Using dry eye treatments for sick corneas

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We have all attended numerous lectures on treating dry eye. We are all comfortable treating red, burning, tearing eyes. Did you ever consider that those tools in your dry eye arsenal are also good for acutely sick eyes? I recently had a patient who drove this point home…even to my ophthalmology partner.

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Not a good day

Recently, a local optometrist referred a gentleman to my associate for evaluation of an abrasion that would not heal. The gentleman had a long-standing history of stem cell failure, and now he had an abrasion. My associate thought that the abrasion had become infected and started treatment with a fluoroquinolone.

I saw him two days later. Pain and redness had increased, and stromal involvement was significant with widespread edema and inability to discern the iris. I vividly remember Dr. Paul Ajamian told me as an intern that this was bad.

Vision was counting fingers on acuity testing. I do not like days when my patient can see only fingers. This is not a good day, and thankfully they happen only about twice a month. The keratoepithelial defect was, unfortunately, huge with a central round stromal infiltrate.

Gulp.

More than an abrasion

This was not a simple abrasion anymore. Given the aforementioned stem cell failure and the fact that it developed while taking a fluoroquinolone, there was nothing easy about this.

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I decided the patient was indeed taking the medications as instructed. I added fortified tobramycin hourly, increased the fluoroquinolone to every two hours, and added preservative-free artificial tears hourly.

I firmly believe that preservative-free tears, particularly when refrigerated, help everything-abrasions, contact lens edema, MGD, allergies, headaches, herpes, bad days when my patients can’t see, and knee pain when I tore my meniscus. “Dry eyes heal slowly, wet eyes heal faster,” I heard Ming Wang, MD, daily from 2001 until 2008.

And because I live in the South, a little prayer. OK, a long prayer. Actually a prayer circle. Return in one day, please, sir.

The next day he looked just as red, just as blurry, and the cornea was essentially unchanged. But the pain was better. Hallelujah. I considered this progress. But it was clear that the patient and I were going to become fast friends because this was going to take a long, long, long time to heal. What could I do to get it to heal faster?

Epithelium healing and stromal involvement

Bear with me while I review corneal wound healing. Following a corneal insult, the broken epithelium exposes the stroma. The stroma is coated with fibrin to protect it from exposure and infection. The fibrin clot has to be removed for the epithelium to heal, so plasmin is activated to accomplish this.

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If the epithelium does not heal quickly enough, plasmin persists, degrading the corneal stroma and activating metalloproteinases and causing further stromal damage.¹ Active forms of MMP-9 have been reported in tears of patients with severe ulcerative disease.² Reduce them using proteinase inhibitors including acetylcysteine, ethylenediaminetetraacetic acid (EDTA), doxycycline, cyclosporine, and autologous serum for example, can aid healing.

I have never used acetylcysteine or ethylenediaminetetraacetic acid. I hope I never do. I have, however, taken a shine to doxycycline, cyclosporine, and autologous serum.

Doxycycline

Doxycycline is great. If this were on a T-shirt, I would buy it and wear it to work. Doxycycline has been shown to reduce MMPs in a variety of applications, including stasis dermatitis associated with venous insufficiency,³ hernia repair,⁴ chronic obstructive pulmonary disease,⁵ gastric ulcers,⁶ and atherosclerosis.⁷ All of these are associated with inflammation, and doxy reduces inflammation.

The problem is it works so well for dermatologists, cardiologists, veterinarians, and eye doctors that it is now expensive. Also, I am very aware of its gastrointestinal side effects after it made my own spouse acutely ill. Multiple times. On the way to work. (Turns out psychiatrists are not as familiar with antibiotics as I thought.)

Despite these concerns, I remain a fan. You can also consider oral azithromycin, often prescribed as a Z-Pak, which was found to be as effective⁸ with a less expensive, five-day treatment.

Related: 4 steps to beating blepharitis

Cyclosporine

Topical cyclosporine reduces ocular inflammation as well by inhibiting T-cell activation and apoptosis. It has been useful in acne rosecea,⁹ superior limbic keratoconjunctivitis,¹⁰ and inflammatory dry eye. Consider this at an increased frequency (four times a day rather than two) to influence wound healing.

