Glaucoma, affecting over 70 million people worldwide, is one of the leading causes of irreversible blindness.
Glaucoma is one of the leading causes of irreversible blindness worldwide. Over 70 million people are affected by glaucoma worldwide, and the global burden is expected to rise with the ageing population. The glaucomas are a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells. It usually happens when fluid builds up in the front part of the eye. That extra fluid increases the pressure in the eye, damaging the optic nerve. Glaucoma is a leading cause of blindness for people over 60 years old. Glaucoma can remain asymptomatic until it is severe, resulting in a high likelihood that the number of affected individuals is much higher than the number known to have it.
The eye constantly makes aqueous humor. As new aqueous flows into your eye, the same amount should drain out. The fluid drains out through an area called the drainage angle. This process keeps pressure in the eye (called intraocular pressure or IOP) stable. But if the drainage angle is not working properly, fluid builds up. Pressure inside the eye rises, damaging the optic nerve.
The optic nerve is made of more than a million tiny nerve fibers. As these nerve fibers die, the subject will develop blind spots in his vision. Th subject may not notice these blind spots until most of the optic nerve fibers have died. If all of the fibers die, the subject will become blind.
Types of Glaucoma
Glaucomas can be classified into 2 broad categories: open-angle glaucoma and angle-closure glaucoma. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression.
Primary open-angle glaucoma
This is the most common type of glaucoma. This type of glaucoma is painless and causes no vision changes at first. It happens gradually, where the eye does not drain fluid as well as it should. As a result, eye pressure builds and starts to damage the optic nerve. Most people with open-angle glaucoma do not notice any change in their vision until the damage is quite severe. For this reason this glaucoma is called the “silent thief of sight.”
Angle-closure glaucoma (also called “narrow-angle glaucoma”)
This type happens when someone’s iris is very close to the drainage angle in their eye. The iris can end up blocking the drainage angle. When the drainage angle gets completely blocked, eye pressure rises very quickly. Angle-closure glaucoma can be an acute process with more immediate signs and symptoms but may also present insidiously and tends to be a more visually destructive subtype. It accounts for approximately half the cases of glaucoma worldwide and, when acute, is considered an ocular emergency because loss of vision can occur within hours to days. By 2020, it is estimated that there will be 21 million cases of primary angle-closure glaucoma, with 5.3 million blind bilaterally.
Glaucoma damage is permanent, it cannot be reversed. Glaucoma management is aimed at reducing IOP, the only modifiable risk factor at this time. The goal fundamentally is to slow or cease structural and functional progression. Medicine and surgery (trabeculoplasty, iridotomy, trabeculetomy, glaucoma drainage devices) help to stop further damage. However, glaucoma is usually controlled with eyedrop drugs.
Current management guidelines from the American Academy of Ophthalmology Preferred Practice Pattern recommend lowering the intraocular pressure toward a target level, which is a value or range of values at which the clinician believes that the rate of disease progression will be slowed sufficiently to avoid functional impairment from the disease.
Several different classes of pressure-lowering medications are available. In general, prostaglandin analogues are the first line of medical therapy. These drugs reduce intraocular pressure by reducing outflow resistance resulting in increased aqueous humour flow through the uveoscleral pathway.
Other classes of topical medications are less effective in lowering intraocular pressure than prostaglandin analogues. They are used as second-line agents or when there is a contraindication or intolerance to the use of prostaglandin analogues. Prostaglandin analogues and carbonic anhydrase inhibitors lower intraocular pressure during both the day and night. Other drugs such as the β-adrenergic blockers and α-adrenergic agonists are effective only during the day and not at night.
Dry Eye and Glaucoma
The prevalence of ocular surface disease is greater in glaucoma patients than in the normal adult population and has been reported to be as high as 60%. The associated tear film dysfunction and dry eye symptoms can contribute towards further deterioration in ocular comfort, vision and quality of life. Although the propensity for dry eye development in glaucoma patients is not fully understood, it is thought to be multifactorial.
Both dry eye and glaucoma diseases are more common in older patients and frequently require topical medications as treatment. Both ocular surface disease and glaucoma are a spectrum of disease and severity but when coexistent can compound each other. This interaction is further complicated by treatments for each condition, which can interact and yield counterproductive effects:
Glaucoma and Dry eye syndrome commonly appear together. Glaucoma treatment may cause chronic inflammation or aggravate a concomitant ocular surface disease. Recent studies have explored the potential association between topical anti-glaucoma medications and meibomian gland dysfunction. Through its adverse effects on lipid layer integrity and tear film stability, meibomian gland dysfunction is a leading cause of evaporative dry eye disease. Ocular surface disease infact is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.
Many clinical studies have suggested that the long-term use of topical anti-glaucoma medications may contribute to dry eye. Ocular surface disorders attributable to the drugs itself or to the drug’s preservatives are common. In particular, increased exposure to benzalkonium chloride, a common preservative in ophthalmic preparations, has been identified to be an independent risk factor for the development of ocular surface disease in glaucoma patients.
Benzalkonium chloride is recognised to destabilise the tear film lipid layer through its detergent-like tensioactive effects, which may promote excessive evaporation of the aqueous tear film. Furthermore, the pro-inflammatory and toxic effects of preservatives can also lead to chronic damage of the ocular surface and disrupt tear film homeostasis. The harmful effects of BAK are time and dose dependent such that in small enough quantities the harmful effects are often well tolerated. It is when patients require multiple medications taken multiples times per day that the negative effects add up and lead to more severe reactions on the ocular surface.
Phosphate buffer and corneal calcification:
Moreover, the anti-glaucoma medications often contain the phosphate buffer. Buffers exist in all ophthalmic preparations to maintain a constant pH to prevent decomposition of active drugs and control tonicity. Various scientific studies demonstrated that the phosphate buffer, used chronically, could cause corneal calcification: calcification occurs when calcium cations and phosphate anions form insoluble crystal within the tissue.
In the cornea, deposition typically occurs as hydroxyapatite. Phosphate buffers in drops occur at higher concentrations than the physiological concentration in the tear fluid. It has been estimated that it would require 20.4 days to form total corneal calcifications between the calcium in tears and unlimited phosphate. Deposition of calcium can be observed as a spectrum of clinical findings, ranging from subtle age-related superficial changes to full-thickness calcification of the entire cornea with visual loss. Infact, both superficial band keratopathy and deeper calcareous calcification have been linked to the presence of phosphate excipients in topical ophthalmic medicines. The European Medicines Agency (EMA) has concluded that patients with ocular surface disease are at greatest risk.
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Managing both conditions, glaucoma and dry eye, effectively is important but can be challenging. Glaucoma is usually treated as a priority as it can lead to blindness, but dry eye symptoms are often reported as more problematic for the subject. Switching to preservative-free and phosphate buffer-free eyedrops helps in patients who have dry eye and glaucoma.
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