The goal of this observational study is to learn more about the relationship between the size and shape of the eye and the shape of the face in healthy young adults. In particular, the study focuses on whether specific eye measurements are linked to certain facial characteristics after growth and development have been completed.

The main question it aims to answer is:

Does the size and internal structure of the eye relate to the three-dimensional shape of the face in young adults aged 21 to 25, and are these relationships different in people who are nearsighted (myopic), farsighted (hyperopic), or have normal vision (emmetropic)?

Refractive errors such as nearsightedness and farsightedness are very common and are largely influenced by the length of the eye (axial length) and other internal eye measurements. During childhood and adolescence, it develops at the same time as the eye socket (orbit) and the bones of the face. However, most previous studies have examined either the eye or the bony orbit separately. Very few have combined detailed eye measurements with modern three-dimensional (3D) facial measurements in the same individuals.

This study will include 120 healthy young adults between 21 and 25 years of age, after facial growth is complete. Participants will be divided into three groups based on their refractive status: myopic (nearsighted), emmetropic (normal vision), and hyperopic (farsighted), with similar numbers of men and women in each group.

All participants will undergo a standard ophthalmologic examination. This will include measurement of visual acuity, refraction (to determine glasses prescription), and detailed eye biometry using a non-contact optical device (IOLMaster 700). The measurements will include axial length (eye length), corneal curvature, anterior chamber depth, lens thickness, and corneal diameter (white-to-white). These are routine, non-invasive measurements commonly used in clinical eye care.

In addition, participants will undergo non-invasive 3D facial imaging. A short video of the face will be recorded while a camera moves around the participant. Using photogrammetry software, this video will be converted into a precise 3D model of the face. From this model, specific facial landmarks will be identified, and distances and proportions of different facial regions (upper, middle, and lower thirds of the face; cheek width; jaw width; chin projection) will be measured. This method does not involve radiation and does not cause discomfort.

The researchers will then analyze whether there are statistical relationships between eye measurements and facial dimensions. They will also compare the three refractive groups to determine whether certain facial patterns are more common in myopic, emmetropic, or hyperopic individuals.

Participation is voluntary. All participants will sign informed consent before enrollment. The study has been approved by relevant ethics committees and will be conducted according to international ethical standards. All data will be anonymized and stored securely. No additional risks are expected beyond those associated with a routine eye examination.

The results of this study may improve understanding of how eye growth and facial development are related. In the long term, this could contribute to better knowledge of the anatomical background of refractive errors and support future interdisciplinary research in ophthalmology, orthodontics, and craniofacial medicine.

This study is designed as a cross-sectional observational investigation aiming to evaluate the relationship between ophthalmologic biometric parameters and three-dimensional craniofacial morphometric characteristics in healthy young adults aged 21 to 25 years, after completion of growth and development. A total of 120 participants are planned to be included. Participants will be divided into three groups according to refractive status: myopes, emmetropes, and hyperopes, with approximately equal numbers in each group and balanced representation by sex. To minimize the influence of population-related morphological variability, only individuals of the same ethnic background will be included.

Eligible participants will be healthy young adults with best-corrected visual acuity of at least 1.0 and normal findings of the anterior and posterior ocular segments. Refractive status will be determined using objective autorefractometry and confirmed by subjective refraction according to standard clinical guidelines. Individuals with a history of ocular or facial surgery, craniofacial anomalies, active or previous orthodontic therapy affecting maxillomandibular relationships, strabismus, amblyopia, ocular or facial trauma, or systemic diseases that may influence facial morphology or ocular biometric parameters will be excluded. To reduce the potential influence of general body proportions on morphometric measurements, only participants with a body mass index between 18.5 and 24.9 kg/m² will be included. All ophthalmologic examinations will be performed in the same healthcare institution according to a standardized protocol. All facial recordings and landmark identification procedures will be conducted by the same investigator to reduce inter-examiner variability and enhance reproducibility.

