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THE EYE is an organ within the human body that can detect light and send electrochemical impulses along the optic nerve to the visual cortex and other areas of the brain involved in sight. Their sole purpose is to detect changes in light from the surrounding and convert them to produce an image recognizable to the organism in question. It allows us to see and interpret the shapes, colors and dimensions of objects in the world by processing the light they reflect or emit.
The Outer Eye consists of:
Eyelids that fulfill two main functions, firstly they protect the eyeball and secondly are responsible for the secretion, distribution and drainage of tears. The space between the lids is termed the palpebral aperture surrounded by a ring of fibres called the orbicularis oculi muscle. The contractions of these muscles ensure that the lid closes firmly. The levator muscle in the upper Iid principally performs the opening of the both upper and lower lids although there are some tenuous fibres, which work to retract the lower lid.
The lids are securely attached to either ends of the bony orbital margin by the media and LP ligaments. Trauma to the medial ligament would result in an impaired eye function and visibility. Blinking distributes tears across the cornea, which maintains the smooth optical surface of the cornea and displaces debris.
The skins of the eyelids are thin and therefore very loosely attached to the underlying tissues, hence inflammation and bleeding is likely to cause considerable swelling. The lids are supplied by an extensive network of blood vessels that form an anastomosis (a network of streams that can either branch out or reconnect, such as blood vessels or leaf veins) between the branches of the external carotid artery via the face and internal carotid artery via the orbit. Hence accounts for the excellent healing when dealing with trauma.
Conjunctiva is a mucous membrane lining the eyelids and covering the interior eyeball upto the edge of the cornea. At the upper and lower reflections between eyeball and eyelid the conjunctiva forms two sacs, the superior and inferiour fornices. Therefore, inflammation can cause gross swelling between the two. The conjunctiva also comprises of an epithelium and underlying stroma.
The epithelium consists of goblet cells, which secrete the mucin component of the tear film. Conjunctival glands contribute to the secretion of the aqueous and lipid layers of the tear film. Hence facilitating free movement of the eyeball and provides a smooth surface as the lids blink with the cornea. The continuous supply of blood at this part of the eye mostly comes from the orbit. The conjunctiva plays an important role in the protection of the eye against microorganisms.
Cornea and sclera, these form a type of a spherical shell that makes up the outerwall of the eyeball. Although the two are very similar in many ways, the cornea is largely modified to transmit and refract light. The scLera on the other hand is collagenous and relatively acellular. It is tough despite being thin (less than 1mm in thickness). Both the cornea and the scLera merge at the corneal edge (the limbus). The cornea consists of a stroma wedged sandwiched between a multilayer epithelium and an inner monolayer of endothelial cells. The cornea itself is very strong as the stroma comprises 90% of the actual thickness made up of a mixture of collagen and extracellular matrix. It has very few cells and nearly no blood vessels.
When compared to the sclera the cornea is very sensitive to touch through the nerve fibres of the trigeminal nerve. If the nerve fibres are exposed, by any chance, due to the degradation of the corneal epithelium it could cause great pain. The cornea itself is avascular meaning that there is no blood supply, hence most of its nutrition is derived by the blood vessels at the limbus, from the aqueous humour in the eye and from the tear film. Sometimes contact lenses may prevent the diffusion of oxygen from the tear film resulting in ulceration. The chief functions of the cornea are protection against invasion of foreign bacteria into the eye followed by the transmission and refraction of light.
The refraction of light is due to the curved shape of the cornea and its greater refractive index compared to that of the air. The cornea is transparent due to the specialized arrangement of the collagen fibrils within the stroma, which must be kept in a stat of dehydration. An energy dependant ion pump present within the walls of the epithelium achieves this. The epithelium has a surface that has a constant turnover of basal cells migrating to the surface and then being shed. With age, the endothelial cells have insufficient pumps to maintain corneal dehydration; as a result, the cornea swells up and looses transparency, termed corneal decompensation.
Tear production and drainage: tears comprise f water, mucus to bind the tear film to the corneal epithelium and outer lipid layer to reduce evaporation of the water present. Tears also include certain chemicals that help to fight against harmful microbes. The lacrimal gland (fig 2) secretes most of the aqueous component of the tear film. It lies in the superotemporal part of the anterior orbit. It is innervated by the parasympathetic fibres carried by the facial nerve. Tears collect in a meniscus on the lower lid of the margin and spread across the ocular surfaces of the eye by blinking and drain into the superior and inferior puncta located at the nasal ends of the eyelid.
