The Keratectasia Volume (KEV) in Corneal Topography to Evaluate the Effect of Corneal Collagen Cross-linking in Pediatric Keratoconus.

The study aimed to evaluate the keratectasia volume (KEV) before and after corneal cross-linking (CXL) in pediatric patients. This study included 40 eyes of 25 pediatric patients (10-19 years) undergoing standard CXL. The support vector machine (SVM) algorithm was applied to transform mass pixels in corneal topography into a three-dimensioned model to calculate the KEV. The KEV, Kmax, K1, K2, Kave, keratectasia area (KEA), and thinnest corneal thickness (TCT) were determined before CXL and at 3, 6, and 12 months after surgery. The correlation between KEV and other parameters (Kmax, TCT, max decentration, eccentricity, and so on) was calculated. The KEV was 4.75 ± 0.74 preoperatively and 4.43 ± 1.22 postoperatively at last follow-up (p < 0.002). There was strong positive correlation between the KEV and Kmax (r = 0.806, p < 0.0005). The preoperat ive KEV was 4.32 ± 0.69 in mild to moderate keratoconus (Kmax < 58D) and 5.27 ± 0.37 in advanced keratoconus (Kmax > 58D) (p < 0.0005, t-test). Postoperative KEV and K readings remained stable at the early stage, and the KEV showed a more drastic decreasing trend than Kmax at sixth month. Statistical significance was found in the KEV between preoperative and 6 months after surgery (p < 0.0005), but not in Kmax and other parameters. In 83.3% (15 eyes out of 18 eyes) of the eyes, the preoperative KEV was greater than 4.6 in patients with significant flattening after CXL. Compared with K readings, the KEV can be regarded as a more sensitive index to evaluate the postoperative morphological changes after CXL in pediatric patients.

Case Series: Application of Topography-guided Contoura Refractive Surgery in Highly Irregular Cornea.

SIGNIFICANCE: Highly irregular cornea leads to poor vision, glare, and starbursts. Although treatment is still at the exploration stage, topography-guided Contoura surgery has excellent potential for the treatment of highly irregular corneas. PURPOSE: This case series reviews three patients (one with abnormal back elevation, one with corneal scar after fungal keratitis, and one with post-laser-assisted in situ keratomileusis central islands) treated with topography-guided Contoura surgery. CASE REPORTS: In case 1, a 19-year-old man underwent topography-guided Contoura refractive surgery in the left eye and wavefront-optimized ablation in the right eye. Post-operative topography of the right eye showed marked inferior steepening and central irregular astigmatism compared with the contralateral eye. In case 2, a 53-year-old man presented with corneal scarring on the right eye after recovering from fungal keratitis. The patient first underwent phototherapeutic keratectomy and photorefractive keratectomy to remove the scarring primarily. He then underwent Contoura to correct hyperopia, which flattened the cornea and improved his vision significantly. In case 3, a 25-year-old man presented with central steepening on topography maps after undergoing laser-assisted in situ keratomileusis. He underwent topography-guided ablation, which improved his visual acuity and normalized the cornea. CONCLUSIONS: Therapy for highly irregular corneas includes wavefront-guided surgery, conservative treatment, corneal transplantation, rigid gas-permeable lenses, and so on. In this case series, topography-guided Contoura refractive surgery provided an excellent option for reducing topographic abnormalities and improving vision.

Corneal Biomechanical Evaluation After Conventional Corneal Crosslinking With Oxygen Enrichment.

PURPOSE: To assess corneal biomechanical changes after conventional corneal crosslinking (CXL), with and without oxygen enrichment. METHODS: Sixty fresh porcine corneas were randomly divided into group 1 (control), group 2 (conventional CXL), and group 3 (conventional CXL in a high-oxygen environment during ultraviolet A [UVA] irradiation). After crosslinking, a 5-mm wide corneal strip was extracted using a double-bladed knife from 12 to 6'o clock. The Young's modulus of each strip was determined by stress-strain measurements. A comparison between the three groups was performed with a one-way analysis of variance. RESULTS: At 4% strain, the Young's modulus of the corneas in groups 1, 2, and 3 were: 0.68±0.20 megapascal (MPa), 1.01±0.23 MPa, and 1.12±0.24 MPa, respectively. The Young's modulus values for groups 2 and 3 showed no statistical significance (P>0.05), However, both groups 2 and 3 were significantly higher than group 1 (P<0.05). At 6% strain, the Young's modulus of the corneas in groups 1, 2, and 3 were: 0.97±0.21, 1.35±0.25, and 1.64±0.44 MPa, respectively, and at 8% strain, the Young's modulus was: 1.29±0.26, 1.72±0.45, 2.20±0.74 MPa, respectively. At 6% and 8% strain, the Young's modulus for the corneas in group 3 was significantly higher than those in both group 1 and group 2 (P<0.05). CONCLUSIONS: Increasing oxygen concentration during UVA irradiation may improve the efficacy of conventional CXL.

