Effect of age and gender on the vertical cup-to-disc ratio in a normotensive population

, age and gender. However, age and VCDR are weakly correlated ( R = 0.24, p = 0.031), with a small increase in VCDR with age. Contribution: This study sheds light on the correlation between demographic factors and the optic disc or nerve head, which could have implications for glaucoma diagnosis, especially concerning the African population.


Introduction
Age and gender can have an impact on the ocular health of a normotensive population, particularly concerning certain eye diseases. 1,2,3Normotensive population refers to individuals who have normal intraocular pressure (IOP) or people whose eye pressure is not high, which is a key characteristic of glaucoma.The normal IOP is generally considered to be between 10 mmHg and 21 mmHg, with an average of 16 mmHg and a standard deviation (s.d.) of 2.5 mmHg. 4The balance between aqueous production and aqueous outflow plays a role in maintaining the IOP, and an increase in the quantity of aqueous produced or a resistance to its outflow may result in high IOP. 5 Although high IOP is a significant risk for developing glaucoma, some people with normal IOP can still be susceptible to normotensive glaucoma. 6Clinically, the vertical cup-to-disc ratio (VCDR) and horizontal cup-to-disc ratio (HCDR) are quantitative measurements that evaluate the optic nerve head and compare the size of the optic cup to the size of the disc in the eye.They play an important role in assessing and diagnosing glaucoma and other optic nerve disorders. 7The degree of pallor and excavation on the disc, along with other morphological changes, has proven Background: Evaluation of the optic disc is an important clinical practice among eyecare practitioners.Inter-observer variability makes it difficult to establish a clear conclusion regarding the estimation of the vertical cup-to-disc ratio (VCDR), especially in the context of glaucoma.
Aim: To determine the effect of age and gender on VCDR in a normotensive population and to estimate the mean VCDR of individuals of African descent.

Setting:
The University Eye Clinic, Imo State University, Owerri, Nigeria.

Methods:
A cross-sectional study was used to assess the VCDR morphology of participants.The mean age was 36.7 ± 12.98 years (range: 18 years -60 years).Descriptive statistics were used to summarise the data characteristics while linear regression was used to determine the correlation of age, gender and VCDR.Data were analysed using Statistical Package for the Social Sciences (SPSS) version 21.

Conclusion:
Our study did not provide statistically significant evidence to support a correlation between VCDR, age and gender.However, age and VCDR are weakly correlated (R = 0.24, p = 0.031), with a small increase in VCDR with age.

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to be the most reliable guide to evaluate glaucoma disease and optic neuropathies. 7,8,9,10This study involves VCDR in African eyes.
Several studies suggest that VCDR varies across different age groups and gender categories. 1,11,12,13One such study revealed that males had 2% and 3% larger optic discs compared to their female counterparts, and there was no association between refractive error and the optic disc measurements.
The participants of this study were 40 years or older, and the researchers concluded that there was no progressive agerelated decline in neural retinal rim area. 1 Analysis of the biological basis for the relationship between eye diseases and sex hormones showed that some types of hormones can modulate ocular blood flow and exert a protective effect on the optic nerve. 3Evidence from research found that the incidence of glaucoma and optic nerve diseases, such as optic neuritis, optic atrophy and Leber's hereditary optic neuropathy 2,14,15 may cause the VCDR to deviate from the normal range and mimic the physiological large cups or glaucoma; however, sometimes indicating the presence of an underlying neuropathy or disease.However, a Mendelian randomisation (MR) method may identify genetic variants and provide a large-scale data on genome association between optic neuropathies and disc enlargement, which is unaffected by potential confounding factors. 16aluating the optic disc is an important clinical practice among eyecare practitioners, particularly optometrists, ophthalmologists and neurologists.The assessment and estimation of VCDR may vary among practitioners because of differences in measurement techniques, imaging technologies and subjective interpretations.This variability makes it difficult to establish a clear conclusion regarding the effect of age and gender on VCDR, especially in the context of diagnosing glaucoma among African populations.Given the paucity of research in this area, this study aimed to provide data on the mean VCDR in a population with normal IOP and determine the influence of age and gender on the cup-todisc ratio (CDR) of individuals of black ethnicity.The findings will enable practitioners to understand the relationship between age, gender and CDR and improve ability to identify changes in the optic disc morphology, which will contribute towards the diagnostic modalities for evaluating and monitoring optic nerve-related diseases.

