Ultraviolet-A absorbance analysis in thin porcine corneas pre-and post-crosslinking

ABSTRACT Purpose: To determine the absorbance coefficient of the thin porcine cornea to ultraviolet-A radiation (365 nm) submitted for crosslinking. Methods: This in vitro, benchtop experiment using cadaver tissue study analyzed 12 porcine corneal lamellas, which were obtained using a microkeratome after mechanical de-epithelization and separated into three thickness groups: 180, 300, and 360 μm. The corneal thickness values were measured by anterior-segment optical coherence tomography. All lamellas had ultraviolet-A (365 nm) absorbance measured with a 96-well plate spectrophotometer using an ultraviolet transparent microplate before riboflavin instillation and preand post-crosslinking according to the Dresden protocol. Results: The ultraviolet absorbance profiles of the 180, 300, and 360 μm groups were obtained as α-coefficients of 12.85, 76.55, and 120.27, respectively. A theoretical formula was calculated though a statistical analysis that demonstrated the correlation between stromal lamellar thickness and ultraviolet absorbance. Conclusions: Corneal thickness and ultraviolet-A spectral absorbance of corneal lamellas showed linear correlation. These findings can potentially contribute to the optimization of ultraviolet-A application during crosslinking, making the treatment of corneas with thickness <400 μm safe and personalized energy delivery for each corneal thickness.

Evaluation of unilateral corneal collagen cross-linking on fellow untreated eyes of patients with keratoconus / A avaliação da reticulação unilateral do colágeno corneano em olhos não tratados de pacientes com ceratocone

ABSTRACT Purpose: This study aimed to examine the effects of unilateral corneal collagen cross-linking treatment on visual acuity and the topographic findings of the fellow untreated eye of patients who had bilateral progressive keratoconus. Methods: Patients with progressive keratoconus who underwent cross-linking treatment were screened retrospectively. A total of 188 untreated eyes of 188 patients whose eyes were treated unilaterally with either standard or accelerated cross-linking and refused cross-linking procedure for the fellow eye were included. Visual acuity and topographic findings of the fellow untreated eyes were obtained preoperatively and postoperatively at the 1st, 3rd, 6th, 12th, 24th, 30th, and 36th months. Results: The change over time of variables examined was similar in the untreated eyes of patients who received standard and accelerated cross-linking methods (p>0.05). At the 12th month, 136 (95.8%) untreated eyes were stable according to progression criteria. Only 4 (8%) eyes were progressive at the 24th month. No progression was observed in any of the 16 patients with a 36-month follow up. Conclusions: The results showed that the fellow untreated eyes of patients with bilateral progressive keratoconus did not have significant progression rates after unilateral cross-linking treatment.

RESUMO Objetivo: Examinar os efeitos do tratamento de reticulação unilateral do colágeno corneano na acuidade visual e os achados topográficos em olhos não tratados de pacientes com ceratocone progressivo bilateral. Métodos: Foram rastreados retrospectivamente pacientes com ceratocone progressivo submetidos a tratamento de reticulação. Foram incluídos no estudo 188 olhos não tratados de 188 pacientes tratado unilateralmente com reticulação padrão ou acelerada e que recusaram o procedimento de reticulação no outro olho. A acuidade visual e os achados topográficos dos olhos não tratados foram obtidos no pré- e pós-operatório no 1º, 3º, 6º, 12º, 24º, 30º e 36º mês. Resultados: As alterações ao longo do tempo foram semelhantes para as variáveis examinadas nos olhos não tratados de pacientes tratados com métodos de reticulação padrão e acelerado (p>0,05). No 12º mês, 136 olhos não tratados (95,8%) estavam estáveis, de acordo com os critérios de progressão. Apenas quatro olhos (8%) mostraram progressão no 24º mês. Nenhuma progressão foi observada nos 16 pacientes que tiveram um acompanhamento de 36 meses. Conclusões: O estudo mostrou que os olhos não tratados de pacientes com ceratocone progressivo bilateral não apresentaram taxas de progressão significativas após o tratamento unilateral com reticulação.

