Vitreoretinal Interface Changes After Anti-vascular Endothelial Growth Factor Treatment in Highly Myopic Eyes: A Real-World Study.

INTRODUCTION: To investigate changes in the vitreoretinal interface after anti-vascular endothelial growth factor (anti-VEGF) treatment in highly myopic eyes. METHODS: Eyes with myopic choroidal neovascularization (mCNV) treated with intravitreal injection of anti-VEGF in a single-center were retrospectively reviewed. Fundus abnormalities and features of optical computed tomography were studied. RESULTS: A total of 295 eyes from 254 patients were recruited to the study. Prevalence of myopic macular retinoschisis (MRS) was 25.4%, and the rates of progression and onset of MRS were 75.9% and 16.2%, respectively. Outer retinal schisis (ß = 8.586, p = 0.003) and lamellar macular hole (LMH) (ß = 5.015, p = 0.043) at baseline were identified risk factors for progression and onset of MRS, whereas male sex (ß = 9.000, p = 0.039) and outer retinal schisis at baseline (ß = 5.250, p = 0.010) were risk factors for MRS progression. Progression of MRS was first detected in outer retinal layers in 48.3% of eyes. Thirteen eyes required surgical intervention. Spontaneous improvements of MRS were observed in five eyes (6.3%). CONCLUSION: Changes in the vitreoretinal interface, such as progression, onset, and improvement of MRS, were observed after anti-VEGF treatment. Outer retinal schisis and LMH were risk factors of progression and onset of MRS after anti-VEGF treatment. Intravitreal injection of ranibizumab and retinal hemorrhage were protective factors for surgical intervention for vision-threatening MRS.

Cataract extraction surgery in patients with uveitis in Taiwan: risk factors and outcomes.

BACKGROUND/PURPOSE: To analyze the preoperative conditions and postoperative outcomes of phacoemulsification and intraocular lens implantation in Taiwanese patients with uveitis. METHODS: This retrospective, consecutive case series study included 121 eyes of 84 patients with uveitis who underwent phacoemulsification and intraocular lens implantation from July 1996 to May 2006. The demographic data, postoperative outcomes, complications, and risk factors with regard to visual prognosis were analyzed. Visual acuity was converted from the Snellen equivalent to logMAR values. RESULTS: This study included 51 men and 70 women with a mean ± SD age of 44.6 ± 18.4 years. The three most common diseases were idiopathic uveitis, Behcet's disease, and Vogt-Koyanagi-Harada disease. The best-corrected visual acuity improved from 1.52 ± 0.83 logMAR units preoperatively to 0.37 ± 0.59 logMAR units postoperative (p < 0.001). The most frequent postoperative complications were posterior capsular opacity (24 eyes) and cystoid macular edema (10 eyes). Anterior uveitis related to HLA-B27 had the best visual prognosis, whereas Behcet's disease had the poorest visual outcome (p = 0.029). Logistic regression analysis indicated that disease etiology (p = 0.011) and preoperative visual acuity (p = 0.020) were related to the postoperative visual prognosis. CONCLUSION: Cataract extraction can improve visual function for most patients with uveitis. Postoperative complications were not uncommon and Behcet's disease had the poorest postoperative visual prognosis.

Topical ganciclovir treatment in patients with cytomegalovirus endotheliitis receiving penetrating keratoplasty.

