CURRENT CONCEPT FOR DIAGNOSIS AND MANAGEMENT OF GLAUCOMA
Dr MR Jain, a glaucoma specialist, is currently Medical Director and Chief MR J ophthalmologist Institute and Jain Eye Hospital Jaipur, India. He has published textbook on glaucoma and a book on ocular inflammation and published 130 scientific papers in India and abroad. In the year 2007, he published a book of public education in Hindi on “EYES: SAFETY AND TREATMENT”
He was awarded Life Time Achievement Award by the Ophthalmological Society Rajasthan in the year 2002 & Life Time Achievement Award by the entire society of ophthalmology in India, 2006
Dr. Jain was awarded the Gold Medal by the “National Academy of Medical Sciences “for clinical research and in the” delivery glaucoma and drugs to the eye. “
Currently Dr. Jain is the Chairman, Dr MR J charitable Trust, President, Lucky seventh, Medicos SMS and State Coordinator for the National Academy of Medical Sciences.CURRENT CONCEPTS IN DIAGNOSIS AND
MANAGEMENT OF GLAUCOMA
PROF. MRJAIN, MS, FICS (USA), FAMS, FACLP (London) MRJINSTITUTE MEDICAL DIRECTOR
& Jain Eye Hospital JAIPUR
E-MAIL: drmrjain55@gmail.com
The definition of glaucoma is based on visually significant organ damage (3). It is strictly the opinion that the IOP related damage can occur at all levels of IOP, and therefore nearly 50 percent of patients with glaucoma remain undiagnosed (4-6). However, the Baltimore Eye Survey and Aravind Comprehensive Eye Study show that the relationship between intraocular pressure and the prevalence of glaucoma is positive. Typically , 21mm Hg is considered a cutoff point.
Top
MODERN diagnostic modalities
Optic nerve head
IMMAGING
1. Technique photography
(a) stereoscopic photographs
2. COMPUTER IMAGE ANALYSIS
(a) optical coherence tomography (OCT )
(b) confocal scanning laser tomography (SCTL)
(c) Scanning laser polarimetry (SLP).
These methods are particularly useful to quantify retinal nerve fiber layer (RNFL) thickness in addition to changes in the disc with suspected glaucoma. There is evidence that retinal nerve fiber layer in glaucoma may show weight loss before changes in land are detected (11-14).
>optical coherence tomography (OCT) to scan a normal two glaucomatous eyes, showing the thickness of the nerve fibers.
Heidelberg Retinal Tomograph (HRT II and HRT) is a confocal laser scanning for the acquisition and analysis of three-dimensional images of the optic nerve head. HRT imaging system has the highest diagnostic accuracy, accuracy, reproducibility and is able to diagnose glaucoma, change before confirmed visual field. (15.16)
Kamal et al (17) and Greaney et al (18) observed that the imaging techniques are not better than the quantitative disc photographs. In addition to the progressive excavation of the optic disc, the neuroretinal rim of the health evidence by its width and the color is very important (8). Localized unilateral notch in the inferiority or superiority temporal temporal neuroretinal rim is a strong indicator of glaucoma. Several other signs as sweet as the asymmetry of cup / disc ratio greater than 0.2, peripapillary halo, disc hemorrhage, Herschler sign of ships exposed floor, ovality vertical optic cup, with a ratio greater than 3 and another few when present, adds to the suspicion of glaucoma. In recent years, more emphasis is given to bleeding through the disk rim of the optic nerve and is considered to be associated the acquisition of the pit of the optic nerve (ON), which is a very strong association of glaucoma (16.19.)
Top
PROMOTION
field recording AUTOMATIC
Introduction
of field testing automated computer really helped us to diagnose glaucoma at an early stage and the supply quantity of documents to monitor and control the progression of glaucoma.
past decade has seen tremendous progress in testing strategies, which made the process fast, accurate, reliable and reproducible. (20.21)
SITA (Swedish Interactive Threshold Algorithm) and TOP (Tendency Oriented Perimetry) test strategies have reduced testing time and provided the variability of automated perimetric tests.
Frequency Doubling Technology (FDT) perimetry is very fast and effective method for detecting glaucomatous field loss.
short-wavelength perimetry
(Automated SWAP) is able to predict the onset and progression of glaucomatous visual field defects much earlier than standard automated perimetry (SAP)
Multifocal Electroretinogram
(mfERG) and multifocal visual evoked potential (mfVEP) provide an objective measure of visual field.
