This article appeared in a journal published by Elsevier.

The attached
copy is furnished to the author for internal non-commercial research
and education use, including for instruction at the authors institution
and sharing with colleagues.
Other uses, including reproduction and distribution, or selling or
licensing copies, or posting to personal, institutional or third party
websites are prohibited.
In most cases authors are permitted to post their version of the
article (e.g. in Word or Tex form) to their personal website or
institutional repository. Authors requiring further information
regarding Elsevier’s archiving and manuscript policies are
encouraged to visit:
http://www.elsevier.com/copyright
 Author's personal copy

Bioscience Hypotheses (2008) 1, 5e8

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/bihy

Introducing the shape of globe as a predisposing

factor for glaucoma
Alireza Mehdizadeh, Amin Hoseinzadeh*, Afsoon Fazelzadeh

School of Medicine, Mashad University of Medical Sciences, Mashad, Iran

Received 29 January 2008; accepted 30 January 2008

KEYWORDS Abstract Glaucoma is a common blinding disease worldwide with a number of risk factors
Glaucoma; such as intraocular pressure, myopia, gender, race and hyperopia. Here we introduce eyeball’s
Predisposing factor; shape as a predisposing factor for glaucoma. If the eyeball is a sphere, the stress distribution is
Shape of globe; homogenous. We assume the eyeball as a non sphere. Then, the distribution of stress will not
Spatial configuration; be homogenous. Different individuals have different eyeball’s shapes and different patterns of
Biomechanics; stress distribution in their eyes. So based on the eyeball’s shape deviation from a sphere they
Stress; will have different risks for glaucoma. The eyeball is routinely considered as a sphere, but
Strain some evidences show that the globe is not a sphere. Two empirical observations are consistent
with the hypothesis. The first is that ethnicity and sex are established risk factors for glau-
coma. On the other hand there are several morphological differences in the body structure
among individuals. According to these anatomical differences, eye’s shape is different among
different races and between two sexes. Secondly, there are some conditions such as myopia
and hyperopia in them the shape of the globe has been changed. These conditions are risk fac-
tors for glaucoma too. Glaucoma screening program for early detection of high risk individuals
is very important. Current diagnostic procedures of glaucoma do not take the shape of eyeball
into account. We suggest using eyeball’s shape for early glaucoma detection. There are three
other factors in addition to eyeball’s shape, including thickness of the globe’s wall, intraocular
pressure, and inner radius that should be measured together for each individual and stress load
should be calculated in different points of the globe. Then eyes with more stress load in site of
injury are more prone for glaucoma. More accurate measurements of the factors which are
contributing in stress value for each case, lead us toward better glaucoma screening.
ª 2008 Elsevier Ltd. All rights reserved.

Introduction

The term glaucoma refers to a group of diseases that have in

* Corresponding author. Tel.: þ98 9177075754; fax: þ98 7118421834. common a characteristic optic neuropathy with associated
E-mail address: hoseinzadeha831@mums.ac.ir (A. Hoseinzadeh). visual field loss [1]. Glaucoma is a complex disease with

