Purpose
To report the clinicopathologic features of corneal involvement in patients with xeroderma pigmentosum.
Design
Retrospective review of corneal histopathology.
Methods
Thirteen corneal specimens of 11 patients with xeroderma pigmentosum who underwent keratoplasty (lamellar/full-thickness) for corneal involvement were studied. Five-micrometer-thick sections were made from all the samples and stained using hematoxylin-eosin and periodic acid–Schiff stains. A light microscopic examination was performed to study the histopathologic changes.
Results
The corneal findings on clinical examination were haze, scarring, vascularization, stromal edema, pigment clumps on endothelial surface, and corneal thinning. The histopathologic evaluation revealed changes in all layers of cornea. Epithelial changes seen were intraepithelial edema, fibrosis, epithelial downgrowths, and pannus formation. The Bowman membrane was fragmented or absent. Stroma was characterized by alteration in the lamellar pattern, scarring, edema, loss of keratocytic nuclei, and calcification. The Descemet membrane was thickened to a variable extent in most specimens and there was marked loss of endothelial cells in all.
Conclusion
Most histologic features are consistent with the previous few reports. The remarkable finding in all corneal specimens was a moderate to severe degree of loss of the endothelial cells. This noteworthy finding supports the ultraviolet (UV) radiation–induced endothelial cell damage in these patients. This has an important clinical implication when planning for anterior lamellar keratoplasty, as endothelial cell density may be subnormal in these patients.
Xeroderma pigmentosum is an autosomal recessive, rare genetic disorder characterized by solar injury to exposed skin and ocular tissues attributable to an enzymatic defect in the ability to repair DNA damage caused by ultraviolet (UV) light. Dermatologic changes are the most conspicuous findings and are mandatory for the diagnosis. Dermatologic involvement is characterized by extreme skin sensitivity to UV light, abnormal skin pigmentation, and high frequency of skin cancers, especially on sun-exposed skin. Ocular manifestations involve the eyelids, conjunctiva, sclera, and cornea. The eyelids are frequently involved. The eyelid skin may atrophy and ectropion may occur; the bulbar conjunctiva may become thin, pigmented, and atrophic, with inflamed patches; and eventually the lesions may become malignant. Cornea in xeroderma pigmentosum may show dryness, haze, edema, exposure keratitis, vascularization, pterygium-like growths, epithelial neoplasms, and opacification. Corneal opacification may result from epithelial/stromal changes or may be secondary to endothelial decompensation as a result of damage owing to chronic sun exposure.
Corneal involvement often necessitates keratoplasty for visual rehabilitation. The decision about the type of keratoplasty (penetrating or selective) depends on the predominant corneal manifestation. Jalali and associates reported encouraging results following penetrating keratoplasty (PK) in 3 patients with xeroderma pigmentosum. We reported 2 cases with xeroderma pigmentosum, where Descemet stripping endothelial keratoplasty (DSEK) was performed for visual rehabilitation. In 1 patient, DSEK was performed for corneal edema attributable to endothelial failure as a result of chronic sun exposure. In the second patient, a deep anterior lamellar keratoplasty (DALK) was performed initially; although uneventful, it failed to maintain graft clarity, presumably owing to a poor endothelial reserve, and therefore a sequential endothelial keratoplasty was performed to restore graft clarity. Considering the fact that UV radiation can lead to endothelial damage, in eyes where anterior lamellar keratoplasty is performed, the surgical results are anticipated to depend on the preexisting endothelial status.
There are few reports describing the histologic corneal changes in xeroderma pigmentosum patients. Pathologic corneal changes in these patients range from disorganized epithelium to Bowman membrane destruction, neovascularization, perivascular infiltration of inflammatory cells in the stroma, and loss of endothelial cells.
The purpose of the report is to examine the histologic changes in the cornea of patients with xeroderma pigmentosum and correlate with the clinical findings.
Methods
The study included 11 patients who were clinically diagnosed to have xeroderma pigmentosum at L.V. Prasad Eye Institute, Hyderabad. Full-thickness corneal buttons were obtained in 9 patients during PK. In 2 of these, full-thickness corneal buttons were obtained from both eyes. In 1 case, a lamellar corneal button was obtained while in another case only a Descemet membrane was obtained. The corneal buttons were cut into 2 halves and both halves were submitted for histopathologic analysis. Five-micrometer-thick sections were made from all the samples and stained using hematoxylin-eosin and periodic acid–Schiff stains. A light microscopic examination was performed by a trained pathologist to study the histopathologic changes.
The number of endothelial cells per high-power field was counted in 12 specimens (the DALK specimen had no Descemet membrane or endothelium). Assessment of the endothelial cells per high-power field in the full-thickness corneal buttons of age-matched subjects of keratoconus who had undergone PK was done for a comparison.