Combined transepithelial phototherapeutic keratectomy and corneal collagen cross-linking for corneal ectasia after small-incision lenticule extraction-preoperative and 3-year postoperative results: a case report.

BACKGROUND: Corneal ectasia after small-incision lenticule extraction (SMILE) is uncommon. To our knowledge, this is the first report of 3-year results of combined phototherapeutic keratectomy (PTK) and corneal collagen cross-linking (CXL) for corneal ectasia after SMILE. CASE PRESENTATION: Herein, we describe a case of prominent corneal ectasia after SMILE treated with PTK combined with CXL 3 years ago. After surgery, maximum corneal keratometry, mean corneal keratometry, spherical equivalent and uncorrected distance visual acuity were significantly improved at follow-up intervals. CONCLUSIONS: Transepithelial PTK combined with CXL for corneal ectasia after SMILE may be an effective and safe treatment in the long term.

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

PURPOSE: The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). METHODS: PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p < 0.001), while the mean best corrected visual acuity improved from 0.21 ± 0.14 logMAR at baseline to 0.04 ± 0.10 logMAR at 12 months postoperatively (p < 0.001). A significant decrease was observed in Kmax and Kmean values from 52.51 ± 6.74 and 43.55 ± 3.37 D at baseline to 45.72 ± 5.18 (p < 0.001) and 40.60 ± 3.05 D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from 419.07 ± 36.56 µm before treatment to 320.93 ± 39.78 µm at 12 months of follow-up (p < 0.001), and there was no significant endothelial cell loss (p > 0.05) beyond 6 months after treatment. CONCLUSION: PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement.

Prospective Cohort Comparison of Visual Acuity and Contrast Sensitivity Between Femto Laser In Situ Keratomileusis and Orthokeratology for Low-to-Moderate Myopia.

PURPOSE: To compare the visual acuity and contrast sensitivity (CS) after femto laser in situ keratomileusis (fLASIK) and orthokeratology (OK) in patients with low-to-moderate myopia. METHODS: A total of 68 patients were enrolled in this prospective cohort study. Of these, 40 eyes from 40 patients with low-to-moderate myopia underwent fLASIK and 28 eyes from 28 patients underwent OK. In addition to uncorrected distance visual acuity and corrected distance visual acuity, photopic and mesopic CS (with CSV-1000E) were tested before treatment and at 1, 3, and 6 months after treatment. RESULTS: The preoperative refraction and CS were not significantly different between the groups (P>0.05). Postoperative visual acuity and refraction were similar (P>0.05). The photopic CS of the fLASIK group was better than that of the OK group (P<0.01). The fLASIK mesopic CS was better than the OK at 3 c/d (P=0.023). In the fLASIK group, only the photopic CS of postoperative 12 c/d decreased at 1 month and 3 months (P<0.01) and 18 c/d decreased at 1 month (P=0.002); whereas in the OK group, all the postoperative photopic CS values decreased at 1 month (all P<0.01) and 3 months (P<0.05) and increased to the normal level at 6 months (P>0.05). While as to the mesopic CS, in the fLASIK group, the 3 c/d, 6 c/d, and 18 c/d decreased at 1 month (P<0.05) and in the OK group, the 3 c/d decreased at 1 month and 3 months (P<0.05) and the 6 c/d decreased at 3 months (P=0.041), and the 12 c/d and 18 c/d decreased at 1 month (P<0.01). CONCLUSIONS: These results show that fLASIK provides better visual quality than OK for patients with low-to-moderate myopia.

