Controlling ocular inflammation before, during and after cataract surgery is of utmost importance to successful outcomes. Current standard of care treatment is use of a topical NSAID and topical corticosteroid preoperatively and postoperatively. Both medications are known to decrease anterior and posterior inflammation — but through different mechanisms.

Despite being the standard of care, these medications’ exact individual roles have not been elucidated, and the roles of NSAIDs remain somewhat controversial. What follows is an examination of these treatment options and their efficacy.

WHAT THE LITERATURE SHOWS

A recent review and network meta-analysis addressed the role of NSAIDs in anterior chamber inflammation after cataract surgery.

The study looked at more than 19 trials and found that, compared to placebo, NSAIDs were more effective in controlling anterior chamber inflammation. Furthermore, the review suggested that diclofenac outperformed other NSAIDs.¹

Another study compared the use of both topical steroids and one NSAID — ketorolac, nepafenac or bromfenac — to the use of topical prednisolone acetate alone.² The study used laser flare photometry as a quantitative measure. Outcomes suggested that the addition of a NSAID to topical prednisolone acetate resulted in a higher reduction of postoperative anterior chamber inflammation at four and eight weeks. Additionally, the same study noted that, when comparing NSAIDs, nepafenac showed slightly better control of anterior chamber inflammation.²

DEFEAT CME

Cystoid macular edema (CME) is the most common cause of decreased vision in patients following cataract surgery. It is thought to result when the blood retinal barrier is disrupted during cataract surgery, causing the release of inflammatory mediators such as prostaglandins. The inflammatory mediators then disrupt the perifoveal retinal capillaries, resulting in fluid accumulation. Rate of occurrence varies from 1% to 19%, depending on the study, and is noted more frequently in patients with any type of increased postoperative inflammation.³

Due to the relationship between prostaglandin release and CME, using topical corticosteroids and topical NSAIDs to reduce postoperative inflammation following cataract surgery has traditionally been thought to prevent CME. However, few studies have assessed the preoperative role of NSAIDs in reducing CME.

One large randomized prospective study compared three groups: one starting topical indomethacin three days preoperatively, one starting topical indomethacin postoperative only and one group not receiving any topical NSAIDs. Assessment of CME by angiography showed no CME in any patient in the group treated with indomethacin preoperatively. Within the other two arms of the study, the rate of CME was 15% of patients treated postoperatively only with indomethacin (P = .001) and 33% in the control group (P < .001).⁴

Recently, a large meta-analysis reviewed patients receiving topical steroids vs. those receiving topical NSAIDs. Results showed that the incidence of CME was higher at one month in the steroid patients (25.3%) vs. the NSAID patients (3.8%).⁵ Further analysis of these studies showed that so-called potent as well as weaker steroids were less effective than NSAIDs in preventing CME.

ABOUT DROPLESS DELIVERY

A new novel method to deliver prophylactic antibiotics and steroids, known as “dropless” surgery, is becoming more common. A retrospective study with more than 900 patients used a preservative-free transzonular formulation of triamcinolone acetonide 15 mg/ml, moxifloxacin hydrochloride 1 mg/ml and vancomycin 10 mg/ml (triamcinolone – moxifloxacin – vancomycin, or TMV) intraoperatively.⁶ Results showed nearly 92% of cases did not require supplemental medication after surgery. The rate of breakthrough inflammation at days 14-21 was 9.2%. The rate of visually significant postoperative CME was 2.0%.

These results suggest that this one-time intraoperative dose of steroids performs well compared to standard topical therapy.

However, a series of recently reported adverse events related to compounded intravitreal injection of triamcinolone and moxifloxacin gives some pause and consideration to the use of “dropless” surgery. According to the FDA, there were reports in the spring of 2017 concerning at least 43 patients who had received these injections all prepared by the same compounding pharmacy after cataract surgery.⁷ During the five-month postop period, these patients’ symptoms included decreased vision, poor night vision, loss of color perception, photophobia, ocular discomfort, pain, glare, halos, headaches, loss of balance and/or nausea. Physicians found a decreased BCVA and visual fields along with macular edema.

While many of these patients have experienced some measure of recovery, some still have significant vision loss.

WHEN IT COMES TO UVEITIS

Uveitic patients are some of the most challenging for controlling postoperative ocular inflammation. Etiologies of uveitis have an impact on prognosis; for example, posterior uveitis is associated with more chorioretinal complications and, subsequently, is responsible for a less favorable outcome.⁸

A prospective study showed that eyes with active inflammation within three months of cataract surgery were more likely to have postoperative macular edema. It also showed that a perioperative course of oral corticosteroids, started two days before surgery, helped to significantly reduce the incidence of postoperative macular edema.⁹

The general consensus is that the addition of or increase in systemic corticosteroid therapy preoperatively is the standard approach for cataract surgery in uveitic eyes. Some surgeons utilize preoperative sub-Tenon’s triamcinolone (40mg in 1 cc) injections (Kenalog, Bristol Myers Squibb) to anticipate postoperative inflammation control, particularly for non-glaucomatous patients without systemic inflammation.

