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Woman experiences decreased vision after cataract surgery
The patient had surgery 2 years prior and experienced visual loss, and she complained of pain after being diagnosed with mild cystoid macular edema.
 Isabel M. Balderas |  Tom Hsu | ||
A 69-year-old woman was referred to the cornea service at the New England Eye Center for immediate evaluation.
The patient was followed by the neuro-ophthalmology service at NEEC for progressive visual loss in the right eye after cataract surgery 2 years prior. After the surgery, the patient complained of decreased vision in the operated eye. Eventually, the patient was sent for retinal evaluation, and an epiretinal membrane was found. A pars plana vitrectomy with membrane peel was performed 5 months before presentation at NEEC, but the vision did not improve.
Examination
The patient was sent for a neuro-ophthalmic exam to try to determine the etiology of the decreased vision. Her best corrected visual acuity was 20/200 in the right eye and 20/20 in the left. The only remarkable finding on examination was a question of disc pallor in the right eye. The patient was sent for an MRI to rule out a compressive lesion. Her medical history was significant only for hyperlipoproteinemia, for which she was taking gemfibrozil. She was in otherwise good general health and denied ever smoking.
When the patient returned 4 weeks later, she complained of 2 weeks of intermittent pain in the right eye. The patient had been diagnosed with mild cystoid macular edema 2 weeks before her return visit, and she was started on topical nepafenac drops four times a day in the right eye. Her BCVA was counting fingers in the right eye and 20/25 in the left (pinhole to 20/20). IOP by applanation was 6 mm Hg in the right eye and 12 mm Hg in the left. Pupils were 4 mm in each eye, but the right pupil was slightly less reactive. Extraocular movements were intact in both eyes, and confrontation visual fields were full. A color photograph of the right eye is shown in Figure 1.
 Figure 1: Color photograph of the right eye showing mildly injected conjunctiva with two central areas of corneal thinning. Images: Smithen LM, Goldstein MH |
What is your diagnosis?
Vision loss
The differential diagnosis in this case includes infectious and noninfectious etiologies.
The corneal presentation seen in Figures 1 and 2 could be caused by infectious keratitis (bacterial, viral or, less likely, fungal) or noninfectious keratitis (neurotrophic keratitis). The central location rules out other causes of corneal melt such as peripheral ulcerative keratitis. Although Mooren’s ulcers can progress to the central cornea, the disease starts peripherally and is extremely painful. In Terrien’s marginal degeneration, corneal thinning begins in the superior nasal periphery with an intact cornea. In our patient, the peripheral cornea was intact, and there was an epithelial defect with localized, centralized corneal melting. The patient had intermittent, moderate pain.
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 Slit lamp photograph of the right eye. The extent of the corneal melt can be seen clearly. The corneal thinning shown in 2a is deeper and larger than the one seen in 2b. |
The key to this case was that the patient was on a topical nonsteroidal anti-inflammatory drop for chronic cystoid macular edema. This patient was cultured for bacterial, viral and fungal causes of the melt to rule out an infectious etiology, which was thought to not be likely, and the patient was diagnosed with a corneal melt secondary to chronic topical NSAID use (Figure 2).
Treatment
Nepafenac use was discontinued, and the patient was placed on ciprofloxacin ointment and oral doxycycline. The patient showed rapid resolution of the epithelial defects with no further melting. All cultures showed no growth after a period of 3 weeks. At her most recent visit, the patient had two corneal scars with slight thinning at the sites of the erosions. She was fit for a hard contact lens in the right eye with a slight improvement in her vision — BCVA returned to her baseline, 20/200. She continues to be evaluated by the neuro-ophthalmology service for the underlying cause of her decreased vision.
Discussion
Corneal melts originate with a small break in the epithelium and are often associated with dry eyes. Failure to re-epithelialize leads to immune mediators and collagenase enzymes attacking the exposed stroma, resulting in ulceration. In essence, corneal melts occur when there is an imbalance between extracellular matrix deposition and degradation of the extracellular matrix by matrix metalloproteinase (MMP). This imbalance can be the result of systemic diseases (collagen vascular diseases such as rheumatoid arthritis, Wegener’s granulomatosis, systemic lupus erythematosus, polyarteritis nodosa, ulcerative colitis, relapsing polychondritis or diabetes mellitus); infectious causes (bacterial, viral, fungal); surgery (corneal melts have been reported after a variety of surgeries including cataract extraction, glaucoma surgery, vitrectomy, refractive surgery and pterygium removal, particularly with the use of mitomycin-C); or medications (topical NSAIDs, mitomycin-C).
A number of NSAIDs have been associated with corneal melts, including generic diclofenac, Voltaren, (diclofenac sodium ophthalmic solution 0.1%, Novartis), Acular (ketorolac tromethamine 0.5%, Allergan) and Acular PF (preservative-free ketorolac tromethamine 0.5%, Allergan), Xibrom (bromfenac ophthalmic solution, Ista) and, in one reported case, Nevanac (nepafenac, Alcon). Generic diclofenac is widely recognized to be the worst offender.
The mechanism by which topical NSAID use is leading to corneal melting is not completely understood. A general, diffuse upregulation in MMP has been found in NSAID-induced corneal melts. Additionally, MMP9, which is not found in normal corneal tissue and is known to be associated with delayed wound closure, has been found to be localized to the site of corneal melts. There have also been some hypotheses that the true source of offense may be the preservatives used in bottling and not the actual medications.
The corneal complications associated with topical NSAID use are typically milder than corneal melts. Topical NSAID use can cause a mild epitheliopathy or a frank epithelial defect. There can also be extreme stromal thinning, descemetocele formation or even corneal perforation.
Most of the literature regarding NSAID-related corneal problems reflects isolated case reports or small case series. There are currently no studies that report the incidence of corneal complications from topical NSAID use. Although serious corneal complications from topical NSAID use are rare, they can be serious, and prescribing ophthalmologists should be aware of these potential problems.
For more information:
- Lindsay M. Smithen, MD, and Michael H. Goldstein, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Smithen and Goldstein have no financial interest in the products mentioned in this article nor are they paid consultants for any of the companies mentioned.
- Edited by Isabel M. Balderas, MD, and Tom Hsu, MD. Drs. Balderas and Hsu can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Balderas and Hsu have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
References:
- Asai T, Nakagami T, et al. Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug. Cornea. 2006;25(2):224-227.
- Bekendam PD, Narváez J, Agarwal M. Case of corneal melting associated with the use of topical nepafenac. Cornea. 2007;26(8):1002-1003.
- Congdon NG, Schein OD, et al. Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs. J Cataract Refract Surg. 2001;27(4):622-631.
- Guidera AC, Luchs JI, Udell IJ. Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs. Ophthalmology. 2001;108(5):936-944.
- Lin JC, Rapuano CJ, et al. Corneal melting associated with use of topical nonsteroidal anti-inflammatory drugs after ocular surgery. Arch Ophthalmol. 2000;118(8):1129-1132.
- O’Brien TP, Li QJ, et al. The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use. Ophthalmology. 2001;10(4)8:656-659.