Yi-Chen Sun

Conjunctival Resection Combined With Tenon Layer Excision and the Involvement of Mast Cells in Superior Limbic Keratoconjunctivitis

PURPOSE To evaluate the effectiveness of conjunctival resection combined with Tenon layer excision in treating superior limbic keratoconjunctivitis (SLK) and the involvement of mast cells in SLK. DESIGN Retrospective, interventional case series. METHODS Forty eyes of 30 SLK patients who were unresponsive to medical treatment received superior bulbar conjunctival resection, and another 20 patients who underwent cataract and retinal surgery served as a control group. The conjunctiva specimens from study and control patients were examined by hematoxylin and eosin staining and immunohistochemistry using antibodies against mast cell tryptase. RESULTS In all operated eyes, the clinical symptoms and signs, including irritation and redness and superior bulbar conjunctival hyperemia and superior tarsal conjunctival papillary hypertrophy, subsided significantly three months after the operation. Only three eyes had recurrence from the margin of conjunctival resection, and this was relieved after reoperation. Keratinized conjunctival epithelium, loss of goblet cells, and increased mast cell numbers (P<.05) were found in the SLK group. CONCLUSIONS Our cases demonstrate that superior bulbar conjunctival resection combined with Tenon layer excision is an effective treatment for SLK. The pathologic findings suggest that mast cells may play a role in the pathogenesis of SLK.

Comparison of corneal epitheliotrophic capacity among different human blood-derived preparations.

Purpose: To compare the corneal epitheliotrophic capacity of different human blood-derived preparations, including cord blood serum (CBS), peripheral blood serum (PBS), and fresh frozen plasma (FFP) on bovine corneal epithelial cells. Materials and Methods: The concentrations of epithelial growth factor, transforming growth factor β1, insulin-like growth factor 1, hyaluronic acid, fibronectin, albumin, glucose, and calcium in different human blood derivatives were evaluated using enzyme-linked immunosorbent assay or biochemical methods. Cultivated bovine corneal epithelial cells were incubated with various blood derivatives, and cell proliferation, migration, and differentiation were evaluated by colorimetric assay, Boyden chamber chemotaxis assay, wounding assay, scanning electron microscopy, and transepithelial electric resistance measurements. Wound closure was assessed using a scratch-induced directional wounding assay. Results: Of the 3 human blood derivatives evaluated, CBS had the highest concentrations of epithelial growth factor, transforming growth factor β1, and hyaluronic acid (P < 0.05). FFP had the lowest concentration of calcium and the highest concentration of glucose (P < 0.05). CBS demonstrated the highest ability to promote cellular proliferation, followed by PBS and FFP (P < 0.05). CBS was also the best in promoting cellular differentiation because scanning electron microscopy demonstrated coherent monolayers of flattened and polygonal-shaped cells with evenly distributed microvilli. Transepithelial electric resistance was noted to be the highest for cells incubated in CBS, indicating formation of well-differentiated cells with functional tight junction (P < 0.05). Cells cultivated with FFP were the least capable of promoting proliferation, migration, and differentiation. Conclusions: Different human blood derivatives may have different concentrations of epitheliotrophic factors. CBS is generally superior to PBS in promoting corneal epithelial proliferation and differentiation.

Interleukin‐1β is increased in the cerebrospinal fluid of patients with small infarcts

Background and purpose:  Interleukin‐1beta (IL‐1β) and interleukin‐6 (IL‐6) are involved in inflammatory responses during large vessel occlusion in animal models. The aim of this study was to investigate the intrathecal levels of cytokines in patients with acute small infarcts.

Overexpression of matrix metalloproteinase-1 (MMP-1) and MMP-3 in superior limbic keratoconjunctivitis.

PURPOSE To explore the presentations of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in superior limbic keratoconjunctivitis (SLK) with typical redundant superior conjunctiva. METHODS Eight surgical specimens from medically refractory SLK patients were examined. Another nine conjunctival specimens from patients who underwent cataract and retinal surgery served as controls. Expression of RNA and proteins of MMPs and TIMPs in conjunctival specimens and cultured conjunctival fibroblasts were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). RESULTS The expression of mRNA of MMP-1 and -3 was detected in six and seven SLK patients, respectively, but was not detected in any case in the control group. IHC showed more prominent immunostaining of MMP-1 and -3 in the subepithelial stroma of the SLK patients than in the controls. After culturing, conjunctival fibroblasts of the SLK patients also shown apparent overexpression of MMP-1 and -3 compared with that in the controls. MMP-9 was not detected in both groups. MMP-2 and TIMP-1 and -2 were detected in some cases in both groups without a statistically significant difference between groups. CONCLUSIONS Overexpression of MMP-1 and -3 was found in surgical specimens and cultured conjunctival fibroblasts from SLK patients. MMP imbalance may contribute to SLK pathogenesis. (ClinicalTrials.gov number, NCT00167050.).