All procedures in the study are non-invasive. Ophthalmologic data will be collected using standard clinical methods, including measurement of best-corrected visual acuity, objective autorefractometry, and keratometry. Detailed ocular biometric parameters will be obtained using optical biometry with the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany). The recorded biometric variables will include axial length, corneal curvature radii, anterior chamber depth, lens thickness, horizontal corneal diameter (white-to-white), and calculated intraocular lens power. All measurements will be performed according to a standardized protocol within the same institution.

Three-dimensional facial morphology will be assessed using standardized video-based 3D imaging. A mobile device will be used to record a video sequence while the camera is moved continuously around the participant in a circular trajectory exceeding 180 degrees, enabling reconstruction of a three-dimensional facial surface model using digital photogrammetry without exposure to ionizing radiation. During recording, participants will be positioned in natural head position, with their gaze directed straight ahead and a neutral facial expression. Lighting conditions and camera distance will be standardized to ensure measurement reproducibility. The recorded video sequences will be processed to generate 3D facial models, which will then be calibrated and standardized prior to analysis. Further processing and morphometric analysis will be conducted using MeshLab software (Visual Computing Lab, ISTI-CNR, Italy).

On each 3D model, standardized anthropometric landmarks will be identified according to established guidelines used in orthodontic and craniofacial analysis. These landmarks will include trichion, glabella, nasion, subnasale, labrale superius, stomion, labrale inferius, supramentale, pogonion, menton, gnathion, right and left zygion, right and left gonion, and right and left tragion. Based on these landmarks, linear distances describing vertical, sagittal, transverse, and depth-related facial proportions will be calculated. Vertical measurements will include the upper, middle, and lower facial thirds (Tr-G, G-Sn, Sn-Gn), total facial height (N-Gn), and subdivisions of the lower facial third (Sn-Sto and Sto-Me). Lip dimensions will be assessed using Ls-Sto and Sto-Li distances. Sagittal proportions will be evaluated by measuring chin and labiomentale projection (Sm-Pg) and lower facial projection (Sn-Pg). Transverse dimensions will include bizygomatic width (ZyR-ZyL) and bigonial width (GoR-GoL). Lateral depth measurements will be determined by distances between tragion and subnasale (TrR-Sn, TrL-Sn) and between tragion and gnathion (TrR-Gn, TrL-Gn). All linear measurements will be calculated automatically within the 3D modeling environment to reduce measurement error associated with two-dimensional techniques.

In addition to ophthalmologic and facial morphometric variables, general anthropometric data including body height and body weight will be recorded, and body mass index will be calculated.

Sample size estimation was performed using G*Power software (version 3.1.9.7). For multiple linear regression analysis, assuming an effect size of R² = 0.10, statistical power of 80%, and significance level α = 0.05, the required sample size is 113 participants for four predictors and 122 participants for five predictors. With the planned sample size of 120 participants and five predictors, the expected power is 78%, which is considered acceptable. For comparisons among the three refractive groups using one-way analysis of variance with a balanced design (n = 40 per group), a total sample of 120 participants allows detection of a medium effect size (Cohen's f = 0.29) with 80% power at α = 0.05. If dimensionality reduction using principal component analysis reduces the number of predictors to approximately three components explaining a substantial proportion of variance, approximately 103 participants would be required to achieve 80% power, while a sample of 120 would provide an estimated power of approximately 87%.