Estudio de biocompatibilidad de matrices poliméricas combinadas, responsivas al pH, con aplicación en Ingeniería de Tejido Óseo / Biocompatibility study of combined pH-responsive polymeric matrices with application in Bone Tissue Engineering

El presente trabajo muestra la obtención de un material a partir de un polímero sintético (TerP) y otro natural, mediante entrecruzamiento físico y su caracterización fisicoquímica y biológica, con el fin de emplearlos para regeneración de tejido óseo. Las membranas fueron obtenidas por la técnica de evaporación del solvente y caracterizadas por espectroscopia FTIR, ensayos de hinchamiento, medidas de ángulo de contacto y microscopia electrónica de barrido (SEM). Se encontró que la compatibilidad entre los polímeros que la constituyen es estable a pH fisiológico y que, al incorporar mayor cantidad del TerP a la matriz, esta se vuelve más hidrofóbica y porosa. Además, teniendo en cuenta la aplicación prevista para dichos materiales, se realizaron estudios de biocompatibilidad y citotoxicidad con células progenitoras de médula ósea (CPMO) y células RAW264.7, respectivamente. Se evaluó la proliferación celular, la producción y liberación de óxido nítrico (NO) al medio de cultivo durante 24 y 48 horas y la expresión de citoquinas proinflamatorias IL-1ß y TNF-α de las células crecidas sobre los biomateriales variando la cantidad del polímero sintético. Se encontró mayor proliferación celular y menor producción de NO sobre las matrices que contienen menos proporción del TerP, además de poseer una mejor biocompatibilidad. Los resultados de este estudio muestran que el terpolímero obtenido y su combinación con un polímero natural es una estrategia muy interesante para obtener un biomaterial con posibles aplicaciones en medicina regenerativa y que podría extenderse a otros sistemas estructuralmente relacionados. (AU)

In the present work, the preparation of a biomaterial from a synthetic terpolymer (TerP) and a natural polymer, physically crosslinked, is shown. In order to evaluate the new material for bone tissue regeneration, physicochemical and biological characterizations were performed. The membranes were obtained by solvent casting and characterized using FTIR spectroscopy, swelling tests, contact angle measurements, and scanning electron microscopy (SEM). It was found that the compatibility between the polymers is stable at physiological pH and the incorporation of a higher amount of TerP into the matrix increases hydrophobicity and porosity.Furthermore, considering the intended application of these materials, studies of biocompatibility and cytotoxicity were conducted with Bone Marrow Progenitor Cells (BMPCs) and RAW264.7 cells, respectively. Cell proliferation, NO production and release into the culture medium for 24 and 48 hours, and proinflammatory cytokine expression of IL-1ß and TNF-α from cells grown on the biomaterials while varying the amount of the synthetic polymer were evaluated. Greater cell proliferation and lower NO production were found on matrices containing a lower proportion of TerP, in addition to better biocompatibility. The results of this study demonstrate that the obtained terpolymer and its combination with a natural polymer is a highly interesting strategy for biomaterial preparation with potential applications in regenerative medicine. This approach could be extended to other structurally related systems. (AU)

Entrecruzamiento del orbicular para el entropión senil mediante técnica de Martínez-Rodríguez modificada

Objetivo: Describir los resultados de la técnica de entrecruzamiento del orbicular, descrita por profesores eméritos del Pando Ferrer, en el entropión senil. Métodos: Se realizó un estudio observacional descriptivo longitudinal retrospectivo con pacientes atendidos en el Instituto Cubano de Oftalmología Ramón Pando Ferrer entre enero del 2021 a junio de 2022. La muestra estuvo constituida por pacientes operados con entropión senil con la técnica de Martínez Rodríguez modificada. Se les realizó examen ocular completo con seguimiento a las 24 h, 7 y 15 días, al mes y a los tres meses posteriores a la cirugía. Las variables utilizadas fueron edad, sexo, lateralidad, tiempo de cirugía y complicaciones. Resultados: La edad media fue de 79,26 años, con predominio del sexo masculino (69,56 %) en 23 pacientes y 26 párpados; siendo 20 casos unilaterales y 3 bilaterales. Se reportó una complicación de hipocorreción (3,84 %) y un tiempo medio de 11,9 minutos. Conclusiones: La técnica descrita es un abordaje efectivo demostrado en la baja frecuencia de complicaciones, sencillo y poco invasivo para entropión senil sin laxitud horizontal grave.

