataracts (23%) localized to the anterior (19%) and/or posterior cortex (14%). With aging, humans experience more frequent anterior and posterior lenticular changes. 51 The lower-than-expected occurrence of cataracts in our study subjects contrasts with the high prevalence observed in humans, where 73% of females and 78% of males aged 65 to 74 develop cataract. 52 We also determined that the extent of nuclear sclerosis formation (as determined by an ophthalmologist using a clinically accepted 0–4 grading scale) should be considered independently from the NS-Pentacam, a measure of crystalline lens density calculated by the Pentacam High-Resolution Tomographer on 0–5 scale. Previous studies have demonstrated the correlation between nuclear sclerosis progression and ultraviolet (UV) light exposure. 53 Thus, this relatively low incidence of advanced nuclear sclerosis in our population of rhesus macaques was unexpected, given that they spend a majority of their life outdoors. This suggests that other physiological properties, such as corneal and lens UV light absorption, may differ in rhesus macaques versus humans or that other unknown environmental factors may be involved. Although the study population was geriatric, total years of life expectancy are greater in humans versus rhesus macaques and could account for the difference in the extent of cataract present at this stage. Further investigation into the multifactorial properties associated with cataract formation is needed for elucidating the underlying mechanisms. This study is not without limitations, most of which are due to the extensive nature of the evaluation, which included multiple tests and parameters collected over several years by different evaluators. One limitation is that not all macaques could be evaluated with all techniques, resulting in some missing data. Another limitation is the use of the American Optometric Association refractive classifications, which are based on human standards and may not fully reflect the unique characteristics of rhesus macaques. Additionally, the AOA classifications are based on subjective refraction, whereas our study employed cycloplegic objective refraction methods for measuring refractive error in rhesus macaques. Therefore, we acknowledge that applying human-based classification criteria to NHP models, combined with the methodological differences in refraction techniques, may result in potential discrepancies. Given the high interest in studying cognition and neurodegeneration in geriatric rhesus macaques, 54 it is imperative that ocular health be assessed as many behavioral tasks require normal vision to complete. This study gives important insights into the incidence of lens changes and refractive error that could impact vision and quality of life in geriatric rhesus macaques. Furthermore, identification of these abnormalities may require provision of environmental enrichment or accommodations to preserve normal behavior and social order. 55,56 5. Conclusion Low hyperopia is the most prevalent refractive error in the geriatric rhesus macaque population at the CNPRC. Further understanding of the mechanisms that lead to low prevalence of myopia, as observed in current study, may provide valuable insights into the underlying factors causing the progression of nearsightedness in human patients. Finally, the low occurrence of vision decreasing crystalline lens changes could be attributed to the difference in the lifespan between rhesus macaques and humans and create an opportunity for additional studies regarding cataract formation and treatment. Abbreviations AC, Anterior chamber ACD, Anterior chamber depth ACV, Anterior chamber volume AL, Axial length Astig, Astigmatism ATR, against-the-rule CCC, Concordance correlation coefficient CNPRC, California National Primate Research CenterD, Diopters IQR, Interquartile range K, Corneal meridian measured in Pentacam LOCS II, Lens opacities classification system II LT, Lens thickness NHPs, Non-human primates NS-Grade, Nuclear sclerosis grade NS-Pentacam, Pentacam nucleus staging SD, Standard deviation SPOTS, Semiquantitative preclinical ocular toxicology scoring system VCD, Vitreous chamber depth Declarations Author Contribution *JMR and KR equally contributed equally to this work and are co-first authorsConceptualization – SMT, GY, CJM, AM. Methodology – SMT, GY, CJM, AM. Data curation – JMR, KR, GY, CJM, AM, HM, ARS, SK, SP, IMC, LSM, AM, CC, LMG, JAR, SMT. Data analysis – JMR, KR, ARG, SMT. Project supervision – SMT. Writing – JMR, KR, SMT. Review and editing - JMR, KR, ARG, GY, AM, IMC, SMT. Acknowledgement This work was supported by the National Institutes of Health U24 EY029904 (AM, SMT), R01 EY033733 (SMT), P30 EY12576, K08 EY027463 (AM), and R01 EY032238 (GY). Additional support for this research came from the California National Primate Research Center Base Grant from the National Institutes of Health, Office of the Director, (NIH) P510D011107. GY was additionally supported by NIH UG1 EY032446, R01 EY034340, Foundation Fighting Blindness, Jack McGovern Coat’s Disease Foundation, Retina Society, and Lions Club International Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.The authors acknowledge the numerous members of the Comparative Ophthalmology and Vision Sciences Laboratory for their contributions throughout the study period, and extend gratitude to Michelle Ferneding and Monica Motta for their invaluable technical support during the research. Additionally, we appreciate the CNPRC staff for their outstanding care of the rhesus macaques, particularly Paul-Michael D. Sosa and Mary Roberts. Data Availability The data that support the findings of this study are available on request from the corresponding author, Sara M. Thomasy. The data are not publicly available. References Orban, G. A. Higher order visual processing in macaque extrastriate cortex. Physiol. Rev. 88 (1), 59–89 (2008). Picaud, S. et al. The primate model for understanding and restoring vision. Proc. Natl. Acad. Sci. U S A . 116 (52), 26280–26287 (2019). 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Spontaneous fundus lesions in elderly monkeys: An ideal model for age-related macular degeneration and high myopia clinical research. Life Sci. 282 , 119811 (2021). Smith, E. L. 3, Hung, L. F. & rd, The role of optical defocus in regulating refractive development in infant monkeys. Vis. Res. 39 (8), 1415–1435 (1999). Tables Table 1. Summary of published studies on refractive error in rhesus macaques. Study Location Animals (n) Age (years) Refractive error 1 Fernandes AG et al . 2023 57 CPRC (free ranging) 120 Birth to 29 Spherical equivalent (mean±SD): 0.30±1.7 D (emmetrope±low hyperopia/myopia) 2 Ma Y et al. 2023 58 AAALAC (unknown) 219 8 to 21 Emmetropes and hyperopes: 37.53% Myopes: 62.47% 3 Zeng B et al. 2021 59 GXBC or ZCBC (indoor) 15 12.4 to 16.1 Emmetropes and hyperopes: 98% Myopes: 2% 4 Qiao-Grider Y et al. 2007 11 Indoor nursery 214 0.07 to 5 Spherical equivalent (mean±SD): 4.17±1.52 D (moderate and high hyperopia) 5 Fernandes A et al. 2003 33 YNPRC (variable) 111 5 to 31 Spherical equivalent (mean±SD): -0.19±3.35 D (emmetrope±moderate hyperopia/myopia) 6 Smith EL 3rd et al. 1999 60 Indoor nursery 121 0.04 to 2 Spherical equivalent (mean): 4.4 D (moderate hyperopia) 7 Bradley DV et al. 1999 10 YNPRC (unknown) 237 Birth to 5 Spherical equivalent (mean±SD): 2±1.2 D (low and moderate hyperopia) 8 Young FA. 1964 9 WNPRC (unknown) 1000 0.7 to 20 Spherical equivalent (mean): 0.21 D (emmetrope) 9 Current study 2024 CNPRC (indoor & outdoor) 95 19 to 29 Emmetropes: 36% Hyperopes: 55% Myopes: 10% Abbreviations: CPRC, Caribbean Primate Research Center; AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care; GXBC or ZCBC, Guangzhou Xiangguan Biotech Co., Ltd. or Zhaoqing Chuangyao Biotech Co., Ltd.; YNPRC, Yerkes National Primate Research Center; WNPRC, Washington National Primate Research Center; CNPRC, California National Primate Research Center. Data are presented as mean ± SD (range) unless otherwise indicated. Table 2. Low hyperopia and emmetropia were the most common refractive errors observed in this population of geriatric rhesus macaques. K (D) Steep Axis (D) Astig (D) ACD (mm) ACV (mm 3 ) LT (mm) VCD (mm) AL (mm) Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N Emmetropia 51.9 2.2 33 98.9 44.2 33 1.6 1.7 33 3.6 0.3 66 132.1 15.4 34 65 4.3 0.2 11.9 0.7 66 19.8 0.7 66 Low hyperopia 50.8 2.3 22 101.2 44.5 22 1.9 1.5 22 3.7 0.5 86 134.5 13.8 29 78 4.3 0.4 11.9 0.7 86 20 1.5 86 Moderate hyperopia 50.7 1 2 89.5 27 2 0.7 1 2 3.7 0.4 11 134.0 13.9 3 11 4.1 0.6 12.3 0.8 11 21 2.6 11 High hyperopia 52.7 1.6 3 97.3 58.2 3 1.7 0.6 3 3.7 0.1 4 122.5 7.8 2 3 3.7 0.5 11.9 0.1 4 18.6 2 4 Low myopia 47.7 3.6 5 142 17.4 5 2.2 1.8 5 4 0.6 11 153.4 20.1 5 10 4.1 0.3 12.8 0.7 11 20.8 0.9 11 Moderate myopia N/A N/A N/A 3.7 0.4 5 112.5 3.5 2 5 4.2 0.3 12.2 0.4 5 20.1 0.3 5 High myopia N/A N/A N/A *2.9 0.4 1 N/A 1 5.0 *16.1 0.4 1 *22.0 0.6 1 The table includes values of keratometry acquired via Pentacam and A-scan measurements of anterior and posterior ocular segment among refractive error categories in geriatric rhesus macaques. The table included following ocular biometry values acquired with Pentacam: K – average keratometry reading measured in diopters (D), Steep Axis – the average location of the steepest meridian in diopters, Astig – average corneal astigmatism measured in diopters (D), and values acquired with the A-scan: ACD - anterior chamber depth measured in millimeters (mm), ACV - anterior chamber volume (mm 3 ), LT – lens thickness (mm), VCD – vitreous chamber depth measured in millimeters (mm), and AL – axial length measured in millimeters (mm). Note – Pentacam values were not available for moderately and highly myopic animals, labeled N/A. In the high myopia group there was only one eye available for evaluation with A-scan, because of this the mean value is equivalent to the measurement in the single eye (marked with asterisc *). Additional Declarations No competing interests reported. 