Cardio Optics

CURRENT CONCEPT IN THE DIAGNOSIS & THE DIRECTION OF GLAUCOMA

(Published by the India of Cipla to be distributed to Indian Ophtalmologues)

Dr. Mr. R. Jain, a specialist of principal glaucoma, is the soon Medical Director and the Institute of J OF R. OF Mr. of Principal Ophtalmologue and Jaipur of Hospital of Eye of Jain, India. It edited the book of Text on Glaucoma and a Book on THE INFLAMMATION EYEPIECE and published 130 scientific papers to India and abroad. In the year 2007, it published the book of public education in hindi on, "the EYES: THE SECURITE &the amplifier; the TREATMENT"

It was attributed the RECOMPENSE OF ACCOMPLISHMENT OF TIME OF LIFE by Rajasthan the Ophthalmological Corporation in 2002 &the amplifier; the RECOMPENSE OF ACCOMPLISHMENT OF TIME OF LIFE by Any India the Ophthalmological Corporation, 2006

Dr. Jain is attributed the Gives an award to OF now by the 'the National Academy of Medical Sciences' for the research and the work clinic in the field of "Delivery of Glaucoma and Drug to the eye".

Soon Dr Jain is the President, Dr Mr. R. J Charitable Confidence, the President, Seventh Happy, Medicos of SMS and Declares Organizing for the National Academy of Medical Sciences.

CURRENT CONCEPTS IN THE DIAGNOSIS AND

THE DIRECTION OF GLAUCOMA

TEACHER. Mr. R.JAIN, Mr.s., F.I.C.S.(USA), FAMS, FACLP (London) M OF DIRECTOR MEDICAL. R. J. THE INSTITUTE

&the amplifier; JAIPUR OF HOPITAL OF EYE OF JAIN

E MAIL: drmrjain55@gmail.com

There was a revolutionary change in the comprehension, the diagnosis and the glaucoma direction. Preceding the glaucoma was defined as a condition of raised the pressure of intraocular, not compatible with health and the eye function. Soon, the American Academy OF Ophthalmology defined the glaucoma as a neuropathie view with the characteristic structural damages to the nerve view, associated with the death of cell of progressive retinal ganglion, the loss of fibers of nerve and the loss of visual field. The importance of pressure of intraocular above 21.0 mm of Hg as an unique factor was minimized in a significant way since of the one third of patients could show the classical damages of glaucomatous with the pressure of normal intraocular (1.2) or despite controlled IOP after glaucoma surgery, there can be the progressive loss of fields.

The glaucoma definition is based on the damages of fine visually significant organs (3). It is agreed in a manner conclusive that IOP related damages can arrive from the all of the levels of IOP, and therefore almost 50 percent of patients of glaucoma remains not diagnosed (4-6). Nevertheless, the Investigation of Eye of Baltimore and Aravind the Etude of Eye Completes reveals that the relation between the pressure of intraocular and the glaucoma predominance is positive. Generally, 21 mm of Hg is considered as a limit point.

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MODERN DIAGNOSTIC MODALITES

IMMAGING VIEW OF TETE OF NERVE

What's more Ophthalmoscopy and what's more of Lamp of Direct well confirmed Slits usage of Indirect Ophthalmoscopy 90 diopters of lens more diagnostic newer the tools are available precisely to envision and to inform subtle changes in the disc, depending on the outline, the color, surrounding and the health of edge of neuroretinal. (7-10) These are as follows:

1. TECHNICAL OF PHOTOGRAPHES

(one) the PHOTOGRAPHS OF STEREO

2. PICTURE INFORMATISEE ANALYZES

(one) the TOMOGRAPHIE VIEW OF COHERENCE (OCTOBER)

(b) EXAMINING CONFOCAL TOMOGRAPHIE LASER (CSLT)

(C) EXAMINING POLARIMETRY OF LASER (SLP).

These methods are especially useful quantitatively to evaluate the layer of fiber of retinal nerve (RNFL) the thickness what's more of the changes in the disc in the presumed cases of glaucoma. It is established that the retinal layer of fiber of nerve in the glaucoma can show to dilute even before the field changes are detected (11-14).

The Tomographie view of Coherence (OCTOBER) the sweeping of a normal one 2 eye of glaucomatous, showing fiber to the nerve the thickness.

