medicina

Article
Particular Anatomy of the Hyperopic Eye and Potential
Clinical Implications
Maria-Cristina Marinescu 1,2 , Dana-Margareta-Cornelia Dascalescu 1,2, *, Mihaela-Monica Constantin 3 ,
Valeria Coviltir 1,2 , Vasile Potop 1,2 , Dan Stanila 4 , Farah Constantin 5 , Cristina Alexandrescu 1,6 ,
Radu-Constantin Ciuluvica 1 and Liliana-Mary Voinea 1

1 Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania

2 Department of Ophthalmology, Clinical Hospital for Ophthalmological Emergencies,
010464 Bucharest, Romania
3 Department of Ophthalmology, Oftaclinic, 040254 Bucharest, Romania
4 Department of Ophthalmology, Faculty of Medicine, Lucian Blaga University, 550169 Sibiu, Romania
5 Department of Ophthalmology, Faculty of Medicine, Ovidius University, 900470 Constanta, Romania
6 Department of Ophthalmology, Bucharest Emergency University Hospital, 050098 Bucharest, Romania
* Correspondence: dana.dascalescu@umfcd.ro

Abstract: Background and Objectives: Hyperopia is a refractive error which affects cognitive and
social development if uncorrected and raises the risk of primary angle-closure glaucoma (PACG).
Materials and Methods: The study included only the right eye—40 hyperopic eyes in the study group
(spherical equivalent (SE) under pharmacological cycloplegia over 0.50 D), 34 emmetropic eyes
in the control group (SE between −0.50 D and +0.50 D). A complete ophthalmological evaluation
was performed, including autorefractometry to measure SE, and additionally we performed Ocular
Response Analyser: Corneal Hysteresis (CH), Corneal Resistance Factor (CRF); specular microscopy:
Endothelial cell density (CD), Cell variability (CV), Hexagonality (Hex), Aladdin biometry: Anterior
Chamber Depth (ACD), Axial Length (AL), Central Corneal Thickness (CCT). IBM SPSS 26 was used
Citation: Marinescu, M.-C.; for statistical analysis. Results: The mean age of the entire cohort was 22.93 years (SD ± 12.069),
Dascalescu, D.-M.-C.; Constantin, 66.22% being female and 33.78% male. The hyperopic eyes had significantly lower AL, ACD, higher
M.-M.; Coviltir, V.; Potop, V.; Stanila,
SE, CH, CRF. In the hyperopia group, there are significant, negative correlations between CH and
D.; Constantin, F.; Alexandrescu, C.;
AL (r −0.335), CRF and AL (r −0.334), SE–AL (r −0.593), ACD and CV (r −0.528), CV and CRF (r
Ciuluvica, R.-C.; Voinea, L.-M.
−0.438), CH (r −0.379), and positive correlations between CCT and CH (r 0.393) or CRF (r 0.435), CD
Particular Anatomy of the Hyperopic
and ACD (r 0.509) or CH (0.384). Age is significantly, negatively correlated with ACD (r −0.447),
Eye and Potential Clinical
Implications. Medicina 2023, 59, 1660.
CH (r −0.544), CRF (r −0.539), CD (r −0.546) and positively with CV (r 0.470). Conclusions: Our
https://doi.org/10.3390/ study suggests a particular biomechanical behavior of the cornea in hyperopia, in relation with
medicina59091660 morphological and endothelial parameters. Moreover, the negative correlation between age and ACD
suggests a shallower anterior chamber as patients age, increasing the risk for PACG.
Academic Editor: Esther
M. Hoffmann
Keywords: hyperopia; emmetropia; corneal hysteresis; corneal resistance factor; endothelial cell
Received: 19 July 2023 density; endothelial cell variability; anterior chamber depth; axial length
Revised: 28 August 2023
Accepted: 11 September 2023
Published: 14 September 2023

1. Introduction
Hyperopia is one of the most frequent refractive errors, both in the pediatric and adult
Copyright: © 2023 by the authors.
populations, with an important potential for impact on the daily quality of life [1]. It is
Licensee MDPI, Basel, Switzerland. estimated that the worldwide prevalence of hyperopia is 4.6% in children and 30.9% in
This article is an open access article adults, with large variations between different geographic regions [2].
distributed under the terms and While common, uncorrected hyperopia, and particularly anisometropia (difference in
conditions of the Creative Commons refractive error between the two eyes), raise an important risk for amblyopia (also known
Attribution (CC BY) license (https:// as lazy eye) during childhood, as evidenced by a recent study performed on a Romanian
creativecommons.org/licenses/by/ pediatric population [3]. Persistent amblyopia has been found to be associated with a poorer
4.0/). self-rated overall health, and to have an impact on mental health and overall well-being [4].

