Normative Profile of Retinal Nerve Fiber Layer Thickness and Lamina Cribrosa-Related Parameters in a Healthy Non-Glaucoma Cynomolgus Monkey Colony.

Purpose: The purpose of this study was to investigate the normal range of ophthalmic parameters and the correlations between systematic and ocular parameters and retinal nerve fiber layer (RNFL) thickness among a healthy non-glaucoma cynomolgus monkey colony. Methods: All included monkeys were given detailed ophthalmic examinations, including anterior and posterior segments. Furthermore, univariate and multivariate linear regression models were conducted to estimate the relationship between systemic and ophthalmic parameters and global RNFL thickness. Results: A total of 349 non-glaucoma monkeys (18.69 ± 2.88 years old) were collected. The global RNFL thickness was 94.61 ± 10.13 µm, and sex-specific differences existed in all sectors. The decreasing trend of RNFL is as follows: inferotemporal, superotemporal, inferonasal, superonasal, temporal, and nasal. For lamina cribrosa (LC)-related parameters, cup depth (P < 0.01), LC thickness (P = 0.014), and Bruch's membrane opening (BMO) - minimum rim width 2 (P = 0.002) were greater in the male group. However, LC depth (P = 0.02), anterior laminar insertion depth-1 (P = 0.009), and mean anterior laminar insertion depth (P = 0.029) of female monkeys were greater than those of male monkeys. In multivariate linear regression, only older age was significantly related to reduced global RNFL thickness (P < 0.001). Conclusions: Our findings suggest the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkeys and humans. Therefore, the impact of this difference on outcomes should be fully considered in laboratory animal studies. Our findings are also significant in terms of developing a normative optical coherence tomography (OCT) database in nonhuman primates (NHPs). Translational Relevance: We found that the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkey colonies and humans should be thoroughly taken into account in laboratory animal studies.

Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Parameters and Their Associated Factors in Cynomolgus Macaques.

Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.

Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Naked-Eye 3-Dimensional Vision Training for Myopia Control: A Randomized Clinical Trial.

Importance: Early onset of myopia increases the risk of high myopia, which can lead to irreversible retinal damage and even loss of central vision. Objective: To investigate the efficacy and safety of naked-eye 3-dimensional vision training (NVT) in preventing the progression of myopia in children. Design, Setting, and Participants: This randomized clinical trial was conducted in 3 hospitals from May 25, 2022, to February 24, 2023. Participants were children (aged 6-18 years) who had a diagnosis of myopia with a spherical equivalent refraction of -0.75 to -6.00 diopters (D). Intervention: Children in the intervention group received 20 minutes of NVT treatment every day, whereas children in the control group lived as usual without vision training. Main Outcome and Measure: The primary outcome was the change in axial length at 6 months. Spherical equivalent refraction (SER) was included as a secondary outcome. Results: Among 263 participants, 125 (47.5%) were male and 138 (52.5%) were female; the mean (SD) age was 10.3 (1.9) years (range, 6.1-15.6 years). A total of 227 patients (86.3%) completed the 6-month follow-up, including 102 in the intervention group and 125 in the control group. In the intervention group, the changes in axial length and SER at 6 months were 0.18 mm (95% CI, 0.16 to 0.20 mm) and -0.25 D (95% CI, -0.31 to -0.19 D), respectively. In the control group, the changes in axial length and SER at 6 months were 0.23 mm (95% CI, 0.21 to 0.25 mm) and -0.35 D (95% CI, -0.41 to -0.30 D), respectively. The differences in AL and SER between the 2 groups were significant (AL difference: -0.06 mm; 95% CI, -0.09 to -0.03; P < .001; SER difference: 0.10 D; 95% CI, 0.02 to 0.19; P = .02). No study-related adverse reactions were reported during follow-up. Conclusions and Relevance: NVT is a safe and promising means to control myopia progression in children with good adherence. Trial Registration: ClinicalTrials.gov Identifier: NCT05468775.

The associations of self-perception, movement competence, and clinical features of young school-aged children with glaucoma.