Clinical Study of Mitomycin C in Reducing Haze Formation After Ultraviolet A/Riboflavin Crosslinking for Keratoconus.

OBJECTIVES: To evaluate the safety and efficacy of mitomycin C (MMC) in haze formation after ultraviolet A/riboflavin corneal crosslinking (CXL) for progressive keratoconus. METHODS: A total of 60 keratoconic eyes of 48 patients were enrolled in this prospective comparative study after obtaining informed consent. In the CXL group, standard corneal CXL was performed, whereas in the CXL+MMC group, 0.02% MMC was used for 30 s soon after CXL. Comprehensive ophthalmologic examinations were performed on all patients before surgery and at 1, 3, 6, and 12 months after surgery. RESULTS: The epithelium recovered within 3 to 4 days after CXL, and the healing time was comparable in the two groups. There was no significant endothelial cell density loss after CXL in both groups. Eyes in both groups showed improvement of uncorrected distance visual acuity (Snellen) and best-corrected visual acuity (Snellen; P<0.05), and there was a decrease in K-max, cylinder degree, and central corneal thickness (CCT) (P<0.05). There was no significant statistical difference between the groups regarding postoperative K-max reduction, refraction, and CCT (P>0.05). Corneal haze scores were significantly higher in the CXL group at 1 and 3 months after CXL (P=0.012 and P=0.028, respectively), but were similar to the MMC group at 6 and 12 months after surgery (P=0.329 and P=0.543, respectively). CONCLUSIONS: Prophylactic intraoperative use of 0.02% MMC can significantly reduce CXL-associated haze formation, especially in the early postoperative period, and no signs of weakening CXL efficacy were observed.

The Evaluation of Corneal Fragility After UVA/Riboflavin Crosslinking.

PURPOSE: To evaluate the fragility of cornea after UVA/riboflavin crosslinking (CXL). METHODS: Sixty New Zealand rabbits received UVA/riboflavin crosslinking treatment (wavelength 365 nm, irradiance 3.0 mW/cm, and total dose 5.4 J/cm) on right eyes. Animals were sacrificed before and immediately after treatment (day 0), day 1, 3, 7, and 28 after treatment. A 4×10 mm corneal strip for biomechanical evaluation was harvested after sacrifice. The corneal fragility was evaluated by measurement of elongation rate, whereby the elongation rate equals elongation length/baseline length. RESULTS: The Youngs modulus and maximal stress were 1.41±0.51 MPa and 5.56±1.84 MPa before CXL, and increased to 2.31±0.68 MPa (P=0.008) and 9.25±2.74 MPa (P=0.04), respectively, on day 0, then maintained a stable level within a 28 days follow-up. The elongation rate was 62.04±9.34% before CXL and decreased to 48.95%±8.24% (P=0.02) on day 0, then maintained a stable level within a 28 days follow-up. CONCLUSIONS: This study showed an increase in the corneal fragility after UVA/riboflavin crosslinking along with an increase in the corneal stiffness. A long-term follow-up should be taken to evaluate the potential deleterious effect of the increasing corneal fragility after UVA/riboflavin crosslinking.

Tat PTD-endostatin: A novel anti-angiogenesis protein with ocular barrier permeability via eye-drops.

BACKGROUND: Endostatin, a specific inhibitor of endothelial cell proliferation and angiogenesis, has been proved to have effects on ocular neovascular diseases by intraocular injection. In order to increase its permeability to ocular barriers and make it effective on fundus oculi angiogenesis diseases via non-invasive administration (eye drops), endostatin was fused to Tat PTD via a genetic engineering method. METHODS: Most of the Tat PTD- endostatin was expressed as inclusion bodies in Escherichia coli, so pure and active Tat PTD-endostatin was prepared by a series of operations, including inclusion body denaturation, refolding and chromatography. The anti-angiogenesis activity of Tat PTD-endostatin was investigated by cell proliferation experiments and chick embryo chorioallantoic membrane assay. In addition, its translocating ability and concrete entry mechanism into cells were also investigated by fluorescence microscope and flow cytometry. The penetrating ability to ocular barriers was also studied by immunohistochemistry. A mouse choroidal neovascularization model was established to investigate the pharmacodynamics of Tat PTD-endostatin. RESULTS: The obtained Tat PTD-endostatin had excellent anti-angiogenesis activity and was superior to Es in cellular translocating. Macropinocytosis may be the dominant route of entry of Tat PTD-endostatin into cells. Tat PTD-endostatin could cross ocular barriers and arrive at the retina after eye-drop administration. In addition, it displayed inhibitory effects on choroidal neovascularization via eye drops. CONCLUSIONS: Tat PTD-endostatin possessed excellent ocular penetrating ability and anti-angiogenesis effects. GENERAL SIGNIFICANCE: Tat PTD is a promising ocular delivery tool, and Tat PTD-endostatin is a potential drug for curing fundus oculi angiogenesis diseases.