Heidelberg Tomograph Retinal (HRT and HRT II) is a laser of confocal that examines the system for the acquisition and the picture analysis to three dimensions of head of nerve view. The system of imagery of HRT has the highest diagnostic precision, precision, reproducibility and can diagnose the glaucoma before the visual confirmed field change. (15.16)

Kamal and Al (17) and Greaney and Al (18) observed that the imagery techniques were not better than the quantitative evaluation of photograph disc. What's more progressive excavation of the disc view, the health of edge of neuroretinal testified by his width and the color is very important (8). The unilateral notch localized in the party inferio-temporel or superio-temporel of edge of neuroretinal is sturdy the informer of glaucoma. Several others sign soft as the asymmetry of proportion of cup bigger disc than 0.2, the ring of peripapillary, the disc hemorrhage, the sign of Herschler of exposed vessels of floor, vertical ovality of compacts view with a proportion of bigger than 3 and few of when present others, adds to the glaucoma suspicion. The latter years, more of importance is given to a disc hemorrhage that crosses the edge of the nerve view and it is considered to be associated with the obtained pit of the nerve view (APON), that is a very strong association of glaucoma (16.19).

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The ADVANCEMENT IN THE FIELD AUTOMATES RECORDING

The introduction of essay of automated computerized field helped us in a significant way to diagnose the glaucoma to a first step just like it furnishes the certain quantity of documentation to check the check and the glaucoma progression.

The last decade saw immense advances in the test strategies, that did the quick, precise, reliable process and reproductible. (20.21)

SITA (the Algorithm of Threshold of Swedish Interactive one) and the SUMMIT (the Tendency A Oriented Perimetry) the test strategies reduced the time of essay and furnished variability of essay of automated perimetric.

The frequency Doubles the Technology (FDT) perimetry is the very quick and effective method to detect the loss of field of glaucomatous.

The Footage of short waves Automated A Perimetry (the ECHANGE) can predict the beginning and the progression of glaucomatous the visual deficits of a lot preceding field that the Norm A Automated Perimetry (the SEVE)

Multifocal Electroretinogram (mfERG) and Multifocal the Potential Visual Evoqued (mfVEP) furnishes a measure objectifies visual field.

The recent studies suggest that the procedures of mfVEP can detect the preceding damages of glaucomatous that the conventional automated perimetry. Goldberg and associates (22) noted that 60 percent of colleagues eyes of patients of glaucoma that had normal Humphrey the visual field was as identified abnormal by the mfVEP.

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INTRAOCULAR PRESSURE

The last decade did not see significant advancement in the methodology to record IOP. Despite several types of tonometers including Applanation Pneumatonograph, Mackay Marg Tonometer Electronique, (23-27), Tonopen XL (tonometer of sanguine flow) (28) and Tonometer same non-contact, Goldman Tonometer remains the Tonometer clinic more reliable, where that it is possible to employ this technique. Tonometer non-contact is convenient to the patient and to the doctor but the readings compares not enough often well with the Goldman Tonometer. The machine needs repeated normalization and has several limitations. Outside of the rigidity of scleral, the abnormal central thickness of the cornea can affect the pressure of reading intraocular (29, 30).

What changed in the last decade is the comprehension of ideal IOP. Such an IOP was edtiqueted as IOP OF TARGET.

Target IOP is defined as that IOP that is sure for this special person. This can be anywhere between the low adolescence to 21 mmHg.

Target IOP is regulated on the following principles:

Has. Loss of Soft Field: Reduce IOP 20% less than initial IOP

B. Moderate Damages: 30% reduction or more.

C. Harsh Damages: 40% reduction or more.

There is not IOP to which an individual is completely sure of the damages of glaucoma and therefore of IOP of target must be individualized to depend on the repeated examination of disc and the fields. The risk factors as the ageing, myopia, heredity, the diabetes etc (31) has to be kept present to the spirit also.

The coming from the Etude of Intervention of Advanced Glaucoma (ACTED) the data suggest that that lowers the IOP the better one, without taking account of the other risks factors that are represented from the standpoint clinic. In the youngest patients, the IOP comparatively should be maintained low (32).