The purpose of the study was to determine the associations of self-perception, motor skills, and clinical features of young school-age children with glaucoma (CG). This is a cross-sectional observational study. Children from preschool to second grade, including CG (N = 19), children with amblyopia (CA, N = 28), and controls (N = 32), completed the Manual Dexterity and Aiming and Catching Scales of the Movement Assessment Battery for Children-2nd edition (MABC-2), including Manual Dexterity, Aiming and Catching, and Balance. CG, CA, and their parent completed the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children, respectively, assessing the child's cognitive competence, peer acceptance, physical competence, and maternal acceptance. The Kruskal-Wallis H test and Bonferroni post hoc test compared motor skills among groups. Spearman's correlation analysis evaluated the correlations between motor skills, self-perception, and clinical features. The CG reported lower peer acceptance than CA (P = 0.040), and the parents of CG reported lower cognitive competence than CG reported (P = 0.046). Compared with controls, CG had worse performance of Aiming and Catching, and Balance (P = 0.018 and P = 0.001), and CA had worse performance of Balance (P = 0.009). The motor skills were comparable between CG and CA. For CG, older age correlated with worse competence of Aiming and Catching (r = - 0.620, P = 0.005), better best-corrected visual acuity of better-seeing eye correlated with higher competence of Manual Dexterity and Balance (r = - 0.494, P = 0.032, and r = - 0.516, P = 0.024), and longer duration of glaucoma correlated with worse competence of Manual Dexterity (r = - 0.487, P = 0.034). CONCLUSION:  Glaucoma and amblyopia have significant negative impacts on children's daily motor skills. The acuity of a better-seeing eye is an important factor influencing motor movement. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR2100050415. WHAT IS KNOWN: • The state of mental health in early childhood influences the development of their future personality and physical development. The prognosis and management of glaucoma may seriously impair the mental health development of the affected children. However, the exploration of psychological aspects and motor movement of childhood glaucoma was limited. WHAT IS NEW: • Children with glaucoma have impaired motor skills and self-perception development, especially in terms of peer socialization.

Trends in prevalence rates of blindness among patients with diabetic retinopathy in high-income countries from 1990 to 2019: A joinpoint regression analysis.

AIMS: Diabetic retinopathy (DR) is the leading cause of blindness in patients with diabetes mellitus (DM). We investigated its trends in high-income countries to gain insights into preventing DR-related blindness in diabetes-epidemic areas. METHODS: For joinpoint regression analysis, we extracted data from the Global Burden of Disease 2019 study and analysed the prevalence trends of DR-related blindness according to DM type, patients' sex and age, region, and nation. RESULTS: Overall, the age-standardised prevalence rate (ASPR) of DR-related blindness has decreased. The prevalence rates of blindness decreased more sharply for Type 1 DM than for Type 2 DM. The ASPR was higher and the decreasing trend was less pronounced in women than in men. Southern Latin America had the highest ASPR, whereas Australasia had the lowest ASPR. Singapore experienced the greatest decline, whereas unfavourable trends were observed in the USA. CONCLUSIONS: Despite decrease in the overall ASPR of DR-related blindness during the study period, large improvement opportunities were identified. As DM prevalence increases and the population ages rapidly in high-income countries, novel effective screening, treatment, and prevention strategies are urgently needed to improve the visual outcomes of individuals with DM or at risk of DM.

Correlation between spherical equivalent and biometry parameters in adult Cynomolgus macaque.

PURPOSE: To characterize the distribution of refractive and ocular biometry parameters and analyze the effect factors of the refractive status in cynomolgus monkey colonies. METHODS: A Population-based cross-sectional study was conducted in adult cynomolgus macaque colonies. Animals were anesthetized with Zoletil 50. Intraocular pressure was measured using the Icare tonometer. Cycloplegic refraction (three drops of 1% tropicamide) and corneal radius of curvature (CRC) were measured using an autorefractor. The spherical equivalent (SE) was calculated. Biometric measurements, including the anterior chamber depth (ACD), lens thickness (LT), and axial length (AL), were obtained by A-scan ultrasonography. The AL-to-CR ratio (AL/CRC) was calculated. Central corneal thickness (CCT) and choroidal thickness (ChT) were measured using the Heidelberg Spectralis HRA OCT. Multiple regression analysis was performed to explore the association between refraction and ocular biometry. RESULTS: Among 263 cynomolgus monkeys (aged 5-26 years), which consisted of 520 eyes, 29.42% had hyperopia, 27.12% had emmetropia, 33.27% had mild-to-moderate myopia and 10.19% had high myopia. The mean SE was -1.27 ± 3.44 Diopters (D). The mean CRC, CCT, AL, and ChT was 5.70 ± 0.22 mm, 454.30 ± 32.40 µm, 18.76 ± 0.89 mm and 188.96 ± 38.19 µm, respectively. The LT was the thickest in the hyperopic eyes. CRC was the lowest, and CCT was the thickest in high myopic eyes. AL increased, while ChT decreased as SE decreased. For the SE variance, AL alone explained 40.5%; age, AL, and CRC together explained 57.5%. CONCLUSIONS: The refractive characteristics and biometry parameters of cynomolgus monkeys are highly comparable to those of humans. AL, CRC, and ChT showed the similar variation tendency in cynomolguses when compared to humans. Cynomolgus monkeys with naturally-occurring refractive errors may be a good animal model for refractive studies.