Fig 2: The Lacrimal Gland
Single canalculli from each Punctum unite in a common canal that ends in the lacrimal sac. From here the tears finally pass down the nasolacrimal duct into the nasal concha. This is what accounts for the unpleasant taste following administration of certain types of eye drops.
At birth, the nasolacrimal duct is not fully developed causing a watery eye and could take up to a year. Acquired obstruction of the canal may result in an acute infection of the lacrimal sac, which manifests as a cellulitic swelling.
The Inner Eye consists of:
Uvea, this consists of the iris and ciliary body anteriorly and the choroid posteriorly.
The Iris largely consists of connective tissue containing muscle fibres, blood vessels and pigment cells. Its posterior surface has a layer of pigment cells, at it's centre is an aperture called the Pupil. The chief function of the iris is to control the entry of light and to reduce intraocular light scatter. Pupil dilation is caused by the contraction of radial smooth muscle innervated by the sympathetic nervous system.
Fig3: The Inner Eye
Pupil constriction occurs when a ring of smooth muscle fibres around the pupil contracts. These are innervated by the parasympathetic nervous system. Iris pigment reduces intraocular light scatter, the amount of pigment determines eye colour: blue eyes having the least amount of pigment and brown the most.
Ciliary body is a specialised structure uniting the iris with the choroid, it makes aqueous humour and anchors the lens via the zonules, through which it controls and regulates lens convexity. Anteriorly the inner surfaces of the ciliary body are folded into ciliary processes, which are the site of aqueous humour formation. Muscle fibres of the ciliary body contract causing its inner circumference to reduce in size. This reduces the tension on the zonules, so that natural elasticity of the lens causes it to convex more to focus on near objects. This occurrence is known as accommodation and is controlled by the PS fibres in the oculomotor nerves. Relaxation has the opposite effect, increasing the tension on the zonules so that the lens pulls flat to allow it to focus on far objects. The posterior part of the ciliary body joins the retina.
Choroid is a thin layer of connective tissue and pigment cells consisting of blood vessels sandwiched between the retina and the sclera. Its sole purpose is to provide oxygen and nutrition to the outer retinal layers. In some diseases, the space between the sclera and the choroid can be prone to fluid or blood accumulation.
Aqueous humour this is present within both the posterior chamber and the anterior chamber as shown in fig 3. The AC is the space between the iris and the cornea. Behind the iris and in front of the lens is the PC, both are connected via the pupil. The ciliary body forms aqueous humour by ultrafiltration and active secretion. The composition strictly prohibits the presence of large proteins and cells, but it does contain glucose, oxygen (O2) and amino acids for the cornea and lens. Neural control is followed via the autonomic nervous system.
The aqueous liquid circulates from the posterior to the anterior chamber, through the pupil, leaving the eye through the trabecular meshwork. This is a specialised tissue in the anterior chamber angle between the iris and the cornea. It resembles a sieve that aqueous fluid can drain out of into the schlemms's canal that rings the circumference of the eye, eventually draining into veins.
Lens this is discus-like formation of a mass of long cells known as fibres. These fibres are unique in nature, at the centre they are compacted into a large nucleus surrounded by less dense fibres, the cortex. The whole lens is somewhat enclosed in a large elastic type capsule which can deform for accommodation. Failure of accommodation can occur with ageing (presbyopia) due to the loss of capsule elasticity and lens deformability. The lens is relatively dehydrated and its fibres contain special proteins that keep it functional.
Vitreous body is 99% water, also containing collagen fibrils which impart cohesion and a gel like consistency. As age, increases the vitreous undergoes liquefaction where it gradually start to loose its gel like properties (degeneration). The vitreous is adherent to the retina at some points, when it degenerates it pulls the retina causing a tear that can lead to retinal detachment. It also helps to cushion the eye from impact or trauma.
