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Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.
Postorino, EI, Rania, L, Aragona, E, Mannucci, C, Alibrandi, A, Calapai, G, Puzzolo, D, Aragona, P
European journal of ophthalmology. 2018;(1):25-31
Abstract
PURPOSE Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). METHODS Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. RESULTS At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. CONCLUSIONS The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.
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Corneal Scarring and Hyperopic Shift After Corneal Cross-linking for Corneal Ectasia After SMILE.
Voulgari, N, Mikropoulos, D, Kontadakis, GA, Safi, A, Tabibian, D, Kymionis, GD
Journal of refractive surgery (Thorofare, N.J. : 1995). 2018;(11):779-782
Abstract
PURPOSE To report a case of severe corneal scarring and hyperopic shift after corneal cross-linking (CXL) for the treatment of ectasia following small incision lenticule extraction (SMILE). METHODS Case report and literature review. RESULTS A 35-year-old man was referred with severe unilateral corneal haze that developed after CXL. The patient had undergone SMILE 4 years earlier in both eyes. Nineteen months postoperatively, the patient presented with bilateral decrease in vision and corneal topography revealed corneal ectasia in the right eye. CXL was performed in the right eye and a deep stromal haze was observed 1 year later. Comparative maps showed progressive corneal thinning with corresponding flattening that induced hypermetropization and astigmatism. CONCLUSIONS CXL after SMILE in this original case resulted in severe deep corneal haze and corneal flattening with hyperopic shift. [J Refract Surg. 2018;34(11):779-782.].
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Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study.
Sadoughi, MM, Einollahi, B, Baradaran-Rafii, A, Roshandel, D, Hasani, H, Nazeri, M
International ophthalmology. 2018;(1):67-74
Abstract
PURPOSE To compare the outcomes of the conventional and accelerated corneal collagen cross-linking (CXL) in patients with bilateral progressive keratoconus (KC). METHODS Fifteen consecutive patients with bilateral progressive KC were enrolled. In each patient, the fellow eyes were randomly assigned to the conventional CXL (3 mW/cm2 for 30 min) or accelerated CXL (ACXL) (9 mW/cm2 for 10 min) groups. Manifest refraction; uncorrected and corrected distant visual acuity; maximum and mean keratometry; corneal hysteresis and corneal resistance factor; endothelial cell density and morphology; central corneal thickness; and wavefront aberrations were measured before and 12 months after the CXL. RESULTS Manifest refraction spherical equivalent and refractive cylinder improved significantly only in conventional group. Uncorrected and corrected distant visual acuity did not change significantly in either group. Also there was no significant change in the maximum and mean keratometry after 12 months. There was significant decrease in central corneal thickness in both groups which was more prominent in conventional group. Endothelial cell density reduced only in the conventional group which was not statistically significant (P = 0.147). CH, CRF, and wavefront aberrations did not change significantly in either group. We did not observe any significant difference in the changes of the variables between the two groups. CONCLUSIONS Accelerated CXL with 9 mW/cm2 irradiation for 10 min had similar refractive, visual, keratometric, and aberrometric results and less adverse effects on the corneal thickness and endothelial cells as compared with the conventional method after 12 months follow-up. However, randomized clinical trials with longer follow-ups and larger sample sizes are needed.
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Comparison of Standard Versus Accelerated Corneal Collagen Cross-Linking for Keratoconus: A Meta-Analysis.
Wen, D, Li, Q, Song, B, Tu, R, Wang, Q, O'Brart, DPS, McAlinden, C, Huang, J
Investigative ophthalmology & visual science. 2018;(10):3920-3931
Abstract
PURPOSE To systematically compare epithelial-off standard (SCXL) to accelerated corneal collagen cross-linking (ACXL) for the treatment of keratoconus. METHODS PubMed, Embase, the Cochrane Library, and the US trial registry were searched for trials comparing SCXL and ACXL for keratoconus up to October 2017. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Primary outcomes were changes in uncorrected distance visual acuity, maximum keratometry (Kmax), and mean keratometry (mean K). Secondary outcomes were changes in corrected distance visual acuity, mean refractive spherical equivalent, central corneal thickness (CCT), and endothelial cell density (ECD). RESULTS Eleven trials were included. For primary outcomes, SCXL showed a greater reduction in Kmax (SMD 0.32; 95% CI 0.16, 0.48) than ACXL. For secondary outcomes, the decrease in CCT (SMD 0.32; 95% CI 0.03, 0.61) and ECD (SMD 0.26; 95% CI 0.06, 0.46) was less with ACXL than with SCXL. For the other outcomes, there were no statistically significant differences. CONCLUSIONS SCXL has a greater effect in terms of reduction in Kmax than ACXL, while ACXL induces less reduction in CCT and ECD than SCXL. Further well-designed randomized controlled trials comparing ACXL and SCXL are indicated.
