Case Presentation
A 72-year-old, very active, white male presented to our office with a desire to reduce his dependence on glasses. His BCVA was 20/40- OD and 20/25 OS, with a refraction of +2.50 -0.25 X 63 OD and +6.00 -5.50 X 3 OS. He had a history of strabismic amblyopia in his right eye. The patient's UCVA was 20/80 OD and 20/200 OS.

The examination revealed diffuse subepithelial opacities in both corneas, consistent with Salzmann's nodules (OS > OD). Most of the nodules were outside the visual axis, located in the corneal periphery (Figure 1). The rest of the examination was within normal limits, aside from 1 to 2+ nuclear sclerotic cataracts. Corneal topography (Zeiss Humphrey, Dublin, CA) showed irregular astigmatism OU. The automated keratometry readings were 43 and spherical in the right eye, and 43.5 X 47.5 in the left. The map of the left eye, however, showed areas of severe central steepening as high as 51.0 D and as shallow as 38.0 D centrally (Figure 2). A hard contact lens overrefraction resulted in vision of 20/40 OD and 20/20 OS. The patient's scotopic pupils measured at the slit lamp were 4 mm, and his pachymetry readings were 560 µm OD and 570 µm OS.

The patient described a gradual decrease in vision OS. His spectacle prescription had changed significantly over the last few years, as well. Past medical records were recalled from 5 years earlier, as older records were not available. Five years before the present visit, the patient's refraction was +2.25 OD and +1.75 -0.75 X 10 OS, yielding vision of 20/80 and 20/40-2. A potential acuity meter test resulted in 20/60 vision OD and 20/25 vision OS. The patient was noted to have Salzmann's nodules OU, worse in the left eye. Three years prior to this visit, his refraction OS was recorded as +3.75 -2.50 X 180 with 20/30 vision.

At the current visit, the patient complained of an imbalance in his vision and unhappiness with his spectacles. He had no strong desire to try contact lenses.

HOW WOULD YOU PROCEED?
1. Would you perform LASIK OS for the current prescription, because the patient corrects to 20/25?
2. Perform phototherapeutic keratectomy (PTK) to remove the Salzmann's nodules, and then consider LASIK?
3. Perform superficial keratectomy or lamellar keratoplasty to remove the corneal pathology, and address the refractive changes in a later procedure?
4. Recommend cataract extraction with a toric IOL, followed by corneal laser ablation for the residual refraction?

SURGICAL COURSE
Two variables make this a challenging refractive case. First, the patient does not have a “healthy” cornea—the discovery of Salzmann's nodules, which appear to be progressive, must be considered. Second, the presence of cataracts in this age group is also a factor in deciding on a comprehensive refractive solution.

Salzmann's nodular degeneration is usually a progressive condition characterized by subepithelial stromal opacities with irregular overlying epithelium. While its etiology is not fully known, Salzmann's is frequently associated with an underlying disorder. The patient had some elements of dry eye, but did not have other obvious corneal or ocular surface disease.

As illustrated by the patient's topography, the nodules and raised epithelium can induce significant astigmatism and refractive change, even if they are apparently outside the visual axis. It is important to recognize that the current refraction and high astigmatism in the left eye is primarily due to the irregular nodules and accompanying epithelial hyperplasia. In a past paper presentation,¹ we showed that similar refractive and topographical changes can occur with epithelial basement membrane dystrophy (EBMD). Although in the case of EBMD, the refractive findings were mostly temporary after LASIK.

The surgeon can remove Salzmann's nodules by performing a manual superficial keratectomy, or with excimer laser PTK.² Unfortunately, recurrence is common with these methods, neither of which has a predictable refractive outcome.^3,4

The presence of incipient cataracts in an older refractive surgery candidate should prompt a discussion with the patient. In my practice, when the early cataract patient refracts to a crisp 20/20, I generally perform LASIK—even on patients in their 60s. If the refraction is significantly hyperopic (>+3.0 D) or the visual acuity is not a sharp 20/20, I usually elect to perform the cataract surgery first.

I had to address this patient's corneal pathology, as it was the main determinant of his refractive state. There is no doubt, however, that his future IOL calculations will be challenging—at best.

Although I have performed superficial keratectomy with satisfactory results in cases of Salzmann's, I decided against it in this case. First, the pathology was diffuse and not typical in appearance. The multiple nodules did not seem to be the type that would easily “peel” with a blade. Second, I wanted to obtain a more predictable refractive outcome, and I therefore elected to perform PTK to treat the underlying condition.

I have had favorable results with PTK for other anterior stromal dystrophies and EBMD. Straightforward PTK performed over the central cornea, however, induces a significant amount of hyperopia, and this would clearly be counterproductive. Because most of the nodules were located paracentrally and peripherally, I thought that a hyperopic PRK would remove the pathology and even treat the patient's underlying hyperopia. I used the oldest refraction I had for the left eye, which was approximately +2.00 D, presuming that the current high hyperopic astigmatism was due to the superficial corneal pathology. My primary goal was to remove the Salzmann's pathology, but the refractive outcome remained important in this case. I counseled the patient that, if necessary, I could later perform a secondary PRK or LASIK procedure for any residual refractive error.