Most of the therapeutic decisions in the glaucoma are based on the pressure of the constant state. The ophtalmologues inform rarely the vagrant or the occasional lances in the pressure or consider the damages that such launch can cause. But such launch occasional damage in a significant way to the RGS (33). The change of Postural in IOP where the IOP is retrieved to increase in the posture of supin in comparison of the meeting of posture, that is ordinary employee in Goldmann or Tonometry non-contact, can lack certain of the cases of glaucoma (23-27).

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PRESSURE OF PERFUSION

The damages of field of Glaucomatous are associated with the decrease in the perfusion pressure of laminate cribrosa and of edge of neuroretinal. It is agreed that the vascular decontrol interferes with the car regulation of perfusion eyepiece and returns the more sensitive eye to the increase of IOP or the decrease of arterial tension. This explains partially the theory of loss of field to the pressure of low intraocular and underlines the meaning to use only these drugs anti- glaucoma, that do not compromise the pressure of perfusion of the disc view (34,35).

The pressure of perfusion of the disc precisely can be measured while following by the techniques:

Heidelberg Flometer Retinal

OBF Tonograph

Examining Doppler Laser Flometry

Color Measures Doppler

Some workers declared that the lack of correct perfusion of disc view is the principal cause of loss of field. Such a decrease in the perfusion pressure can be because of raised IOP or can be independent of the pressure, that explains the event of Tension Glaucoma Low (36-40). Some patients with the glaucoma of normal tension are notably to the risk if they have the history of headache of vasospasm and migraine and that represents the usage of bloqueurs of chain of calcium to prevent the damages of glaucomatous. It is the worthy grade that the pressure of perfusion of the disc view can resume with the decrease of IOP, especially after a successful trabeculectomy (41).

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APOPTOSIS (A PROGRAMS DEAD CELL)

A normal person loses almost 10,000 cells of ganglion per year, and the time they are 80 major years, they will have lost 30 percent of their cells of ganglion. In the glaucoma case open angle, the time the loss of vision becomes apparent, more than 50 percent of cells of ganglion is destroyed.

Apoptosis is a genetically programmed process in that the cells commit suicide, characterized by the chromatic condensation, the intracellular morcellement, and the morcellement of DNA of internucleosomal. (42-44)

The retinal death of cell of ganglion is established when some pathological event, as ischemia, the injury of axonal, or the changes in the laminated cribrosa take to the activation of apoptosis (programed the cell death).

Apoptosis can arrive because of the primary or mechanisms secondary

Primary mechanisms are:

Mechanical tension: Raised IOP can interfere with the flow of axoplasmic demotes essential factors of growth products by the kernel of lateral geniculate.

Vascular compromise: High IOP, the disease or the vascular drugs can reduce the perfusion of nerve view, causing conditions ischedmiques.

Genetic determining: The determining genetic can contribute also to the sensitivity of cells of ganglion to damage (45)

The diseases as the diabetes can do also of the more vulnerable neurones to damage.

Secondary mechanisms:

In this the neuronal damages are believed to be drivings by the toxic factors, as the high levels of glutamate (in the normal levels is a neurotransmitter), oxygen liberates radical, or the oxide nitrique, that can be relaxed by a primary insult, take to the continued damages, even after the primary insult was checked or was dispersed.

Glutamate, an amino acid when in the excess becomes toxic to the neuronal cells, establishing of this manner the process of apoptosis. The dead cells are thought to liberate glutamate and the other amino acids, that keep on the incorrect circle of "Dead Programmed A of Cells of Ganglion". It now is known that glutamate is a normal neurotransmitter in the redtine that when accumulates in the excess probably to the continuation of the continuation of the dead or dying cells the ampler cause damages to the living cells.

Oxygen Liberates Radical (OFR) are molecule oxygen containing that carries one or the ODDER edlectrons. These molecules react with the lipides, the acids nuclediques, and the proteins and cause the cell death. Ischemia that can be independent of the pressure, is supposed to help in the process of liberation of OFR.