BACKGROUND: To report seven cases diagnosed as cytomegalovirus endotheliitis and treated with topical 2% ganciclovir following penetrating keratoplasty. DESIGN: A retrospectively comparative case series. PARTICIPANTS: A retrospective interventional case series, including seven eyes of seven patients with cytomegalovirus endotheliitis after penetrating keratoplasty. METHODS: Clinical and immunological characteristics were studied in seven penetrating keratoplasty cases with positive quantitative polymerase chain reaction results for cytomegalovirus DNA from aqueous taps and treated with topical 2% ganciclovir. MAIN OUTCOME MEASURES: Clinical features and responses to topical 2% ganciclovir. RESULTS: Seven immunocompetent patients experienced acute anterior inflammation with graft oedema and pigmented keratic precipitates after penetrating keratoplasty. Their immunological profiles showed immunoglobulin G cytomegalovirus (+) and immunoglobulin M cytomegalovirus (-) in all cases. Topical 2% ganciclovir was prescribed every 2 to 3 h daily as induction therapy and every 4 h as long-term maintenance therapy. All cases had undetectable cytomegalovirus DNA after follow-up aqueous taps. Topical 2% ganciclovir preserved endothelium of cytomegalovirus-infected grafts at early stage and also provided a steady anticytomegalovirus environment for further regrafting in failed grafts at late stage. Acute inflammation reactivated in two cases and was suppressible by steroid under topical ganciclovir. No delayed re-epithelialization and any toxicity were observed. To date, no case treated in this way had displayed cytomegalovirus recurrence. CONCLUSIONS: Continuous topical 2% ganciclovir and a topical steroid adjusted by anterior inflammation are suggested after penetrating keratoplasty in all cases with cytomegalovirus endotheliitis to prevent cytomegalovirus recurrence.

Expressions of lymphotactin and its receptor, XCR, in Lewis rats with experimental autoimmune anterior uveitis.

BACKGROUND: To demonstrate the expression of lymphotactin and its receptor (XCR) in the iris/ciliary body and popliteal lymph node, and to clarify their roles in experimental autoimmune anterior uveitis (EAAU). METHODS: Uveitis was induced in Lewis rats by injection of melanin-associated antigen into the peritoneum and footpad. At defined time points, mRNA expression levels of lymphotactin and XCR in the iris/ciliary body and popliteal lymph node were measured by semiquantitative polymerase chain reaction. Lymphotactin levels in aqueous humor and serum after immunization were determined by enzyme-linked immunosorbent assay. In a separate experiment, an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), was injected daily into the intraperitoneum after immunization. Cellular sources of lymphotactin were determined by immunhistochemical staining and flow cytometry. RESULTS: Lymphotactin mRNA was upregulated in the iris/ciliary body with a peak level at day 14, which is in line with the disease course. XCR mRNA was expressed maximally and then declined gradually from days 5 to 21. With an expression pattern similar to that of mRNA expression, lymphotactin in aqueous humor had attracted corresponding numbers of leukocytes. PDTC markedly inhibited the expression of lymphotactin in aqueous humor and serum. Immunohistochemical staining and flow cytometry analysis revealed that the expression of lymphotactin was detected in infiltrated inflammatory cells, dominantly CD8+ T cells, and increased along with inflammation. CONCLUSIONS: The lymphotactin and XCR interaction might direct distinct lymphocytes subsets to inflammatory sites. Lymphotactin could regulate the inflammatory process. Lymphotactin expression may be modulated, at least in part, through the NF-κB signaling pathway.

Metastatic choroidal tumors in Taiwan: an 11-year experience.

PURPOSE: To report the clinical features, the primary sites, and overall prognosis of choroidal metastasis. DESIGN: Observational case series. METHODS: Included were all cases of choroidal metastases evaluated at National Taiwan University Hospital over an 11-year period. Patients with blood or lymphoproliferative diseases were excluded. Clinical features were correlated with disease entity and prognosis. RESULTS: A total of 36 patients with choroidal metastases were identified. The mean age was 53.9 +/- 12.8 years. The mean follow-up period was 5.1 +/- 4.2 months. The primary sites of tumors were lung in 18 (50%), breast in eight (22.2%), gastrointestinal tract in three (8.3%), pancreas in two (5.6%), ovary in two (5.6%), kidney in one (2.8%), liver in one (2.8%), and unknown in one (2.8%). Twenty-two patients (61%) died during follow-up. Mean life span after diagnosis was 4.3 months in these 22 patients. CONCLUSIONS: Lung and breast cancers represent more than two thirds of primary tumor sites. Choroidal metastases may indicate terminal status of the underlying malignancy and short survival time.

