Latest developments in glaucoma therapy

pharmacy

 (By Pharm. Harrison Kofi Abutiate)

Glaucoma has recently been reclassified as a “progressive optic neuropathy characterised by a specific pattern of optic nerve head and visual field damage.”

   Now known to occur with or without elevated intraocular pressure, the updated definition of this group of irreversibly blinding disorders does not include the words intraocular pressure. Glaucomatous optic nerve damage should be seen as representing a final common pathway resulting from a number of diseases which affect the eye, similar to end-stage kidney or liver failure.

Glaucoma may therefore be regarded as an ocular manifestation of a systemic disease. We are still faced with problems in diagnosis, workup, and treatment, since we have not elucidated all of the additional risk factors and how they impact the development and progression of glaucoma. We are therefore still limited primarily to treatment oriented at lowering IOP.

Risk factor management and directed therapy, such as evidenced in cardiologists’ approach to heart disease, including management of diet, weight, stress, smoking, exercise and cholesterol levels, must be emphasised in our future management of glaucoma.

Systemic risk factors may consist of a variety of disorders, including cardiovascular abnormalities, serum viscosity and platelet abnormalities and a wide variety of as yet poorly defined molecular, immune, and genetic disorders, including factors common to neurodegenerative disease in general, such as oxidative damage and low grade inflammation.

Recently, an increasing number of reports have associated sleep apnea and low cerebrospinal fluid pressure with glaucoma. It has been conjectured that much of glaucomatous damage due to risk factors other than IOP occurs at night. Newer studies are looking at ocular perfusion pressure in relation to blood pressure, which typically is lowest in the early morning hours during sleep, when IOP is highest.

A combination of higher IOP, low blood pressure (and CSF pressure), and sleep apnea may be particularly dangerous, leading to a significant decrease in ocular perfusion pressure.  Increasing IOP by sleeping with the eye pressed against the hand or pillow is another potential nocturnal risk factor for progression of glaucoma.  Some yoga philosophies advocate that individuals must assume different kinds of inverted positions for some time, in order to give the brain a better blood supply. When in the inverted posture, the intraocular pressure (IOP) rises immediately and remains elevated as long as the position is maintained, going back to normal when the upright position is reassumed. It is possible that this transitory spike of intraocular pressure, practised every day and for many years, can lead to damage to the optic.

Therapy directed toward risk factors other than IOP for glaucoma, although still in its infancy, will hopefully develop into an important part of our armamentarium in future years.

Traditional glaucoma therapy

Prostaglandin Analogues

Latanoprost (Xalatan®), Travaprost (Travatan® and Travatan Z®) Bimatoprost (Lumigan®)

Function: This is the newest class of drugs and acts differently from other glaucoma drops. Pressure is lowered by the drug increasing the rate at which fluid flows out of the eye (uveoscleral outflow). The drug needs to be taken only once a day.

Beta-Blockers

Timolol Maleate (Timoptic®) or (Istalol®), Levobunalol (Betagan®), Carteolol (Ocupress®), Betaxolol (Betoptic®)

Function: Reduces aqueous humour production.

Alpha 2 adrenergic agonist

Brimonidine (Alphagan®) (Alphagan-P)

Function: This is a highly selective alpha2-adrenoceptor agonist. Reduces aqueous humour production and increases uveoscleral outflow.

·  Apraclonidine (Iopidine®)

Function: This drug is used at the time of laser treatment to prevent sudden IOP rises caused by the treatment.

·  Miotics

Pilocarpine (Isoptocarpine®, Pilocar ®)

Function: Drops which help open the eye’s drain and increase the rate of fluid flowing out of the eye.

·  Carbonic anhydrase inhibitors – drops

Dorzolamide (Trusopt®), Brinzolamide (Azopt®)

Function: These lessen the production of fluid in the eye.

Carbonic anhydrase inhibitors – pills/tablets

Acetazolamide (Diamox®), Methazolamide (Neptazane®)

Newer drug on the market

·  PilocarpineOcuserts-a tiny disc impregnated with pilocarpine and worn under the eyelid several days at a time, produces a steady flow of the drug while causing a minimal amount of side effects.

Combinations of some or all these products (Combigan, Azarga, Duotrav, Ganfort, Cosopt, Xalacom, Trusopt) are available to enhance patient compliance.

Future additions to glaucoma therapy

·  Marijuana 

This definitely does lower intraocular pressure. CANASOL, an eye drop created from tetrahydrocannabinol (THC), the active ingredient in marijuana, is available in Jamaica. Unfortunately, although many other derivatives of marijuana have been tested in the US over the last 15 years, none has been deemed sufficiently effective and sufficiently free of side effects to bring to market there for glaucoma treatment.

A number of states have decriminalised the substance to varying degrees; other states have created exemptions specifically for medical cannabis, and several have both decriminalisation and medical laws. Two states, Colorado and Washington, have legalised the recreational use of cannabis. In many of the United States, medical marijuana is available by prescription for patients with glaucoma who have had all other measures fail to control pressure. However, only a few patients are receiving government-provided marijuana cigarettes and a great deal of paperwork is necessary to get permission to receive them.

·  Calcium channel blockers

Calcium channel blockers, like nifedipine and verapamil, have been reported to increase blood flow to the eye and to stabilise the visual field. Thus, instead of lowering IOP (although they appear to do this also), calcium channel blockers increase the resistance of the eye to glaucomatous damage.

There are different types of calcium channel blockers. Some primarily affect the strength with which the heart contracts, while others affect peripheral blood vessels, making them dilate so that more blood can pass through. The calcium channel blockers used in the treatment of glaucoma ideally would be those which increase blood flow to the brain, since the eye and the brain share a common blood supply.

Calcium channel blockers can also lower blood pressure, and a low blood pressure predisposes to glaucomatous damage. Therefore, we do not use these drugs at the present time in patients who have low blood pressure, but only in those with normal or high blood pressure

·  Neuroprotectants

Memantine (taken orally as tablets) – appears to protect the nerve cells against glutamate, a messenger chemical released in excess amounts by cells damaged by certain neurological disorders.(1)

Resveratrol – a natural phytochemical found in grape skins, seeds, chocolate, peanuts, and berries.  A Duke Eye Centre-led study showed that resveratrol is associated with a significant lowering of inflammatory indicators, oxidative damage and age-related degenerative markers in trabecular meshwork cells. (2)

Turmeric/Curcumin – Turmeric is derived from the rhizomes (underground stems) of the plant Curcuma longa, a member of the ginger family. It is responsible for the yellow colour of Indian curry and American mustard. Curcumin, which has powerful antioxidant and anti-inflammatory properties, is the most active constituent of turmeric. Curcumin has shown possible beneficial effects in most of the mechanisms that are thought to be involved in the development and progression of glaucoma and which are the targets for pharmacological intervention including excitotoxic cell damage . (3)

1.   Arch Ophthalmol. 2006;124(2):217-225. doi:10.1001/archopht.124.2.217.

2.   Food ChemToxicol. 2009 Jan;47(1):198-204. doi: 10.1016/j.fct.2008.10.029. Epub 2008 Nov 6.

3.   Can J Ophthalmol. 2007 Jun;42(3):425-38

Pharm. Harrison Kofi Abutiate, FPCPharm, FCIMG, FPSGH is the managing director/CEO of Paracelsus Pharmacy & Marketing Company Ltd., and vice president of World Glaucoma Patients Association.