Childhood obesity is an important health problem, and its prevalence has increased over the past three decades.1,2 Obesity is an important risk factor for hypertension, dyslipidemia, diabetes mellitus, cardiovascular abnormalities, and cancer.2,3 These comorbidities occur and advance in childhood with the increasing prevalence of childhood obesity.2 Obesity is related to many ocular disorders, including cataract, glaucoma, diabetic retinopathy, age-related maculopathy, retinal vein occlusion, pseudo-tumor cerebri, lower eyelid entropion, and floppy eyelid syndrome.4
The Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, NY) can provide in vivo measurements of corneal biomechanical properties related to the corneal status and structures.5 This device provides two important parameters: corneal hysteresis and corneal resistance factor. Corneal hysteresis is a parameter of corneal visco-elasticity, whereas corneal resistance factor is related to the overall resistance of the cornea. The ORA is a useful tool to examine the structure and properties of the cornea. The biomechanical properties of the cornea depend on the stromal structure. Multiple clinical studies have investigated corneal biomechanical properties in various diseases, but no single study has investigated their association with childhood obesity. The primary purpose of this study was to investigate whether there were any changes in the corneal biomechanical parameters of patients with childhood obesity compared with healthy children.
Patients and Methods
Study Population and Design
This cross-sectional study was conducted in the Departments of Ophthalmology and Pediatric Endocrinology at Keçiören Training and Research Hospital and the Department of Ophthalmology at Ulucanlar Eye Training and Research Hospital and complied with the tenets of the Declaration of Helsinki. Approval was obtained from the local ethics committee, and informed consent was obtained from the parents or legal guardians of all children included in the study.
The patients were divided into two groups: 47 children with childhood obesity (study group) and 39 age- and gender-matched healthy children (control group). Obesity was diagnosed according to body mass index (BMI). Body weight was measured with a digital scale (Seca Corporation, Chino, CA) with patients wearing light clothing. Height was measured using a portable stadiometer (Seca Corporation). BMI was calculated as weight in kilograms divided by body surface area in meters squared (kg/m2). Participants were diagnosed as having childhood obesity according to a standardized BMI, considering the growth curve for each gender and the cut-off points proposed by the World Health Organization. Obesity was defined as a BMI in the 95th percentile or higher for age and gender.6
Exclusion criteria for this study were patients with a history of significant ocular disease (eg, refractive error, amblyopia, glaucoma, or uveitis), ocular trauma or surgery, and any systemic disorders that might affect the eyes (eg, uncontrolled diabetes mellitus or hypertension).
Examination Protocol and Study Measurements
Each participant underwent a detailed ophthalmic examination, including best corrected visual acuity by Snellen chart, IOP measurement with Goldmann applanation, biomicroscopic anterior segment examination, and fundus examination.
Following the ophthalmological examination, the ORA was used to measure the biomechanical properties of the cornea.7 The ORA allows cornea compensated IOP (IOPcc) measurements and estimates corneal hysteresis and corneal resistance factor. The ORA generates two separate IOP output parameters: Goldmann correlated IOP (IOPg) and IOPcc.
The ORA measures the corneal response to recess by a quick air pulse. It is based on noncontact tonometry, in which IOP is determined by the amount of air pressure required to applanate the central cornea. The air pulse leads the cornea to move inward past applanation and into a slight concavity before returning to normal curvature. Corneal deformation is recorded via an electro-optical infrared detection system.
The ORA receives corneal biomechanical data by quantifying the differential inward and outward corneal responses to an air pulse over a time span of approximately 20 ms. The air pulse induces the desired indentation/applanation and it symmetrically reverses, which allows the cornea to return to its original shape. The applanation pressure generated during the collapse and the applanation pressure that occurs during the cornea's return, due to its biomechanical properties, are determined by the device. The mean of these two pressures is called IOPg and the difference in pressure is called corneal hysteresis. Corneal hysteresis shows the thickness, hydration, and rigidity of the cornea and the cumulative effect of factors not yet defined. This ORA parameter is thought to represent the viscoelastic nature of the cornea for its “viscous-damping” capacity. Corneal resistance factor is a value obtained from corneal hysteresis, and it provides information on the elastic properties of the cornea. It is accepted as a parameter that reflects the elasticity of the cornea and expresses the total resistance of the cornea.