1756-2392/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bihy.2008.01.009
 Author's personal copy
6 A. Mehdizadeh et al.
a number of risk factors such as intraocular pressure (IOP), my-
opia, gender, race, genetic predisposition and hyperopia [2].
Two principal theories for the pathogenesis of glaucoma
have been described: a mechanical and an ischemic theory
[3]. We introduced a new theory for glaucoma [4], in which
mechanical stress is the main responsible factor for glau-
comatous damage. According to the stress theory, stress
develops glaucomatous damage by two ways:
1. Stress generates strain (tissue deformation) within tis-
sues that experience load. Strain can deform and inter-
rupt the retinal layers, which end in glaucoma. The
magnitude of strain is based on the material properties
of the tissues, including how well the tissues are able to
resist deformations induced by the applied stress [5].
2. Also, stress pressurizes vessels, which leads to obstruc-
tion of retinal vessels and decreased perfusion of the
optic nerve cells and finally cell death [5].
The biomechanical model for the eye
From a geometrical standpoint, a sphere is the set of all
points in three-dimensional (3D) space which is at distance
of ‘‘r’’ from a fixed point of that space, where ‘‘r’’ is a pos-
itive real number called the radius of the sphere. The
sphere is the only complete symmetrical spatial configura-
tion while a spheroid is a quadric surface obtained by rotat-
ing an ellipse about one of its principal axes and in spite of
sphere; it is not completely symmetric [6].
Stress (s) is an applied force and strain is the deforma-
tion in the material to which stress has been applied [7].
Analysis of the eye as an idealized spherical shell is
considered. Within the wall of any pressurized spherical
shell, the two principal stresses reside within the plane of
the sphere wall (the third stress is radial in direction and
minimal in magnitude; Fig. 1).
In the eyeball, linear elasticity theory predicts that the
planar wall stresses are equal and orthogonal, and that
each stress can be approximated by the equation:
Figure 1 Depiction of principal stresses within a thin-walled
spherical pressure vessel of radius R. The two largest principal
stresses, s1 and s2, are equal, at right angles to each other, and
reside within the plane of the wall. The third principal stress,
sr, is minimal in magnitude and directed toward the center of
the sphere [8].
sZPR=2t ð1Þ
where P is the inner pressure (IOP), R is the inner radius of
the sphere (approximately one half of the axial length), and
t is the thickness of the sphere wall (scleral thickness) [8].
Today, the Goldmann applanation tonometer provides
the gold standard for the clinical measurement of IOP [9].
Axial length and scleral thickness were measured ultrason-
ically using A-scan ultrasonography and ultrasound biomi-
croscopy (UBM), respectively [10].
The hypothesis
IOP-related force has a predictable distribution and leads
to predictable levels of IOP-related stress [11]. Stress distri-
bution is homogenous in all points of a sphere. In a non-
sphere configuration for example a spheroid, there is not
complete symmetry (3D); then stress distribution is not ho-
mogenous and stress is less at some points and more at the
others.
If the eyeball is a sphere, then the stress distribution is
homogenous in all its points. Here we assume the eyeball as
a non-sphere. So, the distribution of IOP-related stress
won’t be homogenous and stress magnitude would be less
at some points and more at the others.
Different individuals have different eyeball’s shapes and
different patterns of stress distribution in their eyes. So based
on the eyeball’s shape deviation from a sphere, they will have
more or less stress load in the site of glaucoma injury.
In other words, distribution and magnitude of IOP-related
stress within the site of glaucoma injury for a given level of
IOP are primarily determined by the 3D shape of the eye.
There are other examples of the effect of geometry and
shape on the magnitude and distribution of wall stress [12].
Since stress is the main responsible factor for glaucoma,
risk of glaucoma varies among different populations. So, we
introduce eyeball’s shape as a predisposing factor for
glaucoma.
Discussion
Like all other events in nature, glaucomatous damage has
specific causes and glaucoma presents with specific pat-
terns and does not occur at random [2]. Recognizing glau-
coma predisposing factors helps us understand the
mechanism of disease and guides screening and treatment
toward specific populations and subpopulations.
The eyeball is routinely considered as a sphere, but
there are some evidences show that the globe is not
a sphere. One of them obtained from eyeball imaging
shows that the contours and the plane sections of the
globe are not definite circle (Fig. 2).
Two empirical observations are consistent with the
hypothesis. The first is that ethnicity and sex are estab-
lished risk factors for glaucoma. For example, the preva-
lence of glaucoma is 20e40 times higher in Eskimos than in
Caucasians [13]. Congdon et al. [13] and the Rotterdam
study [14] in their studies found different prevalence of
glaucoma between men and women. There are several
morphological differences in the body structure among in-
dividuals. The false pelvis is shallow in the female and
 Author's personal copy
Introducing shape of the globe as a predisposing factor for glaucoma
Figure 2 MRI slices of the eye. The images are of a female participant’s eye. Scans were taken in the sagittal plane (a) and
through the axial section (b) of the eye. Length measures (millimeters) were taken from both the axial and sagittal sections, height
from the sagittal image, and width from the axial image. A, anterior; P, posterior; N, nasal; T, temporal; S, superior; I, inferior.
(From: Atchison DA, Jones CE, Schmid KL, Pritchard N, Pope JM, Strugnell WE, Riley RA. Eye shape in emmetropia and myopia.
Investig Ophthalmol Vis Sci 2004;45:3380e6.)