Objective: To describe the results of the orbicularis crosslinking technique, described by emeritus professors from Pando Ferrer institute, in senile entropion. Methods: A retrospective, longitudinal, descriptive and observational study was carried out with patients who received attention at Instituto Cubano de Oftalmología Ramón Pando Ferrer between January 2021 and June 2022. The sample consisted of patients with senile entropion operated on with the modified Martinez-Rodriguez technique. They underwent a complete ocular examination with follow-up at 24 hours, 7 and 15 days, one month and three months after surgery. The used variables were age, sex, laterality, surgery time and complications. Results: The mean age was 79.26 years, with a predominance of the male sex (69.56 %) in 23 patients and 26 eyelids; there were 20 unilateral cases and 3 bilateral ones. One complication of hypocorrection (3.84 %) and a mean time of 11.9 minutes were reported. Conclusions: The described technique is an effective approach for senile entropion, demonstrated according to the low frequency of complications, as well as simple and minimally invasive and without severe horizontal laxity.

Cold bandage contact lens use reduces post-photorefractive keratectomy or corneal collagen-crosslinking pain perception in patients

Purpose: To compare post?operative pain perception using bandage contact lens (BCL) stored at 2–8?C (Cold BCL, CL?BCL) or room temperature (23 – 25?C, RT?BCL) after photorefractive keratectomy (PRK) or corneal collagen?crosslinking (CXL) and determine status of nociception associated factors. Methods: In this prospective interventional study, 56 patients undergoing PRK for refractive correction and 100 keratoconus (KC) undergoing CXL were recruited following approval from the institutional ethics committee with informed consent. Patients undergoing bilateral PRK received RT?BCL on one eye and CL?BCL on the other. Pain was graded by Wong–Baker scoring on the first post?operative day (PoD1). Expression of transient receptor potential channels (TRPV1, TRPA1, TRPM8), calcitonin gene?related peptide (CGRP) and IL?6 was measured in cellular content from used BCLs collected on PoD1. Equal number of KC patients received RT?BCL or CL?BCL post?CXL. Pain was graded by Wong–Baker scoring on PoD1. Results: Pain scores on PoD1 were significantly (P < 0.0001) reduced in subjects receiving CL?BCL (Mean ± SD: 2.6 ± 2.1) compared to RT?BCL (6.0 ± 2.4) post?PRK. 80.4% of subjects reported reduced pain scores with CL?BCL. 19.6% reported no change or increased pain scores with CL?BCL. TRPM8 expression was significantly (P < 0.05) increased in BCL of subjects reporting reduced pain with CL?BCL compared to those who did not. Pain scores on PoD1 were significantly (P < 0.0001) reduced in subjects receiving CL?BCL (3.2 ± 2.1) compared to RT?BCL (7.2 ± 1.8) post?CXL. Conclusion: The simple approach of using a cold BCL post?operatively substantially reduced pain perception and could overcome post?operative pain?related limited acceptance of PRK/CXL.

Crosslinking for post-laser-assisted in situ keratomileusis corneal ectasia: Transepithelial flap-on 30 minute and flap-lift 4 minute protocol

Purpose: To evaluate the outcomes of transepithelial corneal collagen crosslinking (CXL) for management of corneal ectasia after laser?assisted in situ keratomileusis (LASIK). Methods: CXL was performed on 18 eyes of 16 patients either with LASIK flap lift (n = 9; 365 nm, 30 mW/cm2, 4 minutes, pulse) or with transepithelial flap?on (n = 9 eyes; 365 nm, 3 mW/cm2, 30 minutes) technique. Postoperative change in maximum keratometry (Kmax), anterior elevation, posterior elevation, spherical equivalent (SE), logMAR uncorrected distance visual acuity (UDVA), aberrations, and central corneal thickness (CCT) were evaluated at 12 months postoperatively. Results: A total of 18 eyes of 16 patients (11 males, 5 females) were included. Overall, Kmax flattened more after flap?on CXL (P = 0.014) compared to flap?lift CXL. The endothelial cell density and posterior elevation were stable throughout the follow?up period. Index of vertical asymmetry (IVA), keratoconus index (KI), and central keratoconus index (CKI) decreased after flap?on CXL at 12 months, postoperatively (P < 0.05), whereas there were no statistically significant changes in these parameters after flap?off CXL group. The spherical aberrations and total root mean square decreased after flap?lift CXL at 12 months, postoperatively (P < 0.05). Conclusion: In our study, transepithelial collagen crosslinking was successfully used to halt disease progression in post?LASIK keratectasia. We recommend flap?on surgical technique for these cases