Study design
This study used a cross-sectional design to assess the VCDR of the eligible population, particularly individuals of African ethnicity.Participants were recruited through a random sampling method across different age groups and genders, ensuring a diverse representation of persons.The study was focussed on normotensive individuals (those with normal IOP), and therefore, findings may not be generalisable to people with existing ocular conditions such as glaucoma.

Study procedure
A standard Snellen acuity chart was used to measure the distance and near visual acuity of subjects, performed at 6 m and 40 cm, respectively.Participants' information was obtained through a clinical record sheet, while a comprehensive eye examination was conducted to assess the internal and external ocular structures.Standard Keeler direct ophthalmoscope was used to objectively examine the posterior segment of the eye to rule out any underlying pathology, such as media opacities, optic neuropathies, retinal diseases and congenital anomalies of the optic disc.All instruments were sterilised with cotton wool and methylated spirits, consisting of 95% hydrous ethanol.Prior to measuring the IOP, the corneal was numbed using one drop per eye of 0.5% Tetracaine HCl solution.The VCDR was estimated with the ophthalmoscope graticule.The graticule consists of an outer circle that coincides with the edge of the optic disc.The concentric circles are calculated to represent a cup/disc ratio of 0.5 for the middle circle and 0.25 for the inner circle.The notches between the outer and the middle circle represent a cup/disc ratio of 0.75.We examined the optic disc of the subjects in a dim-illuminated environment while their eyes were semi-dilated.Clinical findings were documented, including visual acuities for each eye and observations of the optic disc morphology.The size, shape, depth and symmetry of both eyes were assessed, noting any abnormalities such as exudates, nerve fibre layer defects and haemorrhages.Also, we calculated the VCDR by comparing the vertical diameter of the optic cup with the vertical disc diameter.

Data collection and setting
The data in this study were derived from the baseline eye examinations performed on 82 (of 102) individuals who volunteered for the study.The mean age was 36.

Results
Initially, 102 participants were selected for the study, but data from 82 eligible subjects were eventually included in this study.The males were more prevalent (approximate ratio 5:3) compared to females, with percentages of 59.8% and 40.2%, respectively.The global VCDR was 0.34 (95% confidence interval [CI]: 0.23-0.52,s.d.= 0.09).There were no complications caused by the procedures concerned.Table 1 shows the frequency of men and women who participated in the study (49 vs. 33).The mean VCDR for men and women were 0.35 ± 0.08 and 0.33 ± 0.10, respectively.In Table 2, the age group with the highest number of subjects was for the group 43 years -47 years, contributing a percentage of 20.7%.The men were more in number (49 vs. 33) and had a slightly larger average VCDR than the women, with a relative difference of only 0.02 or 2.0%.Overall, the VCDR mean was 0.34 ± 0.09.In Figure 1, the line chart shows the interaction between the VCDR for both genders across different age groups.Group 58 years -62 years had the largest VCDR for both men and women (0.49 vs. 0.55), while the least VCDR was found among the women (0.2).A wider range of VCDR was found in women compared to men (0.35 vs. 0.24), indicating a broader spread of values in the women.Figure 2 shows the distribution of age against VCDR. In

Discussion
We estimated the normative means and variations in the VCDR of a healthy population, consisting exclusively of African descent.Our findings indicate that age had a low positive correlation of 0.24 with VCDR (95% CI: R 2 = 0.057; p = 0.031).However, the coefficient of determination showed that only about 5.7% variability in the VCDR can be explained by age.This is similar to a study conducted by Garway-Heath et al., 11 who found that vertical optic cup diameter and optic disc area increased with age by approximately 0.1 between the ages of 30 years and 70 years.However, they noted that the neuro-retinal rim area declined at a rate between 0.28% and 0.39% per year.In the Rotterdam population-based study, where a total of 5114 white patients, aged 55 years or older, were examined, Ramrattan et al. 17 18 reported the mean VCDR as 0.32 ± 0.14, while we estimated the mean VCDR to be 0.34 ± 0.09 in an African population.
In multiple regression analysis, we noted no significant interaction between VCDR and variation in age and gender (all p > 0.05).This aligns with a large epidemiological study that investigated variations in the normal optic disc, based on race, age, gender and refractive error.Among the individuals who volunteered for this study, all of whom were 40 years and older, no progressive age-related decline was detected in the neural rim area and disc measurements.In addition, neither gender nor refractive error was significantly associated with the size and topography of the optic disc. 1 Ramrattan et al., in their study, reported that age was not a determinant of disc characteristics.They also found that refractive error was weakly related to disc area and neural rim area. 17Considering the influence of gender on the evaluation of the optic disc, our study found that the VCDR for men was slightly larger than that of women by 2%, which corresponds to a previous study that reported that male subjects had 2% to 3% larger optic disc compared with female subjects. 1Another research conducted in the Netherlands, which evaluated the determinants of optic disc characteristics in a general elderly population found that the optic disc was 3.2% larger in men than in women. 17Similarly, Quigley et al. 19 also concluded that women's eyes and discs were smaller than those of men, possibly explaining the smaller cup/disc ratio in women.
In contrast, some research suggests that age may have an effect on VCDR.A study by Kim et al., which investigated the association between optic-CDR and systemic factors in a healthy Korean population, found that the mean vertical VCDR increases with age regardless of gender. 20Another genome-wide association study also identified multiple genetic variants associated with VCDR.They stated that genetic risk score (GRS) was significantly associated with VCDR (p < 0.0001), including factors such as age, gender, central corneal thickness and IOP.In their study, they reported that the weighted GRS explained an additional 2.7% of the variation in VCDR. 21