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NEUROPROTECTION (AMELIORANT CELL SURVIVAL)

The "neuroprotection" of term refers itself to the protection of the healthy but vulnerable neurones of the dead and dying cells that are at the risk of injury same after the abduction of the primary insult. In the glaucoma, the objective of neuroprotection is to limit or to delay depending damages of the pressure or independent of the pressure to the retinal cells of ganglion (RGCs) by the interference with the processes and the substances that cause the death of neuronal cell or while improving ways to signal that increase the neuronal survival under the upsetting conditions. (42.43, 45-47)

The researchers try to find the intrinsic processes or the natural ways to interrupt the process of apoptosis and move the survival of cells of ganglion while bothering the death signals relaxed in the presence of ischemia, provoked by the deprivation of factors of growth, or caused by on the accumulation of amino acids passionants as glutamate (48).

The quantity of Glutamate is shown to increase to double in glazes it in case of the glaucoma.

Neuroprotection is based on the director of

Reduce the risk factors: Lower the IOP, reduce ischemia.

Promote the neuronal survival

And/or bothers the cell death

Additional Glutamate can be toxic to RGSs normal by on the stimulation of BLACK one IT Medthyle-D-Asparate (NMDA) the receivers. The receiver of NMDA is a major type of receiver of glutamate that when on activated can kill the retinal cells of ganglion. Memantine, diverted from amantidine, shows the considerable promise for the effectiveness of neuroprotective in the glaucoma. The non competitive interaction of Memantine with the receiver of NMDA has for result the blockade of the toxic effects of glutamate without the significant effect on the normal cell function. The biggest the activation of receiver of NMDA by glutamate, the most efficiently memantine blocks the action of glutamate, preventing from this manner the death of cell of ganglion. (49)

The Bcl-2 families of proteins of gene executes a central role in the check of apoptosis. The members of Bcl-2 families of gene that promotes the death of programmed cell includes bad and bax; by opposition, the expression of bcl-2 and bcl-xl eliminates the program of apoptic. To date, one -2 ways were identified that increases the expression of bFGF, induce bcl-2 and bcl-xl genes, and improve the availability of important factors of neurotrophic. While active l'alpha-2 receivers in the redtine, Brimonidine (Brimodin) is shown to increase the expression of gene of anti- apoptic, of this manner, preventing the death of cell of retinal ganglion and promote the growth of axonal (50). Brimonidine neutralizes also the acid of Kainic, that is toxic to the neuronal cells.

The antioxidants, liberate the vulture superoxide dismutase radical, catalase and the vitamin E also are found to have the usefulness of neuroprotective potentielle.

The bloqueurs of chain of calcium (diltiazem, nicardipin, nilvadipine, nifedipine etc), semax (Russian neuropeptide), citicoline, eliprodil, riluzole and l-deprenal etc be under consideration as the agents of neuroprotective.

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THERAPIE MEDICALE

With to exist the numerous drugs and the new classes of now available medicines to lower IOP, the practiciens do facing complex decisions as for the treatment strategies for the glaucoma patients. Traditionally, the silly bloqueurs were considered the standard treatment for the glaucoma, but the other agents, as one -2 agonists, the carbon suppressants of anhydrase and prostaglandins offered alternate options to the practicien. More recently, a new group, to knowledge, the group of Prostamide is lit the scene with the complaints of improved security, effectiveness and the accordance of system of dosing by the patient, compared to the previously available agents.

Usually, the drugs anti- glaucoma are chosen base on the following criteria:

Effectiveness is the most vital one

The security of the system profiles

Treatment convenience- preferred the therapy of OD

The therapy cost

Local tolerances

Depend on above the referred criteria, the silly bloqueurs, especially the Timolol, that is the agent more effective of the group, dominated the system anti- glaucoma. The drug is considered completely effective IOP and reducing by 15 to 30 percent, comparatively inexpensive and with the tolerance excellent by the brands of fabric eyepieces the always primary extremely recommended therapy of glaucoma in the world. (Which deserves is unfavorable effects of the systems on the respiratory system and cardio-vasculaire, and the problems as the depression, the impotence, the libido lack, the diabetes and the tension of night hypo (51.52)). The vigilance lack from the doctor can cause the death of the patient because of asthmaticus of statute or the complication cardio-vasculaire. Since the introduction of the drug in 1978, 40 dead drugs induce were retrieved. The poisonousness of the system can be minimized in a significant way if the practicien is prudent in counselor the usage of this drug and takes measures to prevent the absorption of the system by the usage distributors precise, the pressure on the LOWER puncta or using once a day freeze forming (Timolet GFS) the application. The silly selective bloqueurs Betaxolol as, is comparatively sure in the patients with the respiratory problems but is less effective than timolol.

