Because scientists still do not know the exact pathophysiology of glaucoma, current pharmaceutical treatments are designed to lower and maintain IOP within a narrow target range to slow the disease’s progression. We have a variety of topical eye drops for lowering IOP (fixed combinations, preservative-free formulas, etc.), some of which we can combine for specific effects. These drops are generally effective at lowering IOP by 15% to 35%.1
Yet, IOP-lowering medications have certain drawbacks. Foremost, we know that many patients do not comply with their drop regimen. In fact, data from the United States show that patients only use 30% to 70% of their prescribed glaucoma eye drops.2 In France, Nordmann et al used an electronic device called the Travalert® (Alcon) to measure the rate of glaucoma medication compliance in patients, which was 60% in those who were aware that their compliance was being monitored.3 Again in the United States, dispensing records of glaucoma medications in two community retail pharmacies showed that the overall proportion of days covered was only 57% over 12 months, and the medication possession ratio was 71%.4 If patients are only purchasing half the drops they are prescribed, that's a very big issue. Results from the Nordmann et al study mirrored this finding; when we compared the doctors’ estimations with the data from the electronic system, there was a large gap between what patients were using and what doctors thought they were using. Additionally, Okeke et al found that many patients will take their eye drops as prescribed 5 days before their next consultation, and then their use declines over the following month.5 We also know that, as we increase the number of eye drops we prescribe patients, we increase the risk of noncompliance.2
REASONS FOR NONCOMPLIANCE
Why do patients stop using their medications? There are several reasons. Older patients often have difficulties instilling eye drops, especially if they have disabilities. Many simply forget, but there are also patients who misuse their eye drops. I remember one very nice patient who came to see me for the first time. When I asked how they used their eye drops, they told me that they put a drop in their coffee every morning. Then, I asked a member of my family who has glaucoma, "Please show me how you put in your eye drops?" She touched the bottle’s tip to her eyeball. Because she could feel the sensation, she thought she was getting the drops in her eyes. Do you think this misunderstanding is rare? It is not rare. This was my own family member!
If we combine the number of patients who don’t use their eye drops routinely with the number of those who miss their eyes, then we see there is potentially a large population of patients whose IOP is going unmanaged. Unfortunately, nonadherence to glaucoma medication can lead to blindness in this population.
PREVALENCE OF TOXICITY WITH DROPS
As clinicians, we see a high prevalence of signs of ocular surface toxicity in our glaucoma patients (Figure 1). We know that the more drops patients have to use, the more ocular irritation they experience. More than half of patients who receive pharmaceutical treatment for glaucoma have some degree of ocular surface disease, with one-third of these individuals showing signs of severe ocular surface disease.6 Baudouin et al showed a direct correlation between the number and frequency of topical drops patients were using and the severity of their ocular surface disease.6 More than two-thirds of patients who were using three glaucoma medications showed some degree of ocular surface disease.
Figure 1. Obvious signs of medication toxicity in glaucomatous eyes: severe ocular surface inflammation (A), toxic keratitis (B), toxic blepharitis (C), and palpebral eczema (D).
THERAPEUTIC MANAGEMENT
My colleagues and I conducted a departmental study of the reasons why we would change a patient’s glaucoma medication.7 For more than one-third of our patients, the reason we switched their medication was not efficacy, but because of adverse effects to the ocular surface from the eyedrops. If we can’t find a glaucoma drop that is comfortable for patients and does not inflame the ocular surface, then we must perform filtering surgery. However, filtering surgery is much more likely to fail in eyes that have received many eye drops versus eyes that have not received eye drops previously. Baudouin et al published an interesting study in 2021 about the vicious cycle of inflammation in glaucoma treatments.8 In the early stages of glaucoma, there is damage to the trabecular meshwork that increases IOP. So, we prescribe eye drops to decrease the IOP, but these drops may induce inflammation and ocular surface disease. We know that this inflammation can target the trabecular meshwork and raise IOP. Over time, the efficacy of the glaucoma drops decreases, and the inflammation increases the eye’s outflow resistance, thereby contributing to uncontrolled IOP. When we can no longer control the IOP with medication, we do surgery, but the success rate of the surgery is compromised by the damage done to the ocular surface by the drops. There is a spiral to blindness due to pharmaceutical-induced inflammation and toxicity. So, maybe we should think differently.
SUMMARY
In short, we have many kinds of glaucoma medications that are effective at controlling IOP, but these drops have several limitations, from noncompliance, to misuse, to toxicity. Therefore, it may be time to rethink our conventional glaucoma therapy and consider a new treatment algorithm. Perhaps we should use glaucoma drops as a supplemental treatment for glaucoma, because we have other options today.
To hear more from Prof. Labbe, visit https://eyetube.net/spotlight/glaukos-international/glaukos-egs-symposium-2024-video-1
1. Van der Valk R, Webers CAV, Schouten JSAG, et al. Intraocular pressure-lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials. Ophthalmology. 2005;112(7):1177-1185.
2. Quaranta L, Novella A, Tettamanti M, et al. Adherence and persistence to medical therapy in glaucoma: an overview. Ophthalmol Ther. 2023;12(5):2227-2240.
3. Nordmann JP, Baudouin C, Renard JP, et al. Measurement of treatment compliance using a medical device for glaucoma patients associated with intraocular pressure control: a survey. Clin Ophthalmol. 2010:4:731-739.
4. Feehan M, Munger MA, Cooper DK. Adherence to glaucoma medications over 12 months in two US community pharmacy chains. J Clin Med. 2016;5(9):79.