Limitations
The limitations encountered during this research include low volunteer turn-out and difficulty with examining the VCDR of both eyes simultaneously.However, to our knowledge, we meticulously evaluated the VCDR variation in relation to age and gender, as well as estimated the mean VCDR, exclusively for a population of African descent, which should be considered in the evaluation of glaucoma and monitoring of progressive changes in the optic-disc morphology.

Conclusion
Our study did not find statistically significant evidence to support a correlation between age, gender and VCDR.We did find a weak but significant positive correlation between age and VCDR (R = 0.24, p = 0.031).Future studies should explore the complex interplay between the optic disc and other variables to gain a deeper understanding of their influence on glaucoma and optic nerve-related diseases.
Note: The group 58 years -62 years had the largest mean VCDR for both men (0.49) and women (0.55), while the smallest mean VCDR (0.2) was found in women (group 53 years -57 years).VCDR, vertical cup-to-disc ratio; CDR, cup-to-disc ratio.

FIGURE 1 :
FIGURE 1:A line chart showing the interaction between vertical cup-to-disc ratio for both genders across different age groups.

FIGURE 2 :
FIGURE 2:A scatter of the distribution of the age in years and vertical cup-todisc ratio (VCDR).Each dot represents an individual VCDR, and variability in VCDR was weakly associated with an increase in age.
7 ± 12.98 years (range: 18 years -60 years).Out of the 102 selected participants, 20 subjects were excluded, allowing only 33 females and 49 males (n = 82, 80.4% response rate).Study participants were excluded if: they had any ocular pathology or media opacities, age was < 18 years or > 60 years, IOP exceeded 22 mmHg at the time of recruitment and refractive error greater than ± 2 D. The study was conducted at the University Eye Clinic, Imo State University, Owerri, Nigeria.
age and gender were the co-variate independent factors.We adjusted for the confounding factor of age vis-a-vis gender when analysing their correlation with VCDR, respectively.Statistical significance was considered when p < 0.05.Results were presented in group tabulation and reported as mean ± s.d.
USA) and Statistical Package for the Social Sciences (SPSS) version 21.0 software (IBM Corp. Armonk, NY, USA) for analysis.Descriptive statistics were used to summarise the characteristics of data and group means.Simple and multiple regression models were used to determine the correlation between variables, with VCDR as the continuous dependent variable, while simple regression analysis, variability in VCDR showed a weak positive correlation of R = 0.24 with age (Y = 0.003 × Age + 0.246; R 2 = 0.057; p = 0.031).From the regression model, the coefficient of determination shows that only about 5.7% of the variability in the CDR can be explained by age.The low R 2 value shows that the model does not capture much of the variability in the data using only age as a predictor.Both the t-statistics(2.198)and p-value (0.031, α = 0.05) reinforce the idea that the coefficient for age might be significant in predicting changes in the VCDR of the sample population.
Therefore, there is insufficient evidence to confirm a statistically significant relationship among age, gender and CDR (all p-values > 0.05).

TABLE 2 :
Frequency distribution of age, gender and vertical cup-to-disc ratio of participants.

TABLE 1 :
Age, gender frequency and average vertical cup-to-disc ratio distribution of subjects.