Retina its main function is to convert focused light images into nerve impulses. It comprises of the neurosensory retina and the retinal pigment epithelium (RPE). When light projects on the eye, it has to pass through the inner retina to reach the photoreceptors, the rods and cones, which are responsible for converting light energy into electrical energy. Ergo the retina for that reason has to be transparent. Connector neurons then modify and pass on the electrical signals to the ganglion cells, whose axons run along the surface of the retina and simultaneously enter the optic nerve. An area called the macula provides the central vision. At the centre of this part, comprises another area called the fovea, which is for high quality vision and the rest of the retina mainly provides for peripheral vision. Cones are concentrated at the macula, responsible for fine vision (acuity) aswell as colour perception. Rods on the other hand are for vision in low light levels and the detection of movement while running along the whole length of the retina.
Photoreceptors contain visual pigments comprising of retinol (vitamin A) linked to protein (opsin). When light is absorbed, it causes a structural and then a chemical change in visual pigments which results in the electrical hyperpolarisation of the photoreceptor. Outside the neurosensory retina lies the RPE, which is a single layer of pigmented cells that play a significant role in the photoreceptor physiology. RPE cells recycle vitamin A for the formation of photopigments, transport water and metabolites, renew photoreceptors and help to reduce damage by scattered light. Impairment to the RPE with time and age can lead to the loss of sight and retinal function. The retinal artery, vein and the choroid supply the blood circulation for the retina. The retinal vessels enter and leave the eye through the optic nerve and run in the nerve fibre layer. The blood retinal barrier, consisting of tight junctions between the endothelial cells of the retina and the RPE cells, isolate the retinal environment from the systemic circulation. In diabetic retinopathy, disruption of the blood brain barrier occurs leading to retinal oedema and precipitation of lipid plus protein, causing loss of retinal transparency and loss of vision.
Optic nerve this part of the eye contains no photoreceptors and corresponds to the blind spot. Most optic discs have a central cavity, the optic cup, which is pale in comparison with the redness of the surrounding nerve fibres. Loss of such nerve fibres as occurs in glaucoma can result in an increase in the volume of the cup. There are about one million axons in the optic nerve and they are myelinated behind the eyeball.
The process leading to the perception of an image in the brain is in fact utterly complex. It starts at the retina; it converts photons of light into electricity. Light sensitive retinal pigments contain retinol (vitamin A) and opsin (a protein). Light absorption makes a structural change in the retinal cells and chemical change in the opsin, ion channels in the photoreceptor cell membrane are altered and the cell hyperpolarizes. Rod photoreceptors contain rhodopsin that is stimulated by light a wavelength of 505nm. Whereas a cone photoreceptor has three subsets, each containing a pigment that is maximally sensitive to blue, green or red light at this wavelength that helps perceive colour. Dark adaptation takes several minutes requiring regeneration of visual pigments, especially in rods.
Fig 4: rods and cones in the retinal layer
Glaucoma is a slow progressive neurodegenerative disorder associated with the death of retinal and connective nerve fibres classically linked to high intraocular pressure. Hence being a part of a group of neurodegenerative diseases characterised by structural damage of the optic nerve and slow progressive death of Retinal Ganglionic cells (RGC's). Elevated intraocular pressure seems to be traditionally the most significant risk factor for glaucoma. Treatment therefore has been directly linked to its reduction. The term glaucoma should only be used in reference to the entire group of disorders, just as the term cancer is used to refer to another discipline of medicine that encompasses many diverse clinical entities with certain common denominators. It generally is a dysfunction of the aqueous outflow system, which is associated with structural defects in the anterior eye that occur during embryonic and fetal development. As a result, the resistance to aqueous humor outflow may become abnormally high causing an increase in IOP at birth or anytime thereafter. There are many different sub-types of glaucoma but they can all be considered as a type of optic neuropathy caused by mutations in a variety of different transcription factors and classified into two main types, others discussed later.
Primary open angle glaucoma (POAG), and Angle closure glaucoma (ACG), marked by an increase of intraocular pressure (IOP), or pressure inside the eye. When optic nerve damage has occurred despite a normal IOP, this is called normal tension glaucoma. Secondary glaucoma refers to any case in which another disease causes or contributes to increased eye pressure, resulting in optic nerve damage and vision loss. Within the context of a discussion on glaucoma, 'normal' IOP might be defined by as that pressure which does not lead to glaucomatous damage of the optic nerve head. Unfortunately, such a definition could not be expressed in precise numerical terms, as each individual's eye respond uniquely to given pressure levels. Hence, the best that can be done is to describe the distribution of IOP in general populations and in groups of individuals that suffer from glaucomatous damage to establish a sort of risk assessment in terms of pressure ranges.
