One of the key factors contributing to success in refractive surgery is a proper preoperative screening, which includes careful examination, assessment of expectations, and preparation for surgery. The identification and analysis of high-risk cases is an important aspect of this process. 1
It has been postulated that a refractive surgery practice will see far more patients with corneal ectatic dystrophies and other topographic abnormalities than would be expected from the incidence of each disorder in the general population. 2,3 This is thought to be because these patients tend to self-select for refractive surgery owing to their dissatisfaction with glasses or contact lenses. It is especially important to detect refractive surgery candidates with early corneal ectasia. These include keratoconus and keratoconus suspects.
Another ectatic dystrophy that is commonly missed or misdiagnosed is pellucid marginal degeneration. Refractive surgery in these patients could be complicated by a poor outcome and rapidly progressive ectasia. 4–6 We report two cases with signs of early pellucid marginal degeneration to illustrate the key diagnostic criteria for detection of this disease.
A 67-year-old man presented to the Refractive Surgery Center at the University of Washington as a candidate for laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). He began wearing glasses at 30 years of age and had his last change in prescription 5 years before the examination. He used soft contact lenses, which he had discontinued 5 days before the examination. His uncorrected visual acuity was 20/400 in both eyes. His cycloplegic refraction in the right eye was −3.75 = +2.00 × 155, 20/20; and in the left eye, −5.00 = +2.50 × 075, 20/15.
Slit-lamp and posterior-segment examinations were unremarkable in both eyes, without any evidence of corneal thinning or protrusion in both eyes.
Central corneal pachymetry as measured by ultrasound (Kerasonix-1000; OTI Medical Services, Sacramento, CA, U.S.A.) was 481 μm in the right eye and 497 μm in the left eye. Inferior peripheral pachymetry measurements were 451 μm in the right eye and 460 μm in the left eye. Corneal topography revealed inferior perilimbal steepening in the right eye, with the pattern shown in Fig. 1A, as well as inferior elevation of the inferior cornea in that eye (Fig. 1C).
A diagnosis of early pellucid corneal marginal degeneration was made in the right eye and the patient was advised not to have LASIK or PRK. The patient also was told there was a significant risk that pellucid marginal degeneration would develop in the left eye.
A 57-year-old man was examined as a candidate for refractive surgery. He began wearing glasses at 13 years of age and had his last change in prescription 8 years before the examination. He wore soft contact lenses that were discontinued 5 days before the examination. His uncorrected visual acuity was 20/400 in the right eye and counting fingers in the left eye. His manifest refraction in the right eye was −8.50 = +2.50 × 013, 20/20; and in the left eye, −9.00 = +2.00 × 173, 20/20.
Ultrasonic corneal pachymetry measurements (Kerasonix-1000) of the central cornea were 550 μm in the right eye and 541 μm in the left eye. Inferior peripheral pachymetry measurements were 518 μm the right eye and 522 μm in the left eye.
Cornea examination by slit lamp demonstrated superficial punctate keratitis in both eyes but no evidence of corneal thinning, iron lines, or protrusion. The remainder of the slit lamp examination and the examination of the posterior segment were unremarkable in both eyes.
Corneal topography revealed inferior steepening with an area of central corneal flattening (Fig. 1E and F).
A diagnosis of early pellucid corneal marginal degeneration was made. The patient was advised not to undergo LASIK or PRK.
Ectatic corneal disorders or noninflammatory thinning disorders are among the most common abnormalities detected in refractive surgery candidates. 2,3 Most of these cases are keratoconus. Pellucid marginal degeneration is another ectatic corneal dystrophy that is much rarer. Maguire and coworkers 7 first described the topographic abnormalities characteristic of pellucid marginal degeneration and how this pattern differs from keratoconus. Pellucid marginal degeneration frequently is misdiagnosed as keratoconus or merely an irregular corneal pattern despite this characteristic topography. This is especially common in early cases. For example, Schmitt-Bernard et al. 8 reported a case of severe, progressive kerectasia after LASIK with enhancement in a patient whom they believed had keratoconus. Rabinowitz-McDonnell quantitative topographic indexes (Sim K and I/S) also suggested the diagnosis of keratoconus. Review of the topographic maps revealed that the preoperative topography actually had the classic features of pellucid marginal degeneration.
