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Noninvasive direct detection of ocular mucositis by in vivo confocal microscopy in patients treated with S-1.

Chikama T, Takahashi N, Wakuta M, Nishida T - Mol. Vis. (2009)

Bottom Line: S-1 is an oral antineoplastic agent that contains a prodrug of 5-fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the ocular surface.Immunofluorescence analysis revealed the presence of cells positive for one, both, or neither of cytokeratins 12 and 4 in each lesion.S-1 can induce ocular mucositis with dysplasia, likely affecting cellular functions, including differentiation, of the corneal epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. chikama@yamaguchi-u.ac.jp

ABSTRACT

Purpose: S-1 is an oral antineoplastic agent that contains a prodrug of 5-fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the ocular surface. We investigated the effects of S-1 on the corneal epithelium by in vivo confocal microscopy and histopathologic analysis.

Methods: Twelve patients with eye problems related to S-1 treatment participated in the study. Twenty eyes of ten subjects were evaluated by laser-scanning confocal microscopy. Corneal epithelial debridement as a diagnostic therapy and histopathologic analysis were performed for five eyes of three subjects affected in the pupillary zone of the cornea.

Results: Slitlamp examination revealed a local limbal abnormality characterized by epithelial invasion toward the center of the cornea in all 24 eyes. In vivo confocal microscopy revealed an altered structure of the corneal epithelium with abnormal epithelial cells and inflammation. One of five specimens subjected to cytologic diagnosis showed moderate dysplasia. Hematoxylin and eosin staining showed that each abnormal epithelial sheet lacked the stratified structure of the normal corneal epithelium. Immunofluorescence analysis revealed the presence of cells positive for one, both, or neither of cytokeratins 12 and 4 in each lesion.

Conclusions: S-1 can induce ocular mucositis with dysplasia, likely affecting cellular functions, including differentiation, of the corneal epithelium. In vivo confocal microscopy allowed the noninvasive detection of cellular changes in the cornea as an adverse effect of S-1 administration.

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Related in: MedlinePlus

Inflammatory changes in ocular mucositis revealed by in vivo confocal microscopy. In vivo confocal microscopy revealed a high density of dendritic and spherical cells, likely including Langerhans cells, macrophages, monocytes, and neutrophils, in the epithelial basal cell layer (A, B, D) as well as many activated keratocytes in the anterior stroma (C) and a reduced number of subepithelial nerve fibers (F). Fibrosis (arrows) with a circular pattern of degradation of Bowman’s layer was observed in a case that subsequently showed only minor improvement after discontinuation of S-1 administration (E).
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f3: Inflammatory changes in ocular mucositis revealed by in vivo confocal microscopy. In vivo confocal microscopy revealed a high density of dendritic and spherical cells, likely including Langerhans cells, macrophages, monocytes, and neutrophils, in the epithelial basal cell layer (A, B, D) as well as many activated keratocytes in the anterior stroma (C) and a reduced number of subepithelial nerve fibers (F). Fibrosis (arrows) with a circular pattern of degradation of Bowman’s layer was observed in a case that subsequently showed only minor improvement after discontinuation of S-1 administration (E).

Mentions: Abnormalities of the cornea detected in the study patients by in vivo laser confocal microscopy included: (1) cellular defects or turbulence of superficial epithelial cells; (2) disruption of the layered structure of the epithelium; (3) infiltration of inflammatory cells in the basal cell layer of the epithelium or in the shallow stroma; (4) absence or a reduced number of subepithelial nerves; (5) hyper-reflective granular structures at the center of the epithelial basal cell layer; and (6) changes in the structure of palisades at the limbus (Figure 2, Figure 3, and Table 2). None of these findings were apparent in normal eyes.


Noninvasive direct detection of ocular mucositis by in vivo confocal microscopy in patients treated with S-1.

Chikama T, Takahashi N, Wakuta M, Nishida T - Mol. Vis. (2009)

Inflammatory changes in ocular mucositis revealed by in vivo confocal microscopy. In vivo confocal microscopy revealed a high density of dendritic and spherical cells, likely including Langerhans cells, macrophages, monocytes, and neutrophils, in the epithelial basal cell layer (A, B, D) as well as many activated keratocytes in the anterior stroma (C) and a reduced number of subepithelial nerve fibers (F). Fibrosis (arrows) with a circular pattern of degradation of Bowman’s layer was observed in a case that subsequently showed only minor improvement after discontinuation of S-1 administration (E).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2802292&req=5

f3: Inflammatory changes in ocular mucositis revealed by in vivo confocal microscopy. In vivo confocal microscopy revealed a high density of dendritic and spherical cells, likely including Langerhans cells, macrophages, monocytes, and neutrophils, in the epithelial basal cell layer (A, B, D) as well as many activated keratocytes in the anterior stroma (C) and a reduced number of subepithelial nerve fibers (F). Fibrosis (arrows) with a circular pattern of degradation of Bowman’s layer was observed in a case that subsequently showed only minor improvement after discontinuation of S-1 administration (E).
Mentions: Abnormalities of the cornea detected in the study patients by in vivo laser confocal microscopy included: (1) cellular defects or turbulence of superficial epithelial cells; (2) disruption of the layered structure of the epithelium; (3) infiltration of inflammatory cells in the basal cell layer of the epithelium or in the shallow stroma; (4) absence or a reduced number of subepithelial nerves; (5) hyper-reflective granular structures at the center of the epithelial basal cell layer; and (6) changes in the structure of palisades at the limbus (Figure 2, Figure 3, and Table 2). None of these findings were apparent in normal eyes.

Bottom Line: S-1 is an oral antineoplastic agent that contains a prodrug of 5-fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the ocular surface.Immunofluorescence analysis revealed the presence of cells positive for one, both, or neither of cytokeratins 12 and 4 in each lesion.S-1 can induce ocular mucositis with dysplasia, likely affecting cellular functions, including differentiation, of the corneal epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. chikama@yamaguchi-u.ac.jp

ABSTRACT

Purpose: S-1 is an oral antineoplastic agent that contains a prodrug of 5-fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the ocular surface. We investigated the effects of S-1 on the corneal epithelium by in vivo confocal microscopy and histopathologic analysis.

Methods: Twelve patients with eye problems related to S-1 treatment participated in the study. Twenty eyes of ten subjects were evaluated by laser-scanning confocal microscopy. Corneal epithelial debridement as a diagnostic therapy and histopathologic analysis were performed for five eyes of three subjects affected in the pupillary zone of the cornea.

Results: Slitlamp examination revealed a local limbal abnormality characterized by epithelial invasion toward the center of the cornea in all 24 eyes. In vivo confocal microscopy revealed an altered structure of the corneal epithelium with abnormal epithelial cells and inflammation. One of five specimens subjected to cytologic diagnosis showed moderate dysplasia. Hematoxylin and eosin staining showed that each abnormal epithelial sheet lacked the stratified structure of the normal corneal epithelium. Immunofluorescence analysis revealed the presence of cells positive for one, both, or neither of cytokeratins 12 and 4 in each lesion.

Conclusions: S-1 can induce ocular mucositis with dysplasia, likely affecting cellular functions, including differentiation, of the corneal epithelium. In vivo confocal microscopy allowed the noninvasive detection of cellular changes in the cornea as an adverse effect of S-1 administration.

Show MeSH
Related in: MedlinePlus