Expression of CX3C chemokine, fractalkine, and its receptor CX3CR1 in experimental autoimmune anterior uveitis.

PURPOSE: To demonstrate the expression and location of CX3C chemokine, fractalkine, and its receptor, CX3CR1, in the iris/ciliary body and thus establish their roles in experimental autoimmune anterior uveitis, an animal model of human acute anterior uveitis. METHODS: Uveitis was induced in Lewis rats by injection of melanin associated antigen into the peritoneum and footpad. At defined times, fractalkine and its receptor CX3CR1 mRNA expression in the iris/ciliary body were measured by using a semiquantitative polymerase chain reaction method. Fractalkine in aqueous humor was determined by enzyme linked immunosorbent assay. The cellular sources of fractalkine were determined by immunhistochemical staining. In a separate experiment, NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day) was administrated intraperitoneally daily after immunization. The rats were sacrificed on day 14 of immunization. Fractalkine mRNA in iris/ciliary body and fractalkine concentration in aqueous humor were determined after PDTC treatment. RESULTS: Fractalkine mRNA was found to be upregulated in the iris/ciliary body nine days after immunization, preceding clinical disease onset. CX3CR1 mRNA exhibited peak levels at day 14, coincident with disease onset. Fractalkine in aqueous humor showed an expression profile similar to mRNA expression. PDTC (200 mg/kg) markedly inhibited the expression of fractalkine mRNA in the iris/ciliary body, and fractalkine protein in aqueous humor. Immunohistochemical staining revealed that fractalkine was expressed on vascular endothelial cells and infiltrated inflammatory cells. Treatment with PDTC significantly reduced both the number of leukocyte infiltrations in the iris/ciliary body and fractalkine expression on vascular endothelial cells. CONCLUSIONS: The sequential expression of fractalkine may direct distinct CX3CR1 receptor expressing mononuclear cell subsets to inflammatory sites. Fractalkine expression is modulated, at least in part, through the NF-kappaB signaling pathway. These findings provide new insight into the molecular mechanisms of acute anterior uveitis and suggest fractalkine or NF-kappaB as a new drug target for uveitis therapy.

Effects of pyrrolidine dithiocarbamate, an NF-kappaB inhibitor, on cytokine expression and ocular inflammation in experimental autoimmune anterior uveitis.

AIMS: The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor (NF)-kappaB inhibitor, on cytokine expression and suppression of anterior chamber inflammation in experimental autoimmune anterior uveitis. Uveitis was induced in the Lewis rats with the injection of a melanin-associated antigen into the peritoneum and footpad. At defined time points, cytokine mRNA expressions in the iris and ciliary body were measured by using a semiquantitative polymerase chain-reaction method. RESULTS: We found that interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF)-alpha mRNA expression peaked during the active phase of uveitis, whereas interleukin (IL)-10 mRNA increased during the disease resolution. In a separate experiment, PDTC (100 and 200 mg/kg/day) was administrated intraperitoneally daily after immunization. We found that PDTC (100 and 200 mg/kg/day) effectively suppressed ocular inflammation, as indicated by reduced clinical scores and inflammatory cells infiltration in aqueous humor and the iris and ciliary body. CONCLUSIONS: The inhibitory effects of PDTC are mainly resulted from inhibiting the expression of proinflammatory cytokines, TNF-alpha and IFN-gamma but augmenting anti-inflammatory cytokines, IL-10 expression. These findings suggest that the application of NF-kappaB inhibitors may be a potential therapeutic method for the treatment of acute anterior uveitis.

Effects of the NF-kappaB inhibitor pyrrolidine dithiocarbamate on experimentally induced autoimmune anterior uveitis.