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Sustainability of Pain Relief After Corneal Collagen Cross-Linking in Eyes With Bullous Keratopathy.
Ono, T, Mori, Y, Nejima, R, Ogata, M, Minami, K, Miyata, K
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018;(5):291-295
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Abstract
PURPOSE This study aimed to examine the efficiency and sustainability of pain relief produced by corneal collagen cross-linking (CXL) in eyes with bullous keratopathy (BK) and to explore the histopathological changes in the stroma by using in vivo confocal microscopy. DESIGN Prospective observational case series. METHODS Fourteen eyes of 14 consecutive BK patients were treated with CXL with dehydration of the corneal stroma and followed up for 1 year after treatment. The best-corrected visual acuity (BCVA), intraocular pressure, and central corneal thickness (CCT) were examined before the treatments and up to 1 year after. The intensity and frequency of pain were graded on a scale from 0 (minimum) to 10 (maximum). At 1 year after CXL, the corneal stroma was observed using confocal microscopy at depths of 100 and 200 μm. RESULTS The BCVA and CCT did not change significantly. The mean pain intensity and frequency scores were 5.6 and 4.6, respectively, before treatment. The intensity score significantly decreased at 1 week and onward, and the frequency score significantly decreased over 6 months after treatment. The confocal microscopy images showed that keratocytes and nerve fibers were rare and sparsely distributed in the stroma 1 year after CXL. CONCLUSIONS The CXL efficiently relieved pain due to BK for 1 year after treatment. The in vivo confocal microscopy observations and unchanged CCT demonstrated that the persistence of pain relief was due to the inadequate regeneration of nerve fibers in the corneal stroma.
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Corneal Cross-Linking for Pediatric Keratcoconus Review.
Perez-Straziota, C, Gaster, RN, Rabinowitz, YS
Cornea. 2018;(6):802-809
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Abstract
PURPOSE To comprehensively review the available published literature for cross-linking in the pediatric population. METHODS Review of the literature published in English in PubMed. RESULTS Two hundred ten publications were considered. One hundred fifteen were considered relevant to this review. CONCLUSIONS Studies of cross-linking in pediatric patients are sparse, with relatively short follow-up times, and mostly on small groups of patients. Treatment with cross-linking halts progression of keratoconus in the pediatric population, and early treatment seems to be cost-effective compared with later penetrating keratoplasty. Long-term effects and regression rates remain unclear, and further studies are needed in this population.
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Macroporous Poly(GMA-co-EGDMA) for Enzyme Stabilization.
Milosavić, NB, Prodanović, RM, Velićković, D, Dimitrijević, A
Methods in molecular biology (Clifton, N.J.). 2017;:139-147
Abstract
One of the most used procedures for enzyme stabilization is immobilization. Although immobilization on solid supports has been pursued since the 1950s, there are no general rules for selecting the best support for a giving application. A macroporous copolymer of ethylene glycol dimethacrylate and glycidyl methacrylate (poly (GMA-co-EGDMA)) is a carrier consisting of macroporous beads for immobilizing enzymes of industrial potential for the production of fine chemicals and pharmaceuticals.
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Comparison of the Conventional Dresden Protocol and Accelerated Protocol With Higher Ultraviolet Intensity in Corneal Collagen Cross-Linking for Keratoconus.