I also wanted to eliminate the chance of recurrence or PRK-induced corneal haze. I have had very good results using mitomycin C (MMC) in a number of corneal applications. Majmudar et al^5,6 first described its use for preventing recurrence of post-RK subepithelial fibrosis, as well as for treating post-PRK haze. I knew that performing PRK over any activated keratocytes, such as a previous LASIK flap, RK, or status post-PK, has a very high risk of haze. I have also seen a degree of haze in past PTK patients. I successfully treated a case of recurrent Salzmann's nodular degeneration with manual debridement and MMC in the past. That particular patient has not experienced a recurrence in more than 2 years.

I therefore elected to use MMC, in addition to performing PRK in this case.

I performed PRK on the patient's left eye using manual epithelial debridement with a blade; I wanted to ensure that all of the thickened epithelium was removed. I treated the underlying stroma using the Star S2 laser (VISX, Santa Clara, CA) with a +2.00 D treatment. Then, I soaked a round sponge in 0.02% MMC solution and placed it over the ablated bed for 2 minutes. I irrigated copiously and placed a bandage contact lens. Finally, I instilled a topical NSAID, a corticosteroid, and Ocuflox (ofloxacin; Allergan, Inc., Irvine, CA) into the eye and prescribed the same to the patient.

OUTCOME
On postoperative day 1, the patient's UCVA with the bandage contact lens in place was 20/40. He was enthusiastic and relatively free from pain. At 1 week, his UCVA was 20/50-. The epithelial defect had healed, and except for some central punctate keratopathy, the cornea looked clear. At 1 month, the cornea appeared pristine without any sign of Salzmann's nodules. The patient remarked that he could read well without glasses and refracted to 20/30 with a -3.25 D correction. His vision was much clearer than before, and he was pleased. I was surprised by the apparent overcorrection, but knew some regression would take place as the new epithelium remodeled.

Four months postoperatively, the patient was seeing 20/25 with a refraction of -2.00 -1.00 X 130. Recently, at his 1-year follow-up, he returned very happy and grateful, stating that his distance vision had gradually improved. He had a UCVA of 20/40, yielding 20/25 vision with a refraction of -0.75 -0.75 X 180. The left cornea appeared crystal clear (Figure 3). The topography showed smooth central steepening with minimal to no astigmatism (Figure 4). The patient's amblyopic right eye was essentially unchanged with UCVA 20/80 and BCVA 20/50 at +2.75 -0.75 X 180. I am currently planning to perform the same procedure OD.

This case illustrates a few points. First, irregular epithelium can induce a refractive change, even when outside the visual axis. This is true in Salzmann's nodular degeneration, as well as other conditions, including EBMD. Any treatment of the refractive error in these patients should take the underlying pathology into account. Second, although only anecdotal, MMC may be used to prevent a recurrence of Salzmann's nodules. I have had a great deal of success with MMC for many corneal applications, and I have never seen delayed epithelialization or any other late complications in more than 3 years of use. Although late complications are known to occur with MMC use on the sclera and conjunctiva (ie, for trabeculectomies and pterygium), to my knowledge, no complications have been described when it is used only on the cornea. MMC-induced scleral melt or avascular thin blebs are believed to be secondary to its late ischemic effects; the lack of a blood supply to the cornea may explain its relative safety when its use is isolated there.

Finally, if the surgeon plans to perform PTK, he or she should be aware of the possible refractive consequences. In the past, I had “successfully” treated a number of stromal dystrophies, and avoided penetrating keratoplasty using PTK. A good number of those patients, however, became quite hyperopic as a result. In today's refractively conscious environment, PTK treatments should be tailored, not only to the corneal pathology, but also to the underlying refraction. A combination of myopic and hyperopic PRK may be the best manner to perform a “refractively neutral” PTK.

Tal Raviv, MD, is in private practice in New York City, and is an attending cornea and refractive surgeon at the New York Eye and Ear Infirmary. He does not hold a financial interest in any of the products mentioned herein. Dr. Raviv may be reached at (212) 717-4609; Tal.Raviv@NYLaserEye.com

1. Raviv T, Epstein RJ, et al: Transient, Pseudo-Refractive Errors Following LASIK in Eyes With Pre-existing Epithelial Basement Membrane Dystrophy. Paper presentation at ISRS Fall Refractive Surgery Symposium. Orlando, Florida, October 1999
2. Rapuano CJ: Excimer laser phototherapeutic keratectomy: Long-term results and practical considerations. Cornea 16:151-157, 1997
3. Rimmer S, Maloney RK: Myopic shift after removal of Salzmann's nodular degeneration. J Cataract Refract Surg 20:656-657, 1994
4. Oster JG, Steinert RF, Hogan RN: Reduction of hyperopia associated with manual excision of Salzmann's nodular degeneration. J Refract Surg 17:466-469, 2001
5. Majmudar PA, Forstot SL, Dennis RF, et al: Topical mitomycin-C for subepithelial fibrosis after refractive corneal surgery. Ophthalmology 107:89-94, 2000
6. Raviv T, Majmudar PA, Dennis RF, Epstein RJ: Mitomycin-C for post-PRK corneal haze. J Cataract Refract Surg 26:1105-1106, 2000

Figure 1. Preoperatively, the cornea revealed multiple discrete subepithelial opacities consistent with Salzmann's nodular degeneration. Figure 2. The preoperative corneal topography demonstrated severe central astigmatism. Figure 3. One year after PTK and MMC treatment, the cornea was clear without recurrence. Figure 4. The postoperative topography showed regular central steepening with almost no astigmatism following the hyperopic PTK/PRK.