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), Sjogren 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.

The Effectiveness of Tranilast in the Prevention of Posterior Capsular Opacity

PURPOSE: To evaluate the inhibitory effect of tranilast on the formation of posterior capsular opacity (PCO) after a cataract operation ex vivo and in a rabbit model. METHODS: A human lens epithelial cell line (B3) was treated with 0.005-0.1 mM tranilast. Cytotoxicity assessment and effective dosage determination of tranilast were performed using MTT assays. B3 cell lines were cultured in Eagle's minimal essential medium (EMEM) containing 20% FBS with different concentrationsof tranilast, and morphological differences were observed. To investigate the effect of tranilast on cytokine production in B3 cell lines, cells were treated with 0.01 mM tranilast and expression profiles of cytokines were analyzed by RT-PCR. After performing phacoemulsification and intraocular lens implantation in 10 white rabbits, 0.5% tranilast eye drops were given 4 times per day, and the severity of PCO was evaluated bi-weekly using POCOman for 8 weeks after the operation. RESULTS: Cell death was observed in the 0.05 mM tranilast-treated B3 cell lines, and inhibition of epithelial-mesenchymal transition (EMT) was also observed in the 0.01 mM tranilast-treated B3 cell lines. TGF-beta1/2, IL-18, and CDK7 mRNA expression decreased in the 0.01 mM tranilast-treated B3 cell lines. Significant suppression of PCO formation was observed in rabbits treated with 0.5% tranilast eye drops 5 weeks post operative (p<0.05). CONCLUSIONS: The results from this study show that tranilast suppresses EMT through inhibition of TGF-beta, IL-18,and CDK7 expression. The results suggest that tranilast can be used toprevent PCO formation after cataract surgery.

The Effectiveness of Tranilast in the Prevention of Posterior Capsular Opacity

PURPOSE: To evaluate the inhibitory effect of tranilast on the formation of posterior capsular opacity (PCO) after a cataract operation ex vivo and in a rabbit model. METHODS: A human lens epithelial cell line (B3) was treated with 0.005-0.1 mM tranilast. Cytotoxicity assessment and effective dosage determination of tranilast were performed using MTT assays. B3 cell lines were cultured in Eagle's minimal essential medium (EMEM) containing 20% FBS with different concentrationsof tranilast, and morphological differences were observed. To investigate the effect of tranilast on cytokine production in B3 cell lines, cells were treated with 0.01 mM tranilast and expression profiles of cytokines were analyzed by RT-PCR. After performing phacoemulsification and intraocular lens implantation in 10 white rabbits, 0.5% tranilast eye drops were given 4 times per day, and the severity of PCO was evaluated bi-weekly using POCOman for 8 weeks after the operation. RESULTS: Cell death was observed in the 0.05 mM tranilast-treated B3 cell lines, and inhibition of epithelial-mesenchymal transition (EMT) was also observed in the 0.01 mM tranilast-treated B3 cell lines. TGF-beta1/2, IL-18, and CDK7 mRNA expression decreased in the 0.01 mM tranilast-treated B3 cell lines. Significant suppression of PCO formation was observed in rabbits treated with 0.5% tranilast eye drops 5 weeks post operative (p<0.05). CONCLUSIONS: The results from this study show that tranilast suppresses EMT through inhibition of TGF-beta, IL-18,and CDK7 expression. The results suggest that tranilast can be used toprevent PCO formation after cataract surgery.

Relationship Between the Ocular Surface Temperature and the Nasal Predominance in Pterygium

PURPOSE: To study the relationship between the distribution of the ocular surface temperature and the nasal predominance in pterygium. METHODS: In order to identify the distribution of the ocular surface, the surface temperature was measured at four points on the eyelids and on the bulbar conjunctiva with a non-contact thermometer. The ocular surface temperature in the pterygium patient group was compared with that in a normal control group. The temperature difference at each point on the ocular surface was also examined. RESULTS: In both of the patient and the normal groups, the surface temperature on the eyelid was at its lowest on the temporal lower eyelid, and highest on the nasal upper eyelid. On the bulbar conjunctiva, the surface temperature of the nasal conjunctiva was at its lowest, and at its highest on the upper conjunctiva. The most distinctive temperature difference between the patient and control groups was shown on the nasal and temporal bulbar conjunctivas, and statistically significant (p<0.05). CONCLUSIONS: Considering the temperature distribution over the ocular surface, we propose that an intrinsic factor that causes the nasal predominance of pterygium could be the comparatively low local temperature of the nasal bulbar conjunctiva.