Appropriate preoperative screening of patients is one of the most important challenges in refractive surgery. It is essential that patients with disorders like pellucid marginal degeneration that predispose them to poor outcomes are identified and excluded. At the least, patients with signs should be warned about potential complications depending on the abnormality that is detected and the level of suspicion.
In this case report, we provide examples of two patients with topographic and corneal pachymetry evaluations consistent with early pellucid marginal degeneration. Both cases might have been missed or misdiagnosed without careful attention to the clinical signs.
The topography in pellucid marginal degeneration is characterized by a very steep contour in the peripheral inferior cornea with high keratometric powers radiating in toward the center from the inferior oblique meridians (Fig. 1). There typically is an area of flattening down the center of the cornea. This pattern commonly generates a refraction with high against-the-rule astigmatism in advanced cases. Case 1, with very early topographic changes consistent with pellucid marginal degeneration, had oblique astigmatism in the right eye. Both eyes of case 2 had against-the-rule astigmatism. This differs from the typical topographic pattern in keratoconus, which is characterized by central or mid-peripheral steepening without central corneal flattening and an unpredictable astigmatism axis on refraction. 9,10
Elevation corneal maps can be generated using Placido ring-based videokeratoscopy technology. Figure 1C (right eye, case 1), as well as Fig. 1G and H (right and left eyes, case 2) show an inferior paracentral elevated area that corresponds to the steepest area of the cornea. Figure 1D (left eye, case 2) shows a normal corneal elevation map.
Pachymetry measurements also were characteristic. Although the central corneal thickness typically is less than 500 μm in eyes with advanced pellucid marginal degeneration, it may be normal in early cases. This was true in case 2. The normal cornea becomes thicker from the center to the periphery; in these two case, pachymetry measurements in both eyes were thinner in the inferior periphery than they were in the center of the cornea. This is an important finding and should always alert the clinician to an abnormality.
Pachymetric values across the entire cornea constitute a pachymetric map. This, as well as posterior corneal curvature, may be assessed by slit-based videokeratography instruments like the Orbscan (Bausch & Lomb, Orbtek, Inc., Salt Lake City, UT, U.S.A.). 11,12 However, uncertainty regarding the meaning of values derived from the posterior surface of the cornea is a limiting factor. 11,12 Studies have shown that corneal thickness measurements are inaccurate with this instrument. 13 The instrument might provide evidence of relative thinning of the inferior cornea, but that has not been reported.
Pellucid marginal degeneration is recognized on slit lamp examination as a peripheral band of thinning with protrusion (“beer-belly” contour) of the inferior cornea, typically from the 4-o'clock to the 8-o'clock position, accompanied by 1 to 2 mm of relatively normal cornea between the limbus and the area of thinning. 14–18 There should not be any inflammation in the cornea in this disorder. In advanced cases, subtle folds in Descemet's membrane occasionally are seen concentric to the inferior limbus and may disappear with external pressure, similar to Vogt's striae in keratoconus. These typical slit lamp changes could not be observed in the two cases presented because of the early stage of the disease.
The etiology of pellucid marginal degeneration is uncertain, as it is for keratoconus and keratoglobus. It is unknown whether pellucid marginal degeneration, keratoconus, and keratoglobus are distinct diseases or merely phenotypic variations of the same clinical disorder. There appears to be a familial predisposition, 17–19 and these different conditions have been found to coexist in families. 19
Keratoconus has been associated with accelerated keratocyte apoptosis and mitosis. 20 It is unknown whether this association also is present in pellucid marginal degeneration. LASIK or PRK triggers high levels of keratocyte apoptosis associated with the surgery. 21,22 Although there is no direct evidence, it seems plausible that the triggering of accelerated keratocyte apoptosis could be associated with an accelerated disease process.
Abnormal fibrous long-spacing (FLS) collagen with a periodicity of 100 to 110 nm, in contrast to a periodicity of 60 to 64 nm found in normal collagen, was observed in corneas with pellucid marginal degeneration studied by transmission electron microscopy. 23 Similar FLS collagen has been seen in other conditions, including advanced keratoconus, but is not seen in normal cornea stroma. Weakening in the area of FLS collagen in the corneal stroma could result in the thinning observed in pellucid marginal degeneration and other corneal ectasias.
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