The classification of galucomas is based on (a) aetiology, that is the underlying disorder which leads to an alteration in aqueous humor dynamics and, (b) mechanism, the specific alteration in the anterior chamber angle that leads to a rise in IOP. Ergo, one disadvantage of either system is that they suggest that elevated IOP is the only causative risk factor in the glaucomas, which is incorrect. A second disadvantage is that neither system incorporated genetic relationship or basis, which is the underlying aetiology of the vast majority of glaucoma. Glaucoma is the second most common cause of blindness worldwide.
Stages in glaucoma:
Five key stages contribute to the development of glaucoma over time:
The initiating events (Stage 1) include the conditions that set in motion the change of events that may eventually lead to optic nerve damage and visual loss leading to structural alterations. In some glaucomas, this could be a genetic defect with an associated gene or protein abnormality, whereas in other glaucomas this could be du to acquired events such as trauma, inflammation, or a retinal vascular disorder. The structural alterations (Stage 2) are related to tissue changes in the outflow system, leading to increased resistance to aqueous outflow and subsequent elevatation of the IOP. These could be subtle or minute changes in the endothelial cells or the trabecular meshwork or more obvious obstructive mechanisms, such as membranes over the anterior chamber angle (ACG), scar tissue within the meshwork or intraocular debris. The functional alterations (Stage 3) include the blockage or obstruction to aqueous outflow sufficient enough to cause elevation of the IOP that may lead to glaucomatous optic neuropathy (Stage 4) and ultimate or progressive loss of visual field (stage 5). It is however speculative through demographic evidence that the initiating events of stage one have a genetic basis, with alterations to proteins that may head to structural changes in ganglionic cells or the optic nerve head. The structural alteration in stage 2 may be subtle changes in blood vessels supplying blood to the optic nerve head.
Primary Open Angle Glaucoma (POAG)
This type constitutes over half of the people with glaucoma and is referred by many different terms like Chronic Open-angle Glaucoma, and chronic simple Glaucoma. In this context, however it may be called idiopathic Open-angle Glaucoma because of the failure to provide a more precise terminology from the lack of knowledge regarding the related mechanisms. Even though glaucoma comprises of five main steps, it is not yet properly determined what kind of initiation events actually trigger the onslaught of the disease. Nevertheless, it is likely that genetic defects initiate the series of events (hence Chronic) that lead to increased resistance to aqueous humor outflow plus increased susceptibility of the optic nerve head to a particular IOP level.
Pathophysiology of COAG is not entirely known, as there is no visible abnormality of the trabecular meshwork. It is believed that something is wrong with the ability of the cells in the trabecular meshwork to carry out their normal function, or there may be fewer cells present, as a natural result of getting older. The mechanism of damage involves an increased resistance to aqueous outflow within the trabecular meshwork (a circumferential sieve-like structure sitting in the iridocorneal angle through which 90% of the aqueous drains) so causing a rise in IOP. Some believe it is due to a structural defect of the eye's drainage system with time increasing IOP within the eye. Others believe it is caused by an enzymatic problem. These theories, as well as others, are currently being studied and tested at numerous research centers across the country.
Glaucoma is really about the problems, which occur as a result of increased IOP. Latter observations have brought into question the role of IOP in the mechanism of COAG. The average IOP in a normal population is 14-16 millimeters of mercury (mmHg). In a normal population, pressures up to 20 mmHg may be within normal range. A pressure of 22 may be considered suspicious and possibly abnormal. However, not all patients with elevated IOP develop glaucoma-related eye damage. Even though many studies have confirmed a correlation between the level of IOP and the rate of visual field loss in some groups of patients with COAG, this correlation is not seen in all cases. Other causative factors squeeze into the formula for eye damage. What causes one person to develop damage while another does not is a topic of active research even today? As we mentioned earlier, this increased pressure can ultimately destroy the optic nerve cells. Once a sufficient number of nerve cells are destroyed, blind spots begin to form in the field of vision. These blind spots usually develop first in the peripheral field of vision, the outer sides of the field of vision. In the later stages, the central vision, which we experience in `seeing, ´ is affected. Once visual loss occurs, it is irreversible because once the nerve cells are dead; nothing can restore them now.
