We conducted a study to determine if preserved human amniotic membrane can reduce corneal haze induced by excimer laser photoablation. Excimer photoablation was performed bilaterally on 40 New Zealand white rabbits with a 6 mm ablation zone and 120 micrometer depth (PTK) using the VISX Star. One eye was randomly covered with a preserved human amniotic membrane and secured using four interrupted 10 - 0 nylon sutures; the other eye served as control. The amniotic membranes were removed at one week, and the corneal haze was graded with a slit-lamp biomicroscopy by three masked corneal specialists (WC, KH and RF) biweekly for the ensuing 12 weeks. Histology and in situ TUNEL staining (for fragmented DNA as an index for apoptosis) was performed at days 1, 3 and 7 and at 12 weeks. One week after excimer photoablation, the amniotic membrane-covered corneas showed more anterior stromal edema, which resolved at the second week. A consistent grading of organized reticular corneal haze was noted among the three masked observers. Such corneal haze peaked at the seventh week in both groups. The amniotic membrane-covered group showed statistically significant less corneal haze (0.50 plus or minus 0.15) than the control groups (1.25 plus or minus 0.35) (p less than 0.001). The amniotic membrane-covered corneas had less inflammatory response at days 1 and 3, showing nearly nil DNA fragmentation on keratocytes on the ablated anterior stromal and less stromal fibroblast activation. There is less altered epithelial cell morphology and less epithelial hyperplasia at 1 week in these amniotic membrane-treated eyes. We concluded from this study that amniotic membrane matrix is effective in reducing corneal haze induced by excimer photoablation in rabbits and may have clinical applications.
Abstract TUP1 encodes a transcriptional repressor that negatively controls filamentous growth in Candida albicans. Using subtractive hybridization, we identified six genes, termed repressed by TUP1 (RBT), whose expression is regulated by TUP1. One of the genes (HWP1) has previously been characterized, and a seventh TUP1-repressed gene (WAP1) was recovered due to its high similarity to RBT5. These genes all encode secreted or cell surface proteins, and four out of the seven (HWP1, RBT1, RBT5, and WAP1) encode putatively GPI-modified cell wall proteins. The remaining three, RBT2, RBT4, and RBT7, encode, respectively, an apparent ferric reductase, a plant pathogenesis-related protein (PR-1), and a putative secreted RNase T2. The expression of RBT1, RBT4, RBT5, HWP1, and WAP1 was induced in wild-type cells during the switch from the yeast form to filamentous growth, indicating the importance of TUP1 in regulating this process and implicating the RBTs in hyphal-specific functions. We produced knockout strains in C. albicans for RBT1, RBT2, RBT4, RBT5, and WAP1 and detected no phenotypes on several laboratory media. However, two animal models for C. albicans infection, a rabbit cornea model and a mouse systemic infection model, revealed that rbt1Δ and rbt4Δ strains had significantly reduced virulence. TUP1 appears, therefore, to regulate many genes in C. albicans, a significant fraction of which are induced during filamentous growth, and some of which participate in pathogenesis.
Purpose: To determine the roles of transforming growth factor-ß 1 (TGF-ß 1 ), epidermal growth factor (EGF), and cell density on the regulation of the TGFBI gene transcript in a human corneal epithelial cell line (HCE-T). Methods: HCE-T cells (40–50% confluent), which possess the biochemical and morphological phenotype of human corneal epithelial cells, were treated with either TGF-ß 1 (20 ng/ml) or EGF (20 ng/ml) for 0, 24, 48, and 72 h. Total RNA was isolated at each time point from the treated cells and the placebo-treated controls. The TGFBI mRNA transcript level was quantitated using Northern blot analysis. Results: TGF-ß 1 upregulates TGFBI gene transcript in this human corneal epithelial cell line, reaching a peak of 2.5-fold of upregulation at 48 h after TGF-ß 1 treatment and a 1.5-fold at 72 h. In contrast, EGF treatment showed no effect on the TGFBI mRNA level. In addition, the TGFBI gene transcript appears to be cell density-dependent because the transcript level shows a trend of reduction as the cell density increases from 40–50% to full confluency. Conclusion: The TGFBI gene transcript in this human corneal epithelial cell line is upregulated by growth factor TGF-ß 1 , but is not affected by growth factor EGF. Furthermore, cell density appears to be an important regulatory mechanism in controlling the level of TGFBI gene expression in corneal epithelial cells.
