Microcystoid Macular Changes in Association With Idiopathic Epiretinal Membranes in Eyes With and Without Glaucoma: Clinical Insights.

PURPOSE: To describe the clinical and surgical significance of microcystoid macular changes in the inner nuclear layer in patients with idiopathic epiretinal membranes, with and without glaucomatous optic neuropathy. DESIGN: Retrospective case series. METHODS: Clinical charts and spectral-domain optical coherence tomography images of 264 eyes of 234 consecutive patients diagnosed with idiopathic epiretinal membranes were reviewed and analyzed. Surgical data were analyzed in a subgroup of eyes with microcystoid macular changes treated with pars plana vitrectomy and epiretinal and internal limiting membrane peel. In surgical cases, postoperative functional and anatomic results at 1 and 6 months were compared between glaucomatous and nonglaucomatous eyes. Associations of microcystoid macular changes with visual acuity and other morphometric parameters were assessed by means of linear or multiple logistic regressions. RESULTS: Microcystoid macular changes in the inner nuclear layer were diagnosed in 52 out of 264 eyes with epiretinal membranes (19.7%), of which 28 (55.0%) had concomitant glaucoma. The likelihood to develop microcystoid macular changes increased at advanced glaucoma and epiretinal membrane stages. The morphology of microcystoid macular changes was similar between glaucomatous and nonglaucomatous eyes. Forty-four out of 52 eyes (84.6%) with microcystoid macular changes, of which 20 were with glaucoma and 24 without glaucoma, underwent surgery with pars plana vitrectomy and epiretinal and internal limiting membrane peel. At 1 and 6 months after surgery the mean number of microcysts decreased significantly from baseline in nonglaucomatous eyes (P = .003 and P = .002, respectively) and remained unchanged in glaucomatous eyes (P = .400 and P = .700, respectively). CONCLUSIONS: This study reports a high frequency of microcystoid macular changes in the inner nuclear layer in eyes with concomitant epiretinal membrane and glaucomatous optic neuropathy. In glaucomatous eyes, pars plana vitrectomy with epiretinal and internal limiting membrane peel was ineffective in the treatment of microcystoid macular changes.

hCTLA4-Ig transgene expression in keratocytes modulates rejection of corneal xenografts in a pig to non-human primate anterior lamellar keratoplasty model.

BACKGROUND: Human corneal allografting is an established procedure to cure corneal blindness. However, a shortage of human donor corneas as well as compounding economic, cultural, and organizational reasons in many countries limit its widespread use. Artificial corneas as well as porcine corneal xenografts have been considered as possible alternatives. To date, all preclinical studies using de-cellularized pig corneas have shown encouraging graft survival results; however, relatively few studies have been conducted in pig to non-human primate (NHP) models, and particularly using genetically engineered donors. METHODS: In this study, we assessed the potential benefit of using either hCTLA4-Ig transgenic or α1,3-Galactosyl Transferase (GT) Knock-Out (KO) plus transgenic hCD39/hCD55/hCD59/fucosyl-transferase pig lines in an anterior lamellar keratoplasty pig to NHP model. RESULTS: Corneas from transgenic animals expressing hCTLA4-Ig under the transcriptional control of a neuron-specific enolase promoter showed transgene expression in corneal keratocytes of the stroma and expression was maintained after transplantation. Although a first acute rejection episode occurred in all animals during the second week post-keratoplasty, the median final rejection time was 70 days in the hCTLA4-Ig group vs. 21 days in the wild-type (WT) control group. In contrast, no benefit for corneal xenograft survival from the GTKO/transgenic pig line was found. At rejection, cell infiltration in hCTLA4Ig transgenic grafts was mainly composed of macrophages with fewer CD3+ CD4+ and CD79+ cells than in other types of grafts. Anti-donor xenoantibodies increased dramatically between days 9 and 14 post-surgery in all animals. CONCLUSIONS: Local expression of the hCTLA4-Ig transgene dampens rejection of xenogeneic corneal grafts in this pig-to-NHP lamellar keratoplasty model. The hCTLA4-Ig transgene seems to target T-cell responses without impacting humoral responses, the control of which would presumably require additional peripheral immunosuppression.

Proliferation of the ciliary epithelium with retinal neuronal and photoreceptor cell differentiation in human eyes with retinal detachment and proliferative vitreoretinopathy.

BACKGROUND: There is some in vitro evidence that the adult ciliary body might harbor an inactive population of stem/retinal progenitor cells (RPC), or that ciliary epithelial (CE) cells might have the capacity to trans-differentiate, which may result in a balance between neural and epithelial properties. We have reported alterations in the ciliary body (CB) and adjacent vitreous in vivo by endoscopic evaluation of human eyes with a history of retinal detachment (RD) and anterior proliferative vitreoretinopathy (PVR). METHODS: The present study examined with light microscopy three paraffin-embedded phthisic human eyes with RD and anterior PVR. One normal eye, exenterated for an orbital tumor, served as the control. All specimens were stained with hematoxilin and eosin safran (HES), and serial sections were immunostained with antibodies against EGFR, Ki67, CD133, NSE, rhodopsin, and GFAP. RESULTS: We observed: (1) an intense proliferation and displacement of clusters of CE cells into the vitreous base in a "neurosphere-like" fashion; (2) differentiation of CE cells towards early and late neuronal [photoreceptor (PR)] lineages; and (3) strong staining of EGF and EGFR in the CE. Such proliferation, migration, and differentiation were not present in the CE of the control eye. GFAP staining was intensely positive in the three detached retinae, and was negative in the CE of eyes with RD, as well as in the retina of the control eye. CONCLUSIONS: Our observations suggest that EGFR-positive CE cells in the adult human eye in vivo with RD and PVR form "neurosphere-like" structures; their differentiation seems to be directed towards the neural and photoreceptor lineage, and not towards glial formation. In the adult human eye, the CE in a pathological retinal environment such as RD might provide a spontaneous source of donor cells for retinal transplantation.