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Thomasy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYHACNgjF3sDAwANGDAwS+HUwQ7XwHCBZi0QCVD0hLfLTzh978DHHzt7g5hvDD29qDsvINzAfvM2DR4vB7WR2w5nbkhM33M4xlpxz7DCPwQG2ZGu8WqST2aR5tzEnGNzOMWPmYUvjMWDgMZPGp0V+NlhLPdBhZ4Ba/qXxyDfwf8OrheE2WMthxg03eMyYedtseBgO8LDh1QL0i5nkzG3HE2eeSSuWnNtnw2NwmM3Ycg5ehyU+k/i4rdqe7/jhjR/efJOwl29vfnjjDT6HwYDCARiLmRjlYOsaiFU5CkbBKBgFIw4AAKUiRXh3hWjxAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis","correspondingAuthor":true,"prefix":"","firstName":"Sara","middleName":"M.","lastName":"Thomasy","suffix":""}],"badges":[],"createdAt":"2024-08-31 17:59:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5010162/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5010162/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-30581-6","type":"published","date":"2025-12-05T15:57:09+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81504496,"identity":"a1ed8d34-1409-49ca-9a56-cbed52cc06ba","added_by":"auto","created_at":"2025-04-28 05:09:40","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":251880,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLow hyperopia and emmetropia were the most common refractive status observed in this population of geriatric rhesus macaques\u003c/strong\u003e. \u003cstrong\u003eA,\u003c/strong\u003e Retinoscopy was performed on 187 eyes of 95 animals (19–29 years of age); 55 were male and 131 were female. Spherical equivalent refractive error categories were defined as: emmetropia (E, +0.50 to -0.50 D, n=68 eyes, 36%), low hyperopia (LH, +0.75 to +2.00 D, n=86 eyes, 46%), moderate hyperopia (MH, +2.25 to +5.00 D, n=12 eyes, 6%), high hyperopia (HH, \u0026gt; +5.00 D, n=4 eyes, 2%), low myopia (LM, -0.75 to -2.75 D, n=11 eyes, 6%), moderate myopia (MM, -3.00 to -6.00 D, n=5 eyes, 3%), and high myopia (HM, \u0026gt; -6.00 D, n=1 eye, 1%). \u003cstrong\u003eB\u003c/strong\u003e, Both sexes were represented in al the refractive status categories. \u003cstrong\u003eC\u003c/strong\u003e, Refractive error did not significantly change in older macaques, with all the categories represented across ages.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/1f6203a7c57572d36ecfa318.jpeg"},{"id":81504494,"identity":"e7473750-8a2d-44f3-8d4e-86bf832b9a11","added_by":"auto","created_at":"2025-04-28 05:09:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":197449,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBland-Altman plot indicates that Pentacam underestimates the anterior chamber depth (ACD) compared to A-scan. \u003c/strong\u003eThe anterior chamber depth was measured with Pentacam and A-scan ultrasound in 136 eyes. The negative mean difference (bias, thick black line) suggest that Pentacam consistently underestimates the ACD. The vertical axis represents the difference between the two types of measurements and the horizontal axis plots the mean value for the two types of measurements. The dashed lines represent the 95% limits of agreement, and the black line represents a negative slope (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). The concordance correlation coefficient (CCC) was 0.2 with a confident interval of 0.1 – 0.3, indicating poor agreement between the two measurement techniques.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/24f6ce440bbd881bb4e7e7f3.png"},{"id":81504499,"identity":"bff1a3a8-7632-4ddd-98f4-1636e724f082","added_by":"auto","created_at":"2025-04-28 05:09:41","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":169549,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThere was poor agreement between nuclear sclerosis grade determined by examiners (NS-Grade) and nucleus staging determined based on Pentacam internal algorithm (NS-Pentacam).\u003c/strong\u003e The two pie charts demonstrate percentage of eyes affected by various grades of nuclear sclerosis and most commonly observed lens opacities within the evaluated population of geriatric rhesus macaques. NS-Grade (A) represents the degree of nuclear sclerosis, as determined by a physician ophthalmologist or a veterinarian with expertise in ophthalmology in 195 eyes of 99 geriatric rhesus macaques (Lens opacities classification system II - LOCS II: 0 – 4 scale), while NS-Pentacam (B) represents the Pentacam Nucleus Staging, as calculated by anterior segment tomography via the Pentacam in 136 eyes (0 – 5 scale). *Due to rounding of percentages, the cumulative percentage for each figure may appear be \u0026gt; 100%.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/21902c453a9b65a48a091142.jpeg"},{"id":81507054,"identity":"caf1c070-adce-4339-b5b3-5c7dbd4c8c9f","added_by":"auto","created_at":"2025-04-28 05:33:41","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":155168,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCataract was observed in 41% of geriatric rhesus macaque eyes. \u003c/strong\u003eCataract severity (A) was graded as incipient, punctate, incomplete, complete, resorbing while locations (B) included posterior opacity, anterior opacity, nuclear, unspecified location or complete lens. The most frequently observed severity of cataracts was punctate (n=45) and predominantly localized anteriorly (n=37) or posteriorly (n=28). Only a few eyes had complete (n=2) or resorbing (n=1) cataracts. Location and size of cataracts were documented using semiquantitative preclinical ocular toxicology scoring (SPOTS) system. *Due to rounding of percentages the cumulative percentage for each figure may be \u0026gt;100%.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/98f32362d8fc9f7a0f6f9a9c.jpeg"},{"id":81504502,"identity":"5cfc2162-3dd0-4e9a-9397-068c745f1f74","added_by":"auto","created_at":"2025-04-28 05:09:41","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":378965,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBiometric parameters were analyzed across the different refractive error categories to gain further insights into the underlying causes of these refractive states.\u003c/strong\u003e ACD was significantly shallower in older myopes and emmetropes (\u003cem\u003eP\u003c/em\u003e=0.02 in both; \u003cstrong\u003eA\u003c/strong\u003e), likely due to age-related lens thickening in these groups (\u003cem\u003eP\u003c/em\u003e=0.002 and \u003cem\u003eP\u003c/em\u003e=0.008, respectively; \u003cstrong\u003eB\u003c/strong\u003e). By contrast, VCD (\u003cstrong\u003eC\u003c/strong\u003e) and AL (\u003cstrong\u003eD\u003c/strong\u003e) did not significantly change across all refractive error groups in older macaques, consistent with the expectation that globe growth has ceased at this stage. Myopes had significantly deeper ACD (3.77 ± 0.59) when compared to emmetropes (3.59 ± 0.26; \u003cem\u003eP\u003c/em\u003e=0.008) and hyperopes (3.66 ± 0.40; \u003cem\u003eP\u003c/em\u003e=0.012)(\u003cstrong\u003eE1\u003c/strong\u003e). There were no significant differences between LT between the refractive error groups (\u003cstrong\u003eE2\u003c/strong\u003e). Myopes also had significantly deeper VCD (12.59 ± 0.69) when compared to emmetropes (11.90 ± 0.68; \u003cem\u003eP\u003c/em\u003e=0.003) and hyperopes (11.91 ± 0.71; \u003cem\u003eP\u003c/em\u003e=0.001)(\u003cstrong\u003eE3\u003c/strong\u003e). Similarly, myopes had significantly longer AL (20.55 ± 0.83) when compared to emmetropes (19.77 ± 0.72; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) and hyperopes (19.77 ± 0.69; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001)(\u003cstrong\u003eE4\u003c/strong\u003e).