Langerhans cells (LC) belong to the dendritic cell family and mediate Ag presentation in the cornea and ocular surface. Under normal physiological conditions, the central cornea is devoid of LC. ...Centripetal migration of LC plays a critical role in promoting immunoinflammatory responses in the eye including allograft rejection and herpetic keratitis. The molecular mechanisms responsible for ocular LC migration are poorly understood. To examine whether TNF-alpha mediates corneal LC migration and to establish the interaction of IL-1 and TNF-alpha in regulating LC migratory capacity, we utilized gene-targeted knockout mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor II (p75-/-), or both (p55-/-p75-/-). LC migration was induced by thermal cautery or cytokine injection and enumerated by an immunofluorescence assay. Migration of LC after cauterization and TNF-alpha injection was significantly depressed in both p55-/- and p75-/- mice. Similarly, in the first 72 h after intracorneal injection of IL-1alpha, LC migration was reduced in p55-/-, p75-/-, and p55-/-p75-/- mice. In contrast, injection of TNF-alpha in IL-1RI-/- mice led to normal migration of corneal LC indistinguishable from wild-type controls. These results suggest that the IL-1 induction of corneal LC migration is largely mediated by TNFR function, whereas TNF-alpha induction of LC migration is independent of IL-1RI activity. Moreover, the data suggest that both p55 and p75 signaling pathways are important in mediating LC migration in the cornea.
To characterize the chemokines and chemokine receptors that mediate the effect of proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, on the recruitment of MHC class ...II(+) Langerhans cells (LCs) in the corneal epithelium.
A standard model for corneal LC recruitment, application of cautery to the central corneal surface was used, and the differential gene expression levels of a panel of chemokines and chemokine receptors were determined by RNase protection assay. Chemokine receptor-knockout mice were used to evaluate the recruitment of MHC class II(+) LCs to the corneal epithelium. To determine the sensitivity of selected chemokines to IL-1 and TNF-alpha stimulation, the chemokine gene expression pattern was analyzed after blockade of IL-1 and TNF receptors.
CCR1, -2, and -5 were overexpressed in corneas after cauterization. Topical administration of soluble TNF receptor I and IL-1 receptor antagonist, which abrogated corneal LC recruitment, significantly suppressed the gene transcription levels of the ligands of CCR1 and/or -5, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. The recruitment of major histocompatibility complex (MHC) class II(+) LC was significantly suppressed in CCR5(-/-) mice and blockade of RANTES and MIP-1beta, but not in CCR1(-/-), CCR2(-/-)/MIP-1alpha(-/-), or MIP-1alpha(-/-) mice. The evaluation of epithelial CD11c(+) LC cells by confocal microscopy revealed coexpression for CCR5 primarily among B7(-) (CD80(-)/CD86(-)) subsets of these LCs but not among the mature B7(+) subsets of CD11c(+) LCs.
These data suggest that CCR5 plays a critical role in mediating recruitment and mobilization of MHC class II(+) LCs into the corneal epithelium. Targeting CCR5 and its ligands may be a new strategy for modulating immunity.
A 69 years old women underwent uneventful cataract surgery of her left eye with phacoemulsification and posterior chamber intraocular lens implantation in topical anesthesia. Patient was ...postoperatively treated with combination of antibiotic and steroid in decreasing dosages during five weeks: one drop five times a day the first week, three times a day second to forth week and one time a day the fifth week. In each checkup, performed first postoperative day, 7 days, 5 weeks and 12 weeks after the operation, visual acuity with and without correction, tonometry, corneal transparency, biomicroscopy of posterior pole and measure of macular thickness by optical coherence tomography (OCT) were performed. At first day follow-up visit, the patient's visual acuity was 20/25 but 6 weeks after the operation, the patient's vision had worsened to 20/60 after a slow steroid tapper. At that time OCT showed foveal thickening and cystic changes specific for cystoid macular edema (CME). Combination of corticosteroid and non-steroidal anti-inflammatory drug four times daily was included in therapy. The dose was tapered off over the ensuing 8 weeks. The total treatment duration was 12 weeks. At the patient's 2-month follow-up visit, vision has improved to 20/20 and the fovea appeared flat. OCT showed complete resolution of foveal thickening and cystic changes. Combination of corticosteroid and NSAID is effective and safe therapy for treating pseudophakic CME. Patient showed significant improvement in visual acuity and retinal thickness at 2 months post treatment.
