Intraocular Pressure: Protagonist or Supporting Actor in
Glaucoma?
Raffaella Morreale
Bubella
Raffaella Morreale Bubella, Derpartment of Experimental
Biomedicine and Clinical Neuoscience (BioNeC), University of Palermo, Via XII
Gennaio 1G, Palermo, 90100, Italy
Correspondence to:
Raffaella Morreale Bubella, MD, PhD, Derpartment of Experimental Biomedicine and Clinical
Neuoscience (BioNeC), University of Palermo, mVia XII Gennaio 1G, Palermo,
90100, Italy
Email: Rmorrealebubella@email.it
Telephone: +39092225663
Received: March 21, 2015
Revised: June 1, 2015
Accepted: June 5, 2015
Published online: September 6, 2015
ABSTRACT
Glaucoma, one of the principal causes of visual
disability and blindness around the world, is considered a progressive form of
optical neuropathy often associated with elevated intraocular pressure (IOP)
consequent on abnormal elevated resistance to draining of aqueous humour (AH)
through the trabecula (TM) and the Schlemm’s canal. Despite in-depth
researches, its aetiology still remains to be clarified. However, all authors
agree that the main risk factor on which it is possible to act therapeutically
is elevated intraocular pressure (IOP).
© 2015 ACT. All rights reserved.
Key words: Glaucoma; IOP;
Optical neuropathy; Aqueous humour
Morreale BR. Intraocular Pressure: Protagonist
or Supporting Actor in Glaucoma? International Journal of Ophthalmic Research 2015; 1(1): 45-47
Available from: URL: http://www.ghrnet.org/index.php/ijor/article/view/1126
REVIEW
Glaucoma, one of the principal causes of visual disability and
blindness around the world, is considered a progressive form of optical
neuropathy often associated with elevated intraocular pressure (IOP) consequent
on abnormal elevated resistance to draining of aqueous humour (AH) through the
trabecula (TM) and the Schlemm’s canal. Despite in-depth researches, its
aetiology still remains to be clarified. However, all authors agree that the
main risk factor on which it is possible to act therapeutically is elevated
intraocular pressure (IOP).
Actually, a
vast range of clinical studies on a wide scale is in agreement that the
objective of therapy must be to maintain an IOP level such as to arrest the
progression of the glaucomatous process[1,2] keeping repercussions
on patients’ quality of life to the minimum. In this connection, reduction of
IOP, especially if carried out in an early phase of the illness, not only
reduces or arrests its evolution, but can involve improvement of psychophysical
visual sensitivity, with an increase in ampleness of PERG[3] and in
any case a reduction in the typical progressive loss of the visual field[4].
It has been
found that alongside glaucoma patients with raised IOP (HTG) there are others
in whom determination of IOP with the traditional methods shows it to be within
the normalcy range (glaucoma with normal pressure, NTG) and this observation
has challenged the real role of IOP. Fluctuations in IOP and their entities are
therefore considered most relevant.
Study of
variation in intraocular pressure with tonometric curves[5] has
shown that it presents a typical sinusoidal pattern with the acrophase in the
nocturnal hours, probably because of the lying position taken up by the subject
during sleep. During the day too fluctuations are quite frequent, with
differences in values above 6 mm of Hg. This involves a further risk for the
optic nerve[6,7], and hence the need for a diurnal and possibly
nocturnal tonometric check, which is possible today through devices like contact
lens sensors[8].
Fluctuations
are numerous and larger in subjects with type A personality[9,10] in
whom progression of the damage to the visual field proves to be accelerated.
The increase in IOP in these patients could also be connected to the action of
catecholamines on the beta-2 receptors situated in the pigmented epithelium of
the ciliary bodies, which, as is well known, involves an increase in synthesis
of cyclic AMP (AMPc) with a consequent increase in the production of aqueous
humour, one of the factors on which intraocular pressure depends.
IOP is the
result of the balance between the quantity of aqueous humour that the eye
produces and the facility with which it leaves the eye, according to Goldmann’s
classical equation: Po = (F/C) + Pv. [Po = IOP in millimetres of mercury (mm
Hg), F = velocity of aqueous formation, C = facility of outflow and Pv =
episcleral venous pressure].
Fluctuations
in and imperfect control of IOP may also depend on poor compliance of the
patient due to the chronic nature of the treatment and the side effects that
the therapy involves. In this connection, it has been observed that using
preparations devoid of BAC (Benzalkonium chloride) the compliance markedly
increases, and the quality of life, evaluated with the OSDI questionnaire
(Ocular Surface Disease Index), is clearly improved[11].
The
pathogenetic role of IOP fluctuations imposes the use of medicines with
long-term action. Indeed, it is only in this way that the range of diurnal
fluctuations can be reduced[12] with deceleration of the
glaucomatous damage. A more marked reduction in fluctuations can be obtained by
means of trabeculectomy. As K. Mansouri et al observe[13]
this procedure determines a statistically significant increase in reduction of
the average values of the diurnal tonometric curve, also reducing the size of
the fluctuations in comparison to what is observed in subjects in
pharmacological treatment (Latanoprost). This study highlights the pathogenetic
role in regulation of IOP played by the trabecula, whose endothelial cells,
organized in a three-dimensional network, interact with the free radicals that
are formed in the aqueous humour.
Morphological
and biochemical analyses of the trabecula of patients with POAG have revealed
loss of cells, greater accumulation of proteins of the extracellular matrix
(ECM), changes in the cytoskeleton and cellular ageing[14]. Hence
the trabecula constitutes the fabric target of glaucoma and its development and
progression accompany oxidising damage to it, as is confirmed by various
studies[15,16], which have also stressed that the medicines used for
IOP reduction are substances with antioxidant activities able to protect the
cells of the trabecula and their mitochondrial components.
Damage to the
trabecula could point to a genetic predisposition[17], shown to be
frequent in blood relations of subjects with POAG, as the basis on which
oxidizing stress would act, in turn triggering, with further cellular damage,
the increase in IOP.
This increase
is responsible both for the damage to the ganglionic cells, with activation of
apoptosis and consequent irreversible deficits of the visual field, as observed
in animal models[18,19], and for the further damage to the cells of
the trabecula. A vicious circle would thus be activated that is destined to
maintain itself with progressive damage to the ganglionic cells.
Recently, on
the basis of observations in experimental animal models, the hypothesis has
been put forward that an increase in IOP may also be consequent on a NO (Nitric
oxide) deficit. This deficit, as is well known, favours the outflow of aqueous
humour from the anterior chamber, reducing the volume of the cells of the
trabecula and, through relaxation of the smooth musculature, favouring
expansion of the Schlemm’s canal. Ultimately, the increase in IOP would be the
result of the convergence of various factors that each time can variously
overlap.
Hence, from
what has so far been acquired, it can be concluded that IOP plays an ambivalent
role, behaving as a risk factor in certain respects and as a consequence of the
glaucomatous process in others.
Thus the relationship between IOP and glaucoma, though evident, in
various respects still needs to be clarified.
CONFLICT
OF INTERESTS
The author has no conflicts of
interest to declare.
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Peer reviewer: Benjamin Donnadieu, Hopital Nord, Chemin des bourrelys,
13015 Marseille, France.
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