Recent studies suggest that procedures
mfVEP may be able to detect glaucoma damage earlier than conventional automated perimetry. Goldberg and Associates (22) noted that 60 percent of fellow eyes of glaucoma patients who had normal Humphrey visual field were identified as abnormal by the mfVEP.
>
IOP
What has changed in the last decade is the understanding of the ideal of the PIO. This IOP was labeled target IOP.
Target IOP is defined as IOP is safe for this individual. It can be anywhere between a low of 21 mmHg adolescents
Target IOP is placed on the following principles.
a.
Loss light field: reduce IOP by 20% less initial IOP
b. moderate damage:. Save 30% or more
c. Severe damage:. Reduction of 40% or more
There is no PIO in which an individual is completely immune to the damage of glaucoma and thus target IOP should be individualized based on the repeated examination of record and the fields. risk factors such as aging, myopia, heredity, diabetes, etc. (31) also have to keep in mind.
The result of the intervention study glaucoma Advanced (AGIS) data suggest that lower IOP best, regardless of risk factors that are recognized clinically. In younger patients, IOP should be kept relatively low (32).
in glaucoma treatment decisions are based on the most pressure stable condition. Ophthalmologists rarely document or episodic transient spikes in pressure or to consider the damage that can cause these peaks. But such occasional spikes are significantly detrimental to the RGS (33). Changing the posture of IOP, IOP which is reported to increase from supine to sitting, which is generally used in Goldmann tonometry or without contact, can miss some cases of glaucoma ( 23-27).
>perfusion pressure
Infusion
the disk can be measured precisely by the following techniques:
FLOMET Heidelberg retina
OBF Tonograph
Scanning Laser Doppler Flometry
The measures color Doppler
Some workers reported that the absence of correct infusion optical disc is the leading cause of lost ground. Such a reduction in perfusion pressure may be due to elevated IOP, or may be independent of pressure, which explains the appearance of low tension glaucoma (36 – 40). Some patients with normal-tension glaucoma are particularly at risk if they have a history of headaches and migraines vasospasm and that accounts for the use of calcium channel blockers to prevent glaucomatous damage. It is note worthy that perfusion pressure of the optic nerve can recover with the lowering of IOP, especially after trabeculectomy success (41).
Top
APOPTOSIS (programmed cell death)
Apoptosis is a genetically programmed process
in which cells commit suicide, characterized by the chromatic condensation, fragmentation and intracellular DNA fragmentation internucleosomal. (42-44)
death of retinal ganglion cells is initiated when some pathological events such as ischemia, axonal injury, or changes in the lamina cribrosa leading to the activation of apoptosis (programmed cell death)
Apoptosis can occur because of the mechanisms of primary or secondary
primary mechanisms: ..
Stress
mechanical. elevated IOP can affect retrograde axoplasmic flow of essential growth factors produced by the lateral geniculate nucleus
vascular compromise: Elevated IOP , a vascular disease or drugs may reduce the perfusion of the optic nerve, causing ischemic diseases
Determinants
genetic. genetic determinants may also contribute to susceptibility to damage the ganglion cells (45)
Mechanisms> secondary.
glutamate, an amino acid when in excess is toxic to neuronal cells, thus initiating the process of apoptosis. The dead cells are thought to release glutamate and other amino acids, which maintain the vicious circle of “programmed cell death of ganglion.” We now know that glutamate is a neurotransmitter normal in the retina which, when accumulated in excess probably due to dead or dying cells, cause damage to living cells.
Oxygen free radicals (OFR) are molecules containing oxygen that carry one or more unpaired electrons. These molecules react with lipids, nucleic acids and proteins and cause cell death. Ischemia can be independent of pressure, is supposed to help in the process of release of OFR.