Pilocarpine always continues to occupy his importance in the Angle Closing Glaucoma Primary. The drug has the effect synergiste with the silly bloqueurs, brimonidine and the group of acetazolamide of the system and current drugs.

The agents of Adrenergic (agonists) likes dipivefrin, clonidine and apraclonidine limited specific indications since enough often they are associated with conjunctival allergy and the other secondary effects including the decrease in the pressure of perfusion of the disc view.

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NEWER DRUGS

Brimonidine tartrate 0.2%

Latanoprost 0.005%

Bimatoprost 0.03%

Travoprost 0.004%

Unoprostone Isopropyle 0.12%

Dorzolamide 2%

Brinzolamide 1% (Azopt)

Brimonidine Tartrate:

Brimonidine is one-2 selective agonist. This is an analogous one of clonidine. This is about 30 pleats more a -2 selective and has very low affinity for a -1 receivers. Because of this reason, mydriasis and the lid are at the leads as found with non selective agonists as clonidine are eliminated.

His principal mechanism of action is the suppression of aqueous formation, but it also is claimed to increase some degree of uveoscleral out - the flow.

(The merit more significant of brimodine (Brimodin) is his profile of security of the relative system and his applied function of neuroprotection by upregulation of cell factors of survival and neuronal, as bFGF1 in response to the activation of the one -2 receivers of adrenergic, and the increase in the sanguine flow eyepiece. (53-55)) The drug must be inculcated two times a day and his effect of decrease of IOP can be compared to timolol. Fault is higher IOP to the depression. The limiting factor of brimonidine is its allergic reactions in the form of a dermatoconjunctivis of contact and the follicular conjunctivitis (roughly the eyes of 30 percent), that can deserve the interruption of the drug. The latter years, few reports showed the event of uveitis after the extended usage of brimonidine tartrate. The other secondary occasional retrieved effects are the fatigue, the drowsiness and the mouth drought. The newest introduction of preservative liberates brimonidine is retrieved to have a lot of less than allergy (50% reduction) since to the place of the chloride of benzalkonium, the chloride of sodium was used as a preservative. Therapeutically, this is equally effective as briomonidine.

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Analogous Prostaglandin and Prostamides

Prostaglandins and prostamides are the most new group of drugs. Inspite of their heavy cost, they win the big importance because of their higher effectiveness in the reduction of IOP, demand only instillation in 24 hours, and have the profile of the comparatively sure system (56-62)

Prostaglandin and prostamide have a common origin in the membranes cytoplasmique but they are diverted from the lipides of membrane limits different that are mobilized and undergoes biosynthetic ways to their final composites. The analogous ones of alpha of F2 of prostaglandin are diverted from an arachidonic the intermediary acid in their metabolism and their formation, but the prostamides is diverted from a way of anandamide where the different enzymes are implied. Although prostamides is similar structurelment in some respects to prostaglandins, functionally prostamides differs.

Latanoprost, travoprost &the amplifier; bimatoprost is retrieved to diminish IOP by 30 to 40 percent and therefore they can be the choice drug as monotherapy in the eyes that demand lower target IOP. The superior daytime check (24-hour checks) attained with these drugs, prevents from the lances the damages linked to the eyes (56). A comparison of bimatoprost to timolol showed that a number statistiquement significant of patients that use bimatoprost attained IOP of given target every time the point compared to these usage timolol. (63) Latamoprost attained also IOP of target but bimatoprost attained often LOWER IOP.

The analogous ones of Prostaglandin increase the go out of uveoscleral without affecting the go out of trabecular or the production of aqueous humor. The increased exit of uveoscleral seems to be moderated through a modification of the matrix extracellulaire and a relaxation of muscle ciliaire.