Medicina 2023, 59, 1660. https://doi.org/10.3390/medicina59091660 https://www.mdpi.com/journal/medicina

Medicina 2023, 59, 1660 2 of 10

In adults, hyperopia is a known risk factor for primary angle-closure glaucoma

(PACG)—an SE between 1.01 and 3.00 Diopters (D) associates an odds ratio of PACG
of 1.58, while hyperopia over 3 D associates an odds ratio of 3.33, these figures being even
higher in patients younger than 65 years old [5]. Regarding glaucoma, along with the high
intraocular pressure (IOP), another important risk factor is represented by biomechanical
corneal properties. In PACG, corneal hysteresis has been frequently described as lower
compared with healthy controls, even adjusting for age and IOP, and improving after
treatment [6].
Recent literature has shown significant anatomical differences in the hyperopic eye—
such as a higher choroidal thickness in children, which correlates with the axial length [7].
The objective of this study is to better describe the morphological, biomechanical and
endothelial properties of the hyperopic cornea, in relationship with axial length and anterior
chamber depth, and to compare those to a control group of emmetropic eyes.

2. Materials and Methods

This study has a prospective, non-randomized cross-sectional methodology. The
study cohort was formed by applying inclusion and exclusion criteria to all patients who
consecutively presented to the Oftaclinic Ophthalmology practice, in Bucharest, Romania,
between February 2023 and June 2023. The study was conducted in accordance with the
Declaration of Helsinki, and approved by the Research Ethics Committee of Carol Davila
University of Medicine and Pharmacy (protocol code PO-35-F-03/16.01.2023). Informed
consent was obtained from all subjects involved in the study, and from legal guardians in
the case of participants under the age of 18.
The inclusion criteria were:
- For the study group: diagnosis of hyperopia (spherical equivalent (SE) over 0.50 D) [8];
- For the control group: diagnosis of emmetropia (SE between −0.50 D and +0.50 D) [9].
Patients were included in the study and control groups according to the value of
the spherical equivalent calculated after pharmacological cycloplegia (cyclopentolate
10 mg/mL, instilled 3 times every 5 min in both eyes). Furthermore, patients were in-
cluded in the pediatric group (age under or equal to 18 years old) and the adult group (age
over 18 years old).
The exclusion criteria were represented by the presence of ocular pathology, other than
hyperopia (myopia, keratoconus, amblyopia, cataract, glaucoma, vitreoretinal pathology),
the diagnosis of presbyopia or a history of refractive surgery. Furthermore, patients were
excluded in the absence of testing compliance (such as low waveform in Ocular Response
Analyser testing, under 7), if the patient was pregnant or if they disclosed any systemic
pathology (diabetes mellitus, arterial hypertension, dyslipidemia) or systemic chronic
medication. Randomly the right eye of each patient was included in the analysis.
All patients underwent a complete ophthalmological evaluation, including autore-
fractometry, before and after pharmacological cycloplegia—Topcon KR800 (Topcon, Tokyo,
Japan) to measure the spherical error and equivalent (spherical error + 1/2 cylindrical
error), slit lamp examination of the anterior and posterior ocular segments, Goldmann
tonometry. Additionally, patients underwent the following measurements, also under
pharmacological cycloplegia:
- Ocular Response Analyzer (ORA) (Reichert Ophthalmic Instruments Inc, Depew,
NY, USA)—in order to determine corneal biomechanical properties: corneal hystere-
sis (CH), corneal resistance factor (CRF) and the Goldmann-correlated intraocular
pressure IOP (IOPg);
Medicina 2023, 59, 1660 3 of 10

- Aladdin biometer (Topcon, Tokyo, Japan)—to determine the axial length (AL), anterior
chamber depth (ACD) and central corneal thickness (CCT);
- Specular microscopy (Nidek, Gamagori, Japan) in order to determine corneal endothe-
lial parameters: cell density (CD), coefficient of variation of cell area (CV), percent
hexagonality (Hex).
The Ocular Response Analyzer is a non-contact tonometry device applying an air pulse
on the corneal surface and following the corneal deformation and its return to the initial
state using infrared light. The device records 2 applanation pressures, therefore measuring
intraocular pressure and two estimates of corneal viscoelasticity: CH, which represents
corneal capacity to absorb and dissipate energy (equal to the pressure difference between
the first and second applanation) and CRF, which reflects the global corneal resistance
(similar to CH, the second applanation multiplied with a constant) [10]. The measurements
with the highest Waveform score were included in the analysis.
The specular microscopy uses the principle of specular light reflection, in which the
endothelial layer acts as a mirror, transmitting an image of itself to the device, which
analyzes its properties [11].
The Aladdin biometer is an optical low-coherence interferometer measuring ocular
morphological parameters [12], and autorefractometry measures refractive errors following
the principle of retinoscopy (registering the movement of the retinal reflection of a light,
projected towards the eye) [13].

Statistical Analysis
This study includes both categorical and numerical, continuous data. The absolute
and relative frequency were calculated for categorical data. For numerical data, the average
and standard deviation were determined.
Levene’s Test, followed by the t Test, was applied in order to identify significant
differences between the groups (hyperopic and emmetropic, male and female, children
and adults). Pearson’s correlation coefficient (“Pearson’s r”) was calculated to determine
the degree of correlation between variables. A weak correlation has Pearson’s r between
0.3 and −0.3, a moderate correlation between 0.3 and 0.5 or between −0.3 and −0.5, and
a strong correlation over 0.5 or under −0.5. As IOPg may act as a confounding variable,
correlations were calculated controlling for it. The p value of 0.05 is considered a threshold
for statistical significance. The Statistical Package IBM SPSS Statistics for Windows, version
26 (IBM Corp., Armonk, NY, USA) was used to perform the statistical analysis.