Top
> (IMPROVED CELL SURVIVAL)The term “neuroprotection” refers to the protection of healthy but vulnerable neurons in the vicinity of dead and dying cells, which are risk of injury, even after removal of the primary insult. In glaucoma, the goal of neuroprotection is to limit or delay the pressure-dependent or independent of pressure damage to retinal ganglion cells (RMC) by interfering with the processes and substances that cause neuronal cell death or enhancing the signaling pathways that increase neuronal survival in stressful conditions. (42.43, 45-47)
Researchers
are trying to find processes intrinsic or natural ways to interrupt the process of apoptosis and promote survival of ganglion cells from death by inhibiting signals released in the presence of ischemia induced by deprivation factors growth, or caused by the accumulation of more excitatory amino acids such as glutamate (48).
amount of glutamate is demonstrated. amounts to double in the vitreous in glaucoma
neuroprotective
is based on the principle
Reduce risk factors: lowering IOP, reduce ischemia.
Promote neuronal survival
and / or inhibit cell death
excess can be toxic to normal in over RGSS stimulation of N-methyl- D-aspartate (NMDA). The NMDA receptor is an important type of glutamate receptors that when activated can kill more retinal ganglion cells. Memantine, a derivative of amantadine, shows great promise for neuroprotective efficacy in glaucoma . Memantine is non-competitive interaction with the NMDA receptor results in blockade of the toxic effect of glutamate, without significant effect on normal cell function. The greater activation of the NMDA receptor by glutamate blocks more effectively the action of memantine glutamate, thus preventing the death of ganglion cells. (49)
The Bcl-2 family protein gene plays a central role in regulating apoptosis. Members of Bcl-2 family genes that promote programmed cell death misunderstand and BAX, however, the expression of bcl-2 and bcl-xl suppresses the apoptotic program. To date, a tract -2 were identified as increased expression of bFGF, induce bcl-2 and bcl-x gene, and improve the availability of neurotrophic factors important. By activating alpha-2 receptors in the retina, brimonidine (Brimodin) is shown to increase the expression anti-apoptotic genes, thereby preventing retinal ganglion cell death and promote axonal growth (50). Brimonidine also neutralizes kainic acid, which is toxic to neuronal cells.
antioxidants, superoxide dismutase free radical scavenger, catalase and vitamin E are also found to have a neuroprotective potential utility.
blocking calcium channels (diltiazem, nicardipine, nilvadipine, the nifedipine, etc.), semax (Russian neuropeptide), citicoline, eliprodil, riluzole, and L-deprenal etc. are being studied as neuroprotective agents.
Top > > Medical
In general, anti-glaucoma are selected based on the following criteria:
> is more vitalprofiles
security systems
The convenience of preferential treatment OD therapy
Cost of therapy
> Local
pilocarpine
continues to occupy its importance in primary angle-closure glaucoma. The drug has a synergistic effect with beta-blockers, brimonidine group and acetazolamide systemic and topical medications.
adrenergic agents (agonists) as dipivefrine, clonidine and apraclonidine limited specific indications because very often they are associated with conjunctival allergy and other side effects, including reduction of the pressure perfusion of the optic disc.
Back
new drugs
tartrate
brimonidine 0.2%
Unoprostone isopropyl 0.12%
dorzolamide 2%
brinzolamide 1% (Azopt)
brimonidine tartrate
:
Brimonidine is a selective agonist-2. It is an analogue of clonidine. It is about 30 times more selective and has a -2 very low affinity for -1. For this reason, the offset mydriasis and lid that can be found with non-selective agonists such as clonidine are eliminated.
The main mechanism of action the suppression of aqueous formation, but it is also claimed to increase a degree of out uveoscleral flow -.
(Merit’s largest brimodine (Brimodin) is its safety profile and on systemic postulated its function of neuroprotection by the upregulation of factors and neuronal cell survival, as bFGF1 in response to an activation of adrenergic receptors -2, and increased ocular blood flow. (53-55)) The drug should be instilled twice a day and its effect may be lowering IOP compared to timolol. The failure is higher than the low IOP. The limiting factor is its brimonidine allergic reaction in the form of contact and dermatoconjunctivis follicular conjunctivitis (about 30 percent eyes), which may warrant discontinuation of the drug. In recent years, several reports have shown occurrence of uveitis after prolonged use of brimonidine tartrate. Other occasional side effects reported were fatigue, drowsiness and dryness of the mouth. The introduction of new preservative-free brimonidine have far fewer allergies (50% reduction) from the place of benzalkonium chloride, sodium chloride was used as a preservative. therapeutics, it is just as effective that briomonidine.
