As PDCD seldom affects visual acuity and it’s difficult to obtain the corneal tissue, the histopathological study of such corneal dystrophy is rare. Curran et al [15] first performed a histopathological analysis of the cornea from a case of PDCD and found that the keratocytes were enlarged with accumulation of vacuoles in the intracellular compartment containing lipofuscin-like lipoproteins. In an ultrastructural study of a corneal button from a patient with X-linked ichthyosis, Kempster et al [16] found electron-dense polymorphic and lamellated materials along the anterior aspect of Descemet membrane. By contrast, the corneal histopathological features of PDCD and X-linked ichthyosis were similar, and were consistent with the IVCM findings of enlarged keratocytes with intracellular hyperreflective particles in the present case.
In this study, we, for the first time, reported the characteristics of PDCD associated with X-linked ichthyosis using IVCM. We found that the activated keratocytes in the posterior stroma had enlarged cell bodies with a regular arrangement of hyperreflective particles inside. These IVCM findings were similar to the previous reports of isolated PDCD in the literatures [2, 11, 12]. In some other previous studies, the size and morphology of keratocytes in the posterior stroma were reported to be normal in isolated PDCD, although hyperreflective particles were also found in the intracellular and extracellular compartments [9, 10, 13]. The involved corneal layers in PDCD has been reported to be mainly limited within the posterior stroma immediately anterior to Descement membrane as observed by slit-lamp biomicroscopy, and confirmed by Malhotra et al [2] using anterior segment optical coherence tomography. Similarly, some IVCM studies have revealed that the lesion of PDCD was restricted within the posterior stroma [9–13]. However, other IVCM studies have found that the lesion of PDCD was involved in the whole thickness of the corneal stroma [9, 10, 13]. The involvement of corneal endothelial layer was also reported in some PDCD patients [2, 12]. In our present case, using IVCM, we found that the enlarged keratocytes with hyperreflective particles in the posterior stroma were consistent with the histopathological study. We also found hyperreflective particles outside the anterior stroma, which has not been reported previously.
X-linked ichthyosis is a genetic disorder of the skin caused by mutation or deletion of the STS gene on chromosome Xp22.3. The STS gene is composed of 10 exons that span a region of about 140 kb. Up to 90% X-linked ichthyosis patients exhibit large deletions of the entire STS gene and flanking sequences, while a minority show a point mutation or partial deletion of the STS gene [17, 18]. In our case, we demonstrated that the patient had a deletion of the entire STS gene and flanking sequences DXS1139-DXS22S1 using PCR. He had no immediate family history of X-linked ichthyosis, but similar ichthyotic skin was found in his maternal grandmother’s brother. So we speculated that his mother and his maternal mother were heterozygous females, and the STS gene deletion of our patient was hesitated from them. Hung et al [19] also demonstrated that the corneal changes in PDCD and X-linked ichthyosis were associated with deletion of the STS detected with microarray-based comparative genomic hybridization. STS is found throughout the body, including the epidermis, where it is thought to play a role in the steroid production and lipid regulation of the stratum corneum [20]. As STS deficiency leads to elevated plasma levels of cholesterol sulfate, the characteristic feature of posterior stromal opacities in PDCD has been postulated to represent focal accumulations of cholesterol sulfate [7, 16]. Therefore, we propose that STS deficiency may lead to lysosomal dysfunction and lipid metabolism disorder, thus leading to accumulation of undigested substances in the intracellular and extracellular compartments of keratocytes. This may explain the hyperreflective particles in the anterior and posterior stroma identified in our patient by IVCM.