\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/e6eda3e8d19c0bcfffeee353.jpeg"},{"id":97723851,"identity":"1b969a5c-e86e-4272-88fc-600008796b1a","added_by":"auto","created_at":"2025-12-08 16:08:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2680418,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/d3d6668b-bce4-4e70-882a-e317cdfc20a3.pdf"},{"id":81504507,"identity":"31172e71-4084-412e-bc07-2750295429d0","added_by":"auto","created_at":"2025-04-28 05:09:42","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":5664324,"visible":true,"origin":"","legend":"","description":"","filename":"SuppRefractiveErrorinGeriatricPrimates.3.5.25clean.docx","url":"https://assets-eu.researchsquare.com/files/rs-5010162/v1/a71558d8d276f2ffddc34640.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Spontaneous Refractive Error, Ocular Biometry and Age Related Lens Changes in a Population of Geriatric Rhesus Macaques","fulltext":[{"header":"Highlights","content":"\u003cp\u003eLow hyperopia is the most common refractive error in geriatric rhesus macaques (46%).\u003c/p\u003e\u003cp\u003eMyopia is the least common refractive error in geriatric rhesus macaques (10%).\u003c/p\u003e\u003cp\u003eNuclear sclerosis is common (96%) in geriatric rhesus macaques while advanced stage cataracts are rare (2%).\u003c/p\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eNon-human primates (NHPs) have proven to be useful models for studying the human visual system.\u003csup\u003e1\u003c/sup\u003e The genus \u003cem\u003eMacaca\u003c/em\u003e is the most widely utilized NHP model and shares \u0026gt;90% DNA sequence similarity to humans with comparable ocular size, structure and function.\u003csup\u003e2\u003c/sup\u003e Rhesus macaques (\u003cem\u003eMacaca mulatta\u003c/em\u003e) have a lifespan of ~27 years in captivity while aging at a rate nearly 3 times that of humans.\u003csup\u003e3,4\u003c/sup\u003e In general, this species reaches adulthood (i.e. sexual maturity) by 5 years and is considered geriatric after 19 years.\u003csup\u003e5\u003c/sup\u003e Rhesus macaques demonstrate age-related ocular changes similar to humans, including development of cataracts.\u003csup\u003e5,6\u003c/sup\u003e Analysis of spontaneous changes in the geriatric rhesus macaque population may provide better understanding of the natural progression of aging in the human visual system.\u003c/p\u003e\n\u003cp\u003eRhesus macaques raised in research facilities are often the subjects of translational investigations. Due to their similarities with humans, this species has proven to be invaluable for understanding refractive development and ocular changes observed in humans. However, to appreciate the full implication of the findings from studies in rhesus macaques a complete longitudinal observation (birth to geriatric) is necessary.\u0026nbsp;To date, there have been few studies reported in the literature on refractive error in the geriatric rhesus macaque population. (\u003cstrong\u003eTable 1\u003c/strong\u003e). Thus, it is important to establish refractive error and ocular biometry characteristics across the lifespan of this species, particularly geriatric rhesus macaques.\u003c/p\u003e\n\u003cp\u003eMean refractive error distribution changes with age.\u003csup\u003e7,8\u003c/sup\u003e Previous investigations have determined refractive status and anterior segment biometrics in rhesus monkey populations from birth to adulthood.\u003csup\u003e9-11\u003c/sup\u003e Longitudinal studies in rhesus macaques from infancy to adulthood have reported measures of ocular biometry, including corneal curvature, endothelial cell density, axial length (AL), anterior and vitreous chamber depth (ACD and VCD, respectively) and lens thickness (LT).\u003csup\u003e12-19\u003c/sup\u003e The incidence of cataract in rhesus macaques has also been investigated.\u003csup\u003e6\u003c/sup\u003e Uno and colleagues reported that 20% of postmortem rhesus macaque eyes (n=175) had cataract at 20 – 22 years of age with significant increases after 26 years of age; although standardized grading was not performed.\u003csup\u003e6\u003c/sup\u003e By contrast, a lack of lens haze, cloudiness or age-related cataract was documented by Denlinger and coauthors in adult rhesus macaques,\u003csup\u003e20\u003c/sup\u003e with only one primate being affected by a rosette shaped cataract of suspected traumatic etiology.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite detailed categorization of visual and ocular characteristics in young and adult\u0026nbsp;rhesus macaques, there remains limited reports among the geriatric population in this species. The California National Primate Research Center (CNPRC) maintains a population of rhesus macaques ≥19 years of age so that aging studies can be conducted. Thus, a dataset comprised of geriatric refractive and ocular characteristics in rhesus macaques at CNPRC will provide reliable reference for future investigations involving anterior segment anatomy and physiology and provide completeness to existing datasets on the natural progression of changes. Thhe purpose of this investigation was to determine refractive error, ocular biometry and age-related lens changes in the eyes of geriatric (≥19 years of age) rhesus macaques using a cross-sectional study design.\u0026nbsp;\u003c/p\u003e"},{"header":"2. Method","content":"\u003cp\u003e2.1. \u003cstrong\u003eSubjects\u003c/strong\u003e: \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll the animals in this investigation were rhesus macaques (\u003cem\u003eMacaca mulatta\u003c/em\u003e) born and maintained at the CNPRC. The CNPRC is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. Guidelines of the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research were followed. All aspects of this study were in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Ophthalmic examinations were performed according to a protocol approved by the University of California Davis Institutional Animal Care and Use Committee. Phenotypic data was collected from rhesus macaques previously evaluated for drusenoid lesions.\u003csup\u003e21\u003c/sup\u003e Some of the macaques in the present study were included in previous studies by Lin and coauthors\u003csup\u003e5\u003c/sup\u003e (n=67) and Casanova and colleagues (n=52).\u003csup\u003e19\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe indoor animals experienced a 12:12 light-dark cycle, with light levels in the facility varying from 70 to 930 lux depending on the area. The free-range animals were housed in large outdoor enclosures with shaded and unshaded areas and were exposed to light levels as high as 10,000 lux on a clear, sunny day. All animals were transferred to the procedure room for evaluation, where light levels ranged from 700 to 1670 lux. The animals were classified as “Mostly indoor” or “Mostly outdoor” if they spent more than 50% of their lifespan in either environment before their refractive error was measured. In addition, the same classification was recorded for the first 6 years of life to capture the initial phase of eye growth.\u003csup\u003e11\u003c/sup\u003eAll measurements were obtained within a 6-hour period (8 a.m. to 2 p.m.), during which diurnal variations are expected to be minimal and consistent across animals. Consequently, no evaluation of diurnal variation in ocular parameters was conducted.\u003c/p\u003e\n\u003cp\u003eComprehensive ophthalmic examination was performed on sedated animals in the supine position under pharmacologic mydriasis and cycloplegia. Sedation was achieved by intramuscular injection of ketamine hydrochloride (5–30 mg/kg), dexmedetomidine (7.5–15 µg/kg) and/or midazolam (0.10 mg/kg). Topical tropicamide 1% (Akorn Inc., Lake Forest, IL, USA), phenylephrine 2.5% (Paragon BioTeck Inc., Portland, OR, USA) and cyclopentolate 2% (Alcon Laboratories Inc., Fort Worth, TX, USA) were instilled for mydriasis and cycloplegia. Animals were monitored by a trained ophthalmic technician and veterinarian throughout the experiment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.2 \u003cstrong\u003eRefractive error\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eObjective streak retinoscopy was performed by veterinarians with training in ophthalmology using a handheld retinoscope (Welch-Allyn Inc., New York, NY, USA) to determine the refractive status of each eye under cycloplegic conditions. The power and axis of major and minor meridians were measured. Spherical equivalent refractive error was calculated; spherical equivalent refractive error = spherical power (diopters, D) + (cylinder power [D] / 2). Eyes were categorized based on their refractive error into groups defined by the American Optometric Association.