World Glaucoma Week, runs from 7 to 13 March and provides you with an opportunity to educate patients by raising awareness and providing helpful tips about the importance of early diagnosis and appropriate treatment of glaucoma.
A recent study purports that glaucoma may be a cause of, or related to, dry eye and ocular surface disorder. These conditions are of major concern in this chronic, sightthreatening disease – a disease which affects 60 million sufferers worldwide.
Glaucoma is known as the ‘silent thief of sight’ because, in the early stages, there is no pain or any other symptoms. It can steal a patient’s vision before they even know they have the disease. And, once they have it, there is no cure (yet).
If untreated, glaucoma may lead to blindness. However, with early treatment, medication and/or surgery further progression can be halted and you could be responsible for saving the sight of your patient(s).
This is the first (study) that presents information about the effects in patients under actual and current therapy in real–life conditions, which means non-selected patient or therapy
Overview
The Glaucoma Australia association reports that over 300,000 Australians have glaucoma. While it is more common as people get older, it can occur at any age. As our population ages, the proportion of glaucoma patients will increase. What is even more alarming is that the association reports that 50 per cent of Australians who have glaucoma go undiagnosed.
In our hemisphere, more than 34 million people suffer from glaucoma. Of those, 5.6 million are bilaterally blind.
Around the world this equates to 60 million sufferers, with 8.4 million blind. Accordingly, the World Health Organisation Bulletin reports that glaucoma is the leading cause of permanent blindness around the world.
The December 2009 edition of Ocular Surgery News Asia-Pacific quotes cofounder of Glaucoma Australia, Dr. Ivan Goldberg as saying “the most effective way to run a successful glaucoma support organisation is to understand the importance of community awareness.”
Early diagnosis of glaucoma is key to preventing blindness.
An Australian study by Wong et al from the Centre for Eye Research Australia, University of Melbourne, assessed patients for prior knowledge of eye disease, use of eye care services, intraocular pressures, cup-to-disc ratios, visual fields, and examination and photography of optic discs to assess for undiagnosed glaucoma. Their results showed that raised intraocular pressure should not be relied on as the only triggering factor in glaucoma investigations.
Glaucoma Side Effects and Treatment Issues
Glaucoma patients on prolonged topical treatments can present with tear film instability and ocular surface epitheliopathy, collectively known as ocular surface disorder (OSD), which may affect medication compliance and long term control of intraocular pressure (IOP).
These findings are based on a recent Brazilian study which showed that patients chronically using antiglaucomatous medications containing preservatives presented with significantly higher fluorescein staining, lisamine green staining and lower tear film break up time (TFBUT) than the control group. The study showed that tear film and ocular surface were altered in the glaucoma patients and all medications were preserved with benzalkonium chloride (BAK).
Preservatives
Numerous studies and reports have shown a link to the chronic use of preservativecontaining topical ophthalmic products for the treatment of glaucoma and the development or worsening of ocular surface disorder (OSD).
However, the authors of the Brazilian study, from Department of Ophthalmology, University of Sao Paolo, claim “no controlled recent studies have compared the status of glaucoma patients, using chronic topical medications, to control individuals in a community-based setting.
“This is the first (study) that presents information about the effects in patients under actual and current therapy in real- life conditions, which means non-selected patient or therapy,” the authors said.
The authors of the Brazilian study followed 21 patients of the Glaucoma Clinic at the Ribeirao Preto Hospital Sao Paolo, and 20 control individuals. They were subjected to eye examinations for comparison. The control group was selected to match age and gender of the glaucoma group and were without systemic disease and had no past history of ocular surgery or use of topical eye medication.
Eye examinations were followed by an environmental and discomfort questionnaire from the Rocha study, with ten questions and a score range from zero to six, from absent to severe discomfort, including questions on Light sensitivity; Sand sensation; Burning; Vision fluctuation; Vision improvement with eye drops; Tearing; Eye pain in the evening or in the morning; Blurred vision at driving or reading; Discomfort with wind and Discomfort with air conditioning.
Tear film and ocular surface examination consisted of TFBUT, 2 per cent fluorescein and 1 per cent lisamine green staining. Schirmer test – a test for tear production using a strip of filter paper; a measurement of basal and reflex lacrimal gland function – (Ophthlamus Sao Paolo, Brazil) with topical anaesthesia.
According to the paper, “since antiglaucomatous drugs are analogs to neuro transmitters, pro-inflammatory or enzymatic mediators they may interfere in the neuroimmuneendocrine network, disrupting inflammatory and secretory actions. Moreover, benzalkonium chloride as a preservative may induce inflammation or reduce secretion.”
The questionnaire of ocular discomfort indicated mean and standard variation (SD) levels of 7.9+/- 7.2 for controls (p=0.7).
“Our study identified tear instability and epithelial damage, but no greater discomfort or reduced tear secretion.