Corneal hysteresis, corneal resistance factor, IOPcc, and IOPg were measured with the ORA. Three alternate measurements with a waveform score of 7 or greater were taken for each eye, and the average value of these measurements was used.
The Scheimpflug camera combined with a Placido disc corneal topographer (Pentacam HR Scheimpflug imaging system; Oculus Optikgeräte GmBH, Wetzlar, Germany) was used to measure central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber angle (ACA), and anterior chamber volume (ACV). All measurements were taken by an experienced clinician (HK).
Statistical analysis was performed using Statistical Package for the Social Sciences software (version 20.0; SPSS Inc., Chicago, IL). For each continuous variable, the normality of distribution was checked with the Kolmogorov–Smirnov test (P > .05). The independent samples t test, the chi-square test, and Pearson's correlation were used for statistical analysis. A P value of .05 or less was considered statistically significant. All of the results are presented as mean ± standard deviation.
The mean age of patients was 13.28 ± 2.39 years (range: 9 to 17 years) in the study group and 12.62 ± 2.47 years (range: 9 to 17 years) in the control group, with no statistically significant difference determined between the groups (P > .05). The female to male ratio was 30/17 in the study group and 20/19 in the control group, with no difference determined between the groups (P > .05). The mean BMI value was 31.8 ± 1.9 in the study group and 19.8 ± 4.4 in the control group. The mean BMI value was determined to be statistically significantly higher in the study group (P = .001). The standarized BMI value was 2.22 ± 0.15 in the study group and 0.74 ± 0.55 in the control group (P = .001).
The mean IOP was 14.9 ± 2.0 mm Hg in the study group and 14.1 ± 1.3 mm Hg in the control group (P = .003). The mean CCT was 556.81 ± 27.20 µm in the study group and 564.71 ± 33.91 µm in the control group (P > .05). The mean ACV was 209.81 ± 27.62 mm3 in the study group and 197.72 ± 29.54 mm3 in the control group (P = .008). No statistically significant difference was determined between the groups regarding the mean ACD and ACA measurements (P > .05).
The mean corneal hysteresis was 10.56 ± 1.52 mm Hg in the study group and 11.16 ± 1.92 mm Hg in the control group (P = .024). No statistically significant difference was determined between the groups regarding the mean corneal resistance factor or IOPcc and IOPg measurements. Corneal hysteresis showed a significant, positive correlation with corneal resistance factor (P < .001, r = 0.851), IOPg (P = .044, r = 0.213), and CCT (P < .001, r = 0.477). Additionally, corneal hysteresis showed a significant negative correlation with IOPcc (P = .001, r = −0.355), ACA (P = .005, r = −0.294), ACV (P = .019, r = −0.246), and ACD (P = .046, r = −0.211).
The current study evaluated the corneal biomechanical properties eyes in patients with childhood obesity. The results showed that patients with childhood obesity had lower corneal hysteresis and higher IOP measurements compared to the healthy children, whereas no difference was found in the corneal resistance factor, IOPcc, and IOPg measurements of the patients with childhood obesity and healthy children. The patients with childhood obesity had higher ACV measurements compared with the healthy children. The mean CCT, ACD, and ACA were no different between the patients with childhood obesity and the healthy children.