3. Results
The hyperopic, study group was comprised of 40 eyes (67.50% female, 32.50% male;
45.00% adults, 55.00% children), and the emmetropic, control group was comprised of
34 eyes (64.71% female, 35.29% male; 61.76% adults, 38.24% children). Average age in the
hyperopic group was 19.83 years old (age range 6–38), and in the emmetropic group was
26.59 (age range 10–40) (see Table 1).
The hyperopic eyes had significantly lower AL, ACD, higher SE, CH, CRF, and were
from significantly younger patients (see Table 1). There were no significant differences
between males and females, in the entire cohort, study or control group.
There are statistically significant differences between adults and children: lower ACD,
CH, CRF and CD in adult hyperopes and emmetropes, and significantly higher CV in adult
hyperopes compared to pediatric hyperopes (See Table 2).
Medicina 2023, 59, 1660 4 of 10

Table 1. Mean and standard deviation of the age, Spherical Equivalent (SE), Axial Length (AL),
Anterior Chamber Depth (ACD), Central Corneal Thickness (CCT), Corneal Hysteresis (CH), Corneal
Resistance Factor (CRF), Endothelial cell density (CD), Cell variability (CV), Hexagonality (Hex) in
the whole cohort and in the hyperopic and emmetropic groups, with Mean Difference, Standard
Error and p value of Independent Samples t Test.

Mean (±Standard Deviation)

Entire Cohort Hyperopic Study Emmetropic Control Mean Difference
p Value
(n = 74) Group (n = 40) Group (n = 34) (Standard Error)
Age (years) 22.93 (±12.07) 19.83 (±12.37) 26.59 (±10.77) −6.76 (±2.72) 0.015
SE (D) 1.25 (±1.71) 2.25 (±1.79) 0.07 (±0.29) 2.18 (±0.29) <0.001
AL (mm) 23.03 (±0.86) 22.54 (±0.68) 23.61 (±0.69) −1.07 (±0.16) <0.001
CCT (mm) 0.568 (±0.034) 0.566 (±0.030) 0.569 (±0.038) −0.003 (±0.008) 0.738
ACD (mm) 3.47 (±0.38) 3.37 (±0.40) 3.59 (±0.33) −0.22 (±0.09) 0.013
CH (mmHg) 12.39 (±1.56) 12.80 (±1.61) 11.90 (±1.35) 0.91 (±0.35) 0.012
CRF (mmHg) 12.31 (±1.76) 12.71 (±1.91) 11.85 (±1.47) 0.86 (±0.40) 0.036
CD (cells/mm2 ) 3000.65 (±361.51) 3075.70 (±377.27) 2912.35 (±325.63) 163.35 (±82.70) 0.052
CV (%) 28.72 (±4.89) 29.30 (±5.17) 28.03 (±4.52) 0.013 (±0.011) 0.268
Hex (%) 65.68 (±5.26) 65.68 (±5.32) 65.68 (±5.27) −0.00001 (±0.0123) 0.999

Table 2. Mean, standard deviation and p value of the Independent Samples t Test, regarding the
age, Spherical Equivalent (SE), Axial Length (AL), Anterior Chamber Depth (ACD), Central Corneal
Thickness (CCT), Corneal Hysteresis (CH), Corneal Resistance Factor (CRF), Endothelial cell density
(CD), Cell variability (CV), Hexagonality (Hex) in adult and pediatric subjects, in the hyperopia and
emmetropia groups.

Hyperopic Study Group (n = 40) Emmetropic Control Group (n = 34)

Adult (n = 18) Children (n = 22) p Value Adult (n = 21) Children (n = 13) p Value
Age (years) 32.22 (±6.60) 9.68 (±3.06) <0.001 34.14 (±5.55) 14.38 (±2.47) <0.001
SE (D) 2.49 (±2.10) 2.06 (±1.51) 0.458 0.01 (±0.29) 0.17 (±0.26) 0.110
AL (mm) 22.62 (±0.60) 22.48 (±0.74) 0.531 23.55 (±0.59) 23.71 (±0.84) 0.513
CCT (mm) 0.569 (±0.029) 0.564 (±0.032) 0.567 0.561 (±0.032) 0.582 (±0.045) 0.117
ACD (mm) 3.18 (±0.34) 3.52 (±0.39) 0.007 3.39 (±0.21) 3.90 (±0.24) <0.001
CH (mmHg) 11.94 (±1.69) 13.51 (±1.17) 0.001 11.35 (±1.04) 12.79 (±1.35) 0.001
CRF (mmHg) 11.88 (±2.00) 13.39 (±1.56) 0.011 11.18 (±1.17) 12.93 (±1.28) 0.001
CD (cells/mm2 ) 2833.33 (±321.70) 3274.00 (±298.35) <0.001 2749.52 (±213.85) 3175.38 (±306.63) <0.001
CV (%) 31.94 (±4.33) 27.14 (±4.85) 0.002 29.14 (±4.09) 26.23 (±4.75) 0.067
Hex (%) 65.28 (±5.45) 66.00 (±5.31) 0.675 66.86 (±4.39) 63.77 (±6.15) 0.097