Long-Term Results of Presbyopic Corneal Surface Ablation with Eximer Laser

PURPOSE: To evaluate the efficacy, safety, and subjective symptoms of patients who underwent presbyopic corneal surface ablation. METHODS: Excimer laser surgery with MEL80 for refractive errors and presbyopia was performed on 128 eyes of 67 patients. Uncorrected and best-corrected visual acuity, distance-corrected near-visual acuity, spectacle near-addition for Jaeger 1, depth of focus, spherical aberration, and subjective symptoms were evaluated before surgery and 1 year after surgery. RESULTS: This study consisted of a myopia group (56 eyes), an emmetropia group (spherical equivalent or =20/40) was found in 96 eyes (75%) and spectacle near addition for Jaeger 1 decreased. Our results showed a significant increase of spherical aberration (from -0.19 micrometer to 0.11 micrometer) and depth of focus (from 1.45D to 1.69D). A significant positive correlation was found between spherical aberration and uncorrected far and near visual acuity and depth of focus. Loss of two lines of best corrected visual acuity occurred in 11 eyes (8.5%) at far vision and in 7 eyes (5.5%) at near vision. In general, patient satisfaction was good. CONCLUSIONS: Presbyopic corneal ablation with MEL80 showed good distant and near visual results and a wide depth of focus induced by increased spherical aberration.

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)-gamma 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-gamma 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.

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

To determine if the residual corneal stromal bed of 250 micrometer 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 micrometer, were calculated using the published 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 micrometer 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 micrometer 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 micrometer stromal bed were 1.2-6.9%. Compared to the number of eyes with residual stromal thickness less than 250 micrometer, the incidence of keratectasia was relatively low. The residual stromal bed thickness of more than 250 micrometer may possibly be safe, but further observations for long period are necessary.

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(R)) was polymerized with polyethylene glycol (PEG-IOL). The human lens epithelial cells (1x10(4) 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(R). 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+/-1.1x10(3)) tended to be smaller than that of the acrylic controls (3.6+/-1.9x10(3)) 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.

Effect of Polyethylene Glycol Polymerization onto a Foldable Intraocular Lens in Pathogenesis of Posterior Capsular Opacity

PURPOSE: To investigate the effect of polyethylene glycol (PEG)-grafted acryl intraocular lenses on the prevention of posterior capsular opacification (PCO). METHODS: The acrylic surface of an intraocular lens (Acrysof SA 60AT, Alcon) was polymerized with PEG (PEG-IOL). To investigate the degree of cell adhesion to the modified lens surface, human lens epithelial cells (1x10(4) cells/ml) were inoculated on each PEG-grafted and acrylic control lens, and all were cultured in a carbon dioxide incubator for 24 hours. The adhered cells were trypsinized and counted. The PEG-IOL was implanted in 20 New Zealand rabbits after removal of the crystalline lens. The formations of PCO were checked serially through retroilluminated digital photography and severity scores were calculated using POCOman. The cell adherence pattern on the PEG-grafted IOL was examined by scanning electron microscopy. RESULTS: The mean number of adherent cells in PEG-IOL was 3.2+/-1.1x10(3), which tended to be smaller than that of the unmodified acrylic control (3.6+/-1.9x10(3)), but without statistical significance. The mean severity of posterior capsular opacification in PEG-IOL was much lower than in the control, especially at week 3. Scanning electron microscopy revealed more patch-like cells firmly attached to the lens surface in the control. CONCLUSIONS: PEG polymerization of the acrylic IOL may lessen the formation of posterior capsular opacification.

A Novel Application of Amniotic Membrane in Patients with Bullous Keratopathy

To evaluate the efficacy of amniotic membrane in the management of painful bullous keratopathy secondary to the intractable glaucoma and in preventing exposure of drainage devices, we inserted Ahmed valve with amniotic membrane patch graft over the implant itself, and debrided corneal epithelium with amniotic membrane graft over the exposed stroma as a single operation. During the follow-up periods, we monitored vision, intraocular pressure (IOP), presence of ocular pain, and postoperative complications associated with the implants. The mean follow up period was 8.4+/-3.2 months. IOP was well controlled after the intervention. The preoperative mean IOP was measured as 43.9+/-9.0 mmHg and lowered to 16.1+/-1.8 mmHg at the last visit and no complications associated with the implants were noted. Even though the improvement in vision was not prominent, the ocular surface stabilized rapidly and ocular pain associated with bullous keratopathy disappeared soon after surgery. Conclusively the use of amniotic membrane in conjunction with Ahmed valve implantation is an effective way to relieve ocular pain and lessen the chances of complications associated with the implant in patients with intractable glaucoma and bullous keratopathy.