CYTOTOXICITY TESTING OF A NOVEL CROSSLINKED PRF (C-PRF) DEVELOPED FOR DENTAL PULP TISSUE ENGINEERING PURPOSE

Background- Whole pulp amputation followed by pulp space disinfection and ?lling with an arti?cial material causes loss of signi?cant amount of dentin leaving a non-vital and weakened tooth. Regenerative endodontics with its emerging ?eld of modern tissue engineering has demonstrated promising results using stem cells associated with scaffolds and responsive molecules. [1] Introduction- PRF was recognized as the “second generation” of this family of biomaterials. [6] PRF being tested in pulp tissue engineering by different research groups showed mixed results. (7,8) Research studies have shown that the interactions between the cells and their niche are closely related to physicochemical properties of the scaffolding materials [9, 10]. As PRF is a fragile gel its physical character needs to be improved by cross linking and thereby more longer period of liberation of its growth factors and delayed disintegration in physiological system. Aims and Objectives- Aim of our study was to prepare a very economical and autologous biomaterial for pulp tissue engineering by crosslinking of PRF with tannic acid. Our objective was to detect cytotoxic effect of tannic acid in PRF. Methods and Materials- We followed Choukroun et al. protocol to prepare PRF samples from whole venous blood collected from donors. PRF samples were then cross-linked in freshly prepared TA solution in dapendish for 10 minutes at room temperature. Concentrations of TA 1 wt% was used for preparing samples. After crosslinking, the gels were washed with normal saline for 5 min. to ensure that all excess TA was removed. The viability of cells cultured on the scaffolds was assessed through MTT assay (EZcountTM MTT cell Assay Kit, HiMedia, Mumbai, India). Observations- Both MTT Assay and Phalloidine staining showed favourable results of no clear cytotoxic effects of C-PRF. Conclusion- Based on the results of the cell viability analysis it can be concluded that none of the tannic acid crosslinked PRF created any clear cytotoxicity in the MC3T3 cells. So, C-PRF can safely be used as scaffold for dental pulp or similar tissue engineering purposes

Virtual keratoconus monitoring clinic in a tertiary university hospital in the United Kingdom

Purpose: To describe a new pathway for virtual keratoconus (KC) monitoring in the corneal department of a tertiary referral center in the UK during the coronavirus disease 2019 (COVID?19) pandemic. Methods: A virtual outpatient clinic to monitor KC patients (KC PHOTO clinic) was created. All patients from the KC database in our department were included. At each hospital visit, patients’ visual acuity and tomography (Pentacam; Oculus, Wetzlar, Germany) were collected by a health?care assistant and an ophthalmic technician, respectively. The results were virtually reviewed by a corneal optometrist to identify stability or progression of KC and discussed with a consultant if needed. Those with progression were contacted by telephone and listed for corneal crosslinking (CXL). Results: From July 2020 until May 2021, 802 patients were invited to attend the virtual KC outpatient clinic. Of them, 536 patients (66.8%) attended and 266 (33.2%) did not attend. After corneal tomography analysis, 351 (65.5%) were stable, 121 (22.6%) showed no definite evidence of progression, and 64 (11.9%) showed progression. Forty?one (64%) patients with progressive KC were listed for CXL and the remaining 23 patients deferred treatment after the pandemic. By converting a face?to?face clinic to a virtual clinic, we were able to increase our capacity by nearly 500 appointments per year. Conclusion: In pandemic times, hospitals have developed novel methods of delivering safe patient care. KC PHOTO is a safe, effective, and innovative method of monitoring KC patients and diagnosing progression. In addition, virtual clinics can increase the clinic capacity tremendously and reduce the need of face?to?face appointments, which is beneficial in pandemic conditions.

