Ocular Surface Management for the Cataract and Refractive Surgeon

ByEric D. Donnenfeld, MD

The benefits of recent advances in technology that now provide essential tools for many of the 6 million surgeries performed each year are lost with even minimal disruption of the ocular surface. The tear film is the most important refracting surface of the eye, and surgery deleteriously affects the ocular surface. Cataract surgery involves cutting corneal nerves and the use of topical medications containing preservatives that can contribute to the development of dry eye. With LASIK, the flap is transected and the neural plexus ablated. Corneal sensation is vital for epithelial integrity, and with both LASIK and cataract surgery there is significant loss of sensation.¹LRIs and excimer laser photoablation for overcorrection during refractive cataract surgery further increase the denervation and substantially increase the risk of ocular surface disease.

Diagnosis of Dry Eye

Preoperative diagnosis of ocular surface disease is important. The variability of presentation among patients can complicate diagnosis; however, visual fluctuation is a critical symptom that is diagnostic of ocular surface disease. If a patient’s vision varies between blinks, or from morning to evening, or after prolonged effort such as extended time at the computer, ocular surface disease can be assumed unless proven otherwise. Signs of dry eye can be evaluated with several diagnostic tests. Conjunctival staining with lissamine green or rose bengal can facilitate diagnosis within seconds. Positive staining indicates that the ocular surface should be improved before proceeding with surgery. Other tests used in dry eye diagnosis include fluorescein corneal staining, Schirmer test, tear meniscus and debris, and corneal sensation.

Preoperative Care of the Ocular Surface

Steps to avoid dry eye include identifying patients at risk, maximizing tear film stability preoperatively, following a surgical and intraoperative plan designed to minimize dry eye, and using postoperative therapeutic intervention. Artificial tears are universally used and, for the severe dry eye, nonpreserved tears should be used at least 4 times per day preoperatively.² Transiently preserved tears can be used up to 3 times per day for mild dry eye. Preserved tears can be used for very mild dry eye. Gels and ointments are available for overnight use. Nutritional supplements, taken as a combination of flaxseed oil (omega-3 polyunsaturated fatty acids [PUFA]), which thins meibomian gland secretions,³ and fish oil (eicosapentaenoic [EPA] and docosahexaenoic [DHA] fatty acids) to reduce inflammation,^4,5can be very beneficial in optimizing the ocular surface and can be used routinely in all patients. Both are necessary for optimal results. Only medical grade supplements should be taken, and fish oil supplements should be verified to be mercury-free.

Cyclosporine treatment has been shown to significantly improve the ocular surface, and using cyclosporine before and after cataract and refractive surgery can improve tear production, corneal staining, and meibomian gland function, with concomitant significantly improved visual outcomes (Figure 1), reduced number of enhancements, reduced burning and stinging, and improved patient satisfaction.^2,3,6-11 In fact, repeated ablations for LASIK patients may be unnecessary when a healthy ocular surface is maintained, which can be facilitated with cyclosporine treatment.

Figure 1. Postoperative Improvement in Blurred Vision on Cyclosporine

Figure 1. Postoperative Improvement in Blurred Vision on Cyclosporine
Cyclosporine treatment before and after cataract and refractive surgery significantly improves visual outcomes.

Source: Sall K, et al. Ophthalmology. 2000;107:631-639. Reprinted with permission.

Although cyclosporine can reduce burning or stinging sensations as symptoms of dry eye disease, the cyclosporine drops themselves cause significant burning and stinging in approximately 20% of patients, which may affect treatment compliance. The Asclepius Panel, which included several international ocular surface disease specialists, convened to determine the optimum formulation and dosage of corticosteroids to be used with cyclosporine initiating therapy, as a strategy to not only improve outcomes but also prevent the stinging frequently experienced with cyclosporine.

A multicenter study compared an experimental group initiating loteprednol with a group using artificial tears, with both groups starting cyclosporine therapy after 2 weeks.¹² Treatment with loteprednol or the artificial tears was stopped after day 60, while cyclosporine treatment continued. Results of this study supported the rationale for pretreatment with loteprednol. There was a significant improvement in Schirmer testing, and patients had better vision, with reduced stinging and artificial tear use. In addition, cyclosporine induction was facilitated. There was no increase in IOP with the use of loteprednol for 60 days, supporting the safety of this corticosteroid. Both the loteprednol and artificial tears groups experienced significant reductions in the ocular surface disease index at days 14, 30, and 60; however, improvement in the loteprednol group was significantly greater than that in the artificial tears group at all time points (P<.001; Figure 2). Similar effects were observed with corneal staining; at day 60 there was no corneal staining in the loteprednol group, which achieved significantly greater improvement than the tears group (P=.003).¹³Accordingly, combined immunomodulation using cyclosporine and loteprednol, which act on different steps in the inflammation cascade, should work faster and more effectively than use of the drugs as monotherapy.