“Moreover, contradictions in this specific subject related to glaucoma medications were also documented, since the hypothesis that dry eye syndrome (i.e. less tear secretion) related to glaucoma itself was brought up, but not confirmed by the present study and because Schirmer test was similar in glaucomatous and control individuals”
The study showed that those patients undergoing antiglaucoma treatment had significant sign of epithelial damage, but not of ocular surface metaplasia.
The authors acknowledge that due to the heterogeneity of available therapeutic modalities and the variable mechanisms of action, it would be difficult to determine the causes of ocular surface damage.
However, one factor that all the glaucoma medications and other chronic ocular medications, such as artificial tears, administered in the study had in common was the use of the preservative BAK.
BAK is the most common ophthalmic preservative and has been used for this purpose since the 1930s.
“The effects of glaucoma medications or the preservatives in them may induce a proinflammatory environment in the ocular surface which affects tissue cicatrization (the process of a wound healing to produce scar tissue), drug pharmacokinetics, patient compliance and other factors that ultimately would affect IOP control and disease progression,” the study concludes.
It has been hypothesised that glaucoma itself may be a cause of, or related to, dry eye and ocular surface disorder and these conditions are of major concern in this chronic, sight-threatening disease. This is due to the impact they may have on the success of glaucoma treatments.
According to researchers Noecker and Herrygers, from the University of Arizona, who did a Medline search for studies on ocular preservatives and toxicity of glaucoma medications published in English up to December 2002, many patients are affected by both glaucoma and chronic dry eye disease. “In such patients glaucoma treatment can worsen the condition of the ocular surface. Treatment for dry eye disease may cause deterioration of the ocular surface that may limit patients’ ability to tolerate glaucoma therapy.
“Long term use of glaucoma medications has been associated with toxic and inflammatory changes of the ocular surface similar to changes seen in patients with chronic dry eye disease. Biopsies from conjunctiva of glaucoma patients treated with chronic ocular hypotensive medications show an increase in fibroblasts and immune cells much like that seen in patients with chronic dry eye disease,” they reported.
Two classes of preservatives are commonly used in ophthalmic preparations – detergents and oxidants. Noecker and Herrygers, publishing their findings in Clinical and Surgical Ophthalmology in 2003, report that detergent preservatives such as BAK and benzododecinium bromide (BDD) have surfactant effects that disrupt cell membrane permeability. These compounds cause lipid dispersion, which in turn leads to lysis of cytoplasmic contents in micro organisms. They are therefore an “important component of, suppressing microbial growth in the bottle and preventing decomposition of the active drug. Preservatives are needed to preserve the sterility of ophthalmic formulations after multidose bottles are opened. Without preservatives, the contents of multidose containers used twice daily usually become contaminated within one or two weeks.” said Noecker.
The Noecker and Herrygers’ study states “Oxidative preservatives such as stabilised oxychloro complex (SOC) act by penetrating micro organisms’ cell membranes and disrupting cell functions by modifying lipids, proteins, and DNA. Purite, the only preservative on the market to contain SOC, is found in some artificial tears and in the glaucoma medication Alphagan P.”
Research reported by Noecker and Herrygers shows that mammalian cells are only minimally damaged by SOC at concentrations present in ophthalmic solutions.
“Because these cells contain antioxidants, oxidases and catalases, it is thought that they can neutralise low doses of oxidants better than they can neutralise low doses of detergents.”
In another study, Christophe Baudouin, from the Department of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital in France, reported that the conjunctiva and trabecular meshwork in rats dosed for one month with timolol preserved with 0.01 per cent BAK, or with a solution of 0.01 per cent BAK were infiltrated by cells expressing inflammatory or fibroblastic markers. In control rats and rats treated for one month with unpreserved timolol, there was no such cell infiltration. Similar findings were observed in human subjects dosed with two or more glaucoma medications for at least one year.
Baudouin’ study suggests “patients with glaucoma and dry eye disease who require chronic use of ophthalmic medications to control their ocular disease may benefit from formulations that are preservativefree… or contain oxidative preservatives (such as SOC).”
Other studies reinforce these findings of the effect of topical preparations on the ocular surface. A letter to the editor of Ophthalmology published in June 2009, in response to Baudouin’s study, reported the coexistence of glaucoma and dry eye in many of their patients.
Ali and Akpek from the Ocular Surface Diseases and Dry Eye Clinic at The Wilmer Eye Institute in Baltimore, Maryland, retrospectively reviewed the medical records of 539 consecutive patients who were seen at the clinic over a period of two years from January 2004 to January 2006. Their results suggest it is “important to consider the impact that topical glaucoma medications may have with respect to quality of life issues in the dry eye population.”
These findings concur with those of the Medline literature review undertaken by Noecker and Herrygers, mentioned above, that “although corneal epithelial damage and conjunctival infiltration by lymphocytes is probably multifactorial, clinicians should be aware of the affects of the preservatives used in topical medications on the eye.”
For information on glaucoma contact Glaucoma Australia by phone on (AUS) 02 9906 6640 or via email: [email protected] or go to the World Glaucoma Day website: www.wgday.net.