\u003csup\u003e22,23\u003c/sup\u003eEyes with a refractive error ranging -0.50 to +0.50 D were classified as emmetropic. Those with values between +0.75 D to +2.00 D, +2.25 D to +5.00 D, and greater than +5.00 D were categorized as low, moderate, and high hyperopia, respectively. Eyes with values between -0.75 D to -2.75 D, -3.00 D to -6.00 D, and those exceeding -6.00 D were grouped as low, moderate, and high myopia respectively. Any animal with a refractive discrepancy of 1.00 D or more between their eyes was identified as having anisometropia.\u003c/p\u003e\n\u003cp\u003e2.3 \u003cstrong\u003eOcular biometry\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Anterior segment tomography (Pentacam High-Resolution Tomographer, Oculus, Wetzlar, Germany) was performed to measure corneal curvature and anterior chamber (AC) properties, including ACV and ACD. Corneal astigmatism was calculated from corneal curvature measurements. Against-the-rule astigmatism was defined when the cornea was steeper along the horizontal meridian than the vertical one.\u003c/p\u003e\n\u003cp\u003eA-scan ultrasound biometry (Sonomed Pacscan Plus, Escalon, Wayne, PA, USA) was performed to measure ACD (corneal endothelium to anterior capsule of crystalline lens), crystalline LT (anterior capsule to posterior capsule of crystalline lens), VCD (posterior capsule of crystalline lens to inner limiting membrane of retina) and AL (corneal epithelium to inner limiting membrane of retina) as previously described.\u003csup\u003e4\u003c/sup\u003e Specifically, a 10 MHz A-scan probe was perpendicularly placed over the central cornea with a coupling gel (Goniosoft, OcuSoft Inc., Richmond, TX, USA) following topical anesthesia with proparacaine (Bausch \u0026amp; Lomb, Tampa, FL, USA). Five A-scan recordings were obtained on the manual freeze mode when all the required echoes with sufficient height were present and averaged for each eye.\u003c/p\u003e\n\u003cp\u003e2.4 \u003cstrong\u003eOphthalmic examination, including crystalline lens grading:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll macaques underwent a comprehensive ophthalmic examination, including slit-lamp biomicroscopy, indirect ophthalmoscopy (Heine Optotechnik, Gilching, Germany) with a set of condensing lenses of different diopters and intraocular pressure measurement using rebound tonometry (TonoVet; Icare, Vantaa, Finland). Subjects with substantial posterior segment pathology were excluded from this study. Handheld slit lamp biomicroscopy was performed (SL-17, Kowa Optics, CA, USA) by a physician ophthalmologist and a veterinarian with expertise in ophthalmology. Crystalline lens changes including type, location and size of cataracts were documented using the semiquantitative preclinical ocular toxicology scoring (SPOTS) system;\u003csup\u003e24\u003c/sup\u003e lenticular sclerosis was graded (nuclear sclerosis grade, NS-grade) using a clinically accepted (0 – 4) grading scale (\u003cstrong\u003eSupplementary Figure S1\u003c/strong\u003e), lens opacities classification system II (LOCS II).\u003csup\u003e25\u003c/sup\u003e In addition, anterior segment tomography was performed using the Pentacam High-Resolution Tomographer (Oculus, Wetzlar, Germany) to measure the nuclear sclerosis density (Pentacam Nucleus Staging, NS-Pentacam) using a 0–5 grading scale (\u003cstrong\u003eSupplementary Figure S2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e2.5 \u003cstrong\u003eStatistical analysis\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eParametric data was presented as mean ± SD and nonparametric data as median and interquartile range (IQR). To calculate agreement between ACD measures with Pentacam vs. A-scan ultrasound and between, NS-grade vs. NS-Pentacam, a concordance correlation coefficient (CCC) and bias were calculated using values obtained from the same eye. For the CCC, the results were interpreted as previously described, with values of greater than +0.75 indicating good agreement, values between +0.40 and +0.75 indicating moderate agreement, values of less than +0.40 indicating poor agreement and negative values of the same magnitudes, indicating disagreement.\u003csup\u003e19,26,27\u003c/sup\u003e Normality was determined by the Shapiro-Wilk test. For normally distributed data, paired t-tests were used (ACD measures with Pentacam versus A-scan ultrasound values) while for comparisons with non-normal data (NS-Grade versus\u0026nbsp;NS-Pentacam), Wilcoxon signed-rank test was used. Bland-Altman linear regression was used to evaluated agreement between anterior chamber depth measurements with Pentacam (ACD Pentacam) and A-scan ultrasound (ACD A-scan) and simple lienear regression was used to investigate associations with the different parameters.\u0026nbsp;Each rhesus macaque was treated as a random effect and all other variables were considered fixed effects. A Chi-square test was used to evaluate whether the indoor/outdoor environment across the entire lifespan influenced refractive error type (emmetropia, myopia, hyperopia). A \u003cem\u003eP\u003c/em\u003e value of \u0026lt;0.05 was considered statistically significant; GraphPad Prism v9 (GraphPad Software Inc., La Jolla, CA, USA) was used for all analyses. Generalized Estimating Equations (GEE) were used to account for inter-eye correlations when appropriate using R software.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e3.1 \u003cstrong\u003eAnimals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth eyes of 182 geriatric rhesus macaques from the CNPRC were evaluated with a mean age of 22.2±2.5 (19.1 – 30.5) years. Geriatric status was defined as\u0026nbsp;\u0026nbsp;19 years of age (human equivalence of approximately\u0026nbsp;\u0026nbsp;57 years),\u003csup\u003e4\u003c/sup\u003e with human age equivalence estimated at a 1:3 ratio.\u003csup\u003e28,29\u003c/sup\u003e Consistent with the demographics of the CNPRC breeding colony, 140 females and 42 males were included.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.2. \u003cstrong\u003eCycloplegic streak retinoscopy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eObjective cycloplegic streak retinoscopy was used to determine refractive error in 187 eyes of 95 rhesus macaques. Females were overrepresented in the population evaluated (28 males vs 67 females), reflecting the colony proportions.\u0026nbsp;The mean refractive error spherical equivalence was +0.7±1.7 D. Astigmatism was detected in 7 of the 187 eyes evaluated (3.7%). Of these, two eyes exhibited 1.50D of astigmatism, while the remaining five eyes showed ≤0.50 D. In 3 eyes the presence of advanced cataracts prevented streak retinoscopy (see \u003cstrong\u003eSupplementary Figure S3\u003c/strong\u003e). Most geriatric rhesus macaque eyes were hyperopic (n=102, 55%) with emmetropic eyes also commonly observed (n=68, 36%); myopes were least common (n=17, 10%) (\u003cstrong\u003eFigure 1A, Table 2\u003c/strong\u003e). Both sexes were included in all the refractive error groups (\u003cstrong\u003eFigure 1B\u003c/strong\u003e) and the refractive error was not significantly different in older macaques (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.81, \u003cstrong\u003eFigure 1C\u003c/strong\u003e). Anisometropia was observed in 13 rhesus macaques (14%) with nine (69%) qualifying as amblyogenic anisometropia (\u0026gt; 1.00 D hyperopia or \u0026gt; 3.00 D myopia).\u003csup\u003e30\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf the 95 rhesus macaques that underwent streak retinoscopy, only 3 (3.16%) were housed indoors before the age of 6. Of these, 2 had hyperopia and 1 had myopia. Due to the small sample size, statistical analysis could not be performed for this group. However, when comparing the environmental conditions over the entire lifespan of the animals, no significant associations between the indoor/outdoor environment and refractive error were found (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.6929).\u003c/p\u003e\n\u003cp\u003e3.3. \u003cstrong\u003eCorneal curvature and AC properties evaluation with Pentacam High-Resolution Tomographer and A-scan ultrasound biometry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;A Pentacam High-Resolution Tomographer was used to measure corneal curvature and AC properties in 158 eyes of 91 rhesus macaques (75 females and 16 males). Corneal curvature was 52.6 ± 2.6 D (range: 43.0–61.8 D) and against-the-rule (ATR) corneal astigmatism was 1.6 ± 1.3 D x 099 ± 47.3 (range: 0–7.4 D); ACV and ACD were 136 ± 17 mm\u003csup\u003e3\u003c/sup\u003e (range: 102–180 mm\u003csup\u003e3\u003c/sup\u003e) and 3.34 ± 0.3 mm (range: 2.5–4.0 mm), respectively. Ocular biometry measurements were also assessed via A-scan ultrasound biometry in 338 eyes of 171 rhesus macaques (134 females and 37 males). AL was 20.2 ± 1.5 mm (range: 17.5–28.7 mm), ACD was 3.7 ± 0.4 mm (range: 2.2–5.4 mm), LT was 4.1 ± 0.4 mm (range: 2.5–6.5 mm) and VCD was 12.2 ± 1.0 mm (range: 9.3–17.7 mm). \u003cstrong\u003eTable 2\u003c/strong\u003e presents Pentacam keratometry values and A-scan measurements of anterior and posterior ocular segments across refractive error categories in geriatric rhesus macaques.