Glaucoma

Keywords Glaucoma, Intraocular pressure, Optic nerve. Retinal ganglion cell 

Primary open-angle glaucoma (POAG) is a multifactorial chronic optic neuropathy with a characteristic acquired loss of optic nerve fibers. Cupping and atrophy of the optic disc occur in the absence of other known causes. Such damage develops in the presence of open anterior chamber angles. It produces characteristic visual field abnormalities. lOP is too high for the continued health of the eye. 

In the United States (US), multiple population studies [e.g., Framingham (Leibowitz et al., 1980), Baltimore (Tielsch et al., 1991), Barbados (Leske et al., 1997)] have been performed to estimate the prevalence of eye disease, including POAG and ocular hypertension (OHT). 

More than 1.6 million have significant visual impairment from glaucoma, with 150,000 bilaterally blind in the US alone (Tielsch et al., 1991). These statistics emphasize the need to identify and closely monitor those at risk for glaucomatous damage. 

Approximately 6.7 million people are bilaterally blind from POAG worldwide, and more than 2 million people will develop POAG each year (Quigley, 1996). 

Multiple sclerosis (MS) is a devastating disease of the CNS that produces demyelination and inflammation. It is believed that its pathogenesis involves an immune reaction against various components of the myelin sheath. In a study by Lock et al. (2002), the gene expression patterns of brain lesions obtained during autopsies of MS patients were examined by microarray cluster analysis. A total of 1080 genes (from 7026 represented 

Migration of lymphocytic cells — along with the presence of T cells, lL-17 a T cell transcript was fotmd to be elevated. 

Macrophage invasion — the up-regulation of the macrophage mannose receptor, cathepsin S, and macrophage capping protein. Up-regulation of irramme response genes — overexpression of major histocompatibility complex (MHC) and IgG. 

Inflammatory cytokine activity — the lL-1 receptor and TNF receptor up-regulated. 

Down-regulation of myelin synthesis pathway genes. 

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Physostigmme an alkaloid obtained from a West African plant is used in the treatment of glaucoma Treatment of physostigmme with methyl iodide gives a quaternary ammonium salt What IS the structure of this salt" ... 

Ophthalmic dmg dehveiy systems (qv) have been developed to dehvei controlled dmg quantities for a prolonged time (up to seven days) to the eye, eg, pilocarpine [92-13-7J (17). Alza Corp. in conjunction with Ciba-Geigy Corp. originally marketed such a product known as Ocusert to treat glaucoma. 

There are hundreds of topical steroid preparations that are available for the treatment of skin diseases. In addition to their aforementioned antiinflammatory effects, topical steroids also exert their effects by vasoconstriction of the capillaries in the superficial dermis and by reduction of cellular mitosis and cell proliferation especially in the basal cell layer of the skin. In addition to the aforementioned systemic side effects, topical steroids can have adverse local effects. Chronic treatment with topical corticosteroids may increase the risk of bacterial and fungal infections. A combination steroid and antibacterial agent can be used to combat this problem. Additional local side effects that can be caused by extended use of topical steroids are epidermal atrophy, acne, glaucoma and cataracts (thus the weakest concentrations should be used in and around the eyes), pigmentation problems, hypertrichosis, allergic contact dermatitis, perioral dermatitis, and granuloma gluteale infantum (251). 

Adverse effects with atropine therapy include dry mouth, myosis, loss of visual accommodations, constipation, and urinary retention. The dmg can also produce flushing, hyperthermia, delirium, tachycardia, and exacerbate glaucoma (85). 

Fig. 2. Ocusert ocular therapeutic system. The Ocusert system releases pilocarpine at a controUed rate to treat glaucoma. In this schematic representation, the three disks and the ring are shown two-dimension ally. The patient inserts the Ocusert system under the eyeUd, where it releases pilocarpine for seven...

Aceta2olamide, the best example of this class of diuretics (69,70), is rarely used as a diuretic since the introduction of the thia2ides. Its main use is for the treatment of glaucoma and some minor uses, eg, for the a1ka1ini2ation of the urine to accelerate the renal excretion of some weak acidic dmgs, and for the prevention of acute high altitude mountain sickness. 