Therapeutic Keratectomy for Mycobacterium abscessus Keratitis after LASIK

We report successful treatment of a case of Mycobacterium abscessus keratitis after laser in situ keratomileusis (LASIK) with therapeutic lamellar keratectomy. A 34-year-old woman developed a 2 x 2 mm feathery infiltration within the interface inferior to the pupil margin with mild inflammation of the conjunctiva in her left eye 40 days after LASIK surgery. Bacterial culture from the infiltrates of the interface of the stromal bed revealed Mycobacterium abscessus. After combination antibiotic therapy including amikacin and ciprofoxacin was given for 6 weeks, infiltration persisted despite the development of necrosis in the flap tissue. Therapeutic lamellar keratectomy combined with flap removal was performed. No recurrence was found 1 year after the surgery. Therapeutic lamellar keratectomy with flap removal can provide an effective treatment modality for the management of post-LASIK Mycobacterium abscessus keratitis that is unresponsive to medical treatment.

The Relationship Between Anterior Corneal Aberrations and Contrast Sensitivity in Conventional LASIK

Purpose: To evaluate the changes of anterior corneal aberrations before and after laser in situ keratomileusis (LASIK) and to assess the correlation between contrast sensitivity and anterior corneal aberrations. Methods: Right eyes of 51 patients including 6 males and 45 females undergoing conventional LASIK from September 2000 to July 2003 were enrolled. The calculation of anterior corneal aberrations before and after LASIK was obtained by analyzing the corneal topography from TMS-1 by using VOL-CT Version 6.23 software. Contrast sensitivity was measured after LASIK with an MCT 8000 under daytime and nighttime settings and with glare conditions. The differences of the Zernike coefficients and root mean square (RMS) of anterior corneal aberrations before and after LASIK were analyzed. The changes of contrast sensitivity at 1.5, 3, 6, 12, and 18 cpd were added separately for daytime and nighttime contrast sensitivity with and without glare after LASIK and were correlated with the changes of anterior corneal aberrations. Results: Vertical coma, RMS of coma-like RMS of spherical-like, RMS of trefoil-like and RMS of higher-order anterior corneal aberrations increased significantly after LASIK surgery. There were no significant correlations between the changes of anterior corneal aberrations and the changes of contrast sensitivity at daytime and nighttime, with and without glare. Contrast sensitivity at daytime and nighttime decreased at each spatial frequency after LASIK. Conclusions: LASIK surgery induces changes of the anterior corneal aberrations. However, changes in anterior corneal aberrations did not correlate with the changes of contrast sensitivity at daytime and nighttime, with and without glare.

Comparison of corneal epitheliotrophic capacities among human platelet lysates and other blood derivatives.

Purpose To evaluate the corneal epitheliotropic abilities of two commercialized human platelet lysates (HPLs) and to compare the results with other blood derivatives, including human peripheral serum (HPS) and bovine fetal serum (FBS). Methods In vitro, human corneal epithelial cells were incubated in various concentrations (0%, 3%, 5% and 10%) of blood derivatives. Two commercialized HPLs, including UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were tested and compared with HPS and FBS. Scratch-induced directional wounding assay was performed to evaluate cellular migration. MTS assay was used to evaluate cellular proliferation. Cellular differentiation was examined by scanning electron microscopy, inverted microscopy and transepithelial electrical resistance. Sprague-Dawley rats were used to evaluate the effects of the blood derivatives on corneal epithelial wound healing in vivo. Different blood derivatives were applied topically every 2 hours for 2 days after corneal epithelial debridement. The concentrations of epidermal growth factor (EGF), transforming growth factor -β1 (TGF-β1), fibronectin, platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, and hyaluronic acid in different blood derivatives were evaluated by enzyme-linked immunosorbent assay (ELISA). Results In vitro experiments demonstrated statistically comparable epitheliotropic characteristics in cellular proliferation, migration, and differentiation for the two commercialized HPLs compared to FBS and HPS. Cells cultured without any serum were used as control group. The epitheliotropic capacities were statistically higher in the two commercialized HPLs compared to the control group (p<0.05). Among the different concentrations of blood derivatives, the preparations with 3% yielded better outcomes compared to 5% and 10%. In rats, HPLs also caused improved but not statistically significant wound healing compared to HPS. All the blood derivatives had better wound healing ratios than the control group (p<0.05). In the quantification of epitheliotropic factors, UltraGRO and PLTMax had significantly higher levels of EGF, TGF- β1, fibronectin than human peripheral serum (p<0.05). Conclusions Both commercialized HPLs showed comparable corneal epitheliotropic abilities and wound healing rates compared to HPS and FBS in the in vivo and in vitro studies. Our results suggest that HPLs may have the potential to replace HPS in the treatment of corneal epithelial problems.