In the hyperopia group, there are several significant correlations between variables—
all statistically significant ones can be found in Table 3. Thus, in the hyperopia group there
are significant strong negative correlations between Age-CH, Age-CRF, AL-SE, ACD-CV,
Age-CD, moderate negative correlations between Age-ACD, AL-CH, AL-CRF, Hex-CV, CH-
CV, CRF-CV, CD-CV, moderate positive correlations between Age-CV, CCT-CH, CCT-CRF,
ACD-CD, CH-CD. Scatter plots of correlations of age can be found in Figure 1.
 all statistically significant ones can be found in Table 3. Thus, in the hyperopia group there
are significant strong negative correlations between Age-CH, Age-CRF, AL-SE, ACD-CV,
Age-CD, moderate negative correlations between Age-ACD, AL-CH, AL-CRF, Hex-CV,
CH-CV, CRF-CV, CD-CV, moderate positive correlations between Age-CV, CCT-CH,
Medicina 2023, 59, 1660 CCT-CRF, ACD-CD, CH-CD. Scatter plots of correlations of age can be found in Figure 1.
5 of 10

Table 3. Pearson’s r coefficient and p value of correlations between Spherical Equivalent (SE), Axial
Length (AL), Anterior Chamber Depth (ACD), Central Corneal Thickness (CCT), Corneal Hysteresis
3. Pearson’s
Table Corneal
(CH), r coefficient
Resistance and p Endothelial
Factor (CRF), value of correlations
cell densitybetween Spherical
(CD), Cell Equivalent
variability (SE),
(CV), Hexag-
Axial
onalityLength (AL),
(Hex) in Anterior Chamber
the hyperopia group. Depth (ACD), Central Corneal Thickness (CCT), Corneal
Hysteresis (CH), Corneal Resistance Factor (CRF), Endothelial cell density (CD), Cell variability (CV),
Pearson Correlation
Hexagonality Coefficients
(Hex) in the (p Value)
hyperopia group.
Age-ACD −0.447 (0.007)
Pearson Correlation Coefficients (p Value) Age-CV 0.470 (0.004)
Age-CH
Age-ACD −0.544
−0.447(0.001)
(0.007) Age-CD
Age-CV −0.546 (0.001)
0.470 (0.004)
Age-CRF
Age-CH −0.544(0.001)
−0.539 (0.001) ACD-CD
Age-CD −0.546
0.509 (0.002)
(0.001)
Age-CRF
AL-CH −0.539(0.049)
−0.335 (0.001) ACD-CD
ACD-CV 0.509 (0.002)
−0.528 (0.001)
AL-CH −0.335 (0.049) ACD-CV −0.528 (0.001)
AL-CRF −0.334 (0.041) CH-CD 0.384 (0.023)
AL-CRF −0.334 (0.041) CH-CD 0.384 (0.023)
AL-SE −0.593 (<0.001) CRF-CV −0.438 (0.009)
AL-SE −0.593 (<0.001) CRF-CV −0.438 (0.009)
CCT-CH 0.393 (0.019) CH-CV −0.379 (0.025)
CCT-CH 0.393 (0.019) CH-CV −0.379 (0.025)
CCT-CRF
CCT-CRF 0.435
0.435 (0.009)
(0.009) CD-CV
CD-CV −0.396
−0.396(0.019)
(0.019)
Hex-CV
Hex-CV −0.480
−0.480(0.004)
(0.004)

Figure 1. Correlations
Correlationsof
ofage
ageininthe
thehyperopia
hyperopia study
study group:
group: with
with anterior
anterior chamber
chamber depth
depth (scatter
(scatter plot
plot
(A)),(A)),
withwith endothelial
endothelial cell density
cell density (scatter
(scatter plot (B)),
plot (B)), with with corneal
corneal hysteresis
hysteresis (scatter
(scatter plot (C)).
plot (C)).

In the emmetropic group, there are strong negative correlations between Age-ACD,
Age-CD, moderate negative correlations between Age-CH, Age-CRF, AL-CD, Hex-CD,
ACD-CV, Hex-CV and strong positive correlations between CCT-CH, CCT-CRF, ACD-CH,
ACD-CRF, CRF-CD, CH-CD, moderate positive correlations between Age-CV, ACD-CD,
SE-CD, Hex-AL (Table 4).
Medicina 2023, 59, 1660 6 of 10

Table 4. Pearson’s r coefficient and p value of correlations between Spherical Equivalent (SE),
Axial Length (AL), Anterior Chamber Depth (ACD), Central Corneal Thickness (CCT), Corneal
Hysteresis (CH), Corneal Resistance Factor (CRF), Endothelial cell density (CD), Cell variability (CV),
Hexagonality (Hex) in the emmetropia group.

