Hyeon Il Lee

Interleukin-17 in Various Ocular Surface Inflammatory Diseases

Recently, the association of Th-17 cells or IL-17 with ocular inflammatory diseases such as uveitis, scleritis and dry eye syndrome was discovered. We assessed whether interleukin (IL)-17 was present in the tears of various ocular surface inflammatory diseases and the tear IL-17 concentrations were clinically correlated with various ocular surface inflammatory diseases. We measured concentrations of IL-17 in tears of normal subjects (n = 28) and patients (n = 141) with meibomian gland dysfunction (MGD), dry eye syndrome (DES), Sjögren syndrome (SS), Stevens-Johnson syndrome (SJS), graft-versus-host disease (GVHD), filamentary keratitis, and autoimmune keratitis associated with rheumatoid arthritis or systemic lupus erythematosus. Clinical epitheliopathy scores were based on the surface area of corneal and conjunctival fluorescein staining. The mean concentrations of IL-17 in tears of patients with filamentary keratitis, GVHD, autoimmune keratitis, SS, DES, MGD, SJS were significantly higher in order than that in normal subjects. Tear IL-17 concentration was significantly correlated with clinical epitheilopathy scores in the patients with systemic inflammatory disease, while tear IL-17 was not correlated with clinical severity of the cornea and conjunctiva in the dry eye patients without any systemic inflammatory disease. Tear IL-17 is likely to correlate clinically with corneal disease severity only in the patients with systemic inflammatory disease.

Iris and trabecular meshwork pigment changes after posterior chamber phakic intraocular lens implantation

PURPOSE: To evaluate the changes in laser iridotomies, intraocular pressure (IOP), angle structures, and pupil diameter after implantable contact lens (ICL) (Version 4 Staar Surgical) implantation in myopic Asian eyes. SETTING: Department of Ophthalmology, Chung‐Ang University Yongsan Hospital, Seoul, Korea. METHODS: The ICL was implanted in 81 eyes of 43 patients with spherical equivalent greater than −6.00 diopters. Gonioscopy examination was performed 1 day after laser iridotomy and 6 and 12 months after ICL implantation. The changes in laser iridotomy sites, IOP, and pupil diameter were also evaluated. RESULTS: Ten eyes (12.3%) had occlusion or narrowing of the laser iridotomy sites. The angle width was more than 30 degrees in all cases preoperatively but narrowed to less than 20 degrees in 16 eyes (19.8%) 6 months postoperatively. The mean pigment, measured by the semiquantitative method (grade 0 to 4), was 2.03 in the inferior angle, 0.18 in the nasal angle, 0.12 in the temporal angle, and 0.00 in the superior angle 12 months postoperatively. The pigment in all quadrants increased temporally as a result of the laser iridotomy or iris rubbing by the ICL; however, the pigments absorbed gradually and decreased to values before laser iridotomy 12 months postoperatively. There was a temporary increase in IOP from the instillation of steroid eyedrops 1 week and 1 month postoperatively; IOP returned to the preoperative level and remained there 12 months postoperatively. There was a significant decrease in pupil diameter 1 and 3 months postoperatively; the diameter returned to the preoperative size at 6 and 12 months. Pigment dispersion syndrome and pigmentary glaucoma were not seen. CONCLUSION: Implantation of the ICL narrowed the angle width but did not increase trabecular pigmentation compared with values after laser iridotomy, indicating ICL implantation is safe regardless of the pigmentary changes in the trabecular meshwork.

The Safety of 250 µm Residual Stromal Bed in Preventing Keratectasia after Laser in situ Keratomileusis (LASIK)

To determine if the residual corneal stromal bed of 250 µm is enough to prevent iatrogenic keratectasia in laser in situ keratomileusis (LASIK), we studied 958 patients who underwent LASIK from April 2000 to October 2003 retrospectively. The estimated probabilities of the residual stromal bed, that was less than 250 µm, were calculated using the publi- shed flap thickness data of Moria C&B microkeratome. Then we calculated the ratio of the real incidence of keratectasia to the expected the percentage of the patients with less than 250 µm residual stromal bed in our study. Using the LASIK flap thickness data of Miranda, Kezirian and Nagy, the expected probabilities that the residual stroma would be less than 250 µm were 8.8%, 4.3% and 1.5% of the 1,916 eyes respectively, while keratectasia developed in both eyes (0.1%) of 1 patient in our study. The estimated ratio of the keratectatic eyes to eyes with less than 250 µm stromal bed were 1.2-6.9%. Compared to the number of eyes with residual stromal thickness less than 250 m, the incidence of keratectasia was relatively low. The residual stromal bed thickness of more than 250 µm may possibly be safe, but further observations for long period are necessary.