Topical Fluorometholone Versus Diclofenac Sodium in Cases With Perennial Allergic Conjunctivitis.

PURPOSE: To compare the efficacy of diclofenac sodium (DS) 0.1% and fluorometholone (FL) 0.1% in patients with perennial allergic conjunctivitis. METHODS: Fluorometholone 0.1% or DS 0.1% eye drops were topically administrated 4 times daily for 4 weeks in patients with perennial allergic conjunctivitis. Assessment was conducted with a 4-point rating scale (0=none, 1=mild, 2=moderate, and 3=severe) for 4 signs and 5 symptoms. RESULTS: Two hundred sixty-one patients were recruited. The demographics and baseline skin prick scores between both groups were comparable. Mean baseline scores in DS and FL group were 6.77 ± 2.24 and 6.34 ± 2.10, respectively. The scores rapidly decreased to 3.28 ± 1.47 and 2.69 ± 1.44 on day 7. Diclofenac sodium expressed a slower effect compared with FL within the first 3 days of treatment (P=0.01). CONCLUSIONS: The efficacy of topical FL and DS was comparable for the management of cases with perennial allergic conjunctivitis. However, FL led to a more rapid alleviation of signs and symptoms as compared with DS in early days after the initiation of treatment.

Corneal Collagen Cross-Linking Inhibits Corneal Blood and Lymphatic Vessels Temporarily in Alkali-Burned Rabbits.

PURPOSE: This study aimed to explore whether corneal cross-linking (CXL) could regress corneal blood vessels (CBV) and corneal lymphatic vessels (CLV) in alkali-burned rabbits. METHODS: A total of 80 rabbits 2-3 months old weighing 1.5-2.0 kg were randomly divided into four groups: CXL7 group; CTL7 group; CXL14 group; and CTL14 group. Then, 3% sodium pentobarbital 1 ml/kg and tetracaine eye drop 5 g/L were administered before surgery. NaOH 2 mol/L was topically applied to the central cornea to establish the alkali burning model. Then CXL was administered within 2 h in groups CXL7 and CXL14. Corneal opacity and edema, CBV and CLV volume, cluster differentiation 31 (CD31), and lymphatic vessel endothelial receptor 1 (LYVE-1) expression levels were analyzed on days 7 and 14. RESULTS: CXL reduced cornea opacity, CNV, and CLV volumes on day 7 in alkali-burned rabbits. However, CNV and CLV volumes were increased on day 14. CXL also showed down- and upregulation of CD31 and LYVE-1 expression levels on days 7 and 14, respectively. CONCLUSIONS: CXL effectively regulated CBV and CLV in alkali-burned rabbits. The transient angioregression and lymphangioregression induced by CXL may be potentially helpful in vascularized high-risk eyes.

Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium derived factor make low molecular weight heparin-endostatin and polyethylene glycol-endostatin potential candidates for anti-angiogenesis drug.

The aim was to study the effects and action mechanism of endostatin (ES), low molecular weight heparin-endostatin (LMWH-ES) and polyethylene glycol-endostatin (PEG-ES) on endothelial cell proliferation, choroidal neovascularization and zebrafish angiogenesis. Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro. Choroidal neovascularization model was used to evaluate the effects of ES and its derivatives on choroidal neovascularization in vivo. Western blotting was employed to study the effects of ES and its derivatives on the expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in chorioid tissues. Zebrafish model was also used to study the anti-angiogenesis activities of ES and its derivatives. The results showed that ES and its derivatives could significantly inhibit endothelial cell proliferation in vitro (p<0.05), suppress choroidal neovascularization by down-regulating expression of VEGF and up-regulating expression of PEDF in chorioid tissues, and restrain angiogenesis in zebrafish. ES showed better activity in inhibiting endothelial cell proliferation in vitro (p<0.05), but LMWH-ES and PEG-ES showed higher activity in inhibiting choroidal neovascularization in vivo (p<0.05) and angiogenesis in zebrafish (p<0.05). These results indicate that LMWH-endostatin and PEG-endostatin are potential candidates for anti-angiogenesis drug.