A recent study addressed the specific question of phaco cataract surgery in patients with existing anterior uveitis. The researchers proposed treatment with an oral corticosteroid, 30 mg prednisone daily, along with topical NSAIDs and topical corticosteroids three to four times a day. Included in the study were adult patients with juvenile idiopathic arthritis or Behçet’s disease, for whom treatment preoperatively with oral corticosteroids is essential. Oral steroids were tapered over two to three weeks, with topical NSAIDs and steroids given for four weeks then tapered.

This study showed a similar incidence of CME in uveitic patients treated with the mentioned regiment, compared to non-uveitic patients treated with standard topical therapy.¹⁰

IMPLANTS FOR THE DIFFICULT CASES

Other forms of non-anterior uveitis can be very difficult to treat. A large majority of these patients need long-term oral immunosuppression, either in the form of corticosteroids or steroidal-sparing immunosuppressives. Sustained-delivery steroid implants containing the highly lipid-soluble steroid fluocinolone have been used to control all forms of noninfectious uveitis.

The Multicenter Uveitis Steroid Treatment (MUST) Trial studied this long-acting agent compared to standard of care systemic therapy. The investigators found a high incidence of cataract formation after insertions, which offered a unique opportunity to assess how postoperative cataract patients did compared to their fellow eye. This post hoc, subgroup analysis of data from a three-year randomized study evaluated cataract outcomes in uveitic eyes that received the fluocinolone acetonide implant and compared them with those of fellow, nonimplanted eyes.

They reported that eyes undergoing cataract surgery after the implantation had a better visual acuity gain and less postoperative inflammation than the fellow eyes, which were untreated or were managed with regional corticosteroid injections.¹¹

CONCLUSION

Controlling inflammation at the time of cataract surgery is important for maximizing visual outcomes. With careful preoperative and postoperative planning, even eyes predisposed to uncontrolled inflammation can be managed efficiently and successfully. OM

REFERENCES

1. Duan P, Liu Y, Li J. The comparative efficacy and safety of topical non-steroidal anti-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: a systematic review and network meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2017 Apr;255:639-649. Epub 2017 Jan 27.
2. Sahu S, Ram J, Bansal R, Pandav SS, Gupta A. Effect of topical ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09% on postoperative inflammation using laser flare photometry in patients having phacoemulsification. J Cataract Refract Surg. 2015 Oct;41:2043-2048.
3. Sheppard J. Topical bromfenac for prevention and treatment of cystoid macular edema following cataract surgery: A review. Clinical Ophthalmology. 2016;10:2099-2111.
4. Yavas GF, Öztürk F, Küsbeci T. Preoperative topical indomethacin to prevent pseudophakic cystoid macular edema. J Cataract Refract Surg. 2007;33:804-807.
5. Kessel L, Tendal B, Jørgensen KJ, Erngaard D, Flesner P, Lundgaard Andresen J, Hjortdal J. Post-cataract prevention of inflammation and macula edema by steroid and nonsteroidal anti-inflammatory eye drops; a systematic review. Ophthalmology. 2014;121:1915-1924. www.aaojournal.org/article/S0161-6420(14)00389-3/pdf . Accessed Apr. 27, 2016.
6. Tyson SL, Bailey R, Roman JS, Zhan T, Hark LA, Haller JA. Clinical outcomes after injection of a compounded pharmaceutical for prophylaxis after cataract surgery: a large-scale review. Curr Opin Ophthalmol. 2017 Jan;28:73-80.
7. FDA alerts health care professionals of adverse events associated with Guardian’s compounded triamcinolone and moxifloxacin product for intravitreal injection. https://www.fda.gov/Drugs/DrugSafety/ucm569114.htm . Accessed June 22, 2018.
8. Mehta S, Linton MM, Kempen JH. Outcomes of cataract surgery in patients with uveitis: a systematic review and meta-analysis. Am J Ophthalmol. 2014;158:676-692.e7.
9. Bélair 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;148:128-35.
10. Palsson S, Andersson Grönlund M, Skiljic D, Zetterberg M. Phacoemulsification with primary implantation of an intraocular lens in patients with uveitis. Clinical Ophthalmology (Auckland, NZ). 2017;11:1549-1555.
11. Sheppard JD Jr, Nguyen QD, Usner DW, Comstock TL. Post-cataract outcomes in patients with noninfectious posterior uveitis treated with the fluocinolone acetonide intravitreal implant. Clin Ophthalmol. 2012;6:79-85.

About the Authors

Stephen Scoper, MD, is vice president at Virginia Eye Consultants and associate professor, Eastern Virginia Medical School, Norfolk, Va. He is fellowship trained in cornea and refractive surgery.
Financial disclosure: Dr. Scoper performs clinical research for Alcon, Novartis and Topcon. He serves on the speakers bureau for Alcon and Topcon.

Mario Rojas is chief resident in ophthalmology at Eastern Virginia Medical School, Norfolk, Va. He plans to pursue an ocular surface clinical research fellowship at Bascom Palmer Eye Institute. He reports no financial disclosures.

Cecelia Koetting, OD, FAAO, practices at the secondary tertiary surgical center Virginia Eye Consultants in Norfolk, Va. Her primary focus is ocular disease, neuro-optometry and peri-operative care. She also participates in clinical research.
Financial disclosure: Dr. Koetting is a consultant for Alcon.