Sir,

Aim

To report limbal stem cell deficiency in a case of xeroderma pigmentosum that was successfully managed by limbal transplantation and penetrating keratoplasty.

Methods

Interventional case report.

Result

A 28-year-old male with xeroderma pigmentosum had an adherent leucoma with 120° conjunctivalization in the left eye. Corneal impression cytology supported the clinical diagnosis of partial limbal stem cell deficiency. At 1 year after living-related conjunctival limbal allograft, followed by penetrating keratoplasty, the ocular surface was stable and vision had improved to 20/40.

Conclusion

Limbal stem cell deficiency could be considered as an ocular manifestation of xeroderma pigmentosum, suggesting the need for a close follow-up and limbal transplantation procedures if required.

Xeroderma pigmentosum, an autosomal recessive dermatosis, results in cutaneous pigmentary abnormalities and multiple malignancies,1 and may have neurologic and systemic manifestations.2 Ocular manifestations of this disease include ocular surface squamous neoplasia, neovascularization, and keratitis.3

We report a case of xeroderma pigmentosum presenting with features of partial limbal stem cell deficiency in one eye managed by limbal allotransplantation followed by a penetrating keratoplasty, that restored ocular surface stability and vision.

Case report

A healthy 28-year-old male diagnosed with xeroderma pigmentosum presented with diminished vision in both eyes, of several years duration. There was no prior history of exanthematous fever. He had been treated elsewhere for malignant lesions of the skin and nose. In the left eye, his best visual acuity was 20/400. An adherent leucoma was present in the lower one-third of the cornea with 120° conjunctivalization (Figure 1a). In the right eye, his vision was reduced to accurate projection of rays due to a dense vascularized corneal scar. Both eyes had normal lids, conjunctiva, and adequate tear meniscus. Dense corneal scars precluded the view of the remaining anterior and posterior segments. Systemic examination revealed no abnormalities other than hyper- and depigmented lesions of the skin in exposed areas. The differential diagnosis in the left eye included ocular surface squamous neoplasia and partial stem cell deficiency. Impression cytology revealed goblet cells in the inferior quadrant (Figure 2a) with squamous metaplasia in other areas of the cornea (Figure 2c). Adequate goblet cells were noted on the conjunctival surface (Figure 2b). There was no evidence of dysplasia in the epithelial cells. He was diagnosed as having partial limbal stem cell deficiency, and was advised a living-related conjunctival limbal allograft. His unaffected father volunteered to be the donor. After informed consent, the donor tissue was transplanted inferiorly over 0600 h. Histopathology of the excised pannus confirmed conjunctivalization of the cornea and excluded dysplastic changes (not shown). We followed the immunosuppressive regimen described by Tsubota.4 After 3 months when the ocular surface was stable (Figure 1b), a corneal transplant was done. At the last visit, a year following penetrating keratoplasty, his best visual acuity was 20/40. The corneal graft was clear and the inferior limbal graft has been accepted (Figure 1c).

Figure 1
figure 1

(a) Clinical picture of the left eye shows an adherent leucoma with 120° conjunctivalization of the inferior quadrant. (b) At 3 months after a living-related conjunctival limbal allograft, the ocular surface was noted to be stable and there was no recurrence of conjunctivalization inferiorly. (c) Clinical picture of the left eye 3.5 months after PKP, showing a clear and compact corneal graft, with a stable ocular surface and no evidence of conjunctivalization.

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Figure 2
figure 2

(a) Impression cytology from inferior quadrant of cornea showing epithelial cells interspersed with few goblet cells (arrow) characteristic of conjunctivalization of the cornea due to limbal stem cell deficiency (periodic acid Schiff stain, × 125). (b) Impression cytology of conjunctiva of the same eye showing a sheet of conjunctival epithelial cells with multiple goblet cells (arrow). (periodic acid schiff stain, × 500). (c) Impression cytology of nasal quadrant of the left cornea, showing singly scattered polygonal cells with low nuclear-cytoplasmic ratio and pink keratohyaline granules (arrow) in the cytoplasm, indicative of squamous metaplasia. There were no goblet cells noted. (periodic acid schiff stain, × 125).

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Comment

In xeroderma pigmentosum, there is a deficiency of the enzymes responsible for repairing UV light-induced DNA damage.1 Persistence of unrepaired DNA results in somatic mutations, leading to neoplasias. The manifestation of limbal stem cell deficiency in this patient prompted us to speculate that exposure of the limbal stem cells to UV radiation might lead to permanent damage or dysfunction of these cells, or alteration of the stromal microenvironment.

Our patient had features of partial LSCD with 120° conjunctivalization inferiorly. Since ocular surface squamous neoplasia is frequently noted in XP patients, impression cytology aided in exclusion of this entity. The presence of stem cell deficiency could result in a failed corneal graft; therefore, we decided to do a limbal transplant, followed by penetrating keratoplasty. Partial LSCD can be managed conservatively, by repeated mechanical debridement,5 or amniotic membrane transplantation.6 However, the success of these procedures is determined by the presence of healthy residual limbal stem cells. In a patient of xeroderma pigmentosum with high susceptibility to UV radiation-induced damage we anticipated a permanent damage to the residual limbal stem cells and therefore preferred a living-related conjunctival limbal allo-transplant. We support the belief that a penetrating keratoplasty after restoration of ocular surface stability is more beneficial, as has been advocated earlier.7, 8 A simultaneous procedure may result in delivery of less antigenic load to the recipient by utilizing the same donor for both limbal and corneal transplants, and in preservation of the transient amplifying cells.9 The poor long-term outcome following simultaneous limbal transplantation and penetrating keratoplasty has prompted the recommendation of a staged procedure with a 1-year gap.8 Though a stable ocular surface and good vision have been attained following these surgeries, the inherent pathology remains. Photoprotective measures have been advocated and the patient has been cautioned about the possible development of ocular or cutaneous manifestations of XP described earlier. Indefinite immunosuppression remains necessary to ward off limbal allograft rejection.10 The patient is on low doses of cyclosporine ensuring serum trough levels of 50 ng/ml, regular assessment of renal and hepatic parameters, and on close follow-up in conjunction with an internist.

In summary, limbal stem cell deficiency may be one of the ocular manifestations of xeroderma pigmentosum, necessitating a high degree of suspicion and early surgical intervention to prevent visual disability.