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

One-year Efficacy of the Defocus Incorporated Multiple Segment Lens in Chinese Myopic Children.

SIGNIFICANCE: These data demonstrate that defocus incorporated multiple segment (DIMS) lens reduces myopia progression in children during the first year of use. PURPOSE: This study aimed to investigate the efficacy of DIMS myopia control spectacle lens in Chinese myopic children aged 6 to 15 years. METHODS: This is a retrospective study of 1-year longitudinal data. A total of 180 Chinese myopic children were selected from patients at Zhongshan Ophthalmic Center, Sun Yat-sen University, from February 2018 to January 2021. One group consisted of 90 children aged 6 to 15 years, with spherical equivalent refraction -0.50 to -7.75 D (-3.82 ± 1.57 D) and fitted with the DIMS lens. The other group consisted of 90 children fitted with single-vision spectacle lenses and matched with the DIMS group for age, sex, refraction, and progression of myopia in the previous year. One-year myopia progression was measured retrospectively in two groups. Unpaired t test was used to compare the myopia progression between the DIMS group and the control group. Pearson correlation was used to explore the relationship between myopia progression, age, and baseline refraction. RESULTS: After 1 year of DIMS lens wear, myopia progression was significantly lower in the DIMS group (-0.51 ± 0.50 vs. -0.85 ± 0.51 D, P < .001). Myopia progression was positively correlated with age in both groups. The difference between the DIMS and control groups was more pronounced for children aged 10 to 15 years than for children aged 6 to 9 years. CONCLUSIONS: This study confirms that the DIMS lens reduces myopia progression during the first year of use. Efficacy seems to increase with age.

Comparisons of Using Cycloplegic Biometry Versus Non-cycloplegic Biometry in the Calculation of the Cycloplegic Refractive Lens Powers.

INTRODUCTION: This study investigated the difference between the calculation of cycloplegic crystalline lens power (LP) using non-cycloplegic and cycloplegic biometry data in children, and associated factors were explored. METHODS: A total of 821 children were enrolled and only right eye was analyzed. The corneal radii (CR), corneal power (CP), anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) before and after cycloplegia were obtained using IOLMaster 700. Anterior segment length (ASL) was defined as ACD plus LT. The cycloplegic LP was calculated with Bennett's formula. In addition, LP calculated with cycloplegic data was defined as cLP, otherwise it was defined as nLP. The ΔLP (defined as the value as cLP minus nLP) was compared among age, gender, and refractive states groups. Associated factors of ΔLP and |ΔLP| were explored by Pearson's correlation and multivariate linear regression. RESULTS: The mean age of the 821 subjects was 9.83 ± 2.97 years with a mean spherical equivalent refraction (SER) of - 1.06 ± 2.12 D. Overall, the ACD, LT, and ASL were significantly affected by cycloplegia agent (all p < 0.001; paired t test). Conversely, no statistically significant differences were documented in AL, CP, or AL/CR ratio before and after inducing cycloplegia (p = 0.917, p = 0.515, and p = 0.549, respectively). Significant difference was found between nLP and cLP (21.24 ± 1.58 D vs 21.43 ± 1.92 D, p = 0.001). The mean ΔLP was 0.11 ± 0.87 D (range from - 7.01 D to 7.08 D). Significant change in LP was found in low and medium groups, respectively (0.13 ± 0.81 D, p = 0.001; 0.11 ± 0.48 D, p = 0.043). In the multiple regression analysis, |ΔLP| was exclusively associated with ΔASL (ß = 0.172, [95% CI 0.112-0.300], p < 0.001). CONCLUSION: Our results indicated that using cycloplegic biometry could lead to an overestimation in LP for low and moderate myopia eyes. This finding is likely to facilitate the refractive development research in children. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05247099.