Aetiology, Theories of Mechanism of POAG, there are many theories that are supposedly responsible for the cause of POAG. In 1997, Stone and coworkers identified mutations in the myocilin gene as a causative for GLC1A-linked inherited juvenile open- angle glaucoma. Numerous other investigators have confirmed these results. Primary juvenile open-angle glaucoma refers to a subgroup of POAG with autosomal dominant heredity that is accompanied by high intraocular pressure requiring immediate surgical treatment. Studies suggest that it could be because of such mutations
Epidemiology, COAG is by far the most common form of single glaucoma, its frequency being the highest out of all its kind although it is hard to precisely establish the number of individuals with this disorder to the total no. of patients with all forms of glaucoma. This condition lends itself well to epidemiological studies in that it is reasonably common but relatively little is known about its pathogenesis. This is mirrored in the fact that most of the major population studies have been carried out in Europe and North America, areas where POAG is the commonest form of glaucoma. In a British survey of 4,231 individuals between the ages of 40 and 75, one third or 0.28% of the glaucoma population had POAG (16). However in a study of 8,126 subjects in Japan whom were all atleast 40 years of age, open angle glaucoma accounted for 74% of the glaucomas detected. Nevertheless, one must not forget that these epidemiologic surveys must obviously be influenced by the people being studied, as well as the methods and criteria used for patient identification with glaucoma. While there has been significant progress in our understanding of the inheritance pattern and genetic contributions for developmental forms of glaucoma, the underlying causes in most cases of POAG remain unknown. There is considerable evidence that genetic factors do also contribute, with a higher probability of occurring in people who have relatives with POAG. Recent POAG epidemiological studies confirm that a family history of POAG is a major risk factor for the disease [17,66,123]. Between monozygotic twins, concordance of glaucoma is higher than between dizygotic twins supporting a concept of genetic predisposition . The prevalence increases with age, affecting about 10% of people aged over 70 . Major Studies conducted in Baltimore (USA), Beaver Dam (USA), Blue Mountains (AUS), Barbados (WI), Rotterdam (Netherlands), St Lucia (WI) all had a sample size ranging from 2000 to 10,000 patients. Out of these those carried out in the United States suggested that glaucoma is a leading cause of irreversible blindness, second only to macular degeneration; only one half of the people who have glaucoma may be aware that they have the disease; and more than 2.25 million Americans aged 40 years and older had POAG. More than 1.6 million people had significant visual impairment, with 84,000-116,000 bilaterally blind in the United States alone. 3-6 million people, including 4-10% of the population older than 40 years, are currently without detectable signs of glaucomatous damage using present-day clinical testing, but they are at risk due to IOP of 21 mm Hg or higher. Out of these, a rough estimate of 0.5-1% per year of those individuals with elevated IOP will develop glaucoma over a period of 5-10 years. These statistics emphasize the need to identify and closely monitor those at risk of glaucomatous damage. The Barbados Eye Study over 4 years showed a 5 times higher incidence of developing glaucoma in a group of black ocular hypertensive's as compared with a predominantly white population. Prevalence of POAG is 3-4 times higher in blacks than in Caucasians; in addition, blacks are up to 6 times more susceptible to optic disc nerve damage than Caucasians. A higher prevalence of larger cup-to-disc ratios exists in the normal black population as compared with white controls
In summary, these studies indicated a prevalence of POAG in 1.5-2% for Caucasians and 6-8% for Afro-Caribbeans. It is however, important to remember that quoting an overall prevalence figure for POAG is of limited value as race, age and possibly gender have such a profound effect overall that prevalence rates are best stated in relation to these factors (also known as risk factors mentioned later on in the passage).
Incidence of the disease is the rate at which new cases occur within a population during a specified period. The problem with such studies is that they are plagued by difficulties in diagnosing early disease and the need for prolonged follow up of subjects; hence, very few glaucoma incidence studies are done to date. Most incidence rates at present are calculated from the prevalent of the disease at different age ranges. The method was used to calculate incidences in white patients from around 20 cases of POAG per 100,000 persons per year at age 50, to 60,000 cases per 100,000 per year at age 80. Of all the available studies the Bedford survey found an overall annual incidence of 0.048, this is not separated for the different types of age groups and is solely related to Caucasians patients.