The Changes in Corneal Astigmatism after Botulinum Toxin-A Injection in Patients with Blepharospasm

To determine if the involuntary contractions of eyelids may have any effects on the development of corneal astigmatism, we performed this prospective study which includes 19 patients with either essential blepharospasm or hemifacial spasm. In hemifacial spasm, the degree of corneal astigmatism was evaluated between two eyes. Then the topographic changes were checked using vector analysis technique before and after passively opening the eyelids. They were also measured before and at 1 and 6 months after the injection of Botulinum toxin. Resultantly, 20 eyes had the with-the-rule (group1) and 9 eyes against-the-rule (group2) astigmatism. In hemifacial spasm, significantly more astigmatism was found at spastic eyes. The corneal topographic changes after passively opening the eyelids showed 10 eyes with the astigmatic shift to the with-the-rule, while the remaining 19 to the against-the-rule. At 1 month after injection of Botulinum toxin, group 1 showed reduced average corneal astigmatism, whereas group 2 showed increased astigmatism. The astigmatic change vector showed significantly more against-the-rule. In the contrary, 6 months after treatment, corneal astigmatism again increased in group 1 and decreased in group 2. So they took on the appearance of pretreatment astigmatic status eventually. Conclusively eyelids may play an important role in corneal curvature.

The Efficacy of an Acrylic Intraocular Lens Surface Modified with Polyethylene Glycol in Posterior Capsular Opacification

To investigate if the surface modification of intraocular lens (IOL) is efficient in the prevention of posterior capsular opacification (PCO), the acrylic surface of intraocular lens (Acrysof®) was polymerized with polyethylene glycol (PEG-IOL). The human lens epithelial cells (1×104 cells/mL) were inoculated on PEG grafted or unmodified acrylic lenses for the control. The adherent cells on each IOL surface were trypsinized and counted. The every PEG-IOL was implanted in 20 New Zealand rabbits after removal of crystalline lens. The formations of PCO were checked serially through retroilluminated digital photography, and the severity scores were calculated using POCOman®. The cell adherence patterns on each IOL were examined by scanning electron microscopy. As a result, the mean number of adherent cells of PEG-IOL (3.2±1.1×103) tended to be smaller than that of the acrylic controls (3.6±1.9×103) without a statistical significance (p=0.73). However, the mean severity of PCO formation in PEG-IOL was significantly lower than that in the control during the third to sixth weeks after surgery. Scanning electron microscopy revealed that the more patch-like cells were found firmly attached to the IOL surface in control than in the PEG-IOL. Conclusively, PEG polymerization to the acrylic IOL would possibly lessen the formation of PCO after cataract removal.

The Role of Cyclosporine and Mycophenolate in an Orthotopic Porcine-to-Rat Corneal Xenotransplantation

We performed this study to investigate the feature of rejection in porcine-to-rat corneal orthotopic transplantation and to evaluate the effect of cyclosporine and mycophenolate on the xeno-rejection. Orthotopic corneal transplantation was done at 91 Sprague-Dawley rats, and they were divided into 10 groups based on the combination of immunosuppressants including dexamethasone, cyclosporine, and mycophenolate mofetil. Graft survival was analyzed and grafted eyes were examined with Hematoxylin & Eosin and CD4 or CD8 staining. Enzyme-linked immunosorbent assays were done for interleukin-2 (IL-2), IL-4, IL-5, IL-10, and interferon (IFN)-γ in cornea, lacrimal gland, and cervical lymph nodes. The longest median survival of the immune suppressant group was 11.00±1.96 days, which showed no statistical differences compared with that of control (8.00±1.52 days). The neutrophils were prominent in the early phase but soon gave way to the monocytes. The number of CD8+ cells was higher than that of CD4+ cells. IL-2 and IFN-γ markedly increased at 10 to13 days in cornea, lacrimal glands, and cervical lymph nodes, which showed a decrease with immunosuppressants except in the cornea. In conclusion, cyclosporine and mycophenolate could not prevent the rejection in porcine to rat orthotopic corneal xenograft associated with infiltraton of CD8+ and innate immune cells.

Antigenicity of Porcine Cornea in Xenocorneal Transplantation

Purpose: To investigate antigenicity and immunological rejection in porcine-to-murine xenotransplantation as indicator of biofeasibility of the porcine xenograft for human substitute. Materials and Methods: The α-Gal epitope in corneal tissue and cultured porcine cells was stained with Griffonia simplicifolia I isolectin B4. Porcine corneas was orthotopically transplanted to rats. Graft survival, hematoxylin and eosin, CD4 or CD8 staining, and enzyme-linked immunosorbent assays for interleukins and interferon-γ were evaluated. Cultured porcine keratocytes and endothelial cells were mixed with human sera or peripheral blood mononuclear cells for 72 hours. The amount of complement deposited in cells and the number of 51-chromium-releasing cells were assessed. Gene expression was comparatively analyzed using Platinum pig 13K oligo chip in cultured porcine keratocytes and porcine endothelial cells. Results: The distribution of α-Gal epitope was localized to the anterior stromal keratocytes. However, α-Gal was highly expressed in keratocytes and endothelial cells after cultivation. Median survival of porcine grafts was 8 days. Neutrophils and monocytes were prominent in stroma. The number of CD8+ cells was higher than that of CD4+ cells. Interleukin-2 and interferon-γ markedly increased in cornea, lacrimal glands, and cervical lymph nodes after 10 days. Complement deposition and the number of 51-chromium-releasing cells were significantly higher in keratocytes than in endothelial cells. TNFAIP6, CXCL14, and CXCL6 genes were highly expressed in keratocytes compared with in endothelial cells. Conclusion: Porcine-to-rat orthotopic corneal xenograft showed CD8+ cell- and innate immune cell-related stromal rejection, suggesting high cytotoxicity of porcine keratocytes.