Choi, M, Kim, J, Kim, EK, Seo, KY, Kim, TI
Cornea. 2017;(5):523-529
Abstract
PURPOSE To compare the accelerated corneal cross-linking (CXL) protocol and the conventional Dresden protocol in patients with keratoconus in terms of visual acuity, keratometric values, and topographic parameters. METHODS Twenty-eight eyes of 25 patients with primary keratoconus were divided into 2 groups; 15 eyes in group 1 received CXL under the standard Dresden protocol (3 mW/cm for 30 min, dose 5.4 J/cm) and 13 eyes in group 2 were treated with the accelerated protocol (30 mW/cm for 3 min 40 s, dose 6.6 J/cm). Visual acuity, refractive error, keratometry values obtained by both Pentacam and Auto Kerato-Refractometer, corneal thickness, and topometric indexes were compared 6 months postoperatively. RESULTS The visual acuity improved significantly from 0.17 ± 0.16 to 0.08 ± 0.09 logarithm of the minimum angle of resolution in group 1 (P = 0.009). The cylindrical refractive error improved in both groups (P = 0.05 in group 1 and P = 0.011 in group 2), and the spherical equivalent increased in group 1 (P = 0.021). In group 1, the maximum keratometry value decreased by 0.55 ± 0.89 diopters (P = 0.03), and the mean keratometry value decreased by 0.44 ± 0.63 diopters (P = 0.017), whereas the changes in visual acuity, spherical and spherical equivalent refractive errors, and keratometric values in group 2 were not statistically significant. The corneal thickness at the apex decreased significantly in group 1 (P = 0.001), but the change was not significant in group 2. CONCLUSIONS Despite a higher UV dose (6.6 J/cm), accelerated CXL with higher UV intensity and reduced irradiation time showed a smaller topographic flattening effect than did the conventional Dresden protocol in primary keratoconus with documented progression.
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Insights into Formation and Structure of Aβ Oligomers Cross-Linked via Tyrosines.
Zhang, S, Fox, DM, Urbanc, B
The journal of physical chemistry. B. 2017;(22):5523-5535
Abstract
Alzheimer's disease (AD) pathology is hypothesized to be triggered by amyloid β-protein (Aβ) assembly into oligomers. Oligomer size distributions of both predominant Aβ alloforms, Aβ40 and Aβ42, can be determined in vitro using cross-linking followed by gel electrophoresis. Cross-linking, which can occur in vivo in the presence of copper and hydrogen peroxide, was recently shown to stabilize Aβ oligomers by inhibiting their conversion into fibrils. Whereas several studies showed that cross-linking is facilitated by dityrosine bond formation, the molecular-level mechanism of cross-linking remains unclear. Here, we use efficient discrete molecular dynamics with DMD4B-HYDRA force field to examine the effect of cross-linking via tyrosines on Aβ oligomer formation. Our results show that cross-linking via tyrosines promotes Aβ self-assembly, in particular that of Aβ40, but does not account for cross-linked oligomers larger than Aβ40 trimers and Aβ42 tetramers. Cross-linking via tyrosines profoundly alters Aβ40 and Aβ42 oligomer conformations by increasing the solvent exposure of hydrophobic residues, resulting in elongated oligomeric morphologies that differ from globular structures of noncross-linked oligomers. When compared to available experimental data, our findings imply that amino acids other than tyrosines are involved in Aβ cross-linking, a proposition that is currently under investigation.
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A case of in vivo iontophoresis-assisted corneal collagen cross-linking for keratoconus: An immunohistochemical study.
Manetti, M, Favuzza, E, Sgambati, E, Mencucci, R, Marini, M
Acta histochemica. 2017;(3):343-347
Abstract
The standard corneal collagen cross-linking (CXL), that includes the removal of corneal epithelium to permit adequate penetration of riboflavin in the stroma, is an established procedure to halting keratoconus progression. However, as epithelial removal may cause postoperative pain and an increased risk of corneal infection, new therapeutic approaches have been proposed. Iontophoresis is a recently developed non-invasive technique which provides the use of electrical current during CXL to enhance transepithelial penetration of riboflavin into the corneal stroma. Here, we describe for the first time the morphological changes of the corneal stromal compartment in a patient with keratoconus who underwent in vivo iontophoresis-assisted CXL (ionto-CXL) before full-thickness corneal transplantation. Immunohistochemistry for type I collagen and CD34 was performed to investigate the stromal distribution of collagen fibers and keratocytes, respectively. The histology of ionto-CXL-treated keratoconic cornea, collected 6 months after the intervention, was compared with that of healthy corneas and either untreated or standard CXL-treated keratoconic corneas. An attempt to restore a normal stromal architecture was observed in the ionto-CXL-treated cornea compared with untreated keratoconic corneas. In particular, the ionto-CXL-treated cornea showed a parallel distribution of type I collagen fibers, although fiber interweaving appeared less organized than in healthy corneas and standard CXL-treated keratoconic corneas. Moreover, the distribution of CD34-positive keratocytes was improved in keratoconic corneas following ionto-CXL treatment, though a scattered CD34 immunoreactivity was still noticeable in the subepithelial stroma. This study provides histological evidence that ionto-CXL may represent a non-invasive alternative in the management of progressive keratoconus in adults.