Evaluation of effects of riboflavin and/or ultraviolet-A on survival of rat limbal epithelial stem cells in ex-vivo

Purpose: To investigate the effects of riboflavin and/or ultraviolet?A (UV?A) irradiation on the cell viability of ex?vivo?cultured rat limbal stem cells (LSCs). Methods: LSCs of male Wistar rats (N = 12 eyes) were cultured, and immunofluorescence staining was performed to evaluate them. After characterization, these cells were assigned to four groups of control (C), a group that was exposed to UV?A radiation (UV), a group that was treated with riboflavin (R), and a group that cotreated with both UV?A and riboflavin (UV+R). To determine the cell viability of LSCs, these cells were subjected to MTT assay on days 1, 3, and 7 after exposure to UV?A and/or riboflavin. The duration of exposure to UV?A and riboflavin was similar to levels used during the conventional corneal collagen cross?linking procedure. Results: Compared with the viable cells in the control group, there was a significant decrease (P < 0.0001) in the number of LSCs in the UV group during all study days. In the R group, the level of viable LSCs was as same as the level of viable LSCs in the C group. Combined treatment with UV?A plus riboflavin significantly decreased the survival of LSCs on days 1 and 3 (P < 0.0001, P < 0.001, respectively) compared with the control group. Interestingly, in the UV+R group, the photosensitizing effect of riboflavin significantly decreased the cytotoxic effect of UV irradiation 7 days after exposure. Conclusion: These results suggest that the administered UV energy in the presence or absence of riboflavin can damage LSCs. Likewise, riboflavin could decrease the toxic effect of UVA on LSCs

Partial-thickness compression sutures without descemetopexy for management of acute hydrops in keratoconus: A novel surgical technique

This article reports a novel surgical technique of partial-thickness compression sutures without descemetopexy with air or gas for the management of acute hydrops in keratoconus. Two patients presented with localized corneal edema with a Descemet membrane (DM) tear in the left eye. Tomography of the right eye revealed localized steepening with increased maximum keratometry and decreased central pachymetry. They were diagnosed with keratoconus in the right eye and acute corneal hydrops (ACH) in the left eye. Compression sutures were passed through the stroma without touching the DM. The anterior chamber was not entered at all at any point during the surgery. Resolution of edema was noted intraoperatively itself. Further resolution of edema was noted from the first postoperative day which markedly reduced within the first week. A corneal scar with no edema was seen at six weeks. In both the patients, vision at presentation was counting fingers close to face which improved to 20/60 and 20/50, respectively, at the last visit.

Conjunctival collagen crosslinking for the management of bleb leak

The purpose of this article is to evaluate the effectiveness of collagen crosslinking of filtering blebs with 0.1% riboflavin stimulated with ultraviolet A radiation in a case of a thin-walled filtering bleb with leakage following an episode of late blebitis. The time to cessation of the bleb leakage was studied, as well as the intraocular pressure, the visual acuity, and the presence of adverse effects during 4 years of follow-up after treatment. A single session of crosslinking was effective in resolving the leakage of the filtering bleb. There were no adverse effects. The intraocular pressure and the visual acuity remained stable after 4 years of follow-up. Collagen crosslinking with 0.1% riboflavin stimulated with ultraviolet A radiation may prove to be a simple, painless, non-invasive, and repeatable treatment of the leaking bleb with the aim of strengthening the collagen fibers of the conjunctiva and avoiding more invasive surgical treatments.

Association of bone resorption marker β-CTX with hypercalcemia in patients with Graves′ disease / 中国医师杂志

Objective:To explore the association of bone resorption marker β carboxyterminal peptide of collagen Ⅰ (β-CTX) with hypercalcemia in patients with Graves′ disease (GD).Methods:287 patients with GD who were hospitalized in the endocrinology department of Fuyang People′s Hospital from January 2021 to December 2021 were divided into control group ( n=251) and hypercalcemia group ( n=36) according to the corrected blood calcium level. The clinical data and serum β-CTX level of the two groups were compared. Logistic regression model was used to analyze the risk factors of hypercalcemia in GD patients. Pearson correlation was used to analyze the correlation between serum β-CTX level and other indexes. Results:Of the 287 GD patients, 36 were diagnosed as hypercalcemia, and the incidence of hypercalcemia was 12.54%. The levels of free triiodothyronine (FT3), free thyroxine (FT4), blood phosphorus (P) and β-CTX in hypercalcemia group were higher than those in control group, and the total parathyroid hormone (iPTH) in hypercalcemia group were lower than those in control group (all P<0.05). Multivariate Logistic regression analysis showed that FT3 ( OR=1.283, 95% CI: 1.049-1.570, P<0.05), iPTH ( OR=0.924, 95% CI: 0.863-0.989, P<0.05), β-CTX ( OR=2.488, 95% CI: 1.193-5.189, P<0.05) were the influencing factors for hypercalcemia in GD patients. Pearson correlation analysis showed that β-CTX was positively correlated with FT3, FT4, blood calcium, P, alkaline phosphatase (ALP), total procollagen type I amino end terminal peptide (PINP), N-bone-gamma-carboxyglutamic-acid-containing proteins (N-MID) and 25(OH)D, and negatively correlated with iPTH (all P<0.05). Conclusions:β-CTX is highly expressed in the serum of GD patients with hypercalcemia, which is a risk factor for the occurrence of hypercalcemia in GD patients.

