An ocular prosthesis is a custom-made polymeric insert that can be placed in an anophthalmic socket for cosmetic rehabilitation of patients who have lost their eyes. The process of creating such a custom-made ocular prosthesis is time-consuming and labor-intensive because it involves artistic work that is carried out manually. This paper proposes a novel semi-automated method for fabricating customized ocular prostheses using three-dimensional (3D) printing and sublimation transfer printing. In the proposed method, an impression mold of the patient’s anophthalmic socket is first optically scanned using a 3D scanner to produce a 3D model. The ocular prosthesis is then produced via a digital light processing 3D printer using biocompatible photopolymer resin. Subsequently, an image of the iris and blood vessels of the eye is prepared by modifying a photographed image of the contralateral normal eye, and printed onto the 3D-printed ocular prosthesis using a dye sublimation transfer technique. Cytotoxicity assessments of the base material and fabricated ocular prosthesis indicate that there is no adverse effect on cellular viability and proliferation. The proposed method reduces the time and skill required to fabricate a customized ocular prosthesis, and is expected to provide patients with easier access to quality custom-made ocular prostheses.

Purpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis in orbital fibroblasts in Graves' orbitopathy (GO). Methods: Orbital fibroblasts were cultured from orbital adipose/connective tissues of patients with GO and healthy control subjects. Effects of treatment with TGF-β and cigarette smoke extract (CSE) on S1P receptor (S1PR) messenger RNA (mRNA) and S1P expression were evaluated by real-time polymerase chain reaction and Western blotting. To evaluate the role of S1P in fibrosis, cells were pretreated with W146 (S1PR1 antagonist); JTE013 (S1PR2 antagonist); FTY720 (S1PR1 modulator); or 5C (sphingosine kinase-1 blocker) for 1 hour before stimulation with TGF-β, CSE, or IL-1β. Expression of fibrosis-related proteins (collagen Iα, fibronectin, and α-smooth muscle actin [SMA]) and tissue remodeling–related proteins (matrix metalloproteinases [MMPs] and tissue inhibitor of metalloproteinase [TIMP]-1) was then evaluated by Western blotting. Results: Expression levels of S1PR mRNA and S1P in GO orbital fibroblasts increased upon TGF-β and CSE treatment. Treatment with S1PR blockers and 5C inhibited TGF-β and CSE-induced expression of collagen Iα, fibronectin, and α-SMA, as well as IL-1β–induced expression of MMP-1, MMP-2, MMP-9, and TIMP-1. Exogenous S1P treatment without profibrotic stimulants upregulated collagen Iα, fibronectin, α-SMA, MMP-1, MMP-2, MMP-9, and TIMP-1 expression in a dose-dependent manner. Conclusions: Blocking of S1PR activity and inhibition of S1P synthesis led to decreased expression of fibrosis and tissue remodeling–related proteins in primary cultures of orbital fibroblasts derived from patients with GO. Thus, modulation of S1P activity might have therapeutic potential in the suppression of fibrosis in GO.

Purpose: To investigate the clinical features of central retinal vein occlusion (CRVO) in relation to the presence of a prominent middle limiting membrane (p-MLM) sign on presenting optical coherence tomography, which may suggest macular ischemia and poor visual outcome. Methods: Fifty consecutive eyes with acute CRVO of <1 month of symptom duration before presentation were retrospectively reviewed. A hyperreflective line located in the outer plexiform layer (p-MLM) in optical coherence tomography was used as a sign of acute ischemia. Cases with p-MLM were grouped and compared with the group of eyes with no p-MLM sign (non-MLM group) for clinical features including visual acuities, central fovea thickness, and CRVO types. Results: Among the 50 eyes, 14 (28%) eyes showed a p-MLM sign, 21 (42%) eyes did not, and others had equivocal findings. Eyes with p-MLM sign presented worse initial and final best-corrected visual acuity compared with the non-MLM group (1.10 ± 0.72 vs. 0.47 ± 0.49 logMAR in the initial best-corrected visual acuity, P = 0.007; and 1.08 ± 0.86 vs. 0.32 ± 0.41 logMAR in the final best-corrected visual acuity, P = 0.044) in patients with a follow-up duration of 6 months or longer. The p-MLM group eyes showed a higher tendency toward being classified as ischemic type CRVO (57.1 vs. 4.8%, P = 0.001). Conclusion: Central retinal vein occlusion showing p-MLM on optical coherence tomography had worse visual outcome with higher incidence of being classified into ischemic type CRVO.

Purpose: Emerging evidence indicates that the phosphatidylinositol 3-kinase (PI3K)-AKT pathway is involved in the pathogenesis of Graves' orbitopathy (GO). In this study, the therapeutic effects of idelalisib, a selective PI3Kδ inhibitor, on adipogenesis were evaluated in GO orbital fibroblasts in vitro. Methods: Orbital fibroblasts were cultured from orbital connective tissues obtained from individuals with GO and healthy control subjects. Cells were pretreated with idelalisib for 1 hour before stimulation with IL-1β. Inflammatory cytokine expression was measured by Western blotting and ELISAs. The adipogenesis-related downstream mediators of the PI3K/AKT cascade, that is, forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also were measured by Western blotting. After adipogenic differentiation and idelalisib treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator γ (PPARγ) and CCAAT-enhancer–binding proteins (C/EBP) α/β were determined by Western blot analyses. Results: AKT phosphorylation decreased in a dose-dependent manner upon treatment with idelalisib in GO and non-GO orbital fibroblasts. Treatment with idelalisib inhibited the IL-1β–induced expression of IL-6 and IL-8. Idelalisib attenuated the phosphorylation of mTOR and FOXO1, downstream regulators of the PI3K pathway. Oil Red-O staining results revealed a decrease in lipid droplets and suppressed expression of PPARγ and c/EBPα/β upon treatment with idelalisib during adipose differentiation. Conclusions: Idelalisib inhibited proinflammatory cytokine production and adipogenesis in GO orbital fibroblasts in vitro. These results support the potential use of PI3K inhibitors in GO management.