Selecting topical regimens for cataract patients

September 22, 2016

Eyecare practitioners who deal with patients in the perioperative period are well aware of the need for topical therapy. In most cases, a combination of a steroid, a nonsteroidal anti-inflammatory drug (NSAID), and an antibiotic will be used for a few days before the day of surgery and then for a period afterward.


Eyecare practitioners who deal with patients in the perioperative period are well aware of the need for topical therapy.

In most cases, a combination of a steroid, a nonsteroidal anti-inflammatory drug (NSAID), and an antibiotic will be used for a few days before the day of surgery and then for a period afterward.

However, how these agents are used, in what combination, as well as which particular agents are selected is a matter of much debate. Understanding the role and rationale of each may provide a basis for making an informed decision about which agent may be most beneficial in a given scenario.

Topical antibiotics

The role of an antibiotic during the perioperative period is relatively straightforward. Infection control and prevention are of critical importance, even if the risk of developing sight-threatening sequelae is low. E

ndophthalmitis following cataract surgery occurs in about 1 in every 1,000 surgeries.1-3

It is likely that only a fraction of these are truly infectious in nature with potential to affect vision; however, infectious endophthalmitis can have devastating consequences in terms of vision loss (Figures 1 and 2).

Most cataract surgeons use a preoperative preparation of povidone-iodine to achieve a sterile ocular surface.

The role of intracameral antibiotics is considered off-label and gaining in popularity in the United States, although it is routinely used in Europe.4 In addition, several studies have suggested a benefit for this practice.5-7

Selection of the agent used in intracameral preparations, should they be used, requires some forethought. The emergence of fluoroquinolone resistance patterns is concerning, and studies have indicated that prior systemic use of a fluoroquinolone may increase the risk.8

There is also recent evidence of hemorrhagic occlusive retinal vasculitis (HORV) associated with intracameral vancomycin use.9

More typically, patients undergoing cataract surgery are started on a topical antibiotic formulation a few days before surgery as prophylaxis, which is continued through the postoperative period. Again, resistance patterns become important because resistance to one or more antibiotics is prevalent in ocular isolates.10,11

Newer generation fluoroquinolones, such as moxifloxacin (Vigamox, Alcon) and gatifloxacin (Zymar, Allergan) are generally preferred for this reason. Another topical agent, besifloxacin (Besivance, Bausch + Lomb) is the only fluoroquinolone specifically developed for ocular use.

 

Anti-inflammatory drugs

The reason for using anti-inflammatory drugs in the perioperative period is easy to understand: any surgical procedure performed on the eye will induce inflammation, which, in turn, can lead to pain, light sensitivity, redness, and other symptoms.

Modern cataract surgery techniques, including the use of femtosecond laser for several of the steps, are intended to induce less inflammation.

Still, ocular surgery by its very nature is invasive and therefore carries potential to instigate an inflammatory response. Certain underlying risk factors may elevate the risk, including diabetes, uveitis, epiretinal membrane, and history of cystoid macular edema (CME) in the fellow eye.12,13

Most eye care practitioners recognize the need for some form of anti-inflammatory prophylaxis, although opinions differ on whether a combination of NSAIDs and corticosteroids are needed. In addition to their anti-inflammatory properties, NSAIDs also address pain following surgery and prevent mydriasis during cataract surgery.14

Use of NSAIDs specifically for mydriasis is off label, although recently approved is Omidria (ketorolac and phenylephrine, Omeros), a fixed-combination drug that can be placed in the irrigating solution to bathe the intraocular tissues throughout the surgical procedure.

In clinical trials, this intracameral formulation demonstrated the ability to reduce pain and maintain miosis.15 There is also suggestion in animal studies that it provides benefit for reducing inflammation at the retina.16

In addition to addressing pain, the use of NSAIDs and/or corticosteroids in the perioperative cataract period is for the prevention of CME. Most eyecare practitioners are in agreement that prevention is a more effective strategy than treatment, and there are ample studies demonstrating that combination corticosteroids and NSAIDs effectively prevent CME.17-31

The actual rate of CME following cataract surgery is a matter of some debate with studies suggesting rates between 0.1 percent and 2.33 percent when small-incision techniques and phacoemulsification are used.32,33 However, subclinical CME may be apparent on OCT in 4 percent to 11 percent of cases. (Figure 3)34,35

Some eyecare practitioners have looked at the low rates of CME and concluded that exposing patients to additional risks with separate medications may be unjustifiable.