The influence of the choroid on the onset and development of myopia: from perspectives of choroidal thickness and blood flow.

Myopia is the most common type of refractive errors characterized by excessive elongation of the ocular globe. With the increasing prevalence of myopia, improved knowledge of factors involved in myopia development is of particular importance. There are growing evidence suggesting that the choroid plays an important role in the regulation of eye growth and the development of myopia. Studies have demonstrated that thinning choroid is a structural feature of myopia, with a negative correlation between choroidal thickness and axial length, suggesting that the change in choroidal thickness may be a predictive biomarker for long-term changes in ocular elongation. Given the fact that the choroid is primarily a vascular structure capable of rapidly changing blood flow, variations of choroidal thickness might be primarily caused by changes in choroidal blood flow. Considering that hypoxia is associated with myopia and choroidal blood flow is the main source of oxygen and nourishment supply, apart from the effect on myopia possibly by changing choroidal thickness, decreasing choroidal blood flow may contribute to scleral ischaemia and hypoxia, resulting in alterations in the scleral structure and thus leading to myopia. This review aims to provide an overview of recent work exploring the influence of the choroid on myopia from perspectives of choroidal thickness and blood flow, which may present new predictive indicators for the onset of myopia and new targets for the development of novel therapeutic approaches for myopia.

Effects of hydrogen peroxide solution on the biomechanics of porcine cornea.

OBJECTIVES: To determine the biomechanical changes of porcine corneas after the application of hydrogen peroxide(H2O2) solution. METHODS: Fifty-five porcine eyeballs with similar sizes were divided into 11 groups based on the H2O2 application. The eyeballs were treated with the following concentrations of H2O2 solution: 1 mol/L, 500 mmol/L, 250 mmol/L, 125 mmol/L, 62.5 mmol/L, 31.25 mmol/L, 15.63 mmol/L, 7.81 mmol/L, 3.91 mmol/L, 0.9% saline, or blank. The eyeballs were immersed into the solution for 30 min. The biomechanics of each cornea in the different groups was determined soon after the indentation and tensile tests. We calculated the average Young's modulus of the different groups to determine the effects of H2O2 solution on porcine corneas. The comparison between the groups was conducted using ANOVA analysis. Moreover, the safety of each concentration of H2O2 solution on the corneal tissues was determined by histopathological examination. RESULTS: The Young's modulus was significantly different among all the groups (p = 0.003). The modulus was the highest in the group treated with 3.91 mmol/L H2O2 and it was significantly different from that in the group treated with 0.9% saline or the blank group, for both the indentation and tensile tests. Histopathological examination showed that H2O2 at a concentration of ⩾62.5 mmol/L damaged the epithelium, stroma, or both, while H2O2 at a concentration ⩽31.25 mmol/L did not change the morphology of the epithelium or stroma. CONCLUSIONS: Treatment with 3.91 mmol/L H2O2 solution can safely and effectively increase the biomechanical strength of the cornea.

Establishing a Porcine Eye Model for Manual Sub-Bowman Layer Photorefractive Keratomileusis.