Top
prostaglandin analogues and
prostamides
> and prostamides are newer group of drugs. Despite their high cost, they are of greater importance because of their greater effectiveness in reducing IOP, require single instillation in 24 hours, and relatively Profile systemic course (56-62)Prostaglandin
and prostamide have a common origin in the cell membranes, but they come from different membrane lipids are mobilized and undergo the biosynthetic pathways of compounds to their final. analogs of prostaglandin F2 alpha are derived from arachidonic acid in intermediary metabolism and the formation, but prostamides are derived from a process of anandamide in which different enzymes are involved. prostamides are structurally well Similar in some respects, prostaglandins, prostamides functionally different.
Latanoprost, travoprost & bimatoprost are reported to reduce IOP by 30 to 40 percent and where they may be the drug of choice as monotherapy in the eye requiring less target IOP. Superior control day (24 hour control) obtained with these drugs, prevents the tips of the damage caused to the eyes. (56) A comparison of bimatoprost with timolol have shown that a statistically significant number of patients using bimatoprost achieved target IOP at each given time point compared to those using timolol. (63) Latamoprost too reached target IOP, but bimatoprost often achieved lower IOP.
prostaglandin analogues increase uveoscleral outflow without affecting trabecular output or production of aqueous humor. outflows increased uveoscleral appears to be mediated by a modification of the extracellular matrix and a relaxation of the ciliary muscles .
Latanoprost is too
essentially a drug improving the output. There is a 50% increase in the uveoscleral outflow (64-68) and 30% increase in output by a trabecular mechanism, which is not yet explained. There is slight improvement in the flow as well. (69) Latanoprost is reported to increase blood flow to the optic nerve head. (67, 68)
Recent comparative studies show Lataoprost to be more effective than unoprostone and timolol, but less than brimatoprost (56). Bimatoprost lowered IOP by 30% to about 78% of patients, whereas timolol achieved a reduction of 30% in only 61% of patients. (56) Moreover, 62% of patients receiving bimatoprost achieved 40% reduction in IOP compared to 35% of patients receiving timolol. The combination of latanoprost with timolol when used once a day give better IOP lowering than latanoprost alone. (69) Few workers (70,71) noted further reduction in IOP when pilocarpine was used four times a day with the single application of latanoprost .
These drugs are reported to lose efficiency from 10 to 20% when exposed to ultraviolet rays unless kept in brimatoprost opaque bottles in the refrigerator or latanoprost.
Top
carbonic anhydrase inhibitors (CAIS)
> Topical have been developed that have greatly improved systemic side effect profile compared to oral counterparts. However, the topical CAIS are less effective than oral agents. Dorzolamide and brinzolamide reduced the IOP to about 15 to 24% and are not effective in all patients.significant ocular side effects such as burning, stinging, foreign body sensation, superficial punctate keratitis, etc. are noted. In addition in some cases, sulfonamides such systemic effects may be noted. Because of these reasons, these drugs are mainly used as second or third line.
Top
THERAPY
BOOSTER
Brimonidine
(Brimodin) is as effective as pilocarpine when used adjunct to beta-blockers, decrease in IOP of about 15% more. Dorzolamide when added to timolol does not significantly affect IOP. prostamides Prostaglandins and can be used as second line therapy with beta-blockers (69), the agents brimonidine (Brimodin), clonidine and CAI. Pilocarpine when used four times daily with latanoprost, gives additional lowering of IOP. (71) prostamides cause relaxation of the ciliary muscle, and thus is reported as pilocarpine additive
Top
CONTENTS
Considerable progress has been in the diagnosis and management of glaucoma but still some cases can not be labeled as suspect, and medical management remains a challenge.
cholinergic agents and non-selective receptor antagonists -adrenergic receptors have been replaced mostly by new agents that are better tolerated and have fewer ocular and systemic side effects. Although antagonists of beta-adrenergic receptors are highly effective agents that have been PIO line standard treatment for 20 years, but serious side effects cardiopulmonary which limits their use. Concept of apoptosis, the perfusion pressure of the optic nerve, neuroprotection, metabolic toxins, autoimmune processes and genetic mutation added new dimensions to the medical management of glaucoma. brimonidine (Brimodin), an -2 adrenergic agonist, has a good effect of reducing IOP and systemic safety profile and is assumed to have the property of neuroprotection,