June 03, 2019
3 min read

Treat OSD to help reduce IOP

A subtractive strategy rather than additive might be a better approach to ocular surface disease in these patients.

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Treatment of ocular surface disease in glaucoma patients might improve IOP control and reduce the need for filtering surgery, according to a study carried out at Quinze-Vingts National Ophthalmology Hospital in Paris.

“We did a retrospective review of a few cases, and we were able to show that OSD not only is a concern in terms of tolerance and observance, but is also a crucial factor in the treatment to improve IOP control,” Pierre Dubrulle, MD, said.

As shown by several real-life studies, the prolonged use of glaucoma medications causes significant side effects to the ocular surface. The prevalence of ocular surface disease in patients on multiple drops is as high as 40% to 50%. Chronic inflammation is likely caused by a combination of factors, including active compound toxicity, drug interactions, preservatives and concomitant factors such as pre-existing allergies or atopy.

Pierre Dubrulle, MD
Pierre Dubrulle

“Many of the components of IOP-lowering drops are aggressive to the ocular surface. Prostaglandin analogues can provoke hyperemia and short breakup time. Brimonidine is a well-known cause of allergy and uveitis. In addition, many of those drops contain preservatives. This is slowly changing, but benzalkonium chloride was used for many years before we discovered that it was toxic, proinflammatory and pro-oxidative,” Dubrulle said.

Many glaucoma patients take multiple drops for 20 to 30 years, and intolerance develops gradually due to a cumulative effect.

“It may remain almost asymptomatic for quite a long time, and when dry eye symptoms develop, they are often treated with tear substitutes, an additive strategy that ends up worsening the underlying condition rather than treating it, particularly if tear substitutes also contain preservatives,” Dubrulle said.

A subtractive strategy rather than an additive strategy might be a better approach, as shown in this study, he said.

Ten patients with primary open-angle glaucoma uncontrolled with maximal topical treatment were reviewed retrospectively. All patients had advanced, progressing glaucoma and were referred to Quinze-Vingts for filtering surgery. All also had severe ocular surface disease that required treatment before surgery.

“With the ocular surface in poor condition, trabeculectomy is likely to fail, and treatment is therefore mandatory,” Dubrulle said.

The treatment strategy was customized to the individual patient but mostly entailed the switch to preservative-free drops and other classes of IOP-lowering medications with a better safety profile than those habitually used. Potentially allergenic agents, such as brimonidine, were removed, and preservative-free tear substitutes were administered. Lid hygiene was prescribed and some patients were administered doxycycline, cyclosporine A or NSAID agents. All patients were monitored for IOP as well as ocular surface status over at least 6 months.


“When the patients came for the 1-month visit, the ocular surface was significantly better, and much to our surprise, IOP had significantly lowered — this to the point that surgery was no longer needed,” Dubrulle said.

Christophe Baudouin, MD, PhD, chairman of ophthalmology at Quinze-Vingts and co-author of the study, had already hypothesized in previous publications that ocular surface inflammation might be associated with an increase in IOP and that IOP might benefit from the treatment of inflammation.

“The chronic state of inflammation caused by multiple eye drops over many years might extend to deeper tissues, including the trabecular meshwork, and affect filtration. Other mechanisms might be involved, such as chronic inflammatory vasodilation of the episcleral venous network and the faster washout of eye drops through dilated vessels, which would make them less effective,” Dubrulle said.

This study should further encourage glaucoma specialists to seriously consider ocular surface status as a key factor in the evaluation of patients with glaucoma and ocular surface disease as a factor influencing IOP.

“Treating the ocular surface not only lowered IOP and made surgery unnecessary, but also increased tolerance of treatments, improving adherence, glaucoma control and, ultimately, quality of life,” Dubrulle said.

Two of the patients with very advanced glaucoma, in which IOP remained high despite ocular surface disease treatment, underwent successful trabeculectomy on a clean and quiet ocular surface.

Although more attention is given nowadays to drug tolerance, and many glaucoma drops are now preservative-free, too many patients still develop ocular surface disease, and their condition is often overlooked and underestimated. Too many glaucoma specialists just aim at IOP control, even with four different categories of IOP drops, Dubrulle said. It is better to treat less, adopting a subtractive and conservative approach rather than the additive and iatrogenic approach that has been the norm for many years.

“When IOP is not controlled, the first reaction is to add another drug. This may lower IOP for a time but at the cost of cumulative inflammation. This approach needs to be changed,” he said. “To prevent or minimize ocular surface issues, preservative-free drops and fixed combination therapies should be preferred.” – by Michela Cimberle

Disclosure: Dubrulle reports no relevant financial disclosures.