Risk Factors COAG does not seem to have any associated symptoms or warning signs before the development of an attack. Although there is a lot of literature regarding risk factors, it is important to note that when reading the findings of such studies, one must not forget to think how these studies were conducted. Hospital based studies may be subject to selection bias in which certain patients may be over represented in the hospital setting. Good example of these are myopes and diabetics, in which regular eye examinations are likely and so increasing the likelihood of a patient with glaucoma being detected and referred to a clinic. Ergo, hospital settings tend to over-estimate the proportion of glaucoma patients with myopia and diabetes, which would then implicate them as risk factors for the disease. Population studies are more useful than hospital based but such an advantage is lost if the study subjects are not selected randomly. An example of this is if a study asks for volunteers, it is generally those whom have greater concerns regarding glaucoma, e.g. those with a family history of glaucoma, are most likely to present themselves for examinations. So if the sample isn't random, the influence of such factors as family history of glaucoma will be over estimated.
Local risk Factors, there is little doubt that raised IOP plays a big role in OAG and there is strong evidence to support this, the Baltimore Eye study conducted showed that the relative risk for glaucoma rises with IOP. From it a more realistic concept can considered, that an individuals optic nerve has a level of IOP that it can or cannot withstand. At a clinical level, this can be manifest by a patient's presence or absence of visual field decline. If a field loss is occurring, individuals need their IOP reduced to a level that stops or realistically slows this decline.
Myopia Some studies have found a strong association between myopia and POAG. One small-scale hospital based study conducted in the 80s found that there is a two fold excess prevalence of POAG in myopes, while another found a five fold risk14. Yet nevertheless, like diabetes the effect of myopia is overestimated in hospital based studies. It is likely that large-scale population studies will find that the association is much smaller than once thought.
Optic nerve head, the structure of this also plays a role in the pathogenesis of glaucoma and seems to be supported by two main theories. The mechanical theory, being IOP related, suggests that the pressure head acts directly on the lamina cribrosa. Due to insufficient support of this structure both interiorly and exteriorly at the disc margin, it is here the initial damage seems to occur, producing the characteristic arcuate defects. Variations in ganglionic cell support at the disc may explain the variations between IOP susceptibilities between individuals with similar IOPs. The alternative theory related to the vascular mechanism of damage, includes changes within the microcirculation of disc capillaries responsible for glaucomatous changes. Whether this can be classed primary or secondary to IOP has not yet been proved. This is also supported by similar epidemiological studies showing disc variation as a risk factor. The Collaborative glaucoma study 12 indicated that a high ratio between both vertical and horizontal cup and disc was a risk factor for developing field defects. Hence, one of the proposed reasons why black people have a greater prevalence of POAG than white people, despite having no differences in their IOPs. Black people have been noted to have larger discs and cup ratios than their white counterparts. Larger discs and larger cups are more vulnerable to glaucoma damage.
Racial risk factors over the past decade or so large-scale population studies have shown that individuals of African American and African Caribbean origin are at higher risk of POAG compared to Caucasians. The Barbados study5 found a gradient in prevalence by racial group with the highest risk being in those subjects that described themselves as black. A lower prevalence found in those who classified themselves as mixed race and the lowest being in those who were white. Interestingly enough the London afro-Caribbean study20 showed a statistically significant association between IOP and skin colour but not between skin colour and glaucoma. There is also some evidence of the disease presenting itself at a younger age amongst back people1. However, at present time there is little data regarding POAG risk in other racial groups such as those from the Indian sub-continent, Easter Europeans or Hispanics.
Systemic Risk factors
Genetic there is definitively little doubt that a positive family history of glaucoma puts an individual at increased risk of glaucoma. There is a five-twenty times prevalence rate in those with a positive family history. A number of new have been found over time which may relate to glaucoma passing on from offspring to offspring but more research is yet to be conducted. From an epidemioigical point of view, family history and glaucoma are prone to bias, which probably explains the wide difference in prevalence rates among studies. Patients whom know a family member with glaucoma are more likely to present to a clinic and are more likely to attend for surveys. Family history data from a patient can be subject to recall bias. Probably the most accurate estimate between family history and risk is from an unbiased population study with a high response rate such as the Baltimore Eye Study15. This study did not find family history as a significant risk factor for POAG, but less so than in other published studies to date. They found the odds ratio of having POAG for those with siblings with the disease was 3.69, parents with it at 2.17 and children with the disease 1.12.