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 againstthe- 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 Characteristics of Porcine Cornea as a Xenograft

PURPOSE: To investigate the feasibility, in terms of both physical and immunological aspects, of using porcine cornea as a xenograft in humans. METHODS: Corneal diameter, thickness and axial length were compared in 30 porcine and human control eyes. The histological characteristics and the distribution of the xenonatural antibody were also evaluated. In addition, changes in antigenecity were investigated by cultivating individual corneal cells. RESULTS: The mean values of the porcine corneal diameter (14.2+/-0.3 mm) and the thickness (867.2+/-23.8 mm) were larger than those of human, but, on the contrary, the axial length (20.2+/-0.74 mm) and the refractive power (40.4+/-0.9D) were not. The lymphocytes existed in the normal porcine limbus, and the distribution of alpha-gal was confined. However, in the cell culture, the expression of alpha-gal was prominent in both stromal (39.0+/-28.4%) and endothelial cells (87.1+/-4.4%) at the second passage. The expression of class II major histocompatibility antigen was comparable to that of human. CONCLUSIONS: Physical, optical, histological, and immunological characteristics suggest the possibility of using porcine cornea as a xenograft in humans.

A Report of Localized Corneal Amyloidosis Secondary to the Trichiasis

PURPOSE: To report our experience in the diagnosis and treatment of a localized corneal amyloidosis secondary to trichiasis. METHODS: Case 1. A 55-year-old woman visited our clinic due to discomfort of her right eye. Thirty years previously, she received a lower lid blepharoplasty due to lower lid entropion. Biomicroscopy revealed some trichiasis and a 3 mm, grayish-white nodule at the center of the cornea. Case 2. A 30-year-old woman visited our clinic due to chronic irritation of both eyes. Ten and 3 years previously, she received a lower lid blepharoplasty. Biomicroscopy revealed some trichiasis of the right lower lid and a grayish-white, patch-like lesion at the inferior cornea of both eyes. Lamellar keratectomy and amniotic membrane transplantation with careful electrolysis were performed. RESULTS: Hematoxylin and eosin stain revealed a pink, amorphous, hyaline material under the epithelium, and Congo-red stain showed birefringence of the whitish lesion. Electron microscopy revealed multidirectional, fibrillar arrangement. Secondary, localized amyloidosis of the cornea was diagnosed without any systemic involvement. No clues to the origin of the amyloid were found by immunohistochemical staining. By the sixth month after operation, the patients showed favorable vision and no evidence of recurrence. CONCLUSIONS: In the identification of a corneal mass, a secondary, localized amyloidosis should be considered, which can be managed successfully.

Peripheral Retinal Lesions Observed after Preoperative Evaluation for LASIK

PURPOSE: We estimated the incidence of retinal lesions at preoperative evaluation of retina for LASIK and investigate its clinical importance. METHODS: We estimated retrospectively the incidence of retinal lesions of the patients who visited our hospital with the purpose of correction of refractive error. The examination of retina upto periphery was done preoperatively. RESULTS: The mean spherical value and axial length were -6.5 +/- 3.4 diopters (range -26.0 ~ +17.0) and 25.4 +/- 2.0mm (range 15.7 ~ 34.5), respectively. The retinal lesions were found in 189 eyes of 139 persons (12.4%). Among them degenerative changes were found in 48 eyes of 34 persons, chorioretinal scars in 7 eyes of 7 persons, pigmented lesions in 28 eyes of 24 persons, and miscellaneous lesions in 106 eyes of 74 persons. There was a significant increase of spherical value and axial length in the group with retinal lesions -7.9 +/- 4.5 diopters (range -26.00 ~ -2.25), 26.5 +/- 2.3mm (range 23.1 ~ 34.5) compared to that without retinal lesions -6.1 +/- 3.4 diopters (range -25.00 ~ 17.00), 25.4 +/- 2.1mm (range 15.7 ~ 35.4). And the incidence of degenerative change and retinal tear was significantly increased in moderate myopes more than -4 diopters. CONCLUSIONS: LASIK is relatively a kind of safe refractive surgery, but to prevent the unexpected postoperative retinal complications, it is essential to thoroughly examine the retina upto periphery before surgery.