Obesity is defined as an excess of body fat and is usually associated with adipose tissue dysfunction.8 BMI is widely used to measure obesity and standardized BMI is more suitable when adjusted for age and gender.9 Obesity is related to the development of diseases such as hypertension, dyslipidemia, and diabetes mellitus, and cardiovascular diseases.8
Obesity has also been related to visual acuity, although the eye conditions fundamental to this association and the potential implications are uncertain.10 An association has been found between obesity and cataract, age-related maculopathy, diabetic retinopathy, glaucoma, retinal vein occlusion, oculomotor nerve palsy, recurrent lower eyelid entropion, and floppy eyelid syndrome.11 Additionally, myopia, astigmatism, amblyopia, strabismus, and exotropia have been found to be related to obesity.12
The ORA is the only device that can measure in vivo corneal biomechanical parameters, including corneal hysteresis and corneal resistance factor, that depend on corneal viscoelasticity.7 The corneal hysteresis value reflects the corneal viscosity,13 whereas the corneal resistance factor is associated with the overall resistance of the cornea.13 Changes in corneal hysteresis and the corneal resistance factor have been associated with corneal tissue changes in corneal disorders, autoimmune or systemic diseases, or hormonal fluctuations.14–22
To the best of our knowledge, this is the first study to examine the corneal biomechanical properties in childhood obesity. The study results showed significantly lower corneal hysteresis and higher IOP measurements in patients with childhood obesity compared to healthy children. We observed a significant, positive correlation between corneal resistance factor, IOPg, CCT, and corneal hysteresis measurements, and a significant, negative correlation between IOPcc, ACA, ACV, ACD, and corneal hysteresis measurements in patients with childhood obesity.
Corneal hysteresis reflects the viscoelastic property of the cornea and the corneal hysteresis value depends on many factors (eg, corneal thickness, hydration, and rigidity) that are essential to determine corneal biomechanics. In childhood obesity, the disease process causes these factors to change, which might occur with ultrastructural weakening of the cornea. Obesity leads to increased production of proinflammatory cytokines.23 These proinflammatory cytokines might indicate the ultrastructural changes in the cornea. As a result of ultrastructural changes, corneal hysteresis decreases with obesity duration.
Although the relationship between obesity and glaucoma has been investigated in several studies,11 the underlying mechanism remains unclear. However, two major theories of glaucoma may be related to obesity: mechanical and vascular. According to mechanical theory, obesity affects IOP through extreme intraorbital adipose tissue, increased blood viscosity, episcleral venous pressure, and disrupted aqueous outflow facility. Stojanov et al.24 found that increasing orbital fat and impeding aqueous outflow can be a factor for elevated IOP. Çekiç et al.25 claimed that elevated IOP may be related to dysregulation of retrobulbar blood flow. The vascular theory of glaucoma states that abnormal ocular blood flow and perfusion could be predisposing factors for optic nerve head damage.4
It has been reported that the effect of obesity on vascular function could be related to autonomic and endothelial function, and that it is mediated with neurotropin deprivation, release of excitatory amino acids, and leptin.4 It is produced by adipocytes and plays a key role in obesity-related complications. Leptin has been demonstrated to increase oxidative stress in endothelial cells, promote smooth muscle cell migration, and increase angiogenic activity.26–28 Marseglia et al.29 reported that leptin may be associated with obesity-related oxidative stress. In a study by Caballero et al.,30 elevated IOP was explained by trabecular meshwork malfunctioning.
Glaucoma is a major cause of blindness and is associated with progressive damage to the optic nerve.31 The most important risk factor for glaucoma is increased IOP. Corneal hysteresis has been found to be related to glaucoma and is lower in glaucomatous eyes compared to normal eyes.31 Lower corneal hysteresis has been shown to be related to optic nerve head damage and glaucomatous visual field.31 Pacheco-Cervera et al.32 reported that the retinal nerve fiber layer thickness is reduced.
The current study demonstrated that corneal hysteresis is significantly related to BMI in childhood. These results showed a statistically significant difference in corneal hysteresis measurements between the patients with childhood obesity and healthy children. The mean corneal hysteresis was determined to be lower in patients with childhood obesity. The mean IOP was significantly higher in children with obesity than the healthy children. A possible reason for changes in the tissue level in these children could be related to the damaging factors of obesity, especially proinflammatory cytokines.
This study had several limitations, primarily the small sample size. Another limitation was that retinal nerve fiber layer thickness measurements were not taken. Despite these limitations, this study can be considered of value as the first study to draw attention to corneal hysteresis and IOP in childhood obesity. Further research with a greater number of patients is required to further understand the association between corneal hysteresis and childhood obesity.