Latanoprost is also essentially a drug gone out improving. There is 50% increase in the go out of uveoscleral (64-68) and 30% increase in the go out of trabecular by a mechanism, that is nevertheless to be explained. There is the insignificant improvement of flood also. (69) Latanoprost is retrieved to increase the sanguine flow at the head of nerve view. (67, 68)

The recent comparative studies show to Lataoprost to be more effective than unoprostone and Timolol but less than brimatoprost. (56) Bimatoprost lowered IOP by 30% in roughly 78% of patients, while timolol attained 30% reduction in only 61% of patients. (56) of more, 62% of patients that receive Bimatoprost obtained 40% reduction in IOP compared to 35% of patients that receive Timolol. The combination of Latanoprost with when used timolol gives once a day to better lowering IOP than only latanoprost. (69) few workers (70.71) noted the additional decrease in IOP when pilocarpine was used four times a day with only the application of Latanoprost.

The biggest inconvenience of prostaglandins and prostamides is secondary effects significant eyepieces shown in the form of a conjunctival hyperemia (15%), prick and burn (30-40%) and the growth of (20-22%), of sensations of foreign body of wicks of eye, the increased pigmentation of fabric of iris and periorbital including the eyelids, cystoid the edema maculaire, the herpa¨s keratitis simplex, and uveitis.

These drugs are retrieved to lose the effectiveness by 10 to 20% if exposed to the ultraviolet rays unless kept in the opaque bottles brimatoprost or in refrigerator latanoprost.

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THE CARBON SUPPRESSANTS OF ANHYDRASE (CAIs)

Current CAIs was developed that improved a lot the profile of secondary effect of the system when compare to their oral counterparts. Nevertheless, the current CAIs is less effective than the oral agents. Dorzolamide and brinzolamide reduce IOP by roughly 15 to 24% and are not effective in all the patients.

The secondary effects significant eyepieces like to burn, pricking, the sensation of foreign, superficial body to punctuate keratitis etc are noted. Besides, in certain cases, sulpha as the effects of the system could be noted. Because of these reasons that these drugs especially are employed as the therapy of second or third line.

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ADJUNCTIVE THERAPIE

Brimonidine (Brimodin) is as effective as pilocarpine when used adjunctively with the silly bloqueurs, diminishing the IOP almost 15% more. When additional Dorzolamide to timolol affects not in a significant way IOP. Prostaglandins and Prostamides can be used as the second line of therapy with the silly bloqueurs, (69) brimonidine (Brimodin), the agents of clonidine and CAI. When used Pilocarpine four times a day with latanoprost, gives the decrease of additional IOP. (71) The relaxation of cause of Prostamides of muscle ciliaire and therefore of pilocarpine is retrieved to be the additive

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RESUME

The a lot of progress was done in the diagnosis and the glaucoma direction but of always number of case can be only edtiqueted as suspicious and the medical direction remains always to challenge.

The agents of Cholinergic and not selective one -the opposing ones of receiver of adrenergic were replaced mostly by the newest agents that more better are tolerated and has secondary effects less, eyepieces and system. Although the opposing ones of receiver of silly adrenergic are the very effective agents that iop-abaissant that was the standard line of treatment for last 20 years but their secondary effects serious cardiopulmonaires limit their usage. The concept of apoptosis, the pressure of perfusion of the disc view, neuroprotection, the toxins of metabolism, the autoimmune process and the genetic mutation added new dimensions to the medical direction of glaucoma. brimonidine (Brimodin), one one -2 agonist of receiver of adrenergic, has good IOP lowering the effect and the profile of security of the system and is applied to have the property of neuroprotection but the reactions eyepieces always are a challenge. The treatment with the agents of CAI likes that dorzolamide and brinzolamide cannot be considered the first therapy of line and is effective only in someone. Secondary effects of the system and eyepieces limit their usage.

Prostaglandins and prostamides promise drugs because of their effect of decrease of improved IOP, once an application of day and the high profile of security of the system. Nevertheless, their secondary effects eyepieces are a serious question of worry, especially in the white population.

We always are to the ideal research of a drug with the sure profile, to lower significant IOP and to proved neuroprotection without compromising the pressure of perfusion of the disc view. Memantine probably could be the drug of tomorrow to be used with the other drugs of hypotensive eyepieces as a "cocktail" to attain the desired results.

A new paradigm of direction of glaucoma emerged; that foresees that the success clinic more simply is not measured by the level of check of pressure of intraocular attained but also by the quality of the patient of life, therapy profitability, and the preservation in the long term of visual function.

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