Glaucoma almost always follows a congenital
or acquired lesion of the anterior segment of the eye that mechanically
obstructs the aqueous drainage.
The obstruction may be located between the
iris and lens, in the angle of the anterior chamber, in the trabecular
meshwork, in Schlemm’s canal, or in the venous drainage of the eye.
Glaucoma resulting from a hypersecretion of aqueous humor is extremely
rare, if it occurs at all.
Glaucoma may develop in a person with no
apparent underlying eye disease (primary glaucoma) or it may follow a
known antecedent or concomitant ocular disorder (secondary glaucoma).
By tradition the term congenital glaucoma refers to glaucoma
caused by an obstruction of the aqueous drainage by developmental
anomalies, even though the intraocular pressure may not become elevated
until early infancy or childhood.
Most cases of congenital glaucoma are
males (60% to 70%), and an X-linked recessive mode of inheritance is
common.
The developmental anomaly usually involves both eyes and, while
often limited to the angle of the anterior chamber, may be accompanied by
a variety of other ocular malformations.
Congenital glaucoma is often
associated with a deep anterior chamber, corneal cloudiness, sensitivity
to bright lights (photophobia), excessive tearing, and enlarged eyes (buphthalmos).
- Primary Glaucoma:
Primary glaucomas are of
two types :
1) Open angle glaucoma and
2) Closed angle (narrow-angle)
glaucoma.
1. Primary Open Angle Glaucoma: Primary open-angle glaucoma, the commonest type of glaucoma and an
important blinding disorder affecting patients over the age of 40 years and occurs principally in the
sixth decade.
The intraocular pressure becomes elevated insidiously and
asymptomatically, and while almost always bilateral, one eye may be
affected more severely than the other.
With time, damage to the retina and
optic nerve causes an irreversible loss of peripheral vision.
The angle of
the anterior chamber is open and appears normal, but an increased
resistant to the outflow of the aqueous humor is present within the
vicinity of Schlemm’s canal.
Individuals with
diabetes mellitus and myopia appear to have an increased risk of primary
open-angle glaucoma.
2. Primary Closed Angle Glaucoma: Primary
narrow-angle glaucoma occurs, especially after the age of 40 years, in
individuals who possess an abnormally narrow angle, in which the
peripheral iris is displaced anteriorly towards the trabecular meshwork.
When the pupil is constricted (miotic), the iris remains stretched, so
that the chamber angle is not occluded.
However, when the pupil is dilated
(mydriasis), the iris obstructs the anterior chamber angle, thereby
impairing aqueous drainage and resulting in sudden episodes of intraocular
hypertension.
This is accompanied by ocular pain, and halos or rings are seen around
lights.
In such individuals the intraocular pressure may also become
elevated if the pupil becomes blocked, for example by a swollen lens, and
aqueous humor accumulates in the anterior chamber.
Primary
closed-angle glaucoma affects both eyes, but it may become apparent in
one eye 2 to 5 years before it becomes apparent in the other.
The
intraocular pressure is normal between attacks, but after many episodes
adhesions form between the iris and the trabecular meshwork and cornea
(peripheral anterior synechiae) and accentuate the block to the outflow of
the aqueous humor.
- Secondary Glaucoma: The causes of
secondary glaucoma are many, and the anterior chamber angles may be open
or closed. Because the underlying disorder is usually limited to one eye,
secondary glaucomas are usually unilateral.
"Low Tension Glaucoma" :
The
characteristic visual field defect and all of the ophthalmoscopic features
of chronic simple (open-angle) glaucoma often occur in the elderly without
an elevation in intraocular pressure. While some eyes might be
hypersensitive to normal intraocular pressure, most cases of this "low
tension glaucoma" probably represent an infarction of the optic nerve
head.
Traumatic
glaucomas represent a very heterogeneous group of entities due to a
variety of pathomechanisms which increase the intraocular pressure in
the early or late phase after traumatic injury (blunt or penetrating
injury, acid or alkali burn). Little is known about the real
prevalence of traumatic glaucoma. Angle recession, hyphema-associated
and lens-associated mechanisms are the most common causes of traumatic
glaucoma after blunt ocular trauma. Secondary angle closure due to
peripheral anterior synechiae is the most common pathomechanism
leading to glaucoma in patients with penetrating eye injury or acid or
alkali burn. Early anti-inflammatory therapy for eye injuries is the
most important step in the prevention of traumatic glaucoma. Although
no general recommendations exist, topical potent corticosteroids
significantly decrease the risk of glaucoma development. Medical and
surgical treatment of traumatic glaucoma has often been disappointing.
Therefore the visual prognosis of these eyes is often restricted.
Antiglaucomatous drugs that reduce the secretion of aqueous humor (e.
g., beta-blockers) should be preferred. Mitomycin-augmented
trabeculectomy is the surgical method of first choice in patients with
open angle traumatic glaucoma. Transscleral cyclophotocoagulation
represents the method of first choice in secondary angle closure
glaucoma due to anterior peripheral synechiae. New surgical techniques
will increase the possibilities of an effective reduction of the
intraocular pressure in secondary angle closure glaucoma. These new
procedures are endoscopic cyclophotocoagulation, retinectomy, and the
implantation of drainage devices via the pars plana. Further
evaluation and modifications of these surgical techniques should
markedly improve the visual prognosis of eyes with secondary angle
closure glaucoma. For a few types of traumatic glaucoma (e. g., after
epithelial ingrowth) no effective treatment modality is available at
present.