Pearson Correlation Coefficients (p Value)

Age-ACD −0.702 (<0.001) Age-CV 0.425 (0.014)
Age-CH −0.455 (0.008) ACD-CV −0.390 (0.025)
Age-CRF −0.445 (0.009) Hex-CV −0.463 (0.007)
CCT-CH 0.574 (<0.001) ACD-CD 0.383 (0.028)
CCT-CRF 0.571 (0.001) CRF-CD 0.560 (0.001)
ACD-CH 0.566 (0.001) CH-CD 0.562 (0.001)
ACD-CRF 0.561 (0.001) SE-CD 0.441 (0.010)
AL-CD −0.452 (0.008) Age-CD −0.553 (0.001)
Hex-CD −0.372 (0.033) Hex-AL 0.425 (0.014)

4. Discussion
Corneal biomechanics represent an emerging domain in adult and pediatric ophthal-
mology, with proven value in refractive surgery [14] and diseases such as glaucoma [15,16],
keratoconus [17], and other refractive errors such as myopia [18]. In our study, both CH
and CRF were significantly higher in hyperopes compared to emmetropes, and in children
compared to adults. A large scale study, involving over 93,000 eyes, has led to similar
results: CH is higher in younger people, however that study has involved significantly
older people (between the ages of 40 and 69), and has also revealed a difference between
genders in terms of CH, which was not present in our study [19]. A study which divided
the participants in age decades revealed that CH and CRF are significantly different be-
tween the ages of 10 and 69, with the average values in the 10–19 age bracket being most
significantly higher than in other decades. Moreover, CH and CRF were on average higher
in females and, similar to our study, were higher in hyperopes (compared to myopes and
emmetropes) [20].
Biologically, this may be explained as aging induces reduced elasticity and compliance
in the cornea through the effect of oxidative stress, protein glycation and, ultimately,
collagen crosslinking [21].
There is an important relationship between corneal thickness and corneal hysteresis
and resistance factor—a strong correlation has been established through multiple stud-
ies [22,23], including through multivariate analysis [24]. This can be easily explained, as
the elasticity and viscosity of the cornea, of which CH and CRF are markers, are increased
as the corneal thickness is increased [25].
Corneal thickness is an ocular parameter which may be influenced by several systemic
pathological processes—such as accumulation of advanced glycation end products in the
stroma or endothelial dysfunction, which all lead to an increase in central or peripheral
corneal thickness [26]. Specifically, an increase of corneal thickness has been detected in
diabetes mellitus (DM) [27], hyperparathyroidism, gout, and a decrease in connective tissue
disease such as Ehlers-Danlos Syndrome, Marfan Syndrome [26].
In our study, CCT is correlated with CH and CRF both in emmetropes and in hyper-
opes, and the latter two are different between the two refractive groups. However, no
significant difference in CCT was observed—it is known that corneal biomechanics are
influenced by biological properties such as the tridimensional organization of collagen
fibers, extracellular matrix components, or osmotic pressure [28], and thus may explain the
increased CH and CRF of the hyperopic cornea, for the same CCT.
One important relationship to discuss pertains to the anterior chamber depth. Hyper-
opia, a shallow central anterior chamber and a short axial length are all known risk factors
Medicina 2023, 59, 1660 7 of 10

for primary angle-closure glaucoma [5,29]. As expected, our study reveals a lower AL and
ACD in hyperopic patients. Interestingly, it also reveals a negative correlation between age
and ACD, both in emmetropes and hyperopes, suggesting a lower anterior chamber depth
as patients grow older. Other studies confirm this association between ACD and either age
or refractive error, some data even supporting the fact that the largest rate of ACD decrease
occurs in the second decade of life [30]. In tandem with the anterior chamber depth, lens
parameters are of importance in angle-closure glaucoma. It is reported that in PACG, the
lens thickness is higher and the relative position of the lens is more anterior [31].
A Cochrane review suggests that, in PACG, lens extraction, which acts on relieving the
pupillary block and on increasing the ACD, is a feasible therapeutic approach, with benefits
in terms of visual field progression and quantity of IOP-lowering medication needed [32].
Several studies have investigated the correlation between CH and CRF and morpho-
logical parameters, such as the ACD or AL [25,33]. However, results were conflicting—in
our study, there is a positive correlation between ACD and the corneal biomechanical
parameters in emmetropes, while the correlation is statistically significant between AL
and corneal biomechanics in hyperopes. In a study of almost 1000 eyes, linear regression
analysis identifies anterior chamber depth and volume as factors influencing CH in a
model adjusted for age and gender, however the correlation is no longer significant in a
multivariate model which includes other factors such as CCT or corneal curvature [25]. In
a study of pediatric eyes, a multivariate analysis reveals that CH and CRF are both nega-
tively correlated with AL, with no correlation with ACD [33]. Similarly, in our hyperopic
cohort ACD did not correlate with corneal biomechanics, while in the emmetropic group an
inverse correlation was found. These differing results suggest that more research is needed,
and that refractive state may have a big influence over the biomechanical—morphological
interactions.
The corneal endothelium is the innermost layer of the cornea, consisting of tightly
interconnected cells, with an essential role in maintaining proper corneal hydration and
transparency [34]. It is a single-cell layer, with limited capacity for regeneration [35]. In
normal eyes, the annual rate of cell loss is 0.6%, and there are several systemic and ocular
conditions which may increase this rate during the course of the patient’s life [34,36].
Similarly, in our study there is a correlation between age and cell density and variability,
also a significant difference between adults and children, which suggest a decrease in
density and uniformity of endothelial cells as patients age. However, as the present study
is cross-sectional, a rate of cell loss could not be calculated to compare the hyperopic and
emmetropic patients.
The corneal endothelium is an ocular structure which may be influenced by systemic
conditions, such as diabetes mellitus. Several morphological alterations have been recorded
in DM, including reduced cell density, polymorphism, and a higher cell loss rate which
correlates with longer disease duration and low glycemic control [37]. Endothelial cell
dysfunction has been described also in the context of hyperlipidemia, smoking or in patients
with a history of ischemic stroke [34].
As stated previously, hyperopia is a significant PACG risk factor, and several studies
have found lower CD in PACG compared to open-angle glaucoma [38] or compared to
healthy controls [35]. Both in emmetropes and in hyperopes we have found a correlation
between CD, CV and ACD—a shallower anterior chamber is correlated with a decrease in
endothelial cell density and increase in variability, which may have important repercussions
over the patient’s lifetime.
Our study has found statistically significant, moderate-to-strong correlations between
CH and CRF and endothelial cell count and variability. However, to the best of our
knowledge, these findings differ from those in the literature, where no significant correlation
has been found between biomechanical and endothelial corneal parameters in healthy
volunteers [39] or in patients with cataract [40]. As the level of corneal hydration, which
is regulated by the endothelial pump function, may influence corneal biomechanics [39],
Medicina 2023, 59, 1660 8 of 10