Comparative study of corneal thickness and thinnest point position of keratoconus measured by Pentacam HR and RTVue OCT / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P&#x003C;0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P&#x003E;0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.

Comparison of corneal epithelial remodeling and corneal aberration changes after FS-LASIK and FS-LASIK Xtra / 中华实验眼科杂志

Objective:To investigate the status of corneal epithelial remodeling and changes in corneal aberration after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and FS-LASIK combined with corneal collagen cross-linking (FS-LASIK Xtra), and to analyze the relationship between corneal epithelial thickness (CET) and corneal aberration.Methods:A cohort study was conducted.A total of 172 patients (172 eyes) who underwent FS-LASIK at Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine were enrolled from June 2021 to February 2022.The 172 eyes were divided into FS-LASIK group (94 eyes) and FS-LASIK Xtra group (78 eyes) according to the surgical procedure, with a total follow-up of 6 months.The cornea was divided into a central 2-mm ring and a ring of 2-5 mm centered on the central cornea.CET at 9 regions in the central 0-5 mm area was measured by OCT before and at 1, 3 and 6 months after surgery, and the corneal higher-order aberration (HOA) was measured by the iTrace visual function analyzer.The main outcomes were the increase in CET (ΔCET), and corneal HOA at 6 months after surgery.The relationship between central corneal ΔCET and corneal aberration was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine (No.2021yh-009). Written informed consent was obtained from each subject.Results:At 1, 3 and 6 months after surgery, the central, superior, superior nasal, nasal, inferior nasal, inferior, inferior temporal, temporal and superior temporal ΔCET were significantly smaller in FS-LASIK Xtra group than in FS-LASIK group (all at P<0.05). In FS-LASIK Xtra group, 6-month postoperative central, superior, superior nasal, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 3- and 6-month postoperative temporal ΔCET were significantly larger than that at 1 month after surgery, and 6-month postoperative superior temporal ΔCET was significantly larger than those at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, 3- and 6-month postoperative central, superior, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 6-month postoperative superior nasal ΔCET was significantly larger than that at 3 months after surgery, and 6-month postoperative nasal, inferior nasal, temporal, superior temporal ΔCET were significantly larger than those at 1 and 3 months after surgery (all at P<0.05). There was no significant difference in vertical trefoil, vertical and horizontal coma changes at different time points after surgery between both groups (vertical trefoil: χ2group=4.27, P=0.118; χ2time=0.01, P>0.05.vertical coma: χ2group=5.74, P=0.057; χ2time=0.08, P=0.957.horizontal coma: χ2group=3.97, P=0.137; χ2time=0.51, P=0.773). The tilted trefoil changes at 1, 3 and 6 months after surgery of FS-LASIK Xtra group were significantly larger than those of FS-LASIK group (all at P<0.05). The 6-month spherical aberration change in FS-LASIK Xtra group was significantly higher than that at 1 month after surgery, and the 6-month spherical aberration change in FS-LASIK group was significantly higher than that at 1 and 3 months after surgery (all at P<0.05). The 6-month total HOA change in FS-LASIK group was significantly lower than that at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, central corneal ΔCET was weakly positively correlated with spherical aberration at 1 and 6 months after surgery ( rs=0.257, P=0.008; rs=0.244, P=0.012), and was weakly positively correlated with total HOA ( rs=0.253, P=0.009; rs=0.279, P=0.004). Conclusions:The postoperative ΔCET after FS-LASIK Xtra is smaller than that after FS-LASIK, but the homogeneity of ΔCET in each region is similar between the two groups.The changes in corneal HOA after surgery are similar in both groups, and there is a certain association between the overall epithelial distribution and corneal aberration.