Primary
open angle glaucoma : Morphological bases for the understanding of the
pathogenesis and effects of antiglaucomatic substances.
Ophthalmologe. 2007 Feb;104(2):167-79.
The pathogenesis
of glaucomatic illnesses is poorly understood. An increase in ocular
pressure can be caused by an increase in the secretion of aqueous
humour or a reduction in its outflow. In the elderly, outflow is
reduced while at the same time less aqueous humour is produced. This
balance is easily disturbed, so that age represents a risk factor for
glaucoma in addition to increased ocular pressure. Therapeutic
possibilities involve, on the one hand, reducing the secretion of
aqueous humour, for example using, beta blockers, carbonic anhydrase
inhibitors and clonidine. On the other hand, aqueous humour outflow
can also be influenced by drugs. Conventional outflow is increased by
the administration of miotics. The uveoscleral outflow can be
increased by prostaglandin derivates. Drugs which only influence
trabecular outflow are not yet available. Future therapeutic
possibilities involve new aspects of the pathophysiology, e.c. the use
of growth factors, free radical scavenging enzymes and choroidal blood
flow.
Does the
aqueous humor have a role in mitogen-activated protein kinase (MAPK)
intracellular signaling in Glaucoma?Med
Hypotheses. 2007;68(2):299-302. Epub 2006
Sep 29
Glaucoma is a
common blinding disease worldwide. Glaucoma treatment today is based
on reduction of aqueous humor production or increase aqueous humor
drainage. By medical manipulation, the treatment goal is to reduce the
main risk factor, elevated intra ocular pressure. Here we hypothesize
that the aqueous humor has a role, beside oxygen and nutrient supply,
in transferring signaling to the trabecular meshwork. This signaling
might be delivered from the ciliary body were the aqueous humor is
produced, or from the lens or the cornea. Recently in our lab we
proposed that MAPKs present in the aqueous humor are a novel signal
involved in glaucoma pathology. Here we show that this pathway exists
at an unexpected, extracellular media. Western blot analysis of
aqueous humor from congenital glaucomatic rabbits and a rat model of
induced elevated intra ocular pressure (IOP) were found to express
several signaling members of the MAPK family. Although these members
are usually found in an intracellular environment, they can be
detected at an extracellular environment, namely the aqueous humor.
These signaling proteins are found also in normal eyes. Moreover the
MAPK signaling proteins are found in the active phosphorylated form
and in non-active form in elevated IOP animals as well as in the
control, normal IOP groups. Understanding the signaling cascade, at
the aqueous humor, opens a new area for treatment of glaucoma
patients. By interfering with the signaling cascade, taking place at a
reachable location, the anterior chamber, we will be able to
manipulate these protein effects on the trabecular meshwork.
Open angle
glaucoma: epidemiology, pathogenesis and prevention. Recenti
Prog Med. 2006 Jan;97(1):37-45.
There is
growing evidence that reactive oxygen species (ROS) play a key role in
the pathogenesis of primary open angle glaucoma (POAG). The occurrence
of oxidative DNA damage in trabecular meshwork (TM) has been
demonstrated by measuring the increase of 8-hydroxy-2'-deoxyguanosine,
the most abundant DNA oxidative alteration, which is significantly
increased in glaucoma-bearing subjects as compared with unaffected
controls. Several lines of evidence support the hypothesis that ROS
play a fundamental pathogenic role, including the following: (a)
outflow resistance in the anterior chamber increases in the presence
of high levels of hydrogen peroxide; (b) TM possesses abundant
antioxidant activities; (c) significant increases in superoxide
dismutase and glutathione peroxidase activities were detected in the
aqueous humour of glaucoma patients; (d) hydrogen peroxide compromises
TM integrity. The existence of a significant correlation between
oxidative DNA damage and intraocular pressure in glaucoma patients has
been reported. POAG patients appear to have a genetic predisposition
rendering them susceptible to ROS-induced damage because of a more
frequent deletion, as compared to controls, of the gene encoding for
glutathione-S-transferase M1, a pivotal anti-oxidant activity.
Furthermore, oxidative stress, occurring not only in TM but also in
retinal cells, appears to be involved in the neuronal cell death that
characterizes POAG. These considerations could bear relevance for POAG
prevention and suggest that genetic analyses and the use of drugs or
dietary measures attenuating the effects of ROS, if validated in
future studies, could be useful tools contributing to the control of
this disease.
Neovascular
glaucoma, as a typical secondary glaucoma, is due to ocular or
(earlier) systemic diseases. The formation of a fibrovascular membrane
on the anterior surface of the iris (rubeosis iridis) and extending
into the chamber angle leads to irreversible obliteration of the
outflow system, with a corresponding rise in intraocular pressure. The
most frequent cause is retinal ischaemia resulting either from
vascular occlusion or from diabetic alterations. The differential
diagnosis must include acute angle-closure glaucoma and uncontrolled
open-angle glaucoma. Treatment is aimed at eliminating the actual
cause or at least reducing the risk factors (e.g. by retinal laser
coagulation), or consists in cyclodestructive procedures.
Medicamentous therapy comprises anti-inflammatory agents (steroids,
cycloplegic agents) and substances that reduce the production of
aqueous humour (carbonic anhydrase antagonists, beta blockers). In the
near future, antiangiogenic medication might be another effective
option. For end-stage neovascular glaucoma, the implantation of
drainage devices is also discussed.