more studies are needed in order to identify the factors that modulate the relationship
between CH, CRF and endothelium parameters.
Our study shows the inverse correlation between age and biomechanical parameters
(CH and CRF), anterior segment morphology (ACD) and endothelial layer parameters
(Cell density, variability or hexagonality). However, it is cross-sectional; therefore, it does
not follow the patients’ evolution over time, in relation to these variables. Prospective
follow-up studies of hyperopic cohorts are needed, in order to assess this evolution over
decades and to evaluate the PACG risk.

5. Conclusions
Our research suggests a significant difference between young emmetropes and hy-
peropes in terms of ACD, CH and CRF. Moreover, there are significant correlations in
the hyperopic group: negative between age and either ACD, CD, CH or CRF, between
morphological and biomechanical parameters (AL, CCT and CH, CRF), endothelial and
either morphological or biomechanical parameters (ACD-CD, ACD-CV, CH-CD, CRF-CV,
CH-CV). The negative correlation between age and ACD, both in emmetropes and hy-
peropes, suggests a shallower anterior chamber as patients grow older, increasing the
risk for PACG. Considering the amblyopia risk in children and the PACG risk later in life
that hyperopia raises, a long-term ophthalmological follow-up plan could be a reasonable
suggestion for young hyperopes.

Author Contributions: All authors had equal contributions, equal to the first author. All authors
have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki, and approved by the Research Ethics Committee of Carol Davila University of Medicine
and Pharmacy (protocol code PO-35-F-03/16.01.2023).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study, and from legal guardians in the case of participants under the age of 18.
Data Availability Statement: The datasets generated during and/or analyzed during the current
study are available from the corresponding author on reasonable request.
Acknowledgments: Publication of this paper was supported by the University of Medicine and
Pharmacy Carol Davila, through the institutional program Publish not Perish.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Kandel, H.; Khadka, J.; Goggin, M.; Pesudovs, K. Impact of Refractive Error on Quality of Life: A Qualitative Study. Clin. Exp.
Ophthalmol. 2017, 45, 677–688. [CrossRef] [PubMed]
2. Hashemi, H.; Fotouhi, A.; Yekta, A.; Pakzad, R.; Ostadimoghaddam, H.; Khabazkhoob, M. Global and Regional Estimates of
Prevalence of Refractive Errors: Systematic Review and Meta-Analysis. J. Curr. Ophthalmol. 2017, 30, 3–22. [CrossRef] [PubMed]
3. Mocanu, V.; Horhat, R. Prevalence and Risk Factors of Amblyopia among Refractive Errors in an Eastern European Population.
Medicina 2018, 54, 6. [CrossRef] [PubMed]
4. Bountziouka, V.; Cumberland, P.M.; Rahi, J.S. Impact of Persisting Amblyopia on Socioeconomic, Health, and Well-Being
Outcomes in Adult Life: Findings from the UK Biobank. Value Health 2021, 24, 1603–1611. [CrossRef]
5. Shen, L.; Melles, R.B.; Metlapally, R.; Barcellos, L.; Schaefer, C.; Risch, N.; Herrinton, L.J.; Wildsoet, C.; Jorgenson, E. The
Association of Refractive Error with Glaucoma in a Multiethnic Population. Ophthalmology 2016, 123, 92–101. [CrossRef]
6. Sit, A.J.; Chen, T.C.; Takusagawa, H.L.; Rosdahl, J.A.; Hoguet, A.; Chopra, V.; Richter, G.M.; Ou, Y.; Kim, S.J.; WuDunn, D.
Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of
Ophthalmology. Ophthalmology 2023, 130, 433–442. [CrossRef] [PubMed]
7. Gerena Arévalo, V.A.; Ruiz-Moreno, J.M. Choroidal Thickness in a Hyperopic Pediatric Population. Diagnostics 2022, 12, 2330.
[CrossRef]
8. Monika, M.; Durajczyk, M. Evaluation of the Prevalence of Refractive Defects and Ocular Function in a Group of 1518 Children
Aged 8 Years in Northwestern Poland-A Retrospective Study. J. Clin. Med. Res. 2023, 12, 2880. [CrossRef]
Medicina 2023, 59, 1660 9 of 10