Stem Cell Factor and Thymic Stromal Lymphopoietin Overexpression With Correlation to Mast Cells in Superior Limbic Keratoconjunctivitis.

Purpose: To investigate the differential expression of stem cell factor (SCF) and thymic stromal lymphopoietin (TSLP) and their correlation to mast cells, between patients diagnosed with superior limbic keratoconjunctivitis (SLK) and normal subjects. Methods: A laboratory investigation included 22 surgical specimens of the superior bulbar conjunctiva from 17 patients with medically refractory SLK and 5 control subjects who underwent cataract or retinal surgery. Protein expression of tryptase, SCF, and TSLP in conjunctival specimens was detected by immunohistochemistry. The number of mast cells was correlated with immunohistochemistry intensity of SCF and TSLP. Results: In patients with SLK, higher immunostaining intensity of SCF and TSLP was found in the conjunctival epithelium than that in the conjunctival subepithelial stroma. SCF and TSLP staining in the conjunctival epithelium was significantly more intense in patients with SLK than in normal subjects. In addition, there was a significant correlation between the number of tryptase (+) mast cells in conjunctival subepithelial stroma and TSLP immunointensity in the conjunctival epithelium and subepithelial stroma. Conclusions: Overexpression of SCF and TSLP was found in the conjunctival epithelium of patients with SLK. Significant correlation between TSLP grading and the number of mast cells was also found. SCF and TSLP may be involved in promoting mast cell migration and activation contributing to the pathogenesis of SLK.

Bilateral Mycobacterium chelonae Keratitis After Laser in Situ Keratomileusis

Lactococcus lactis cremoris is one of the lactic acid bacteria. It is associated with dairy food products. L. lactis cremoris is classified as nonpathogenic and possibly even beneficial to health. In recent years, however, its pathogenic potential is increasingly being understood. Human infections due to L. lactis cremoris (Streptococcus lactis), include septicaemia, cerebellar abscess, and periodontitis. Eikenella corrodens is part of the normal flora in the human oral cavity. It is increasingly being recognised as a human pathogen. It has been reported in canaliculitis, dacryocystitis and even endophthalmitis. For an opportunistic infection to occur with these commensals, first, there should be a substantial increase in the number of the opportunistic bacteria. Second, the host defence should be depressed. Both factors could have been responsible for the canaliculitis in our patient: First, our patient had periodontal disease, which might have resulted in an overgrowth of the two organisms in the oropharyngeal area. Second, an immunocompromised state related to her diabetes mellitus might have precipitated an opportunistic infection by both L. lactis cremoris and E. corrodens. In any chronic canaliculitis not responsive to conventional treatment, and especially in an immunocompromised individual, we should have a high index of suspicion for unusual organisms, or even a mixed infection, as in our case. With prompt and appropriate antibiotics, the clinical outcome appeared favourable. As far as we are aware, this is the first reported human ocular infection by L. lactis cremoris. This organism should be added to the list of etiological agents causing canaliculitis.

Anterior segment optical coherence tomography evaluation of ocular graft-versus-host disease: a case study

To explore ocular graft-versus-host disease (GVHD), anterior segment optical coherence tomography (AS-OCT) imaging of eyelids, tear meniscus, cornea and conjunctiva is performed in subsequent sessions on a patient who has ocular GVHD after allogeneic related donor stem cell transplant. The OCT results are presented together with those from a normal subject. OCT imaging is promising in visualizing several ocular GVHD manifestations, such as abnormal meibomian gland orifice (MGO), conjunctival keratinization, conjunctival hyperemia and chemosis, corneal epithelium opacification, thinning and sloughing. This case study demonstrates the capability of AS-OCT in the imaging and monitoring of ocular GVHD, which may be useful in the development of current ocular GVHD staging system and the clinical management for GVHD treatment.