Clinical efficacy evaluation of accelerated epithelium-off corneal collagen cross-linking on corneal ectasia after keratorefractive surgery / 中华实验眼科杂志

Objective:To investigate the efficacy and safety of accelerated epithelium-off corneal collagen cross-linking (CXL) in the treatment of corneal ectasia after keratorefractive surgery.Methods:An observational case series study was performed.Twelve patients (22 eyes) diagnosed with corneal ectasia after keratorefractive surgery in the First Affiliated Hospital of Army Medical University were enrolled from January 2016 to December 2018.All the patients received accelerated epithelium-off CXL and were followed up for 12 months.Before and 1 week, 1, 3, 6, and 12 months after the operation, the uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (LogMAR) unit were measured.The sphericity, cylindricity, and spherical equivalent were examined by Topcon auto refractor.The maximum keratometry (Kmax) of the front surface, mean keratometry (Km) of the front surface, Km of the back surface, symmetry index of front surface (SIf), symmetry index of back surface (SIb), thinnest corneal thickness (TCT), total aberrations, total high-order aberrations, coma aberration, trefoil aberration and spherical aberration were detected by the Sirius analyzer.The depth of corneal demarcation lines was determined by optical coherence tomography.The intraocular pressure was measured by the non-contact tonometry.The corneal endothelial cell density was assayed by the endothelial cell densitometry.The inflammatory reaction and haze were observed with a slit lamp at different time points after surgery.This study adhered to the Declaration of Helsinki.The study protocol was approved by the First Affiliated Hospital of Army Medical University (No.KY2020063). Written informed consent was obtained from each patient before entering the cohort.Results:Among the 22 eyes of 12 cases, 3 eyes of 2 cases (13.64%) underwent small incision lenticule extraction, and 19 eyes of 10 cases (86.36%) underwent excimer laser in situ keratomileusis.The UCVA (LogMAR), BCVA (LogMAR), cylindricity and spherical equivalent before the operation were 0.61±0.42, 0.24±0.23, (-2.83±2.39)D, (-3.60±2.66)D, which were significantly worse than 0.45±0.31, 0.12±0.15, (-2.11±1.67)D, (-3.12±2.31)D at 12 months after the operation ( t=4.054, 4.956, -3.728, -2.742; all at P<0.05). The front surface Kmax, front surface Km and SIf at 12 months after the operation were (48.37±5.80), (41.49±3.04), (5.36±4.07)D, which were significantly lower than (49.61±5.97), (41.66±2.97), (5.85±4.18)D before the operation ( t=5.949, 2.278, 2.719; all at P<0.05). There was no significant difference in sphericity, Km of the back surface, SIb, TCT, total aberrations, total high-order aberrations, coma aberration, trefoil aberration, spherical aberration, intraocular pressure and endothelial cell density between before and 12 months after the operation (all at P>0.05). Grade 0.5-2 haze occurred in 8 eyes of 4 patients one month postoperatively.After administration of prednisolone acetate eye drops, haze decreased or disappeared 3 months postoperatively, with UCVA and BCVA unchanged.A corneal demarcation line with a depth of (285.40±51.61)μm was found in 11 eyes of 6 cases at 1 month after operation. Conclusions:Accelerated epithelium-off CXL can significantly improve visual acuity, reduce corneal astigmatism and corneal curvature, as well as effectively prevent the progress of corneal ectasia.