9. Hagen, L.A.; Gilson, S.J.; Akram, M.N.; Baraas, R.C. Emmetropia Is Maintained Despite Continued Eye Growth From 16 to
18 Years of Age. Investig. Ophthalmol. Vis. Sci. 2019, 60, 4178–4186. [CrossRef]
10. Roberts, C.J.; Liu, J. Corneal Biomechanics: From Theory to Practice; Kugler Publications: Amsterdam, The Netherlands, 2017; ISBN
9789062998760.
11. Chaurasia, S.; Vanathi, M. Specular Microscopy in Clinical Practice. Indian J. Ophthalmol. 2021, 69, 517. [CrossRef]
12. Mandal, P.; Berrow, E.J.; Naroo, S.A.; Wolffsohn, J.S.; Uthoff, D.; Holland, D.; Shah, S. Validity and Repeatability of the Aladdin
Ocular Biometer. Br. J. Ophthalmol. 2014, 98, 256–258. [CrossRef] [PubMed]
13. Brodie, S.E. 2022–2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision... Rehabilitation Print; American
Academy of Ophthalmology: San Francisco, CA, USA, 2022; ISBN 9781681045436.
14. Pniakowska, Z.; Jurowski, P.; Wierzbowska, J. Clinical Evaluation of Corneal Biomechanics Following Laser Refractive Surgery in
Myopic Eyes: A Review of the Literature. J. Clin. Med. Res. 2023, 12, 243. [CrossRef] [PubMed]
15. Potop, V.; Coviltir, V.; Schmitzer, S.; Corbu, C.; Ionescu, I.C.; Burcel, M.; Dăscălescu, D. The Relationship Between Corneal
Hysteresis and Retinal Ganglion Cells—A Step Forward in Early Glaucoma Diagnosis. Med. Sci. Monit. 2020, 26, e924672.
[CrossRef] [PubMed]
16. Potop, V.; Coviltir, V.; Corbu, C.; Burcel, M.G.; Ionescu, C.I.; Dascalescu, D.M.C. Corneal Hysteresis, A Glaucoma Risk Factor
Independent of The Intraocular Pressure. Rev. Roum. Des Sci. Tech. Série Électrotechnique Énergétique 2019, 64, 297–300.
17. Tur, V.M.; MacGregor, C.; Jayaswal, R.; O’Brart, D.; Maycock, N. A Review of Keratoconus: Diagnosis, Pathophysiology, and
Genetics. Surv. Ophthalmol. 2017, 62, 770–783.
18. Marinescu, M.; Dascalescu, D.; Constantin, M.; Coviltir, V.; Burcel, M.; Darabus, D.; Ciuluvica, R.; Stanila, D.; Voinea, L.; Potop,
V. Corneal Biomechanical Properties in Myopic and Emmetropic Children. Eur. Rev. Med. Pharmacol. Sci. 2023, 27, 3580–3589.
[CrossRef]
19. Zhang, B.; Shweikh, Y.; Khawaja, A.P.; Gallacher, J.; Bauermeister, S.; Foster, P.J. UKBiobank Eye and Vision Consortium
Associations with Corneal Hysteresis in a Population Cohort: Results from 96 010 UK Biobank Participants. Ophthalmology 2019,
126, 1500–1510. [CrossRef]
20. Sharifipour, F.; Panahi-bazaz, M.; Bidar, R.; Idani, A.; Cheraghian, B. Age-Related Variations in Corneal Biomechanical Properties.
J. Curr. Ophthalmol. 2016, 28, 117. [CrossRef]
21. Murphy, M.L.; Pokrovskaya, O.; Galligan, M.; O’Brien, C. Corneal Hysteresis in Patients with Glaucoma-like Optic Discs, Ocular
Hypertension and Glaucoma. BMC Ophthalmol. 2017, 17, 1. [CrossRef]
22. Hashemi, H.; Jafarzadehpur, E.; Mehravaran, S.; Yekta, A.; Ostadimoghaddam, H.; Norouzirad, R.; Khabazkhoob, M. Corneal
Resistance Factor and Corneal Hysteresis in a 6- to 18-Year-Old Population. J. Cataract. Refract. Surg. 2014, 40, 1446–1453.
[CrossRef]
23. Refai, T.A. Correlation between Apical Protrusion in the Scheimflug Imaging and Corneal Hysteresis and Corneal Resistance
Factor by Ocular Response Analyzer, among Refractive Non-Keratoconic Egyptian Patients. Electron. Physician 2015, 7, 1394–1398.
[CrossRef] [PubMed]
24. Rosa, N.; Lanza, M.; De Bernardo, M.; Signoriello, G.; Chiodini, P. Relationship Between Corneal Hysteresis and Corneal
Resistance Factor with Other Ocular Parameters. Semin. Ophthalmol. 2015, 30, 335–339. [CrossRef] [PubMed]
25. Hwang, H.S.; Park, S.K.; Kim, M.S. The Biomechanical Properties of the Cornea and Anterior Segment Parameters. BMC
Ophthalmol. 2013, 13, 49. [CrossRef] [PubMed]
26. Shah, R.; Amador, C.; Tormanen, K.; Ghiam, S.; Saghizadeh, M.; Arumugaswami, V.; Kumar, A.; Kramerov, A.A.; Ljubimov, A.V.
Systemic Diseases and the Cornea. Exp. Eye Res. 2021, 204, 108455. [CrossRef] [PubMed]
27. del Buey, M.A.; Casas, P.; Caramello, C.; López, N.; de la Rica, M.; Subirón, A.B.; Lanchares, E.; Huerva, V.; Grzybowski, A.;
Ascaso, F.J. An Update on Corneal Biomechanics and Architecture in Diabetes. J. Ophthalmol. 2019, 2019, 7645352. [CrossRef]
28. Sedaghat, M.-R.; Momeni-Moghaddam, H.; Azimi, A.; Fakhimi, Z.; Ziaei, M.; Danesh, Z.; Roberts, C.J.; Monfared, N.; Jamali, A.
Corneal Biomechanical Properties in Varying Severities of Myopia. Front. Bioeng. Biotechnol. 2021, 8, 595330. [CrossRef]
29. Weinreb, R.N.; Aung, T.; Medeiros, F.A. The Pathophysiology and Treatment of Glaucoma: A Review. JAMA 2014, 311, 1901.
[CrossRef]
30. Phu, J.; Tong, J.; Zangerl, B.; Le, J.L.; Kalloniatis, M. Cluster Analysis Reveals Patterns of Age-related Change in Anterior Chamber
Depth for Gender and Ethnicity: Clinical Implications. Ophthalmic Physiol. Opt. 2020, 40, 632. [CrossRef]
31. Trikha, S.; Perera, S.A.; Husain, R.; Aung, T. The Role of Lens Extraction in the Current Management of Primary Angle-Closure
Glaucoma. Curr. Opin. Ophthalmol. 2015, 26, 128–134. [CrossRef]
32. Ong, A.Y.; Ng, S.M.; Swaroop Vedula, S.; Friedman, D.S. Lens Extraction for Chronic Angle-closure Glaucoma. Cochrane Database
Syst. Rev. 2021, 2021, CD005555. [CrossRef]
33. Bueno-Gimeno, I.; Martínez-Albert, N.; Gené-Sampedro, A.; España-Gregori, E. Anterior Segment Biometry and Their Correlation
with Corneal Biomechanics in Caucasian Children. Curr. Eye Res. 2019, 44, 118–124. [CrossRef]
34. Vaiciuliene, R.; Rylskyte, N.; Baguzyte, G.; Jasinskas, V. Risk Factors for Fluctuations in Corneal Endothelial Cell Density (Review).
Exp. Ther. Med. 2022, 23, 129. [CrossRef] [PubMed]
35. Kang, D.; Kaur, P.; Singh, K.; Kumar, D.; Chopra, R.; Sehgal, G. Evaluation and Correlation of Corneal Endothelium Parameters
with the Severity of Primary Glaucoma. Indian J. Ophthalmol. 2022, 70, 3540–3543. [CrossRef]
Medicina 2023, 59, 1660 10 of 10