Figure 2. Ocular Surface Disease Index (OSDI)

Figure 2. Ocular Surface Disease Index (OSDI)
Pretreatment with loteprednol before initiating cyclosporine therapy results in a significantly greater reduction in the OSDI compared to pretreatment with artificial tears.

Source: Holland EJ, et al. Ophthalmology Times. 2007; 32: S7-S16.

Severe Dry Eye

Severe dry eye must be controlled before LASIK or cataract surgery.¹⁴ If it persists, punctal plugs can be considered. However, they can worsen dry eye, and should be used only after inflammation and lid disease are controlled.² Oral doxycycline 50 mg twice-daily for 2 weeks, then 20 mg daily can also be effective.¹⁴ Autologous serum drops are another preoperative care option to optimize surgical outcomes.

Lid Disease

For managing lid disease preoperatively, hot compresses are an essential part of therapy, and nutritional supplements may be beneficial for all patients.¹⁵ Topical antibiotics, in particular azithromycin, improve the lipid component of the tear film and meibomian gland secretions. Topical antibiotics are routinely used for patients with combined disease. Topical cyclosporine and short-term corticosteroids can be effective as standard care and in severe cases, oral doxycycline may be warranted.

Preoperative Care Summary

The suggested preoperative approach for managing the ocular surface is to begin with tears. If the patient has lid margin disease, then thermal massage, topical antibiotics, and doxycycline should be added. All patients should get nutritional supplements, and topical anti-inflammatories with steroids are recommended by some clinicians for all patients. Punctal plugs, oral antibiotics, and autologous serum drops are appropriate for severe refractory dry eye. Diligent attention to the ocular surface will result in not only improved surgical outcomes, but also increased patient satisfaction.

References

Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED, Detorakis S, Koufala K, Perry HD. Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 1997 Jan-Feb;23(1):34-8.
Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, Dua HS, Hom M, Karpecki PM, Laibson PR, Lemp MA, Meisler DM, Del Castillo JM, O'Brien TP, Pflugfelder SC, Rolando M, Schein OD, Seitz B, Tseng SC, van Setten G, Wilson SE, Yiu SC; Dysfunctional tear syndrome study group. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006 Sep;25(8):900-7.
Ambrósio R Jr, Tervo T, Wilson SE. LASIK-associated dry eye and neurotrophic epitheliopathy: pathophysiology and strategies for prevention and treatment. Journal of Refractive Surgery. 2008 Apr;24(4):396-407.
Brown NA, Bron AJ, Harding JJ, Dewar HM. Nutrition supplements and the eye. Eye. 1998;12 ( Pt 1):127-33.
Sullivan BD, Cermak JM, Sullivan RM, Papas AS, Evans JE, Dana MR, Sullivan DA. Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjögren's syndrome. Advances in Experimental Medicine and Biology. 2002;506(Pt A):441-7.
Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000 Apr;107(4):631-9.
Ursea R, Purcell TL, Tan BU, Nalgirkar A, Lovaton ME, Ehrenhaus MR, Schanzlin DJ. The effect of cyclosporine A (Restasis) on recovery of visual acuity following LASIK. Journal of Refractive Surgery. 2008 May;24(5):473-6.
Salib GM, McDonald MB, Smolek M. Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dry-eye patients having laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2006 May;32(5):772-8.
Owen JP. Effect of Topical Cyclosporine 0.05% on Enhancement Rates in Myopic LASIK Patients. Presented at: Association for Research in Vision and Ophthalmology (ARVO); 2008. Abstract 3367.
Roberts CW, Elie ER. Dry eye symptoms following cataract surgery. Insight. 2007 Jan-Mar;32(1):14-21; quiz 22-3.
Donnenfeld ED, Roberts C, Perry H, Solomon R, Wittpenn J, McDonald M. Efficacy of Topical Cyclosporine versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation. Presented at: Association for Research in Vision and Ophthalmology (ARVO); 2007. Poster B1041.
Holland EJ, Donnenfeld ED, Lindstrom RL, Pflugfelder SC, Sheppard JD, Solomon KD. Expert Consensus in the Treatment of Dry Eye Inflammation. Ophthalmology Times. 2007;32:S7-S16.
Donnenfeld ED, Sheppard JD, Holland EJ, Slonim CB, Solomon R, Solomon KD, McDonald MB, Perry HD, Lane SS, Pflugfelder SC. Prospective, Multicenter, Randomized Controlled Study on the Effect of Loteprednol Etabonate on Initiating Therapy With Cyclosporin A. Poster presented at: The 2007 American Academy of Ophthalmology Annual Meeting; November 2007; New Orleans, LA.
Toda I. LASIK and dry eye. Comprehensive Ophthalmology Update. 2007 Mar-Apr;8(2):79-85; discussion 87-9.
Donnenfeld ED. Minimizing Post-LASIK Dry Eye. Ophthalmology Management. 2004. http://www.ophmanagement.com/article.aspx?article=86170.

