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Glaucoma Myth Busters: Myths About Prostaglandin Analogues and Inflammation

Existing research does not show an association.

By: Khin P. Kilgore, MD, Jason D. Jensen, MD, Sean J. McCafferty, MD
Glaucoma Physician March 1, 2023 Vol Ophthalmology Management 27, Issue March 2023 Page(s): 30, 31

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Prostaglandin analogues (PGA) are often the first-line topical medication in managing glaucoma due to their relatively higher efficacy rates and convenient once-daily dosing.1 These topical medications are generally well tolerated. They are metabolized too quickly to reach plasma concentrations that would cause systemic inflammation, likely explaining their favorable systemic tolerability.2,3 The major ocular adverse effects include hyperemia and increased iris and periocular pigmentation. Over the past 25 years of PGA use, there have been an abundance of case reports and retrospective studies suggesting PGAs are associated with cystoid macular edema (CME). These studies have led to ongoing controversy around their use in the perioperative period or in proinflammatory patients. This article examines the literature surrounding the probability of PGAs causing CME, pseudophakic CME (PCME), NSAID mitigation of PCME, and increased intraocular inflammation in uveitis.

MYTH 1: PGAs Routinely Cause Cystoid Macular Edema

Because prostaglandins are metabolites of arachidonic acid,4 the association between PGAs and CME, or other manifestations of intraocular inflammation, seems intuitive. The reality is that PGAs in isolation do not typically cause CME.5 In one meta-analysis, latanoprost was shown to have 17 incidences of CME in 12,170, patients, or just 0.14%.6

The most rigorous studies to date show that bimatoprost, for instance, has a strong safety profile, with low incidence rates of CME (0.3%) and uveitis (0.01%).6-8 Furthermore, most published articles discussing the incidence of CME in PGAs patients are case reports with small patient populations, nearly all with patients who had additional risk factors for developing CME, as discussed below.9

MYTH 2: PGAs Should Be Stopped Before Cataract Surgery

Preoperative PGA use has been associated with PCME10 in patients with both complicated and uncomplicated cataract,11 but studies have been limited by size, retrospective natures, and confounding patient factors such as diabetes mellitus, epiretinal membrane, or history of uveitis or retinal vein occlusions.12 Studies reporting PCME after cataract surgery are further limited by the known association between cataract surgery and PCME, with a PCME diagnosis rate of 1.2% to 2%13,14 and evidence of angiographic PCME at day 60 in 19% even in eyes without operative complications or patient risk factors.15 In contrast, the 5-year incidence rate of macular edema in patients receiving latanoprost was reported at 2.4% in a large randomized study.5 PGA use, specifically, has not been demonstrated to increase PCME risk, suggesting it does not need to be routinely stopped before cataract surgery.13,14

MYTH 3: NSAIDs Should Be Started After Cataract Surgery in Patients on PGA

Pseudophakic CME is known to be higher in eyes with operative complication or patient risk factors as noted above, reported at a rate of 2.6% to 5.6%, but NSAID use has not shown a reduced incidence of clinically significant PCME in patients without risk factors.13,14 NSAIDs are often added if PCME is encountered postoperatively, but should it be started routinely in conjunction with a postoperative steroid in PGA patients?

Proponents of starting NSAIDs in patients thought to be at higher risk of CME, including PGA patients, often cite Miyake et al (1999). The study found higher incidence rates of angiographic CME in patients on postoperative steroids if they had concurrent PGA use, but not if the PGA patients were on postoperative NSAIDs.16 Furthermore, Miyake et al (2001) found comparable findings in a similar study using timolol instead of PGA.17 A 2015 American Academy of Ophthalmology report ultimately concluded that CME after cataract surgery tends to resolve spontaneously, and that there was no strong evidence demonstrating any long-term benefit to concurrent NSAID therapy.18 Despite these recommendations, many ophthalmologists still recommend NSAIDs routinely or for patients with PCME risk factors.14

MYTH 4: PGAs Should Not Be Used in Uveitic Glaucoma Patients

An early study examining suspected latanoprost-induced uveitis showed a “significant incidence” of 4.9% of eyes. However, each case of iritis was mild with just trace cell in each eye.19

Multiple additional studies have been done since, and a meta-analysis that included 214 studies with 12,170 patients on latanoprost reported a uveitis incidence of 0.48%.6 Bimatoprost, in the same meta-analysis, had an incidence of 0.01%. Although prostaglandins are not without risk, the data shows a relatively low incidence in which eyecare providers may view the pressure-lowering benefit as outweighing the small risk of CME.

Conclusion

Many ophthalmologists are hesitant to use PGAs postoperatively in patients with a history of CME or uveitis. Although clinicians must use their case-specific clinical judgment, the existing body of research does not support a significant incidence of these PGA-induced complications. Additionally, NSAID use does not appear to have clear evidence of benefit for routine use in patients on prostaglandins undergoing cataract surgery. GP

Khin P. Kilgore, MD, is a glaucoma specialist and comprehensive ophthalmologist at Arizona Eye Consultants in Tucson, Arizona, and a clinical assistant professor in the department of ophthalmology at the University of Arizona in Tucson.

Jason D. Jensen, MD, is a glaucoma specialist and comprehensive ophthalmologist at Arizona Eye Consultants.

Sean J. McCafferty, MD, is founder and partner at Arizona Eye Consultants, and the president and CEO of CATS Tonometer, Intuor Technologies, LLC. The authors report no relevant disclosures.

References

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