Yet, whereas corticosteroids more generally act at various points of the inflammatory cascade, NSAIDs specifically target the cyclooxygenated pathway and shut down later prostaglandin activity that may lead to macular swelling or CME. Thus, pairing the two classes of medications is synergistic in reducing inflammation.

While FDA labeling for NSAIDs indicates that they are off label for prevention of intraoperative miosis, several agents are indicated for the management of postoperative pain and inflammation, such as Ilevro (nepafenac ophthalmic suspension 0.3%, Alcon) and Prolensa (bromfenac ophthalmic solution 0.07%, Bausch + Lomb).

Factors affecting agent selection

In my practice, we follow the prevailing sentiment to use both NSAIDs and a corticosteroid drop. In patients deemed not at high risk for CME, we start NSAIDs one day preoperatively and use them for four weeks postop. In patients at high risk, we start NSAIDs one week preop and continue their use for several weeks postop.36

Rarely, we will drop the NSAID component when patients exhibit hypersensitivity to the NSAID class. It is more likely (although still rare) that we will suspend use of the corticosteroid, which may occur if there is an IOP spike during use or in the presence of active infection.

About 30 percent of the population is steroid responders, and about 5 percent are severe steroid responders who have an IOP elevation above 31 mm Hg.37 Those rates are informative, but they do not necessarily dictate how we will manage a patient with a steroid response.

We are following cataract patients on the first day postop, and we will see the patient back at one week and one month-there are ample clinical visits already built into the follow-up in which to measure and follow IOP.

More to the point, the health of the optic nerve and other glaucoma risk factors are going to strongly influence how we respond to a pressure elevation, even one that rises into the 30s.

We may add a glaucoma medication or we may switch agents: difluprednate (Durezol, Alcon) is much more likely to induce a steroid response than either prednisolone acetate 1% (Pred Forte, Allergan) or loteprednol etabonate 0.5% (Lotemax, Bausch + Lomb).38,39

With NSAID selection, patients’ compliance with the medication is an important consideration. As a rule of thumb, adherence to prescription protocols declines as the complexity of the regimen increases-including number of drops and number of administrations.40

A once-a-day formulation may be preferable to an agent used twice a day; however, dosing frequency is only one part of the story. Other factors, including the drug’s bioavailability and residence time on the ocular surface, will determine if there are adequate levels of drug to have a meaningful effect while the lipophilicity and solubility factor in whether the drug will penetrate the ocular surface.

A new NSAIDs slated to launch commercially later this year is a low-dose bromfenac formulation (0.075%; BromSite, Sun Pharma) formulated in DuraSite (Sun Pharma), which is a synthetic polymer-based formulation that extends the time of a drug in the eye relative to conventional topical therapies.41

Bromfenac is already well-known ophthalmic and frequently prescribed NSAID. As for Durasite, many of us are already familiar with this vehicle, which is utilized in other ocular medications such Azasite (Merck) and Besivance (Bausch + Lomb).

 

BromSite was approved for both management of postoperative inflammation and for prevention of ocular pain, the only NSAID to gain that specific indication. In a study of 407 patients, significantly more patients treated with BromSite were 100 percent inflammation free as compared to vehicle (57 percent and 38 percent in separate studies vs. 19% and 22%, respectively).41
 

The potential to prevent pain adds something to the role of the NSAID in the pre- and postop period. In the phase 3 study, more patients were 100 percent pain-free as compared to vehicle in the BromSite group (77 percent and 82 percent vs. 48 percent and 62 percent, respectively).41

This aspect should not be undervalued because, in my experience, pain is a frequent concern of patients undergoing ocular surgery.

In our practice, wherever possible, we try to use branded drugs because FDA labeling indicates that the drugs had to have been rigorously tested in clinical trials, a criterion that does not apply to generic alternatives.

In fact, in our practice, if patients state a preference for generic formulations, we make them sign a waiver indicating that they have been informed about the potential effects of their choice.

Generics certainly can play a role, and they sometimes offer a lower cost alternative depending on the insurance status, but patients should be made aware that they can be associated with unpredictable efficacy and the potential to induce different side effects than their branded comparators.

Choosing topical agents

The weight of evidence suggests that both NSAIDs and corticosteroids should be used for prevention of inflammation in the postop period, even as the field has moved toward less invasive surgeries with lower potential to induce complications.