PURPOSE: To determine the effect of pyrrolidine dithiocarbamate (PDTC), a nuclear factor (NF)-kappaB inhibitor, on chemokine and chemokine receptor expression and thus elucidate the role of NF-kappaB in the pathogenesis of experimental autoimmune anterior uveitis (EAAU). METHODS: Uveitis was induced in Lewis rats with the injection of melanin-associated antigen into the footpad. PDTC (200 mg/kg and 100 mg/kg) was administered intraperitoneally daily, beginning 1 day after the immunization. The clinical inflammatory activity of the anterior chamber was recorded daily and scored. Immunohistochemical staining and an electrophoretic mobility shift assay assessed the effect of PDTC on NF-kappaB activation in the iris/ciliary body tissues. Gene expression profiles of chemokine and chemokine receptors were semiquantitatively examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Aqueous chemokine levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: PDTC significantly attenuated the clinical scores and monocyte/lymphocyte infiltration in rats with EAAU. PDTC effectively inhibited NF-kappaB activation in the iris and ciliary body, and markedly inhibited the expression of chemokine genes, including monocyte chemoattractant protein (MCP)-1, regulated-on-activation normal T-cell expressed and secreted (RANTES), and interleukin (IL)-8 and chemokine receptors genes including CCR2, CCR5, and CXCR3. CONCLUSIONS: Activation of NF-kappaB appears to play an important role in the pathogenesis of EAAU, through transcriptional control of MCP-1, RANTES, and IL-8 gene expression. Blocking NF-kappaB reduces ocular inflammation and may be an effective strategy in the treatment of acute anterior uveitis.

Expression of chemokine and receptors in Lewis rats with experimental autoimmune anterior uveitis.

The purpose of this study is to investigate the sequential expression of certain chemokines and chemokine receptors in the iris-ciliary body and popliteal lymph nodes of Lewis rats and, thus, to establish their roles in experimental autoimmune anterior uveitis. Uveitis was induced with the injection of melanin-associated antigen intraperitoneally and into the left foot. The clinical severity of the uveitis was scored. At defined time points, CC chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1, and regulated-upon-activation normal T-cell expressed and secreted), CXC chemokines (interferon gamma-inducible protein-10, stromal-derived factor-1, and interleukin-8), and receptor (CCR2, CCR3, CCR5, CXCR1, CXCR2, CXCR3, and CXCR4) mRNA expression were semiquantified by using a reverse-transcriptase reaction followed by polymerase chain reaction. The concentrations of macrophage inflammatory protein-1 and regulated-upon-activation normal T-cell expressed and secreted in aqueous humor were determined by means of enzyme-linked immunosorbent assay. Levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1 and interferon gamma-inducible protein-10 started increasing before the clinical onset of disease; these might have been involved in the initial recruitment of inflammatory cells. The level of regulated-upon-activation normal T-cell mRNA, however, started rising concurrently with the onset of clinical disease, suggesting that this chemokine may exert amplifying role in generating uveitis. Stromal-derived factor-1 exhibited an early and high level of expression with the increase of cognate receptor, CXCR4, indicating that stromal-derived factor-1 plays a role in either promoting angiogenesis or attracting for T-cells. Instead of upregulation like other chemokine receptors, interleukin-8 receptors, CXCR1and CXCR2, mRNA could not be detected in accord with the increase of interleukin-8. These findings appeared that downregulation of chemokine receptors on neutrophils may make themselves less respond to interleukin-8 and subsequently lead to decreased recruitment of neutrophils into the iris-ciliary body. In addition, the expression of chemokine receptors in popliteal lymph nodes were earlier than those in the iris-ciliary body. This sequence of expression may reflect the process of T lymphocytes maturation and differentiation. Monocyte chemoattractant protein-1 protein was immunohistologically detected in the ciliary epithelium and infiltrating leukocytes. The above results suggest that chemokines, which act on T cells and monocytes, are sequentially upregulated during the clinical course of experimental autoimmune anterior uveitis, and thus, may contribute to the pathogenesis of acute anterior uveitis.