Clinical Analysis of 350 Low Vision Patients

The number of low vision patients and the demand for low vision rehabilitation are increasing as the life expectancy and visual impairment due to largely untreatable ocular conditions are.It is therefore, imperative to recognize the importance of low vision aids, which have recently been developed actively.To evaluate the efficacy of low vision aids for low vision rehabilitation, we reviewed the clinical records of 350 patients who had visited our low vision clinic more than twice and had been prescribed with low vision aids. According to the data analysed, optic nerve atrophy, macular degeneration and retinitis pigmentosa were the leading causes of visual impairment in those patients.The purposes to visit our low vision clinic were to read books, read letters on the black board, identify a person at a distance, etc.Hand-held magnifiers, aspheric doublet lens and telemicroscope with plus cap were commonly used for near vision, while Keplerian and Galilean telescope were popular aids for distant vision.Visual acuity after prescription was improved when it was compared with that before prescription.Majority of the patients benefited from attending low vision clinic.These results suggest that the optical low vision aids were required to rehabilitate the visually impaired patients.

A Case of Sarcoptes Scabiei Infestation of Eye Lid

The infestation caused by itch mite, Sarcoptes scabiei brings about very severe itching aggravated at night, and has a very high transmissibility. The lesions are commonly found on lower abdomen, thigh, axilla, interdigital area, buttocks, and genitalia. But it is rare to find the mite on eye lid. We have experienced a 33 year-old female patient who complained of persistent itching and foreign body sense in upper eyelid, and found a mite there. Then it was removed mechaincally, and the symptoms disappeared without any particular treatment. So we report a case of eye lid infestation by S.scabiei with the review of literatures.

The Study of Toxicity of Mitomycin C and Steroid as Eyedrops in Rabbit Cornea

To investigate the drug effect of topical Mitomycin C in various concentrations combined with steroid, we used 30 rabbits whose corneal epitheliums were abraded intentionally. They were divided into 5 groups. Using MMC in various concentrations and steroids, we instilled them into right eyes and saline into left eyes as control. We measured the healing rate at a interval of 12 hours. Three months later, we sacrificed one of them and examined the pathological changes from various ocular tissues. We found many complications such as corneal edema, ulcer, opacity and definite delay of wound healing when the concentration higher than 0.04%MMC was used. There were also decreased fibroblast cells in H-E staining. The steroids seemed not to pose any influence on the effect of MMC. In conclusion, we must take the great care in the use of MMC, and the concentration should be low when used. In addition, we still think there ought to be more studies as to the effect of steroids according to MMC levels.

The Study of Toxicity of Mitomycin C and Steroid as Eyedrops in Rabbit Cornea

To investigate the drug effect of topical Mitomycin C in various concentrations combined with steroid, we used 30 rabbits whose corneal epitheliums were abraded intentionally. They were divided into 5 groups. Using MMC in various concentrations and steroids, we instilled them into right eyes and saline into left eyes as control. We measured the healing rate at a interval of 12 hours. Three months later, we sacrificed one of them and examined the pathological changes from various ocular tissues. We found many complications such as corneal edema, ulcer, opacity and definite delay of wound healing when the concentration higher than 0.04%MMC was used. There were also decreased fibroblast cells in H-E staining. The steroids seemed not to pose any influence on the effect of MMC. In conclusion, we must take the great care in the use of MMC, and the concentration should be low when used. In addition, we still think there ought to be more studies as to the effect of steroids according to MMC levels.

The Effect of Intravitreal and Subconjunctival Ciprfloxacin in the Treatment of S.Aureus Endophthalmitis

To investigate the therapeutic effect of ciprofloxacin for the treatment of endophthalmitis, we used 18 rabbits with Staphylococcus aureus induce dendophthalmitis. The rabbits were assigned into three groups according to the treatment regimen; those who were not given any drug into group I, those who were given 100 microgram/ml ciprofloxacin intrvitreally into group II, and those who were given 2 mg/ml ciprofloxacin subconjunctivaly for 5 days into group III. We assessed clinical score, culture result of vitreous aspirate and pathologic finding of various ocular tissue. We found clinically significant decrease in clinical score in group II, but there were no significant differences in the vitreous culture and in the histologic findings among the study groups. In conclusion, we assume that intravitreal injection of ciprofloxacin may be the better treatment modality to treat endophthalmitis by S.aureus. In addition we still think there ought to be more studies as to the determination the dosage of ciprofloxacin and the use of steroid in combination.