Correlation of histologic endothelial cell counts with specular microscopic cell density was also performed using the equation: cell density = (no. of endothelial cells per high-power field × 145) + 668.
Results
Eleven specimens were full-thickness corneal buttons obtained after PK, 1 was anterior lamellar corneal tissue following DALK, and 1 was a stripped Descemet membrane following DSEK. Table 1 and Figure shows the clinical and histopathologic features in the specimens studied. Table 2 shows a comparison of histopathologic features of this study with the existing reports.
| Case No. | Age of Patient (y) | Eye | Clinical Features | Specimen | Epithelium | Bowman Membrane | Stroma | Descemet Membrane | Endothelium |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 16 | OD | Vascularized corneal scar | Full-thickness CB | 3-5 cell layered with intraepithelial edema, subepithelial fibrosis | Absent | Edema, scarring with irregular collagen pattern | Thickened | Few endothelial cells |
| 2 | 16 | OS | Vascularized corneal scar | Lamellar CB | 3-5 cell layered thick, areas of hyperplasia, attenuation, downgrowths, subepithelial bullae, spheroidal degeneration | Focally fragmented | Scarred with irregular lamella | – | – |
| 3 | 27 | OS | Scar, corneal edema | Full-thickness CB | 4-6 cell layered, subepithelial and intraepithelial bullae, basal cell edema, regenerative atypia | Fragmented | Edematous, irregular arrangement of lamella | Mild thickening, posterior collagenous layer focally | Endothelial cells absent |
| 4 | 27 | OD | Corneal scar | Full-thickness CB | 3-5 cell layered, basal cell edema, epithelial downgrowths, subepithelial fibrosis, pannus, subepithelial bullae | Thickened, fragmented | Edema, patchy loss of keratocytic nuclei | Markedly thickened, posterior collagenous layer formation | Loss of endothelial cells |
| 5 | 41 | OD | Corneal scar | Full-thickness CB | 3-5 cell layered, irregular, subepithelial fibrosis | Absent | Thin, compact, scarring with loss of lamellar pattern | Thickened | Very few endothelial cells |
| 6 | 23 | OS | Vascularized corneal scar | Full-thickness CB | 3-5 cell layered, irregular, subepithelial fibrosis | Replaced by fibrous tissue | Calcified mass in stroma, scarred, blood vessels, perivascular lymphoplasmacytic infiltrates with few epithelioid cells and granulomas, elastotic degeneration | Minimal thickening | Absent endothelial cells |
| 7 | 29 | OD | PED, status/post TA application | Full-thickness CB | 3-5 cell layered, separation from Bowman at places, subepithelial fibrosis | Partly destroyed with subepithelial fibrosis | Edema, patchy loss of keratocytic nuclei, focal stromal defect, scarring, neovascularization, chronic infiltrates | Markedly thickened with guttate changes | Loss of endothelial cells |
| 8 | 29 | OS | Corneal scar | Full-thickness CB | 2-5 cell layered, subepithelial fibrous membrane | Intact; mild thickening | Edema, loss of lamellar pattern, peripheral vascularization | Thickened | Loss of endothelial cells |
| 9 | 20 | OS | Corneal scar and edema | Full-thickness CB | 1-3 cell layered, irregular with pigmented cells in basal cells, regenerative atypia | Fragmented | Spheroidal degeneration, irregular keratocytic nuclei, peripheral blood vessels | Thickened | Very few endothelial cells |
| 10 | 16 | OD | Vascularized corneal scar, edema | Full-thickness CB | Irregular, epithelial downgrowths, pigmentation with basal cell edema | Fragmented, lost at the site of epithelial downgrowths | Spheroidal degeneration, edema, vascularization, fibrosis | Thickened, breaks | Focal presence of few endothelial cells |
| 11 | 21 | OS | Vascularized corneal scar | Full-thickness CB | 1-3 cell layered, focally denuded, fibrosis, basal cell edema | Thickened, partly destroyed by subepithelial fibrosis, 1 edge shows subepithelial fibrovascular pannus | Scarring, focal clustering of keratocytic nuclei | Thickened, focally fragmented, partly buried in posterior stroma with retrocorneal fibrous membrane, adherent pigment cells | Loss of endothelial cells |
| 12 | 21 | OD | Corneal edema with haze, pigments on endothelial surface | Descemet membrane | – | – | – | Mild thickened, adherent pigments | Very few endothelial cells |
| 13 | 22 | OS | Vascularized corneal scar, edema | Full-thickness CB | 2-4 layered, basal cell edema, fibrosis | Replaced by fibrous tissue | Scarring, vascularization | Thickened – mild | Loss of endothelial cells |
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