\u003c/p\u003e\n\u003cp\u003e3.3.1 \u003cstrong\u003eDifferences in ACD measured via Pentacam tomography versus A-scan ultrasound\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDifferences in ACD measured via tomography (ACD Pentacam) versus A-scan ultrasound (ACD A-scan) are represented in \u003cstrong\u003eFigure 2\u003c/strong\u003e. Bias of ACD Pentacam versus ACD A-scan was equal at -0.3 and a significantly negative slope was identified indicating that Pentacam consistently underestimates the ACD (\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001). The CCC of 0.2 demonstrated poor agreement between the two techniques and a Wilcoxon test demonstrated a statistically significant difference in ACD between the two measurements (Pentacam = 3.4±0.3 mm; A-scan = 3.7±0.4 mm, \u003cem\u003eP\u003c/em\u003e \u0026lt;0.0001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.4 \u003cstrong\u003eSlit lamp biomicroscopy findings in the lens\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWith slit lamp biomicroscopy, 191 of 195 (98%) eyes of 99 macaques had nuclear sclerosis. Median NS-grade was 1 (1–2) and 47 eyes (24%) had a grade \u0026gt;2 (\u003cstrong\u003eFigure 3A\u003c/strong\u003e). \u0026nbsp;Four eyes had no nuclear sclerosis (grade 0), two eyes had a complete cataract, and one eye had a resorbing cataract \u003cstrong\u003e(Figure 4A)\u003c/strong\u003e. Punctate cataracts were most frequently observed (45 of 198 eyes, 23%) followed by incipient and incomplete cataracts (22 and 12 of 198 eyes, 11% vs. 6%). Cataracts were most frequently located in the anterior and posterior cortex (37 and 28 of 198 eyes, 19% vs. 14%) \u003cstrong\u003e(Figure 4B).\u003c/strong\u003e Median NS-Pentacam, as calculated by anterior segment tomography via the Pentacam in 136 eyes of 75 primates was 0 with an interquartile range of 0 to 0, with only 18 eyes having score \u0026gt;0 (13%). Nuclear sclerosis grade vs. NS-Pentacam were compared in \u003cstrong\u003eFigure 3A-B\u003c/strong\u003e. Bias of NS-grade versus NS-Pentacam was identified at 1.4 with a significant negative slope (\u003cem\u003eP\u003c/em\u003e=0.3) and poor correlation (CCC=0.2); a Wilcoxon test confirmed statistically significant differences between the two measurement types (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001) suggesting that the Pentacam Nucleus Staging significantly underestimates the degree of nuclear sclerosis when compared to the gold standard slit lamp grading of nuclear sclerosis. As expected, a significant increase in NS-Grade and NS-Pentacam scores with age (19.1–30.5 years) was observed using simple linear regression (\u003cem\u003eP\u003c/em\u003e=0.0004 and \u003cem\u003eP\u003c/em\u003e=2.3E-11, respectively).\u003c/p\u003e\n\u003cp\u003e3.5 \u003cstrong\u003eRefractive status and ocular non measurements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBiometric parameters were analyzed across the different refractive error categories to gain further insights into the underlying causes of these refractive states. We observed that the ACD was significantly shallower in older myopes and emmetropes (\u003cem\u003eP\u003c/em\u003e=0.02 in both;\u003cstrong\u003e\u0026nbsp;Figure 5A\u003c/strong\u003e), likely due to age-related lens thickening in these groups (\u003cem\u003eP\u003c/em\u003e=0.002 and \u003cem\u003eP\u003c/em\u003e=0.008, respectively;\u003cstrong\u003e\u0026nbsp;Figure 5B\u003c/strong\u003e). By contrast, VCD (\u003cstrong\u003eFigure 5C\u003c/strong\u003e) and AL (\u003cstrong\u003eFigure 5D\u003c/strong\u003e) did not significantly change across all refractive error groups in older macaques, consistent with the expectation that globe growth has ceased at this stage. Myopes had significantly deeper ACD (3.77±0.59) when compared to emmetropes (3.59±0.26; \u003cem\u003eP\u003c/em\u003e=0.008) and hyperopes (3.66±0.40; \u003cem\u003eP\u003c/em\u003e=0.012, \u003cstrong\u003e\u0026nbsp;Figure 5E\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e). There were no significant differences between LT between the refractive error groups (\u003cstrong\u003eFigure 5E\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e). Myopes also had significantly deeper VCD (12.59±0.69) when compared to emmetropes (11.90±0.68; \u003cem\u003eP\u003c/em\u003e=0.003) and hyperopes (11.91±0.71, \u003cem\u003eP\u003c/em\u003e=0.001; \u003cstrong\u003eSuppl. Figure 5E\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e). Similarly, myopes had significantly longer AL (20.55±0.83) when compared to emmetropes (19.77±0.72; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) and hyperopes (19.77±0.69, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001; \u003cstrong\u003e\u0026nbsp;Figure 5E\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e).\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eHerein, we report refractive error, ocular biometry characteristics and age-related lens changes in a large geriatric rhesus macaque population at the CNPRC. While refractive error has been previously reported in immature and adult rhesus macaques\u003csup\u003e31,32\u003c/sup\u003e,\u0026nbsp;our study measured refractive error and lens changes in a large population of rhesus macaques ≥19 years of age.\u0026nbsp;We determined that low hyperopia and emmetropia were the most common refractive states in this geriatric population consistent with previously shown hyperopic emmetropization in adolescent macaques with an average refractive value of +2.00 D.\u003csup\u003e33\u003c/sup\u003e In the present study, myopia was less common (n=17, 10%) in geriatric rhesus macaques with high myopia being the least common refractive error (n=1, 1%). Indeed, Tzu-Ni Sin and colleagues described this non-human primate model of myopic foveoschisis amongst a cohort of 40 myopic rhesus macaques with AL \u0026gt;21 mm (age 7.3–29.0 years old) at the CNPRC.\u003csup\u003e34\u003c/sup\u003e We note that cycloplegic retinoscopy may overestimate the degree of hyperopia in this population versus psychophysical methods.\u003csup\u003e35\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNevertheless, the predominance of low refractive error is expected in rhesus macaques given their lifestyle. Limited near activity and outdoor living likely reduce the stimulus for myopia progression and subsequently also reduces the risk of myopia-related ocular health complications, including retinal detachment.\u003csup\u003e36-39\u003c/sup\u003e While there is no direct evidence linking indoor housing to refractive errors in rhesus macaques, existing studies suggest that environmental factors, particularly lighting conditions, may influence refractive error development.\u003csup\u003e40\u003c/sup\u003e Exposure to natural outdoor light has been shown to reduce the risk of myopia in rhesus macaques, with those housed under dim light conditions more likely to develop refractive errors.\u003csup\u003e41,42\u003c/sup\u003e Therefore, in our study, the low number of animals housed indoor in the first six years of life (3.16%) likely contributed to the generally low incidence of refractive errors observed in our colony. Given the low prevalence of myopia in rhesus macaques, further understanding of the mechanisms that lead to this may provide valuable insights into the underlying factors causing the progression of nearsightedness in human patients. Further studies involving a broader sample size and varying housing conditions will be crucial in understanding how early environmental factors, including light exposure, affect refractive error development in rhesus macaques.\u003c/p\u003e\n\u003cp\u003eIn the present study, anisometropia (≥1.00 D) was present in 14% of the geriatric rhesus macaques that were refracted. The prevalence of anisometropia in the human population varies widely depending on inclusion criteria, but can generally be estimated at ~19%.\u003csup\u003e43\u003c/sup\u003e In the current study, a notable proportion of rhesus macaques had a degree of anisometropia that if present in early life could have put them at potential risk for amblyopia. However, the purview of this study was limited, and we were unable to determine if this amblyogenic anisometropia was present early in life among our population.The best estimate of amblyopia among humans is 2% with anisometropic and strabismic amblyopia accounting for 90% of all amblyopic cases.\u003csup\u003e30,44\u003c/sup\u003e Interestingly, no rhesus macaques included in this investigation demonstrated frank signs of large angle strabismus during clinical examination, whereas strabismus in the human population is estimated to be between 2–5%.