Autologous serum

Autologous serum is also spectacular, although technically it’s not a drug. Unfortunately, nondrugs are not covered by insurance no matter how magical they may be to us. Use of autologous serum has been shown to be beneficial in cases where conventional therapy has failed¹¹ and is a great alternative when patients do not have insurance to cover the cost of expensive topical medications. You can use it profusely without worry of dermatitis or medicamentosa.

Omega-3s

And let’s not forget omega-3 fatty acids. Fish oil has been found to be beneficial in PRK wound healing¹² in addition to dry eye.¹³

Consider these options next time you have a large ulcer or slow-healing abrasion after you get traction with your topical antibiotic. It is not just about the antibiotic anymore.

References

1. Baum E, Doan A. Morphology and Response of Corneal and Conjunctival Disease. Copeland and Afshari’s Principles and Practice of Cornea: Volume 1. New Delhi: Jaypee Brothers Medical, 2013.

2. Singh A, Maurya OP, Jagannadhan MV, Patel A. Matrix metalloproteinases (MMP-2 and MMP-9) activity in corneal ulcer and ocular surface disorders determined by gelatin zymography. J Ocul Biol Dis Infor. 2012 Dec 29;5(2):31-5.

3. Maroo N, Choudhury S, Sen S, Chatterjee S. Oral doxycycline with topical tacrolimus for treatment of stasis dermatitis due to chronic venous insufficiency: A pilot study. Indian J Pharmacol. 2012 Jan;44(1):111-3.

4. Tharappel JC, Ramineni SK, Reynolds D, Puleo DA, Roth JS. Doxycycline impacts hernia repair outcomes. J Surg Res. 2013 Sep;184(1):699-704.

5. Dalvi PS, Singh A, Trivedi HR, Ghanchi FD, Parmar DM, Mistry SD. Effect of doxycycline in patients of moderate to severe chronic obstructive pulmonary disease with stable symptoms. Ann Thorac Med. 2011 Oct;6(4):221-6.

6. Singh LP, Mishra A, Saha D, Swarnakar S. Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress. World J Gastroenterol. 2011 Jul 28;17(28):3310-21.

7. Rodriguez-Granillo GA, Rodriguez-Granillo A, Milei J. Effect of doxycycline on atherosclerosis: from bench to bedside. Recent Pat Cardiovasc Drug Discov. 2011 Jan;6(1):42-54.

8. Kashkouli MB, Fazel AJ, Kiavash V, Nojomi M, Ghiasian L. Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double masked open label clinical trial.  Br J Ophthalmol. 2015 Feb;99(2):199-204.

9. Ong HS, Patel KV, Dart JK, Praestegaard M. Topical cyclosporin A as a steroid-sparing agent for ocular rosacea.  Acta Ophthalmol. 2016 Jun 17. doi: 10.1111/aos.13137.

10. Sivaraman KR, Jivrajka RV, Soin K, Bouchard CS, Movahedan A, Shorter E, Jain S, Jacobs DS, Djalilian AR. Superior Limbic Keratoconjunctivitis-like Inflammation in Patients with Chronic Graft-Versus-Host Disease. Ocul Surf. 2016 Jul;14(3):393-400.

11. De Pascale MR, Lanza M, Sommese L, Napoli C. Human Serum Eye Drops in Eye Alterations: An Insight and a Critical Analysis. J Ophthalmol. 2015;2015:396410.

12. Ong NH, Purcell TL, Roch-Levecq AC, Wang D, Isidro MA, Bottos KM, Heichel CW, Schanzlin DJ. Epithelial healing and visual outcomes of patients using omega-3 oral nutritional supplements before and after photorefractive keratectomy: a pilot study. Cornea. 2013 Jun;32(6):761-5.

13. Liu A, Ji J. Omega-3 essential fatty acids therapy for dry eye syndrome: a meta-analysis of randomized controlled studies. Med Sci Monit. 2014 Sep 6;20:1583-9.