Optimizing patient care: Managing glaucoma and ocular surface disease

November 9, 2008

Long-term treatment of glaucoma is needed in many cases to prevent progression of the disease to vision loss. Paradoxically, the treatments that can be extremely effective at lowering IOP also can have a harmful side effect that causes additional eye problems. Dysfunctional tear syndrome and ocular surface disease (OSD) are common in patients with glaucoma, due to the extended use of topical medications containing a preservative that can harm the ocular surface. Aging also is associated with a higher rate of dry eye, so the demographics of patients with glaucoma also influence their risk of developing ocular surface disease.

Long-term treatment of glaucoma is needed in many cases toprevent progression of the disease to vision loss. Paradoxically,the treatments that can be extremely effective at lowering IOPalso can have a harmful side effect that causes additional eyeproblems. Dysfunctional tear syndrome and ocular surface disease(OSD) are common in patients with glaucoma, due to the extendeduse of topical medications containing a preservative that canharm the ocular surface. Aging also is associated with a higherrate of dry eye, so the demographics of patients with glaucomaalso influence their risk of developing OSD.

Patient management will be enhanced with a thorough understandingof the prevalence of OSD in patients with glaucoma, treatmentmethods for the combined morbidities, and preventionstrategies.

Up to half of patients being treated with topical glaucomamedications may have symptoms of OSD, according to Donald L.Budenz, MD, MPH, professor of ophthalmology, epidemiology, andpublic health at the University of Miami Miller School ofMedicine. In addition, the severity of the score on the OcularSurface Disease Index (OSDI) rises in correspondence with thenumber of glaucoma medications taken by patients.

As the signs and symptoms of OSD are moreprevalent in patients with glaucoma treated with topicalmedication than in their peers without glaucoma, it is clear thatawareness of OSD must be a component of patient management, Dr.Budenz added. He was one of several speakers at a continuingeducation symposium held during the annual meeting of theAmerican Academy of Ophthalmology in Atlanta. The program washeld at the Atlanta Marriott Marquis.

OSD is any condition that adversely affects tear film functionand stability, including dysfunctional tear syndrome and dry eyesyndrome. The term also encompasses blepharitis, meibomian glanddysfunction, aqueous tear deficiency, and preservativetoxicity.

OSD can be caused by a number of factors, but one that has cometo the forefront recently is the presence of preservatives intopical medication, said Clark L. Springs, MD. Dr. Springs isassistant professor of ophthalmology, cornea, cataract, andrefractive surgery at Indiana University School of Medicine,Indianapolis. Benzalkonium chloride (BAK) is the most commonlyused preservative, an ingredient in more than 70% of ophthalmicmedications. While it has a beneficial role, it may beproblematic when present in a high concentration in a single dropor due to the accumulation of doses with multiple drops duringlong-term treatment, Dr. Springs said.

BAK may impact ocular surface health by decreasing epithelialcell integrity and causing a secondary increase in conjunctivalinflammatory cells, loss of goblet cells, reduction in tearfunction, and a decrease in tear break-up time (TBUT). It alsonegatively affects cellular physiology. Study results of thelong-term impact of BAK suggest that using BAK-free medicationsis the best practice, when possible, Dr. Springs said.

Malik Kahook, MD, assistant professor of ophthalmology anddirector of clinical research, Rocky Mountain Lions EyeInstitute, University of Colorado, Denver, outlined severalpreclinical and clinical studies on glaucoma and OSD. Conclusionsdrawn from several of these suggest that BAK causes deleteriouschanges to ocular surface cells both in vitro and in vivo. Inaddition, there seems to be a clear advantage to oxidizingpreservatives in an animal model, Dr. Kahook said. Oxidativepreservatives include an ionic- buffered preservative system(SofZia, Alcon Laboratories), stabilized oxychloro complex, andsodium perborate. They penetrate cell membranes, disrupt cellularprocesses, and dissipate on contact. Detergent preservatives suchas BAK disrupt membranes and are also typified by cell lysis andirreversible binding.

He added that a prospective study of tear break-up time showedthat changing from a BAK-preserved prostaglandin analog to anon-BAK formulation resulted in measurable improvement in bothTBUT and OSDI.

Speakers at the program also shared practical tips on workingwith patients who have glaucoma and OSD. Dr. Springs suggestedthat this combination of disorders has a significant impact onpatients' quality of life but that patients often feel"dismissed" by their physicians and resigned to seeing littleimprovement. For their part, clinicians often view patient visitsfor dry eye as a "time sink" and also underappreciate thecontribution of topical medications with BAK to patients'OSD.

Until recently, treatment strategies were limited to hydratingand lubricating and adding ever more medications to the regimen,Dr. Springs said, while now the choices that reflect a newunderstanding of the complexity of OSD and its relationship toglaucoma include stabilizing tear film, limiting preservatives,and decreasing inflammation. The range of treatment options alsoincludes tear supplements, tear retention, tear stimulation,biological tear substitutes, a diet emphasizing consumption ofessential fatty acids, and environmental strategies. The latterincludes not only avoiding topical preservatives but limitinganticholinergic medications such as drugs used to treatallergies, depression, and hypertension. Humidifying theenvironment is also an important strategy.

Dr. Budenz reminded the audience that clinical trial patients donot mirror glaucoma patients from the community, who have farmore variability, and that treatment ideally should be a blend ofexpert opinion and scientific literature as well asindividualized. Therapy should take into account the severity ofglaucoma and other factors that could affect treatment, such asOSD. When patients have both OSD and glaucoma, the clinicianneeds to assume the role of a detective, investigating what iscausing the glaucoma to progress and the source of the OSDsymptoms. Although artificial tears are the first-line therapyfor OSD, clinicians should avoid the urge to add them right awayand instead determine whether the cause of the OSD isblepharitis, poor tear production, poor tear viscosity, toxicityfrom drops, or other factors.

In cases of severe OSD and glaucoma, a sound course of action isto discontinue all topical medications for at least a month, Dr.Budenz recommended. During their period, oral carbonic anhydraseinhibitors can be used to control IOP. After the washout period,BAK-free topical medications can be reintroduced one at a timeuntil the pressure in controlled. If these measures areinsufficient, trabeculoplasty or incisional surgery may be neededto control the IOP.

The program chairman and moderator was Robert D. Fechtner, MD,professor of ophthalmology and director, Glaucoma Division,Institute of Ophthalmology and Visual Science, New Jersey MedicalSchool, University of Medicine & Dentistry of New Jersey,Newark.

This continuing medical education activity was jointly sponsoredby the New York Eye and Ear Infirmary and cme², inpartnership with Ophthalmology Times, and was supportedthrough an unrestricted educational grant from Alcon LaboratoriesInc.

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