5. Okeke CO, Quigley HA, Jampel HD, et al. Interventions improve poor adherence with once daily glaucoma medications in electronically monitored patients. Ophthalmology. 2009;116(12):2286-2293.
6. Baudouin C, Renard J-P, Nordmann J-P, et al. Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. Eur J Ophthalmol. 2012;23(1):47-54.
7. Van Went C, Alalwani H, Brasnu E, et al. Corneal sensitivity in patients treated medically for glaucoma or ocular hypertension. J Fr Ophtalmol. 2011;34(10):684–690.
8. Baudouin C, Kolko M, Melik-Parsadaniantz, Messmer EM. Inflammation in glaucoma: from the back to the front of the eye, and beyond. Prog Ret Eye Res. 2021;83:Article ID: 100916. Available at: https://www.sciencedirect.com/science/article/pii/S1350946220300884?via%3Dihub.
INDICATIONS FOR USE: The iStent inject® is intended to reduce intraocular pressure safely and effectively in patients diagnosed with primary open-angle glaucoma, pseudo-exfoliative glaucoma or pigmentary glaucoma. The iStent inject® can deliver two (2) stents on a single pass, through a single incision. The implant is designed to stent open a passage through the trabecular meshwork to allow for an increase in the facility of outflow and a subsequent reduction in intraocular pressure. The device is safe and effective when implanted in combination with cataract surgery in those subjects who require intraocular pressure reduction and/or would benefit from glaucoma medication reduction. The device may also be implanted in patients who continue to have elevated intraocular pressure despite prior treatment with glaucoma medications and conventional glaucoma surgery. CONTRAINDICATIONS: The iStent inject® System is contraindicated under the following circumstances or conditions: • In eyes with primary angle closure glaucoma, or secondary angle-closure glaucoma, including neovascular glaucoma, because the device would not be expected to work in such situations • In patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS/PRECAUTIONS: • For prescription use only. • This device has not been studied in patients with uveitic glaucoma. • Do not use the devices if the Tyvek® lid has been opened or the packaging appears damaged. In such cases, the sterility of the device may be compromised. • Due to the sharpness of certain injector components (i.e. the insertion sleeve and trocar), care should be exercised to grasp the injector body. Dispose of device in a sharps container. • iStent inject® is MR-Conditional; see MRI Information below. • Physician training is required prior to use of the iStent inject® System. • Do not re-use the stent(s) or inserter, as this may result in infection and/or intraocular inflammation, as well as occurrence of potential postoperative adverse events as shown below under “Potential Complications.” • There are no known compatibility issues with the iStent inject® and other intraoperative devices (e.g., viscoelastics) or glaucoma medications. • Unused product & packaging may be disposed of in accordance with facility procedures. Implanted medical devices and contaminated products must be disposed of as medical waste. • Due to the sharpness of certain injector components (i.e. the insertion sleeve and trocar), care should be exercised to grasp the injector body • The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. If intraocular pressure is not adequately maintained after surgery, the surgeon should consider an appropriate treatment regimen to reduce intraocular pressure.
INDICATION FOR USE: The iStent inject® W, is intended to reduce intraocular pressure safely and effectively in patients diagnosed with primary open-angle glaucoma, pseudo-exfoliative glaucoma or pigmentary glaucoma. The iStent inject® W, can deliver two (2) stents on a single pass, through a single incision. The implant is designed to stent open a passage through the trabecular meshwork to allow for an increase in the facility of outflow and a subsequent reduction in intraocular pressure. The device is safe and effective when implanted in combination with cataract surgery in those subjects who require intraocular pressure reduction and/or would benefit from glaucoma medication reduction. The device may also be implanted in patients who continue to have elevated intraocular pressure despite prior treatment with glaucoma medications and conventional glaucoma surgery. CONTRAINDICATIONS: The iStent inject® W System is contraindicated under the following circumstances or conditions: • In eyes with primary angle closure glaucoma, or secondary angle-closure glaucoma, including neovascular glaucoma, because the device would not be expected to work in such situations. • In patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS/PRECAUTIONS: • For prescription use only. • This device has not been studied in patients with uveitic glaucoma. • Do not use the device if the Tyvek® lid has been opened or the packaging appears damaged. In such cases, the sterility of the device may be compromised. • Due to the sharpness of certain injector components (i.e. the insertion sleeve and trocar), care should be exercised to grasp the injector body. Dispose of device in a sharps container. • iStent inject® W is MR-Conditional; see MRI Information below. • Physician training is required prior to use of the iStent inject® W System. • Do not re-use the stent(s) or injector, as this may result in infection and/or intraocular inflammation, as well as occurrence of potential postoperative adverse events as shown below under “Potential Complications.” • There are no known compatibility issues with the iStent inject® W and other intraoperative devices. (e.g., viscoelastics) or glaucoma medications. • Unused product & packaging may be disposed of in accordance with facility procedures. Implanted medical devices and contaminated products must be disposed of as medical waste. • The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. If intraocular pressure is not adequately maintained after surgery, the surgeon should consider an appropriate treatment regimen to reduce intraocular pressure. • Patients should be informed that placement of the stents, without concomitant cataract surgery in phakic patients, can enhance the formation or progression of cataract. ADVERSE EVENTS: Please refer to Directions For Use for additional adverse event information. CAUTION: Please reference the Directions For Use labelling for a complete list of contraindications, warnings and adverse events.
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