PMC3704602_01
Pedigree of the enucleated eye.. Notes: A c.731T>C mutation in CAPN5 was inherited in a dominant fashion in a family with ADNIV (autosomal dominant neovascular inflammatory vitreoretinopathy). In the most recent generation, there were five affected, and four unaffected siblings. The enucleated eye was from a male sibling (arrow).
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His grandmother and mother were affected, along with four sisters and one brother (Figure 1).
Stage V ADNIV (autosomal dominant neovascular inflammatory vitreoretinopathy).. Notes: (A) The right eye is phthisical. The vitreous (v) is filled with hemorrhage and fibrosis (f). The cornea (c) is depressed and the sclera (s) is shrunken. The optic nerve (on) is atrophic. Scale bar = 1 cm. (B) Masson's trichrome stain shows a square shaped, thickened sclera (s). The cornea (c) is distorted and the anterior chamber is collapsed. Fibrovascular membranes (fm) cause tractional detachment of the ciliary body (cb) and membranes (m) cause traction on the retina (r). The lens (l) is fragmented. The optic nerve (on) is atrophic. Scale bar = 0.5 cm.
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Gross examination of the eye revealed a shrunken, distorted phthisical globe (Figure 2A). The optic nerve was atrophic, and there was replacement of axons by collagenous bands (Figure 2B). Microscopic examination showed typical features of phthisis bulbi (Figure 2B).
Anterior segment of the cornea.. Notes: (A) Cornea reveals folded Bowman's membrane and stromal (st) disorganization without neovascularization. Epithelium (e) (H&E). (B) Lens (l) reveals cataractous changes including Morgagnian globules and lens fiber degeneration. Vitreous hemorrhage (vh) (H&E). (C and D) Iridocorneal angle (a) is occluded (arrow in C) by fibrous membrane (f) (C, H&E; D, MT) stromal (st); iris pigment epithelium (p). (E and F) Iris shows extensive inflammatory cell infiltrate (arrows in E, F) into iris stroma (s) (H&E). Descemet's membrane (d), iris (i), iris stroma (s), iris pigment epithelium (p), membrane (m). Scale bar = 250 mum.. Abbreviations: H&E, hemotoxylin and eosin stain; MT, Masson's trichrome.
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In the anterior segment, the corneal epithelium appeared normal, but Bowman's membrane showed dystrophic calcium deposits consistent with calcific band keratopathy (Figure 3A). The stroma did not show evidence of neovascularization (Figure 3A). The lens capsule was intact, and there were severe cataractous changes (Figure 3B). The iridocorneal angle was occluded by fibrous membranes, highlighted in a Masson's trichrome stain (Figure 3C and D). The iris showed significant chronic inflammation consistent with chronic uveitis (Figure 3E and F).
Vitreous hemorrhage and membrane.. Notes: (A) Vitreous hemorrhage (vh) and fibrovascular membranes (fm) cause tractional retinal detachment (r) (H&E). Vitreous membranes (m). (B) Tractional detachment and vitreous hemorrhage (MT). Vitreous hemorrhage (vh) and fibrovascular membranes (fm) cause tractional retinal detachment (r). (C and D) Vitreous membranes (m) and red blood cells (H&E). Scale bar = 250 mum.. Abbreviations: H&E, hemotoxylin and eosin stain; MT, Masson's trichrome.
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The vitreous was filled with hemorrhage, fibrous membranes, and showed a tractional retinal detachment (Figure 4).
Retina.. Notes: (A) Cell infiltrates (arrows) are present in the retina (r) and choroid (ch), and retinal pigment epithelium is atrophic (arrow head) (H&E). (B) An epiretinal membrane (erm) overlies the retina (MT). (C) Osseous metaplasia (om) replaces the retina and choroid is indicated (arrow). (D) Extensive gliosis of retina (r) is highlighted by a glial fibrillary acidic protein stain (brown); vitreous (v). Scale bar = 250 mum.. Abbreviations: H&E, hemotoxylin and eosin stain; MT, Masson's trichrome.
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The retina showed extensive degeneration, and most of the nerve fiber layer, retinal ganglion cells, inner plexiform layer, outer plexiform layer, and photoreceptor cells were absent (Figure 5). Dense gliotic scars replaced the retina, which was confirmed by positive glial fibrillary acidic protein immunohistochemistry (Figure 5D). The choroid was focally hyalinized and calcified, and there appeared to be inflammatory cell infiltrates that were overwhelmingly lymphocytic in nature (Figure 5A).
Lymphocyte infiltration.. Notes: Cluster of Differentiation-3 (CD3) T-cell marker was identified in cells (brown color reaction, arrows) infiltrating the: (A) iris, (B) supraciliary space (ss), (C) retina (r), and (D) vitreous (v) and retinal blood cells (rbc). Scale bar = 250 mum.
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CD3 cells (T-cell receptor and a specific molecular marker of T cells) were found throughout the uvea (Figure 6).