From the Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida.
Presented at the CEDAS meeting at the Association for Research in Vision and Ophthalmology annual meeting; May 2–6, 2010; Fort Lauderdale, Florida.
Supported by an unrestricted grant from NIH Center Grant P30 EY014801 and Research to Prevent Blindness.
Address correspondence to Sonia H. Yoo, MD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 N.W. 17 Street, Miami, FL 33136. E-mail: firstname.lastname@example.org
Salzmann nodular degeneration is characterized by bluish-gray subepithelial infiltrates elevated above the cornea surface.1,2 It is defined as a progressive degeneration developed by fibrous overgrowth. The degeneration can be bilateral and the shape of the nodules can be focal or diffuse.2
Ultra-high–resolution optical coherence tomography (UHR-OCT) is a new imaging technique that allows visualization of light-scattering tissues with an axial resolution of 3 μm. The image quality of this system is similar to an optical biopsy, which has been used previously to detect in vivo characteristics of Descemet’s membrane in patients with Fuchs’ dystrophy.3 We present clinical features of a case with atypical Salzmann nodular degeneration. We studied the in vivo morphological structure of the cornea with in vivo confocal microscopy and UHR-OCT.
A 59-year-old woman had been observed at our institution for symptoms of blurry vision, dryness, itching, and tearing in both eyes since 2008. Her ocular and medical history included dry eye, acne rosacea, hypothyroidism, and hypertension. The patient had been using topical 0.05% cyclosporine emulsion for 6 months and 100 mg of oral doxycycline for 3 months.
Best-corrected visual acuity was 20/25 in both eyes with a refraction of −1.50 +2.00 × 170 in the right eye and −1.25 +3.75 × 180 in the left eye. Slit-lamp examination revealed bilateral, circular, gray haze at the peripheral cornea with localized surface elevations in both eyes (Figs. 1 and 2). There was a clear zone separating the outer margin of the degeneration from the limbus. The inner margins were indistinct and the degeneration was less significant in the nasal and temporal parts of the cornea. The appearance of the central cornea was normal with punctate fluorescein staining in both corneas.
Figure 1. Slit-lamp pictures of the patient. (A) Right eye and (B) left eye. White arrows demonstrate outer margin of the degeneration. Yellow arrows demonstrate inner margin of the degeneration.
Figure 2. Slit-lamp picture of the left eye. Red arrow demonstrates localized surface elevation.
The patient underwent examination with the NIDEK Confoscan 4 (NIDEK, Gamagori, Japan). There were irregular hyperreflective areas, activation of keratocytes, and unstructured extracellular background in the peripheral cornea (Fig. 3).
Figure 3. Confocal microscopy of the right eye. (A) Superficial stroma of the peripheral cornea demonstrate activated keratocytes (white arrows) and hyperreflective background, (B) increased hyperreflectivity at deep stroma prevents imaging of endothelium.
UHR-OCT was performed as described in detail previously in the literature.3 A novel, custom-built spectral-domain UHR-OCT was used. A 3-module superluminescent diode laser light source was used with a center wavelength of 840 nm. The calibrated axial resolution of the system was approximately 4 μm in the air and approximately 3 μm in the water or tissue with a refractive index of approximately 1.39.4 The calculated depth range was 3.1 mm in air. The A-line (depth scan) rate of the OCT system was 24 kHz. Thirty-two radial scans were acquired with a scan width of 8 mm. The system used telecentric scan geometry for corneal imaging and custom-built software to process the raw data.
UHR-OCT imaging displayed the degeneration as a prominent bright white deposition in the corneal epithelium and corneal stroma (Fig. 4). Epithelial lesions induced localized corneal surface elevations with epithelial thinning. The Bowman layer was demonstrated in all images. Subepithelial lesions were less significant in the nasal and temporal parts in both corneas. There was diffuse stromal involvement in all quadrants with indistinct posterior margins. The posterior stroma and Descemet’s membrane were normal in UHR-OCT images. UHR-OCT findings were consistent with Salzmann nodular degeneration.5
Figure 4. Ultra-high–resolution optical coherence tomography (UHR-OCT) of the patient. (A) Right eye and (B) left eye. Dashed lines correspond to the section of UHR-OCT image. White arrows correspond to the Bowman layer. There is significant epithelial thinning and surface elevation above the nodules. Asterisk corresponds to the stromal scarring. White bar = 100 microns.
We present clinical features of a case with atypical, Salzmann nodular degeneration. Although Salzmann nodular degeneration can be bilateral, corneal infiltrates were almost perfectly symmetrical and located at the periphery in both corneas of our patient. We chose to defer a tissue sample due to the good visual acuity and peripheral location of the degeneration. We therefore used UHR-OCT to obtain an optical biopsy from our patient, which helped us to make the diagnosis of Salzmann nodular degeneration.