\u003csup\u003e45\u003c/sup\u003e Possibly due to presence of darker scleral pigmentation in rhesus macaques creates more challenges in diagnosing strabismus in this species and anisometropia may be the more common risk factor for amblyopia in the rhesus macaque population. A future survey of spontaneous anisometropia and possible amblyopia among normal young rhesus macaques will be important for understanding the mechanism of disease in humans. In addition, the seemingly low prevalence of strabismus in this population warrants further investigation. Furthermore, it will be important to assess amblyopia, with a particular focus on evaluating the role of high bilateral isometropia in the development of amblyopia in this animal model. The quality of life in geriatric primates with amblyopia may further decrease as they develop presbyopia, leading to discomfort and visual impairment. Unfortunately, presbyopia was not evaluated in current study, but it would be an important future investigation topic in geriatric rhesus macaques.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Corneal tomography confirmed that rhesus macaques have significantly steeper mean corneal curvature (52.6 ± 2.6 D) versus humans (43.8 ± 1.4 D).\u003csup\u003e46\u003c/sup\u003e ATR corneal astigmatism is known to increase with age in humans.\u003csup\u003e47\u003c/sup\u003e Our study confirmed an elevated incidence of ATR corneal astigmatism (1.6 ± 1.3 D) in this geriatric rhesus macaque population. Subjects with corneal astigmatism \u0026gt;2.00 D was approximately 30% and \u0026gt;3.00 D was approximately 15%. Conversely, the low presence of irregular astigmatism (despite steep mean corneal curvature) and minimal corneal pathological findings during anterior segment evaluation is suggestive of a low frequency of corneal dystrophy, including keratoconus, in this population. Future studies should utilize corneal topography to better understand the incidence of anterior and posterior corneal irregularity in this species to confirm its potential as a model for elucidating the mechanisms associated with corneal dystrophies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnterior and posterior biometry measurements in geriatric rhesus macaques are similar to those of geriatric humans.\u003csup\u003e48,49\u003c/sup\u003e As previously reported by our group, in our study ACD (3.7 ± 0.4 mm versus 2.5, range: 2.5 – 2.5 mm\u003csup\u003e48\u003c/sup\u003e, respectively) was greater while LT (4.1 ± 0.4 mm versus 4.5, range: 4.4 – 4.5 mm,\u003csup\u003e48\u003c/sup\u003e respectively) and VCD (12.2 ± 1.0 mm versus 15.6, range: 15.5 – 15.6,\u003csup\u003e48\u003c/sup\u003e respectively) was lower in geriatric rhesus macaques compared to humans.\u003csup\u003e48,49\u003c/sup\u003e Relative to AL, the ratio of ACD:LT:VCD is ~1:1:3 in geriatric rhesus macaques and ~1:2:6 in humans 60–64 years of age.\u003csup\u003e48,50\u003c/sup\u003e Our study also confirmed poor agreement between ACD measurements obtained with two different methods, A-scan ultrasound and the Pentacam High-Resolution Tomographer. Future studies utilizing the ACD measurement should consider the variability of this measure between instruments during study design. In addition, an equivalent validation process should be performed for the corneal curvature and AC parameters obtained with the Pentacam.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough previous studies, including those from our group and others, have reported ocular biometric measurements in rhesus macaques, this study is the first to categorize these parameters by refractive error.\u003csup\u003e5,33\u003c/sup\u003e This approach offers a more comprehensive understanding of the relationship between biometric alterations and refractive changes, thereby advancing the characterization of aging in rhesus macaques. In our rhesus macaque population, we confirmed that myopic individuals exhibit significantly longer ACD, VCD and AL than emmetropes and hyperopes, consistent with an axial component to their refractive error. In all refractive error groups, LT was higher in older individuals, as it has been described to occur with age in this species.\u003csup\u003e5,33\u003c/sup\u003e However, we did not observe statistically significant differences in biometric parameters between hyperopic and emmetropic individuals. Based on these findings, we hypothesize that the nature of refractive error in this animal model is mixed—primarily axial in myopes, whereas hyperopia may be driven by refractive components, as their biometric measurements alone do not fully account for the observed refractive error. It is important to note that determining the precise nature of hyperopia was beyond the scope of this study, and future investigations should consider collecting additional data to further elucidate the underlying mechanisms.\u003c/p\u003e\n\u003cp\u003eIn this study, 24% of rhesus macaque eyes had nuclear sclerosis that would visually impair humans (≥ 3 grade); 2% of eyes assessed had grade 4 nuclear sclerosis. In our population, we observed a lower occurrence of cataract than anticipated (41%) with the most frequently observed type being punctate cataracts (23%) localized to the anterior (19%) and/or posterior cortex (14%). With aging, humans experience more frequent anterior and posterior lenticular changes.\u003csup\u003e51\u003c/sup\u003e The lower-than-expected occurrence of cataracts in our study subjects contrasts with the high prevalence observed in humans, where 73% of females and 78% of males aged 65 to 74 develop cataract.\u003csup\u003e52\u003c/sup\u003e We also determined that the extent of nuclear sclerosis formation (as determined by an ophthalmologist using a clinically accepted 0–4 grading scale) should be considered independently from the NS-Pentacam, a measure of crystalline lens density calculated by the Pentacam High-Resolution Tomographer on 0–5 scale. Previous studies have demonstrated the correlation between nuclear sclerosis progression and ultraviolet (UV) light exposure.\u003csup\u003e53\u003c/sup\u003e Thus, this relatively low incidence of advanced nuclear sclerosis in our population of rhesus macaques was unexpected, given that they spend a majority of their life outdoors. This suggests that other physiological properties, such as corneal and lens UV light absorption, may differ in rhesus macaques versus humans or that other unknown environmental factors may be involved. Although the study population was geriatric, total years of life expectancy are greater in humans versus rhesus macaques and could account for the difference in the extent of cataract present at this stage. Further investigation into the multifactorial properties associated with cataract formation is needed for elucidating the underlying mechanisms.\u003c/p\u003e\n\u003cp\u003eThis study is not without limitations, most of which are due to the extensive nature of the evaluation, which included multiple tests and parameters collected over several years by different evaluators. One limitation is that not all macaques could be evaluated with all techniques, resulting in some missing data. Another limitation is the use of the American Optometric Association refractive classifications, which are based on human standards and may not fully reflect the unique characteristics of rhesus macaques. Additionally, the AOA classifications are based on subjective refraction, whereas our study employed cycloplegic objective refraction methods for measuring refractive error in rhesus macaques. Therefore, we acknowledge that applying human-based classification criteria to NHP models, combined with the methodological differences in refraction techniques, may result in potential discrepancies.\u003c/p\u003e\n\u003cp\u003eGiven the high interest in studying cognition and neurodegeneration in geriatric rhesus macaques,\u003csup\u003e54\u003c/sup\u003e it is imperative that ocular health be assessed as many behavioral tasks require normal vision to complete. This study gives important insights into the incidence of lens changes and refractive error that could impact vision and quality of life in geriatric rhesus macaques. Furthermore, identification of these abnormalities may require provision of environmental enrichment or accommodations to preserve normal behavior and social order.