deep in the male. The pelvis inlet is transversely oval in the
female but hurt shaped in the male. The pelvis cavity is
roomier in the female than in the male, and the distance
between the inlet and the outlet is much shorter. The pel-
vic outlet is larger, the sacrum is shorter, wider and flatter
and the pubic arch is more rounded and wider in the fe-
male than in the male [15]. The angle of the elbow is
more valgus in the female than in the male [16].
Tallness varies among different races. Pelvic inlet shape
is different among women of different races and is
classified into four groups: gynecoid, android, anthropoid
and platypelloid according to its shape [15].
In the eye we can see structural differences among
different ethnicities and sexes; for example axial length
and optic disc area are bigger in blacks than whites [17].
Anterior chamber depth and eye size are smaller in women
than men [18].
According to these anatomical differences that exist in
body structure, variation in shape of the eyeball is also
possible.
Secondly, there are some conditions such as myopia
and hyperopia in which, the shape of the globe, for
example its axial length has been changed. These condi-
tions are considered as risk factors for glaucoma [2] and
the current explanation of this relationship is that ana-
tomical alterations of the eyeball’s shape in such condi-
tions may involve trabecular meshwork [19] but in our
theory this anatomical alteration directly leads to increas-
ing the risk of glaucoma by changing the distribution of
IOP-related stress load.
Since glaucoma has no clinical manifestation until the last
stages and is one of leading causes of irreversible blindness
throughout the world [20], glaucoma screening program for
early detection of high-risk individuals and their management
is very important. Current glaucoma screening methods in-
clude IOP measurement, optic nerve head and peripapillary
retinal evaluation and visual function tests [21].
Current diagnostic procedures of glaucoma do not take
the shape of eyeball or oculometric measurements into
account.
7
We suggest using eyeball’s shape for early detection of
glaucoma. There are three other factors in addition to
eyeball’s shape, including thickness of the globe’s wall
which was shown previously by authors to be related with
central corneal thickness (CCT) [22], pressure (IOP), and in-
ner radius that should be measured together for each indi-
vidual and stress load should be calculated in different
points of the globe. Then eyes with more stress load in
the site of glaucoma injury are more prone to glaucoma.
References
[1] Introduction and definitions. In: Glaucoma. San Francisco:
American Academy of Ophthalmology; 2004e2005. p. 3.
[2] Coleman A. Epidemiology of glaucoma. In: Morrison J,
Pollack I, editors. Glaucoma: science and practice. New
York: Thieme; 2002. p. 2.
[3] Flammer J, Orgul S, Costab VP, Orzalesic N, Krieglsteind GK,
Serrae LM. The impact of ocular blood flow in glaucoma.
Prog Retin Eye Res 2002;21:359e93.
[4] Mehdizadeh AR, Hoseinzadeh A, Fazelzadeh A. What is the
real cause of glaucoma? Med Hypotheses 2007;69:459e60.
[5] Hoseinzadeh A, Movahedi MM, Mehdizadeh AR. A novel
mechanism for the pathogenesis of glaucoma based on
biomechanical properties of the eye. Iran J Med Phys 2007;
4:10e6.
[6] Hilbert D, Cohn-Vossen S. Geometry and the imagination. 2nd
ed. Chelsea: American Mathematical Society; 1999.
[7] Brown K, Congdon N. Corneal structure and biomechanics:
impact on the diagnosis and management of glaucoma. Curr
Opin Ophthalmol 2006;17:338e43.
[8] Bellezza AJ, Hart RT, Burgoyne CF. The optic nerve head as
a biomechanical structure: initial finite element modeling.
Invest Ophthalmol Vis Sci 2000;41:2991e3000.
[9] Smith MF, Doyle JW. Clinical examination of glaucoma. In:
Yanoff M, Duker JS, Augsburger JJ, editors. Ophthalmology.
2nd ed. St Louis, Missouri: Mosby; 2004. p. 1431.
[10] Oliveira C, Tello C, Ritch R, Liebmann JM. Correlation
between central corneal thickness, scleral thickness and re-
fractive error [ARVO abstract]. Invest Ophthalmol Vis Sci
2004;45:e-abstract 963.
 Author's personal copy
8 A. Mehdizadeh et al.
[11] Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. The op-
tic nerve head as a biomechanical structure: a new paradigm
for understanding the role of IOP-related stress and strain in
the pathophysiology of glaucomatous optic nerve head
damage. Prog Retin Eye Res 2005;24:39e73.
[12] Wells DR, Archie Jr JP, Kleinstreuer C. Effect of carotid artery
geometry on the magnitude and distribution of wall shear
stress gradients. J Vasc Surg 1996;23:667e78.
[13] Congdon N, Wang F, Tielsch JM. Issues in the epidemiology and
population-based screening of primary angle-closure
glaucoma. Surv Ophthalmol 1992;36:411e23.
[14] Dielemans I, Vingerling JR, Wolfs RCW. The prevalence of
primary open-angle glaucoma in a population based study in
the Netherlands. Ophthalmology 1994;101:151e5.
[15] The pelvic walls. In: Snell RS, editor. Clinical anatomy. 7th ed.
Baltimore: Lippincott Williams & Wilkins; 2004. p. 335e53.
[16] The upper limb. In: Snell RS, editor. Clinical anatomy. 7th ed.
Baltimore: Lippincott Williams & Wilkins; 2004. p. 570e1.
[17] Oliveira C, Harizman N, Girkin CA, Xie A, Tello C,
Liebmann JM, et al. Axial length and optic disc size in normal
eyes. BJO 2007;91:37e9.
[18] Risk factors for glaucoma. In: Gupta D, editor. Glaucoma: di-
agnosis and management. Philadelphia: Williams & Wilkins;
2005. p. 6.
[19] Harris A, Rechtman E, Siesky B, Jonescu-Cuypers C,
McCranor L, Garzozi H. The role of optic nerve blood flow in
the pathogenesis of glaucoma. Ophthalmol Clin N Am 2005;
18:345e53.
[20] Epidemiology. In: Gupta D, editor. Glaucoma: diagnosis and
management. Philadelphia: Lippincott Williams & Wilkins;
2005. p. 3.
[21] Glaucoma screening. In: Shields MB, editor. Textbook of glau-
coma. 4th ed. Baltimore: Williams & Wilkins; 1998. p. 137e41.
[22] Mehdizadeh AR, Hoseinzadeh A, Fazelzadeh A. Central
corneal thickness as a risk factor for glaucoma. Med Hypothe-
ses 2007;69:1205e7.