Reliability of automatic anthropometric landmark recognition will be evaluated on a subsample comprising 10 to 15% of the total sample by repeated 3D processing and calculation of the intraclass correlation coefficient to assess reproducibility. Descriptive statistics will include mean and standard deviation for normally distributed variables, and median with interquartile range for non-normally distributed variables. Normality will be assessed using the Shapiro-Wilk test and homogeneity of variances using Levene's test. Bivariate associations between ocular biometric and facial morphometric variables will be analyzed using Pearson's correlation coefficient for normally distributed variables and Spearman's coefficient when normality assumptions are not met. Partial correlation analyses controlling for sex, body height, and BMI will also be performed to evaluate associations independent of general body proportions. Separate multiple linear regression models will be constructed for each dependent variable, with the possibility of including covariates. Group differences between refractive categories will be analyzed using one-way analysis of variance when assumptions are satisfied, Welch's ANOVA in the presence of heterogeneity of variances, or the Kruskal-Wallis test if normality assumptions are violated. Effect sizes will be expressed as partial eta squared. Exploratory principal component analysis will be applied to reduce dimensionality of morphometric variables and identify dominant patterns of variability, and resulting components may be included in further correlation or regression analyses. In addition to absolute linear measures, standardized morphometric ratios will be calculated to differentiate size effects from shape effects. All statistical analyses will be performed using SPSS Statistics 25.0, with significance set at α = 0.05.

The study will be conducted in accordance with the Declaration of Helsinki, ICH-GCP guidelines, and applicable data protection regulations. Ethical approval has been obtained from the Ethics Committee of the Clinical Hospital Center Sestre milosrdnice and the Ethics Committee of the School of Dental Medicine, University of Zagreb. All participants will provide written informed consent prior to inclusion. Participation will be voluntary, with the right to withdraw at any time without consequences for further treatment or medical care. All collected data and facial documentation will be anonymized using coded identifiers and stored in a secure electronic database accessible only to the research team. If photographs or three-dimensional facial representations are used in scientific publications or in the doctoral dissertation, identifiable features will be additionally protected. Given the non-invasive nature of the procedures, which include standardized 3D facial imaging and routine ophthalmologic biometric measurements, no additional risks beyond those associated with standard ophthalmologic examination are expected. The study will be conducted and reported in accordance with STROBE guidelines for observational research.

Inclusion Criteria:

Healthy young adults aged 21 to 25 years.

Same ethnic background (to reduce population-related morphological variability).

Best-corrected visual acuity ≥ 1.0.

Normal findings of the anterior and posterior ocular segments.

Refractive status determined by objective autorefractometry and confirmed by subjective refraction.

Body mass index (BMI) between 18.5 and 24.9 kg/m².

Willingness to participate and provision of written informed consent.

Exclusion Criteria:

Previous ocular surgery.

Previous facial surgery.

Craniofacial anomalies.

Active or previous orthodontic therapy that may affect maxillomandibular relationships.

Strabismus.

Amblyopia.

Ocular trauma.

Facial trauma.

Systemic diseases that may affect facial morphology or ocular biometric parameters.

Study participants will be selected from the population of healthy young adults aged 21 to 25 years who undergo routine ophthalmologic examination at the participating healthcare institution. The source population consists of individuals of the same ethnic background with completed craniofacial growth, normal ocular health, and no history of ocular or facial surgery, craniofacial anomalies, orthodontic treatment affecting maxillomandibular relationships, ocular or facial trauma, strabismus, amblyopia, or systemic diseases influencing facial morphology or ocular biometric parameters. Eligible individuals must have best-corrected visual acuity ≥ 1.0 and a body mass index between 18.5 and 24.9 kg/m². Participants will be stratified according to refractive status into myopic, emmetropic, and hyperopic groups.

Individual participant data that do not permit direct or indirect identification will be shared in an open scientific repository following publication of the main study results. We will share fully anonymized quantitative datasets containing ocular biometric parameters, including axial length, anterior chamber depth, lens thickness, corneal curvature values, horizontal corneal diameter (white-to-white), and spherical equivalent. We will also share three-dimensional facial morphometric variables derived from standardized anthropometric landmarks, including calculated linear distances and standardized ratios. In addition, we will provide relevant demographic and anthropometric variables necessary for interpretation of the results, such as age, sex, body height, body weight, and body mass index, all in anonymized form.