To investigate the molecular pathology underlying BIGH3-related corneal dystrophies (CDs) and to further delineate genotype-phenotype specificity.Sixty-one index patients with CDs were subjected to phenotypic and genotypic characterization. The corneal phenotypes of all patients were assessed by biomicroscopy and documented by slit lamp photography. The BIGH3 gene was amplified exon by exon from constitutional DNA to perform single-strand conformation polymorphism (SSCP) analysis, followed by direct bidirectional sequencing of abnormal conformers.The phenotypes of CDs were classified as lattice CD in 30 patients, Groenouw type I in 12 (CDGGI), Avellino in 7 (CDA), Reis-Bückler in 8 (CDRB), and Thiel-Behnke in 4 (CDTB). Fifty occurrences of 16 distinct mutations were identified, including 8 novel mutations responsible for lattice type IIIA in three patients (CDLIIA), intermediate type I/IIIA (CDLI/IIIA) in four patients, and atypical CDL with deep deposits in one patient (CDL-deep).Disease-causing mutations were identified in 80% of the patients (50/61). All mutations localize in two regions of kerato-epithelin: the amino acid R124 and BIGH3 fasc domain 4. This study also confirms the mutation hot spot at positions R124 and R555 with nearly 50% of the mutations targeting these two amino acids (24/50). In addition the corneal phenotypes induced by changes at R124 and R555 are amino acid specific: R124C in CDLI, R555W and R124S in CDGGI, R124H in CDA, R124L in CRRB, and R555Q in CDTB. In CDLIIIA, CDLI/IIIA, and CDL-deep the genotype-phenotype correlation is domain specific, with all changes occurring at the boundary or within the fasc4 domain.
PURPOSE: To compare the efficacy of conventional laser in situ keratomileusis (LASIK) in treating corneal astigmatism and in treating noncorneal ocular residual astigmatism. SETTING: Private practice, Nashville, Tennessee, USA. DESIGN: Retrospective case series. METHODS: The records of dominant eyes of consecutive patients who had LASIK were retrospectively analyzed to compare the efficacy of LASIK in eyes with predominantly anterior corneal astigmatism with the efficacy in eyes with predominantly ocular residual astigmatism (ORA). The ORA was determined by vector analysis using refractive cylinder and topographic astigmatism. Preoperatively, the ratio of ORA to preoperative refractive cylinder (R) was used to divide the patients into 2 groups; that is, eyes with predominantly anterior corneal astigmatism (ORA/R ratio <1.0) and eyes with predominantly ORA (ORA/R ratio ≥1.0). Efficacy was determined by examining the magnitude of the remaining uncorrected astigmatism and comparing the index of success (proportion of preoperative refractive astigmatism that remained uncorrected by LASIK) between the 2 groups. RESULTS: The study evaluated 61 eyes of 61 patients. Conventional LASIK was twice as efficacious in the low-ORA group as in the high-ORA group. The index of success was 0.24 and 0.50, respectively, and the difference between groups was statistically significant (P = .036). CONCLUSION: The efficacy of astigmatic correction by LASIK was significantly higher in eyes in which the preoperative refractive astigmatism was located mainly on the anterior corneal surface than in eyes in which it was mainly located posterior to the anterior corneal surface. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.