36. Reinprayoon, U.; Jermjutitham, M.; Kasetsuwan, N. Rate of Cornea Endothelial Cell Loss and Biomechanical Properties in Fuchs’
Endothelial Corneal Dystrophy. Front. Med. 2021, 8, 757959. [CrossRef] [PubMed]
37. Ramm, L.; Spoerl, E.; Pillunat, L.E.; Terai, N. Is the Corneal Thickness Profile Altered in Diabetes Mellitus? Curr. Eye Res. 2020, 45,
1228–1234. [CrossRef] [PubMed]
38. Sugumaran, A.; Devasena, M.A.; Thomas, M.; Periyathambi, D. A Cross Sectional Study on Evaluating the Corneal Endothelial
Cell Density and Central Corneal Thickness in Eyes with Primary Glaucoma. J. Fam. Med. Prim. Care 2022, 11, 4650–4654.
[CrossRef]
39. Akova-Budak, B.; Kıvanç, S.A. Does Corneal Hysteresis Correlate with Endothelial Cell Density? Med. Sci. Monit. 2015, 21, 1460.
[CrossRef]
40. Iancu, R.C.; Bujor, I.A.; Iliut, ă, C.; S, tefania, T.; Ungureanu, E.; Pas, ca, I.G.; Istrate, S. Correlations between Corneal Biomechanics
and Specular Microscopy in Patient with Cataract. Rom. J. Ophthalmol. 2020, 64, 132. [CrossRef]

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