OBJECTIVE: To establish a porcine eye model for manual sub-Bowman layer photorefractive keratomileusis (SBPRK), which is a reformed surface ablation refractive surgery that results in preserving the corneal Bowman layer (BL). METHODS: The SBPRK group consisted of eleven eyes of 8 healthy pigs with BL flaps by mechanical technique followed by laser ablation. Regarding the remaining 5 eyes, 3 random eyes had transepithelium photorefractive keratectomy (TransPRK) (the TransPRK group), while the other 2 eyes were untreated (the blank control group). All the pigs were followed up for 8 weeks. Slit-lamp biomicroscopy and optical coherence tomography (OCT) were examined before the surgeries and at 1 week, 4 weeks, and 8 weeks after the surgeries. RESULTS: In a few days after the surgery, 3 eyes of the SBPRK group were excluded from the study because of poor healing of the corneal flaps. At the 1st postoperative week, one eye had an irregular defect of about 3 mm in the central corneal epithelium area; the cornea of the other 7 eyes had just light edema with intact epithelium just like the cornea of the TransPRK group. At the 4th week, in the SBPRK group, the cornea was slightly hazy (haze stage 1). While in the TransPRK group, the cornea was hazier (haze stage 2). At the 8th week, in the SBPRK group, both corneas were almost transparent, and the edges of the BL flaps could not be clearly seen. Meanwhile, in the TransPRK group, the corneal haze became lighter and thinner. OCT showed that, in the SBPRK group, there was high reflection in the BL layer, and it was obvious at 1 week postoperation, decreased at 4 weeks, and calmed down at 8 weeks. However, in the TransPRK group, the high reflection diffused in the anterior corneal stroma at 1 week postoperation, enhanced at 4 weeks, and weakened at 8 weeks. CONCLUSIONS: Preserving the BL while conducting surface refractive surgery may result in less haze than TransPRK. However, further study is still needed, and this technique still requires refining until it becomes a standard clinical procedure.

Evaluation and ultrastructural changes of amniotic membrane fragility after UVA/riboflavin cross-linking and its effects on biodegradation.

This study aims to evaluate the changes of fragility and ultrastructure of amniotic membrane after cross-linking by UVA/riboflavin.Forty-nine fresh amniotic membranes were randomly divided into 3 groups. Eighteen were in group A (CX group) and immersed in 0.1% riboflavin solution for 10 min for UVA/riboflavin cross-linking. Sixteen were in group B (B2 group), soaked for 10 min with 0.1% riboflavin. After soaking, membranes in group A and B were transferred into corneal preservation solution. Fifteen pieces were in group C, directly into corneal preservation solution. The biomechanical and ultrastructural changes of the amniotic tissue before and after cross-linking were examined (CX group = 13, B2 group = 11, C group = 15). The amniotic membrane tissue of group A (n = 5) and B (n = 5) was transplanted into 16 eyes of the rabbits, respectively, and the dissolution time of the amniotic membrane tissue was investigated.After cross-linking, compared with the control group, the elastic modulus of the low-stress area of the amniotic membrane (Elow) was higher, while the elastic modulus of the high-stress area of the amniotic membrane (Ehigh) was lower, with no significant difference in the tensile strength. Also, the collagen fibers showed coarse and bamboo-like changes. In group A, amniotic membranes began to dissolve 4 weeks after conjunctiva transplantation, and all amniotic membranes were dissolved and absorbed 6 weeks after conjunctiva transplantation. In group B, some amniotic membrane tissues were still visible 6 weeks after conjunctiva transplantation.This study suggested that after amniotic membrane cross-linking, the brittleness was increased, the hardness was enhanced, and the morphology of the collagen fiber was changed. The cross-linked amniotic membrane showed resistance to tissue dissolution.

Vitamin K2 inhibits the growth of hepatocellular carcinoma via decrease of des-gamma-carboxy prothrombin.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K(2) on the production of DCP as well as tumor cell growth and invasion. METHODS: Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K(2) was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC. RESULTS: Vitamin K(2) (2-40 muM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K(2), the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivity was well correlated with the decrease of DCP in the serum of mice. CONCLUSION: Vitamin K(2) might suppress the growth and invasion of HCC cells via decrease of DCP.

Whether Keratectasia Area Shown in Corneal Topography Is Appropriate for Evaluating the Effect of Corneal Cross-Linking for Keratoconus: A 12-Month Follow-Up Study.