\u003csup\u003e55,56\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eLow hyperopia is the most prevalent refractive error in the geriatric rhesus macaque population at the CNPRC. Further understanding of the mechanisms that lead to low prevalence of myopia, as observed in current study, may provide valuable insights into the underlying factors causing the progression of nearsightedness in human patients. Finally, the low occurrence of vision decreasing crystalline lens changes could be attributed to the difference in the lifespan between rhesus macaques and humans and create an opportunity for additional studies regarding cataract formation and treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAC, Anterior chamber\u003c/p\u003e\n\u003cp\u003eACD, Anterior chamber depth\u003c/p\u003e\n\u003cp\u003eACV, Anterior chamber volume\u003c/p\u003e\n\u003cp\u003eAL, Axial length\u003c/p\u003e\n\u003cp\u003eAstig, Astigmatism\u003c/p\u003e\n\u003cp\u003eATR, against-the-rule\u003c/p\u003e\n\u003cp\u003eCCC, Concordance correlation coefficient\u003c/p\u003e\n\u003cp\u003eCNPRC, California National Primate Research CenterD, Diopters\u003c/p\u003e\n\u003cp\u003eIQR, Interquartile range\u003c/p\u003e\n\u003cp\u003eK, Corneal meridian measured in Pentacam\u003c/p\u003e\n\u003cp\u003eLOCS II, Lens opacities classification system II\u003c/p\u003e\n\u003cp\u003eLT, Lens thickness\u003c/p\u003e\n\u003cp\u003eNHPs, Non-human primates\u003c/p\u003e\n\u003cp\u003eNS-Grade, Nuclear sclerosis grade\u003c/p\u003e\n\u003cp\u003eNS-Pentacam, Pentacam nucleus staging\u003c/p\u003e\n\u003cp\u003eSD, Standard deviation\u003c/p\u003e\n\u003cp\u003eSPOTS, Semiquantitative preclinical ocular toxicology scoring system\u003c/p\u003e\n\u003cp\u003eVCD, Vitreous chamber depth\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e*JMR and KR equally contributed equally to this work and are co-first authorsConceptualization \u0026ndash; SMT, GY, CJM, AM. Methodology \u0026ndash; SMT, GY, CJM, AM. Data curation \u0026ndash; JMR, KR, GY, CJM, AM, HM, ARS, SK, SP, IMC, LSM, AM, CC, LMG, JAR, SMT. Data analysis \u0026ndash; JMR, KR, ARG, SMT. Project supervision \u0026ndash; SMT. Writing \u0026ndash; JMR, KR, SMT. Review and editing - JMR, KR, ARG, GY, AM, IMC, SMT.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThis work was supported by the National Institutes of Health U24 EY029904 (AM, SMT), R01 EY033733 (SMT), P30 EY12576, K08 EY027463 (AM), and R01 EY032238 (GY). Additional support for this research came from the California National Primate Research Center Base Grant from the National Institutes of Health, Office of the Director, (NIH) P510D011107. GY was additionally supported by NIH UG1 EY032446, R01 EY034340, Foundation Fighting Blindness, Jack McGovern Coat\u0026rsquo;s Disease Foundation, Retina Society, and Lions Club International Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.The authors acknowledge the numerous members of the Comparative Ophthalmology and Vision Sciences Laboratory for their contributions throughout the study period, and extend gratitude to Michelle Ferneding and Monica Motta for their invaluable technical support during the research. Additionally, we appreciate the CNPRC staff for their outstanding care of the rhesus macaques, particularly Paul-Michael D. Sosa and Mary Roberts.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author, Sara M. Thomasy. The data are not publicly available.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOrban, G. A. Higher order visual processing in macaque extrastriate cortex. \u003cem\u003ePhysiol. 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Association between previous cataract surgery and cognition among middle-aged and older Chinese: the China health and retirement longitudinal study (CHARLS). \u003cem\u003eBMC Ophthalmol.\u003c/em\u003e \u003cb\u003e23\u003c/b\u003e (1), 243 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNitzan, I. et al. Visual impairment and cognitive performance: A nationwide study of 1.4 million adolescents. \u003cem\u003eOphthalmic Physiol. Opt.\u003c/em\u003e \u003cb\u003e44\u003c/b\u003e (5), 819\u0026ndash;828 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFernandes, A. G. et al. Age-Related Differences in Ocular Features of a Naturalistic Free-Ranging Population of Rhesus Macaques. \u003cem\u003eInvest. Ophthalmol. Vis. Sci.\u003c/em\u003e \u003cb\u003e64\u003c/b\u003e (7), 3 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa, Y., Lin, Q., Zhao, Q. \u0026amp; Jin, Z. B. Prevalence and Characteristics of Myopia in Adult Rhesus Macaques in Southwest China. \u003cem\u003eTransl Vis. Sci. Technol.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e (3), 21 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng, B. et al. Spontaneous fundus lesions in elderly monkeys: An ideal model for age-related macular degeneration and high myopia clinical research. \u003cem\u003eLife Sci.\u003c/em\u003e \u003cb\u003e282\u003c/b\u003e, 119811 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith, E. L. 3, Hung, L. F. \u0026amp; rd, The role of optical defocus in regulating refractive development in infant monkeys. \u003cem\u003eVis. Res.\u003c/em\u003e \u003cb\u003e39\u003c/b\u003e (8), 1415\u0026ndash;1435 (1999).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Summary of published studies on refractive error in rhesus macaques.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnimals (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eRefractive error\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eFernandes AG \u003cem\u003eet al\u003c/em\u003e. \u003cem\u003e2023\u003c/em\u003e\u003cem\u003e\u003csup\u003e57\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eCPRC (free ranging)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003eBirth to 29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eSpherical equivalent (mean\u0026plusmn;SD): 0.30\u0026plusmn;1.7 D\u003cbr\u003e\u0026nbsp;(emmetrope\u0026plusmn;low hyperopia/myopia)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eMa Y \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003e2023\u003csup\u003e58\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eAAALAC (unknown)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e8 to 21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eEmmetropes and hyperopes: 37.53%\u0026nbsp;\u003cbr\u003e\u0026nbsp;Myopes: 62.47%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eZeng B\u003cem\u003e\u0026nbsp;et al.\u0026nbsp;\u003c/em\u003e2021\u003csup\u003e59\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eGXBC or ZCBC (indoor)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e12.4 to 16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eEmmetropes and hyperopes: 98%\u0026nbsp;\u003cbr\u003e\u0026nbsp;Myopes: 2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eQiao-Grider Y \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003e2007\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eIndoor nursery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e0.07 to 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eSpherical equivalent (mean\u0026plusmn;SD): 4.17\u0026plusmn;1.52 D\u003cbr\u003e\u0026nbsp;(moderate and high hyperopia)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eFernandes A \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003e2003\u003csup\u003e33\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eYNPRC (variable)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e5 to 31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eSpherical equivalent (mean\u0026plusmn;SD): -0.19\u0026plusmn;3.35 D\u003cbr\u003e\u0026nbsp;(emmetrope\u0026plusmn;moderate hyperopia/myopia)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eSmith EL 3rd \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003e1999\u003csup\u003e60\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eIndoor nursery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e0.04 to 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eSpherical equivalent (mean): 4.4 D\u003cbr\u003e\u0026nbsp;(moderate hyperopia)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eBradley DV \u003cem\u003eet al.