Background. An 85-year-old man developed faint crystallike white precipitates in the mid peripheral stroma of his left cornea 3 weeks after undergoing penetrating keratoplasty. The patient had been initially treated with 1% prednisolone acetate ophthalmic suspension and 0.3% gatifloxacin eyedrops to his left eye from the first day postoperatively. Three weeks later, the precipitates were more numerous, larger, and diffuse in distribution. Gatifloxacin was discontinued and substituted with a neomycin–polymixin B–dexamethasone ophthalmic ointment. Methods. A detailed history, physical examination, laboratory workup, and tandem scanning confocal microscopy were performed. Results. Tandem scanning corneal confocal microscopy confirmed the presence of crystals in the cornea. Conclusions. Gatifloxacin, a fourth-generation fluoroquinolone, can cause intrastromal macroscopic crystalline deposits through a compromised corneal epithelium, similar to what has been described for ciprofloxacin, a second-generation fluoroquinolone.
Since the advent of keratorefractive surgery and its rising popularity, irregular astigmatism has become an increasingly important issue for ophthalmologists and optometrists. Despite the success of LASIK and PRK, there are more and more patients experiencing visual quality problems due to the non-physiological modification of the corneal structure. Among these complications, irregular astigmatism is perhaps the most difficult to treat.The first of its kind, Irregular Astigmatism: Diagnosis and Treatment synthesizes our knowledge and understanding of irregular astigmatism and addresses state-of-the-art technology in management and treatment. Dr. Ming Wang, assisted by Dr. Tracy Swartz, has led a team of internationally known experts in the field to produce this innovative, comprehensive, and logically presented text, which includes more than 300 illustrations to supplement the information provided.This book contains: history and optics of regular and irregular astigmatisms; useful criteria for diagnosis and classification; current state-of-the-art technologies for treatment; suggestions for future direction in treatment technology. Every physician who performs keratorefractive surgery understands that in reducing a patient's refractive error, there is a possibility of creating irreversible effects on visual quality. Irregular Astigmatism: Diagnosis and Treatment is intended to help prevent and reduce the iatrogenic creation of irregular astigmatism, as well as provide effective treatment when postoperative complications do arise.Treatment technologies addressed herein are: discussion of complications including: decentered treatment; small optical zone; central island; oblate cornea; destablized cornea; UV corneal cross-linking; intacs intracorneal rings; penetrating and lamellar keratoplasties; C-CAP; custom wavefront- and topography-driven treatments; lens surgery and toric IOL; and conductive keratoplasty.In addition, this text systematically separates two distinctly different etiological groups of irregular astigmatism - that of a structurally stable cornea and that of a structurally unstable weak cornea - and comprehensively presents all treatment modalities for each.With the maturation of keratorefractive technology in recent years, effective treatment for iatrogenic irregular astigmatism is quickly developing. Irregular Astigmatism: Diagnosis and Treatment provides everything refractive surgeons, ophthalmologists, and optometrists need to know about this important topic.
Abstract Background Implantable collamer lens implantation (ICL) is a form of ‘foldable’ posterior chamber phakic intraocular lens refractive surgery that generally does not impair cornea and natural accommodation. The potential advantages of the ICL over keratorefractive laser procedures include less induction of higher order aberrations (HOAs) and enhanced retinal image magnification. On the other hand, Small Incision Lenticule Extraction (SMILE), currently, one of the most popular refractive surgery procedures, also offers excellent visual outcomes, particularly for eyes with low to moderate amount of myopia. The aim of this study is to evaluate whether ICL/TICL (toric ICL) is comparable to SMILE for low to moderate myopia in terms of refractive outcomes at 3 and 18 months post-operatively. Methods/Design: This is a prospective randomized study. A total of 300 participants will be randomized into two groups, ICL/TICL group and SMILE group. Eligible participants with spherical equivalent (SE) less than − 6.0 diopter(D) will be recruited. Following randomization, participants will be followed at 1, 3, 6, 12 and 18 months. The primary outcome is the refractive predictability at every postoperative point after surgery, which is the proportion of the number of eyes achieving a postoperative SE within ± 0.5 D and ± 1.0 D of the intended target. Secondary outcome parameters include visual acuity, refraction, adverse events and quality of vision measurements. Discussion This trial will provide information on whether ICL has comparable, if not superior, refractive outcomes compared to the established SMILE for low to moderate myopia, thus providing evidence for translation into clinical practice. Trial registration: Chinese clinical trial registry (ChiCTR) 2200055372.