Diuretics are one of the dmg categories most frequendy prescribed. The principal uses of diuretics are for the treatment of hypertension, congestive heart failure, and mobilization of edema fluid in renal failure, fiver cirrhosis, and ascites. Other applications include the treatment of glaucoma and hypercalcemia, as well as the alkafinization of urine to prevent cystine and uric acid kidney stones. 

G.J. (gastrointestinal). Refers to the digestive system. Glaucoma. Increased intraocular pressure. 

Grtin-spat, m. a variety of diopside. -star, m. glaucoma, -stein, m. (Geol.) greenstone, -stich, m. greemsh tinge or cast, -stift, m. green pencil, -sucht, /, chlorosis. 

Therapeutic Function Carbonic anhydrase inhibitor, diuretic, treatment of glaucoma Chemical Name N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl] acetamide Common Name —... 

Therapeutic Function Carbonic anhydrase inhibitor glaucoma treatment Chemical Name 48-Olchloro-m-benzenedisulfonamide Common Name DIclofenamid... 

F Partial agonist Antagonist Nasal decongestion, glaucoma, shock, cardiopulmonary resuscitation... 

FIGURE 9.23 The pro-drug dipivalyl epinephrine enters the cornea of the eye to allow esterase to produce epinephrine in the eye to alleviate high pressure in glaucoma. 

Selective AR agonists are undergoing clinical trials for cardiac arrhythmias and pain (Ai) cardiac imaging and inflammation (A2a) colon cancer, rheumatoid arthritis, psoriasis, and dry eye (A3). Selective AR antagonists are either in or advancing toward clinical trials for kidney disorders (Ax) Parkinson s disease (A2a) diabetes and asthma (A2B) cancer and glaucoma (A3). 

Neurological diseases Huntington s disease (A), amylotrophic lateral sclerosis (A,I), Parkinson s disease (A), traumatic brain injury (A,I), glaucoma (A)... 

ChEI treatments have been expanded also to include other dementias and CNS disorders, e.g. delirium, traumatic brain injuries and memory impairments, as well as myasthenia gravis, glaucoma and parasite infections. 

Anti-cholinergics Tiotropium bromide remains bound to M3-receptors for up to 36 h, and requires only daily intake, whereas other anti-cholinergics (e.g. ipratropium, oxytropium) have to be given up to four-times daily and are often used as maintenance treatment. Possible side-effects are dry mouth, metallic taste after inhalation and very rarely close-angle glaucoma. 

The use of CA inhibitors as diuretics is limited by their propensity to cause metabolic acidosis and hypokalemia. Their use can be indicated in patients with metabolic alkalosis and secondary hyperaldosteronism resulting for example from aggressive use of loop diuretics. Furthermore, CA inhibitors are effective dtugs to produce a relatively alkaline urine for the treatment of cysteine and uric acid stones as well as for the accelerated excretion of salicylates. Perhaps the most common use of CA inhibitors is in the treatment of glaucoma. 

Findings obtained from experimental studies suggest that induction of iNOS mediates inflammatory or ischemic brain damage and that excessively activated nNOS under excitotoxic or ischemic conditions produces NO that is toxic to surrounding neurons. Selective inhibition of iNOS or nNOS may be neuroprotec-tive. This is also the case in glaucoma and diabetic... 

CYP1B1 (chromosome 5) has been linked to primary congenital glaucoma. CYP1B1 is not regularly expressed in liver but is often found in various kinds of tumours. It metabolizes retinoids and many aromatic amines and PAHs to potentially carcinogenic products. 

For example, PGF201 agonists such as latanaprost have been developed as eyedrops to reduce intraocular pressure for the treatment of glaucoma. Topical instillation of these agonists is effective in lowering intraocular pressure and may be used as a first-line therapy for the treatment of glaucoma. 

Lerdelimumab Monoclonal antibody TGF- 32 and TGF-p3 Postoperative scarring in glaucoma patients... 

When a -adrenergic blocking ophthalmic preparation, such as timolol, is administered to patients with glaucoma, it is important to insist that they have periodic follow-up examinations by an ophthalmologist. At these examinations, the intraocular pressure should be measured to determine the effectiveness of drug therapy. 

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