This study reports early outcomes of a cohort of presbyopic patients treated with Intracor. The study took place from December 2010 to May 2011 and was conducted in University Eye Hospital ..."Svjetlost", Zagreb, Croatia. 95 eyes were enrolled in this prospective clinical trial (49 patients with non dominant eye and 23 with bilateral treatment). All patients gave informed consent prior to enrollment. Follow up consisted of uncorrected and corrected distant and near visual acuity, record of topographic changes, visual disturbances and patient satisfaction at 1 week, 1 and 3 months after the surgery. In this study Intracor procedure presented as both safe and effective with all eyes gaining several lines of uncorrected near visual acuity (UNVA), and achieving good uncorrected distant visual acuity(UDVA) as well. UDVA was affected by a mild myopic shift, which was effective in reducing mild preexisting hyperopia in some patients but led to a mild myopic outcome in previously emmetropic patients. Statistically significant improvement in UDVA and UNVA was observed in all time points. At 3 months of postoperative follow up all patients gained several lines of UNVA with monocular UNVA Jaeger system 1.67 +/- 0.28. UDVA showed slight improvement over time and initial myopic shift showed tendency of slight decrease with all patients achieving 1.0. Overall patients satisfaction was very high (98%) with only a few (3 patients, 5 eyes) reporting mild halo and glare at 3 months postop.Intracor procedure has proven its short-term safety and efficacy in treating presbyopia. However, longer follow up period is needed.
Bullous keratopathy (BK) is a chronic corneal edema with or without subepithelial bullae as a result of a loss of the endothelial cells. 15 patients with BK after cataract surgery with intraocular ...lens implantation, due to Fuchs dystrophy (n = 3) or corneal endothelial trauma (n = 12) were included in the study. All patients were treated by amniotic membrane transplantation (AMT). Corneal epithelial cells in patients suffering from BK secreted 3.91 +/- 3.09 pg/mL of IL-1 alpha, 4446 +/- 16.8 pg/mL of TNF and 81.43 +/- 37.81 pg/mL of VEGF-I. Levels of all 3 investigated cytokines were significantly higher as compared to controls (p < 0.005). Amniotic membranes that were used to treat investigated patients contained 638.98 +/- 613.98 pg/mL of IL-1ra, 0.026 +/- 0.009 pg/mL of sTNF and 81.39 +/- 21.01 pg/mL of VEGF-R. Beneficial clinical effect of the AMT in treating BK could be explained by its natural production of pro-inflammatory cytokine antagonists such as IL-ra, sTNF antagonist and VEGF-R.
Diabetic macular edema is the leading cause of moderate visual deterioration in patients with diabetic retinopathy. Ranibizumab) blocks vascular endothelial growth factor (VEGF) induced ...hyperpermeability of blood vessels. In this prospective case series we investigated the efficacy and safety of anti-VEGF treatment in reduction of central retinal thickness (CRT) and improvement in visual acuity (VA) in patients with diabetic macular edema (DME). 9 patients were followed up for 6 months and treated monthly with intravitreal ranibizumab. VA and CRT were measured at each visit. Treatment was discontinued as the peak improvement of either parameter was reached and reinstituted in case of deterioration/recurrence of edema. Study endpoints included: VA using ETDRS chart, CRT and number of injections at 6 months. Mean VA from all 9 patients increased by 0.3 lines of logMAR (p < 0.05 compared to baseline), and CRT decreased from 515 +/- 123 microm to 310 +/- 110 microm. The improvement of VA after ranibizumab injection was in correlation with a decrease in CRT. Mean of 4 injections were needed to control the disease during the follow-up period. Ranibizumab treatment was effective in VA and reducing CRT. Several injections were needed to control the disease. Regular OCT examinations and retreatment are advised in order to maintain initially reached VA.
Introduction: The first generations of multifocal intraocular lenses (MFIOLs) were designed to provide patients good distance and near vision, but intermediate was not satisfactory. Trifocal, a ...bifocal of low-add and quadrifocal MFIOLs were invented, offering possibility to correct vision for distance, near, and intermediate tasks. The novel IOL, extended range of vision (EROV), is covering mostly intermediate and distance vision, with lower level of photic phenomena.
Cataract surgery is the most common surgery in ophthalmology. The aim of cataract surgery is to restore vision in eyes in which the natural lens became opacified mostly due to the aging of the lens, ...or the presence of other ocular diseases, which promote earlier cataract formation. During cataract surgery, artificial intraocular lens (IOL) is implanted into the lens capsule and the value of the IOL is planned before surgery based on the preoperative IOL calculation. However, in the significant number of patients, cataract surgery may end up with a postoperative refractive error in which case patients have to wear glasses to reach the full vision for both distance and near correction (if monofocal IOL is used during cataract surgery!). Modern cataract surgery becomes more and more a refractive procedure as well, especially when multifocal and/or toric IOLs are implanted. However, in some specific cases where such IOLs are not applicable, high postoperative refractive error after cataract surgery can significantly influence the quality of the obtained vision. One such example is cataract surgery after penetrating keratoplasty. In this chapter, results of a novel approach of post-PK ametropia correction, namely implantation of sulcus placed AddOn IOLs (also called a piggyback lens) will be presented.
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