Age and diabetes Increasing age also has a big role to play as a risk factor. This is because with increasing age, weakness of muscles follow within the eye, the blood circulation reduces and the retina becomes prone to blood clots. All the population studies conducted have all shown an increased prevalence of POAG with an increase in age. Diabetes is also associated with increase in POAG, diabetics have fluctuating glucose levels harmful for the retina within the eye. It has been long implicated as a risk factor for POAG. Wilson et al. had similar findings but his studies were both hospital based and as described above comes with its problems. The Rotterdam and Blue Mountains Eye Studies did find an increased risk with diabetics.
Neuroprotection is a relatively new term in the ophthalmological field related to physiological protection of undamaged, and rescue of damaged, retinal ganglionic cells (RGCs) embedded in the eye. Neuroprotection refers to a set of therapies for preventing neurons from dying as the result of a disease process, in this case being glaucoma. Its final goal is to keep the neurons alive and to prevent cell death.
Reason for neuroprotection?
Glaucomatous optic neuropathy one way or the other results in loss of retinal ganglionic cells, hence it is reasonable to expect that protecting them from death might just serve as one component of any treatment. Neurons in higher vertebrates are unable to divide after birth, so this would imply that the supply of neurons available at birth must last the life of the organism. At the present state of biomedical research it is not possible to replace dead retinal ganglionic cells with functional new ones using stem cells. The ramification of this chain of reasoning is that protecting the retinal ganglionic cell from death is necessary in order to prevent its irreversible loss of functional capacity, as replacement or substitution is not yet possible. While most organs and extracranial tissues area innervated by nerves of the peripheral nervous system, the eye is unusual in that it contains central nervous system type neurons. This difference is significant as PNS axons are capable of regeneration after injury while CNS axons are not. The human retina consists of over one million RGCs. Significant loss of these result in visual disability. Because these neurons cannot bee replaced, this inescapingly implies permanent loss f function. In some cases the permanent loss is not as dramatic as the quantitative loss of neurons, simply because there is enough plasticity within the rest of the within the rest of the CNS to compensate for some loss of neurons. Therefore, loss of even a sizable proportion of neurons will not necessarily become manifest on standard tests of visual function.
Criteria for evaluating Neuroprotection
In order to evaluate any pharmacological agent and to maintain sufficient neuronal function for useful vision in the face of damage to retinal neurons or axons, several steps are required. First, the death of the neuron in question must be protected. Second, either the integrity of its connections (dendrites and axons) must be maintained, or some mechanism of dendritic sprouting and axonal regeneration must be introduced. Third, the electrical, biochemical and energetic requirements needed for transmission of the impulses that code for vision must be preserved. The most important fourth point being, the disease process that necessitated the first three steps must be arrested. If this is not done, then the neuroprotective strategy may eventually fail in the face of an attack. However according to Wheeler Et Al. four main criteria were widely known to be used in studies for the neuroprotective agent in question. Firstly, have (a) specific target(s) in the retina or the optic nerve. Secondly, increase RGC survival in laboratory models of glaucoma. Thirdly, the agent must reach the target at a neuroprotective concentration after clinical dosing and fourthly, display neuroprotective activity in human trials.
Since on the most part, standard therapies for glaucoma focus on the arresting of the progression of the disease by lowering the intraocular pressure. In many cases, there is progressive structural and functional loss despite excellent pressure lowering. Hence, in these cases neuroprotection may be the only viable therapy. A major advantage of neuroprotective therapy is that it may be effective when there is no known therapy. The majority of research on neuroprotection according to my insight has focused on preventing death of neurons, while maintenance of neuronal connections and their functional capacity has usually been considered subordinate to this. In part, this reflects the fact that if neurons cannot be saved, then a therapy addressed to its function becomes moot. However, since the methods of maintaining neuronal survival in face of a disease have increasingly been validated in a variety of in vitro and animal models, one must not forget that future prospects of clinical therapy will demand attention to these issues.
Targets for Neuroprotection and related treatment
Retinal ganglionic cells and their axons eventually die in glaucoma, the mechanisms responsible by which they are damaged and apoptosis represent targets for neuroprotection.