Selecting the particular agents to use in the perioperative regimen may not be as straightforward as the dosing frequency because the bioavailability and retention time on the ocular surface may be additional factors to consider. Formulations with vehicles designed to improve ocular retention may become an important part of the armamentarium if they prove as useful in routine clinical practice as they appear to be in clinical trials.

A final consideration in selecting agents for use in the perioperative regimen relates to patients’ preference. Specifically, patients opting for premium IOLs tend to have higher expectations for their outcome.

Although this article deals specifically with the use of topical medications, I would be remiss to not mention the potential to add OCT as a potential consideration in premium IOL patients as an added safeguard.

As noted above, the rate of subclinical CME is much higher than clinically apparent CME, but the residual inflammation still has potential to lead to negative outcomes. In such cases, offering treatment in conjunction with a steroid will typically provide therapeutic benefit. Note that this is considered off-label usage.

References

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2. Miller JJ, Scott IU, Flynn HW Jr, et al. Acute–onset endophthalmitis after cataract surgery (2000–2004): incidence, clinical settings, and visual outcomes after treatment. Am J Ophthalmol. 2005 Jun;139(6):983–7.

3. Keay L, Gower EW, Cassard SD, et al. Postcataract surgery endophthalmitis in the United States: analysis of the complete 2003 and 2004 Medicare database of cataract surgeries. Ophthalmology. 2012 May;119(5):914-22.

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5. Shorstein NH, Winthrop KL, Herrinton LJ. Decreased postoperative endophthalmitis rate after institution of intracameral antibiotics in a Northern California eye department. J Cataract Refract Surg. 2013 Jan;39(1):8–14.

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17. Rosetti L, Bujtar E, CastoldiD, et al. Effectiveness of diclofenac eye drops in reducing inflammation and the incidence of cystoid macular edema after cataract surgery. J Cataract Refract Surg. 1996;22 (Suppl l):794-9.

18. McColgin AZ, Raizman MB. Efficacy of topical Voltaren in reducing the incidence of post operative cystoid macular edema. Invest Ophthmol Vis Sci. 1999;40:S289.

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20. Efficacy of diclofenac eyedrops in preventing postoperative inflammation and long-term cystoid macular edema. Italian Diclofenac Study Group. J Cataract Refract Surg. 1997 Oct;23(8):1183-9.

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22. Tauber S, Gessler J, Scott W, et al. The effect of topical Ketorolac 0.4% on cystoid macular edema following routine cataract surgery. Association for Research in Vision and Ophthalmology (ARVO) Meeting, Fort Lauderdale, Florida, April 30-May 4, 2006. 683.

 

23. Fry EL, Fry LL. Nepafenac versus Ketorolac tromethamine in the prevention of postoperative cystoid macular edema. American Society of Cataract & Refractive Surgery (ARCRS) Meeting, San Diego, CA, April 27 – May 2, 2007. R26B. May; 114(5):881-9.

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29. Yung CW, et al. The effect of topical ketorolac tromethamine 0.5% on macular thickness in diabetic patients after cataract surgery. American Academy of Ophthalmology, New Orleans, LA, November 10-13, 2007. PO257.

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34. Belair ML, Kim SJ, Thorne JE, et al. Incidence of cystoid macular edema after cataract surgery in patients with and without uveitis using optical coherence tomography. Am J Ophthalmol. 2009 Jul;148(1):128-35.

35. Perente I, Utine CA, Ozturker C, et al. Evaluation of macular changes after uncomplicated phacoemulsification surgery by optical coherence tomography. Curr Eye Res. 2007 Mar;32(3):241-7.

36. O’Brien TP. Emerging guidelines for the use of NSAID therapy to optimize cataract surgery patient care. Curr Med Res Opin. 2005 Jul;21(7):1131-7.

37. Jonas JB, Degenring RF, Kreissig I, et al. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology. 2005 Apr;112(4):593-8.

38. Cable MM. Intraocular pressure spikes using difluprednate 0.05% for postoperative cataract inflammation. Inves Ophthalmol Vis Sci. 2010 Apr;51:1981.

39. Pleyer U, Ursell PG, Rama P. Intraocular pressure effects of common topical steroids for post-cataract inflammation: are they all the same? Ophthalmol Ther. 2013 Dec;2(2):55-72.

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