Symmetrical, peripheral corneal degenerations are associated with systemic lipid metabolism disorders.6,7 These disorders include corneal arcus, anterior embryotoxon, and Schnyder’s crystalline dystrophy. Corneal arcus and anterior embryotoxon are characterized with circular lipid accumulations in the peripheral cornea. Although there is a clear interval (lucid interval of Vogt) separating the limbus from the depositions, these degenerations typically involve Descemet’s membrane and deep layers of the stroma without the involvement of the epithelium. Schnyder’s crystalline dystrophy is a rare dystrophy that is also associated with hyperlipidemia.8 However, epithelial involvement is unlikely and Bowman layer is disrupted in cases with Schnyder’s crystalline dystrophy.9 Additionally, confocal microscopy demonstrates typical intra-stromal crystal depositions in cases with Schnyder’s crystalline dystrophy.10
Histological studies describe Salzmann nodular degeneration as uninflamed dense collagenous tissue elevation located above the normal corneal surface with thinning of the overlying epithelium.2,11 UHR-OCT has recently been suggested as a new technique to perform non-invasive optical biopsies in evaluation of corneal degenerations and dystrophies.12 The advantage of UHR-OCT is the ability to make non-invasive histological analysis in early stages of corneal degenerations and to get in vivo morphologic images without tissue sampling. UHR-OCT displays Salzmann nodular degeneration as prominent bright white subepithelial deposits with thinning of the overlying epithelium.5 Subepithelial nodules also demonstrate prominent processes at the edge of the nodules with stromal scarring below the Bowman layer. In our case, UHR-OCT images displayed similar morphological findings to Salzmann nodular degeneration.5 Although we do not have tissue samples, our previous studies demonstrated good correlation between UHR-OCT images and histology.3,5
Confocal microscopy studies reported unstructured stroma with increased extracellular reflectivity in Salzmann nodular degeneration.13,14 These findings are compatible with the irregularly arranged collagen within the nodule and the underlying stroma. We have also used confocal microscopy in our patient, which demonstrated normal corneal structure in the center. In the periphery, the lesions demonstrated irregular hyperreflectivity and unstructured extracellular background. These findings are also similar to previous confocal microscopy findings in Salzmann nodular degeneration.
There are other imaging modalities that can be used in the evaluation of corneal degenerations. Scheimpflug camera optically analyzes in vivo morphology of the anterior segment. However, optical systems have limited resolution and are affected by cornea clarity and iris reflections. Ultrasound biomicroscopy has limited image quality in the cornea and is especially useful in the evaluation of structures behind the iris.15 Very-high–frequency ultrasound has been reported to demonstrate reliable epithelial thickness map of the corneal surface. However, the resolution of the very-high–frequency ultrasound is 21 μm, which prevents this system from visualizing the Bowman layer separately.16
Salzmann nodular degeneration can present with bilateral, symmetrical, circular opacities. UHR-OCT helped us reveal the in vivo morphological characteristics of the opacities and allowed for a diagnosis without tissue sampling. UHR-OCT has the potential to be used in the diagnosis of patients with atypical corneal degenerations.
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- Shousha MA, Perez VL, Wang J, et al. Use of ultra-high-resolution optical coherence tomography to detect in vivo characteristics of Descemet’s membrane in Fuchs’ dystrophy. Ophthalmology. 2010;117:1220–1227. doi:10.1016/j.ophtha.2009.10.027 [CrossRef]
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- Robin JB, Schanzlin DJ, Verity SM, et al. Peripheral corneal disorders. Surv Ophthalmol. 1986;31:1–36. doi:10.1016/0039-6257(86)90049-4 [CrossRef]
- Barchiesi BJ, Eckel RH, Ellis PP. The cornea and disorders of lipid metabolism. Surv Ophthalmol. 1991;36:1–22. doi:10.1016/0039-6257(91)90205-T [CrossRef]
- Battisti C, Dotti MT, Malandrini A, et al. Schnyder corneal crystalline dystrophy: description of a new family with evidence of abnormal lipid storage in skin fibroblasts. Am J Med Genet. 1998;75:35–39. doi:10.1002/(SICI)1096-8628(19980106)75:1<35::AID-AJMG8>3.0.CO;2-P [CrossRef]
- Weller RO, Rodger FC. Crystalline stromal dystrophy: histochemistry and ultrastructure of the cornea. Br J Ophthalmol. 1980;64:46–52. doi:10.1136/bjo.64.1.46 [CrossRef]
- Kobayashi A, Fujiki K, Murakami A, et al. In vivo laser confocal microscopy findings and mutational analysis for Schnyder’s crystalline corneal dystrophy. Ophthalmology. 2009;116:1029–1037. doi:10.1016/j.ophtha.2008.12.042 [CrossRef]
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- Vajzovic LM, Karp CL, Haft P, et al. Ultra high-resolution anterior segment optical coherence tomography in the evaluation of anterior corneal dystrophies and degenerations. Ophthalmology. 2011;118:1291–1296.
- Linke S, Kugu C, Richard G, et al. An in vivo confocal microscopic analysis of Salzmann’s nodular degeneration: pre- and post-surgical intervention. Acta Ophthalmol. 2009;87:233–234. doi:10.1111/j.1755-3768.2008.01243.x [CrossRef]
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