\u003c/em\u003e 1999\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eYNPRC (unknown)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003eBirth to 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eSpherical equivalent (mean\u0026plusmn;SD): 2\u0026plusmn;1.2 D\u003cbr\u003e\u0026nbsp;(low and moderate hyperopia)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003eYoung FA. 1964\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eWNPRC (unknown)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e0.7 to 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eSpherical equivalent (mean): 0.21 D\u003cbr\u003e\u0026nbsp;(emmetrope)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 3.09278%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.4021%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCurrent study 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCNPRC (indoor \u0026amp; outdoor)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.3093%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.433%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19 to 29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.268%;\"\u003e\n \u003cp\u003eEmmetropes: 36%\u003cbr\u003e\u0026nbsp;Hyperopes: 55%\u003cbr\u003e\u0026nbsp;Myopes: 10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviations: CPRC, Caribbean Primate Research Center; AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care; GXBC or ZCBC, Guangzhou Xiangguan Biotech Co., Ltd. or Zhaoqing Chuangyao Biotech Co., Ltd.; YNPRC, Yerkes National Primate Research Center; WNPRC, Washington National Primate Research Center; CNPRC, California National Primate Research Center. Data are presented as mean \u0026plusmn; SD (range) unless otherwise indicated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Low hyperopia and emmetropia were the most common refractive errors observed in this population of geriatric rhesus macaques.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eK (D)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSteep Axis (D)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAstig (D)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eACD (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eACV (mm\u003csup\u003e3\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLT (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVCD (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAL (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEmmetropia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e51.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e98.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e44.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e132.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e19.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLow hyperopia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e50.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e101.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e44.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e134.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate hyperopia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e50.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e89.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e134.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh hyperopia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e52.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e97.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e58.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e122.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e18.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLow myopia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e47.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e17.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e153.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e20.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e20.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate myopia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e112.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e20.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh myopia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e*2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 11px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e*16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e*22.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe table includes values of keratometry acquired via Pentacam and A-scan measurements of anterior and posterior ocular segment among refractive error categories in geriatric rhesus macaques.\u0026nbsp;The table included following ocular biometry values acquired with Pentacam: K \u0026ndash; average keratometry reading measured in diopters (D), Steep Axis \u0026ndash; the average location of the steepest meridian in diopters, Astig \u0026ndash; average corneal astigmatism measured in diopters (D), and values acquired with the A-scan: ACD - anterior chamber depth measured in millimeters (mm), ACV - anterior chamber volume (mm\u003csup\u003e3\u003c/sup\u003e), LT \u0026ndash; lens thickness (mm), VCD \u0026ndash; vitreous chamber depth measured in millimeters (mm), and AL \u0026ndash; axial length measured in millimeters (mm). Note \u0026ndash; Pentacam values were not available for moderately and highly myopic animals, labeled N/A. In the high myopia group there was only one eye available for evaluation with A-scan, because of this the mean value is equivalent to the measurement in the single eye (marked with asterisc *).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"refractive error, ocular biometry, nuclear sclerosis, geriatric, rhesus macaques, cataract","lastPublishedDoi":"10.21203/rs.3.rs-5010162/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5010162/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe purpose of this investigation was to determine refractive error, ocular biometry and age-related lens changes in a population of geriatric rhesus macaques (\u003cem\u003eMacaca mulatta\u003c/em\u003e) from the California National Primate Research Center (CNPRC).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eOphthalmic examination was performed in 182 rhesus macaques \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\ge\\:\\)\u003c/span\u003e\u003c/span\u003e 19 years of age using a cross-sectional study design, including streak retinoscopy, anterior segment tomography, A-scan ultrasound biometry and handheld slit lamp biomicroscopy.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMedian spherical equivalent refractive error was +\u0026thinsp;0.75 D with an interquartile range (IQR) of 0 to 1 D. Most eyes were hyperopic (n\u0026thinsp;=\u0026thinsp;102, 55%) or emmetropic (n\u0026thinsp;=\u0026thinsp;68, 36%); myopic eyes were least common (n\u0026thinsp;=\u0026thinsp;17, 10%). Anisometropia was present in 13 subjects (14%). Mean (\u0026plusmn;\u0026thinsp;SD) corneal curvature was 52.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 D (n\u0026thinsp;=\u0026thinsp;79). Mean (\u0026plusmn;\u0026thinsp;SD) axial globe length was 20.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 mm, anterior chamber depth was 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 mm, lens thickness was 4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 mm, and vitreous chamber depth was 12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 mm (n\u0026thinsp;=\u0026thinsp;86). Median (IQR) nuclear sclerosis grade (n\u0026thinsp;=\u0026thinsp;99, 96%) assessed with the lens opacities classification system II was 1 (1\u0026ndash;2).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLow hyperopia is the most common refractive error in the geriatric rhesus macaque population at CNPRC. This study provides reference values for an isolated geriatric rhesus macaque population and broadens our understanding of refractive error and lens opacities in geriatric rhesus macaques which may serve as a model for studying novel therapeutics for presbyopia and cataract.\u003c/p\u003e","manuscriptTitle":"Spontaneous Refractive Error, Ocular Biometry and Age Related Lens Changes in a Population of Geriatric Rhesus Macaques","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 05:09:35","doi":"10.21203/rs.3.rs-5010162/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-04T05:32:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-29T16:01:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153348498165807017739952893001832862884","date":"2025-04-23T13:22:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-21T10:49:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-07T13:07:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-17T20:24:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"57708f60-f724-473d-aebd-7f727889b130","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":47444590,"name":"Biological sciences/Zoology"},{"id":47444591,"name":"Health sciences/Anatomy"},{"id":47444592,"name":"Biological sciences/Developmental biology/Ageing"}],"tags":[],"updatedAt":"2025-12-08T16:01:42+00:00","versionOfRecord":{"articleIdentity":"rs-5010162","link":"https://doi.org/10.1038/s41598-025-30581-6","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-05 15:57:09","publishedOnDateReadable":"December 5th, 2025"},"versionCreatedAt":"2025-04-28 05:09:35","video":"","vorDoi":"10.1038/s41598-025-30581-6","vorDoiUrl":"https://doi.org/10.1038/s41598-025-30581-6","workflowStages":[]},"version":"v1","identity":"rs-5010162","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5010162","identity":"rs-5010162","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}