DISCUSSION

When cataract patients have combination dry eye/blepharatis, what is the therapeutic regimen, when is a response expected, and when can surgery be scheduled?

Eric D. Donnenfeld, MD: I consider their symptoms, look at lissamine green staining of the conjunctiva, and look at fluorescein staining of the cornea. If they have corneal staining, they are not candidates for surgery until it is resolved. If they have conjunctival staining, I proceed with surgery. When I see staining of the conjunctiva or cornea, which I see in about 25% to 30% of patients, I usually initiate artificial tear therapy. If I believe they have tissue damage due to dry eye, they need immunosuppressive therapy, so I start them on loteprednol 4 times a day for 2 weeks. Then I start them on cyclosporine and have them return 2 weeks after starting the cyclosporine. If the corneal staining is gone, we proceed with surgery. If it persists, we will usually add punctal plugs. Every patient gets nutritional supplements as well.

Edward J. Holland, MD: I am more conservative with refractive surgery and premium IOLs. If there is any corneal staining, their vision will be affected. I’d rather delay surgery, even if it dissatisfies the patient. For the routine cataract patient, if there is minimal corneal staining, we can start treatment and schedule surgery. If there’s central corneal staining, it may cause inaccuracy in IOL calculations, so I delay the surgery of that patient.

Donnenfeld: You have to be cognizant of the fact that you may have plus or minus a half to three-quarters of a diopter error in your measurements with a keratometry if the patient has significant staining. Because of this, you may have to repeat the A-scan and IOL master.

How do you educate patients to administer the drops, such as azithromycin and loteprednol, properly?

Donnenfeld: After they have put the drop in, we instruct the patients to close their eyes and massage. The drop gets into the lids and sticks to them. We start with twice daily for 2 days, and then once daily for approximately 2 weeks, and it significantly improves the ocular surface. Adding loteprednol to this therapy, will improve the ocular surface more rapidly.

Richard L. Lindstrom, MD: Patients should wash their hands first, apply some warm compresses, then apply the drop. They should close their eyes for 30 seconds and rub it in the lid margins.

John D. Sheppard, MD, MMSc: If a patient has significant conjunctival findings and there are any corneal findings, I strongly recommend using loteprednol. Azithromycin will have no effect on corneal infiltrates or neovascularization. So the steroid is critical in patients with corneal disease.

Lindstrom: I put them on the cyclosporine, but if you start with a steroid you’ll have a response within a week, and most patients can be treated within a couple of weeks.

How does fluorometholone (FML) compare with loteprednol in terms of efficacy and safety?

Sheppard: I believe loteprednol shows greater efficacy. You have to use more FML to get the same effect that you do with a more potent agent. As a result, more benzalkonium chloride toxicities are created. So we generally do not use FML.

Donnenfeld: In my estimation loteprednol is as potent as prednisolone acetate or dexamethasone on the ocular surface. For anything in front of Descemet’s membrane, loteprednol gives you all the effect and none of the complications of a strong steroid like difluprednate or prednisolone acetate, so it is the only steroid I use in these cases. Also, it does not raise IOP or cause cataracts the way some of the stronger steroids can.

Holland: The interest in FML began because of concern about IOP elevation. Loteprednol provides the same safety parameter as FML, but it is an efficacious steroid in terms of its ability to reduce inflammation.

Lindstrom: FML seems to reduce the impact of matrix metalloproteinases, so if the patient has recurrent erosion syndromes or corneal melts, it might be worth considering if the steroid is continued.

How long do you use doxycycline? Do you use it intermittently?

Holland: Duration of treatment depends on the patient. We put the patient on doxycycline for 4 to 8 weeks and see the response. I typically try to rotate them off, so I will see the patient back at 2 months. If the patient is doing well, and the symptoms have improved, I will taper the loteprednol and stop the doxycycline. Some patients may continue to do well for many months without the drugs, and then have to go back on the same therapy. Symptoms will return in other patients as soon as doxycycline is stopped. The patients learn to titrate the medication on their own. Do not be afraid to use long-term low dose doxycycline. There are ongoing clinical trials using low dose doxycycline in the prevention of atherosclerotic heart disease, so it is actually a safe medication.

Donnenfeld: Azithromycin and doxycycline are similar medications, and we now use azithromycin before doxycycline. If azithromycin fails, then we try doxycycline. We use azithromycin the same as doxycycline and we have not observed systemic side effects.

Why is loteprednol used for 2 weeks before starting the cyclosporine, instead of starting them together?

Donnenfeld: If the patient has seen multiple doctors previously with no improvements, starting with loteprednol is definitely the best option. If you think the patient is not going to have complaints and will follow your directions, starting them together is very reasonable.

Holland: The reason not to start them together is that 17% of patients who get cyclosporine therapy will have redness and pain on initiation of therapy. Treating the inflammation on the surface of the eye with loteprednol first and then starting cyclosporine therapy reduces that reaction to 1%.