PURPOSE: To analyze the keratectasia area (KEA) shown in corneal topography before and after corneal cross-linking (CXL) in patients with progressive keratoconus (KC) and figure out whether KEA is appropriate for evaluating the effect of CXL. METHODS: A retrospective analysis was conducted in 34 eyes from 24 progressive KC patients who have underwent CXL from 2015 to 2017. Area with K-value more than 47D shown in the corneal topography was marked and identified as KEA. Keratometry (K1, K2, and Kmax), KEA, thinnest corneal thickness (TCT), and endothelial cell density (ECD) were evaluated preoperatively or at months 3, 6, and 12 postoperatively. The changes of KEA before and after operation were evaluated. The relation of KEA and other parameters, including Kmax and TCT, was analyzed. RESULTS: Linear regression model revealed the KEA, Kmax, K1, and K2 decreased after CXL in model y = 0.9622 -0.02408 x (P<0.05), y = 0.9982 -0.003469 x(P<0.05), y = 0.9977 + -0.001347 x(P<0.05), y = 0.9992 + -0.001779 x(P<0.05) (y represents KEA, Kmax, K1, or K2; x represents time (month)). The KEA is significantly decreased in early stage (before month 3) (P<0.05); however, the Kmax, K1, and K2 have no significant decrease in early stage (P= 0.09, 0.19, 0.32). CONCLUSIONS: The KEA is more sensitive than K-value in describing the morphological changes of cornea after CXL, especially in early stage after treatment.

Management of Corneal Ectasia after LASIK with Phototherapeutic Keratectomy Combined with Photorefractive Keratectomy and Collagen Cross-Linking.

BACKGROUND: To evaluate the efficacy of phototherapeutic keratectomy (PTK) combined with photorefractive keratectomy (PRK) and riboflavin with ultraviolet-A collagen cross-linking (CXL), performed sequentially on the same day, in the management of corneal ectasia after LASIK. METHODS: This retrospective review comprised consecutive patients with corneal ectasia after LASIK. The patients were administered PTK and PRK on the previous corneal flap, and CXL was given on the same day by the same surgeon. The main outcome measures included age, sex, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent refraction, cylinder equivalent refraction, steep and flat keratometries (K), central corneal thickness (CCT), endothelial cell count, corneal haze, and ectasia stability. Mean follow-up period was 6, 12, and 24 months. RESULTS: Sixteen eyes of twelve patients were included in the study. Twenty-four months after administration of PTK combined with PRK and CXL, a significant improvement in UDVA was observed. Mean cylinder equivalent refraction was significantly reduced at 6, 12, and 24 months postoperatively. However, no significant reduction was observed in spherical equivalent refraction. A significant reduction in the flat K and steep K values was observed. No significant change in mean CCT value was observed. Mean endothelial cell count and morphology were unchanged between preoperative and postoperative patients. In addition, no obvious corneal haze was observed. CONCLUSIONS: PTK combined with PRK and CXL on the same day is a safe and effective treatment in improving visual acuity in selected patients with corneal ectasia after LASIK.

Semaphorin 7a participants in pterygium by regulating vascular endothelial growth factor.

AIM: To investigate the relationship between semaphorin 7a expression and cell proliferation and migration in pterygium fibroblasts. METHODS: Twenty-six patients with surgically diagnosed pterygium were enrolled, including 15 cases of primary pterygium and 11 cases of recurrent pterygium. In addition, 12 cases of normal conjunctival tissue were collected. The expression of semaphorin 7a in normal conjunctival tissue, primary pterygium and recurrent pterygium was detected by real-time polymerase chain reaction. Recurrent pterygium fibroblasts were isolated and cultured, and the expression of semaphorin 7a was silenced by small interfering RNA (siRNA) interference technique. Furthermore, the effects of si-semaphorin 7a interference on the mRNA and protein levels of ß1-integrin, vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor (VEGFR), and on fibroblast proliferation were analyzed. Transwell assay was used to detect the effect of semaphorin 7a interference on fibroblast migration. RESULTS: Semaphorin 7a was highly expressed in the primary pterygium and recurrent pterygium samples than that of the normal conjunctival tissue. Compared with the primary pterygium, the expression of semaphoring 7a in the recurrent pterygium samples was significantly increased (P<0.05). The mRNA and protein expression levels of ß1-integrin, VEGFA and VEGFR were decreased after si-semaphorin 7a transfection, and as well as the cell proliferation and migration. CONCLUSION: Semaphorin 7a might play important roles in the pathogenesis of pterygium by affecting the expression of ß1-integrin, VEGFA and VEGFR.