Characteristics of corneal stromal demarcation line after different cross-linking methods in keratoconus and its influence on the cross-linking effect / 中华实验眼科杂志

Objective:To compare the characteristics of corneal stromal demarcation line after different surgical methods of riboflavin/ultraviolet A corneal collagen cross-linking (CXL) in early keratoconus, and analyze the influence of the demarcation line on the cross-linking effect.Methods:A non-randomized controlled clinical study was conducted.Sixty-nine eyes of 69 patients treated with riboflavin/ultraviolet A CXL in the Eye Hospital of Shandong First Medical University from May 2019 to February 2021 were included.According to the cross-linking methods, the patients were divided into epithelium-on treatment group (21 eyes) and epithelium-off treatment group (48 eyes). There were 25 eyes in 5.4 J energy group and 44 eyes in 7.2 J energy group.The morphology and changes of corneal stromal cross-linking reaction (corneal stromal demarcation line) were observed at 2 weeks, 1, 3 and 4 months after operation.Changes in the thinnest corneal thickness (TCT), uncorrected visual acuity (UCVA, LogMAR), best corrected visual acuity (BCVA, LogMAR) and corneal maximum curvature (Kmax) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.2019.05). Written informed consent was obtained from each subject.Results:Of the 69 eyes after operation, 44 eyes (63.77%) had demarcation lines, and 25 eyes (36.23%) had no demarcation lines.The occurrence rate of demarcation lines in the epithelium-on treatment group was 79.17%(38/48), which was significantly higher than 28.57%(6/21) in the epithelium-off treatment group ( χ2=16.186, P<0.01). The occurrence rate of demarcation line in 5.4 J energy group was 72.00%(18/25), and the 7.2 J energy group was 56.80%(25/44), with no significant difference ( χ2=1.565, P=0.302). Slit lamp microscopy and anterior segment-optical coherence tomography showed that the demarcation line appeared at 1-2 weeks after operation, gradually converged and strengthened after 1 month, turned diffuse, blurred and faded by degrees after 2-3 months, and basically disappeared after 4 months.The depth of the demarcation line reached 141-423 μm, with an average depth of (263.44±84.22)μm.Scanning laser confocal microscopy showed that corneal stromal cells were activated and light reflection was enhanced after CXL.Collagen fibers extended vertically and horizontally, crisscrossed, and were in a reticular arrangement.The TCT decreased from preoperative (458.69±38.28)μm to (443.86±36.54)μm at 4 months after operation, showing a statistically significant difference ( t=6.705, P<0.001). There was no significant difference in the TCT reduction between groups with and without demarcation lines ( t=1.684, P=0.100). At 4 months postoperatively, the UCVA of all eyes increased from preoperative 0.74±0.37 to 0.69±0.38, and the difference was statistically significant ( t=2.109, P=0.039). There was no significant difference in BCVA between before and after operation ( t=1.006, P=0.319). There was no significant difference in change of UCVA and BCVA between groups with and without demarcation lines ( t=0.065, P=0.949; t=0.346, P=0.730). There was no significant difference in Kmax in all patients between before and after operation ( t=0.050, P=0.950). There was no significant difference in the Kmax change between groups with and without demarcation lines ( t=-0.739, P=0.464). The change in TCT in the epithelium-off treatment group was significantly greater than that in the epithelium-on treatment group ( t=2.815, P=0.008). There was no significant difference in UCVA, BCVA and Kmax changes between epithelium-on and epithelium-off treatment groups (all at P>0.05). There was no obvious corneal scarring, infectious keratitis, corneal endothelial decompensation or other complications. Conclusions:The demarcation line after CXL may be a sign of the depth of cross-linking reaction, which is more prone to occur after the epithelium-off operation method.Both the epithelium-on and epithelium-off operation methods have similar therapeutic effects.Demarcation line after different cross-linking methods has no significant influence on the cross-linking effect in keratoconus.

Application of proanthocyanidin in the treatment and repair of deep caries / 口腔疾病防治

@#Proanthocyanidin (PA), as a kind of natural plant polyphenol, have a variety of biological functions, such as promoting remineralization, inducing collagen cross-linking, inhibiting protease activity and inhibiting bacteria. Therefore, PA could be broadly used in the clinical application of treatment and repair of deep caries in the future; for example, PA could promote dentin remineralization, improve resin-dentin bonding durability and improve the dentin acid erosion effect. This application potential of PA arises from several features, firstly, PA can not only promote dentin remineralization on its own or with other remineralizers but also exhibits antibacterial effects, which can inhibit acid production while reducing the formation of cariogenic pathogens and their biofilms. Based on the above features, PA can reduce the incidence of caries disease; thus, PA improves deep caries and long-term effects after treatment. In addition, PA added to adhesives or etch agents can improve the etching and bonding effect of dentin by inducing collagen cross-linking and inhibiting protease activity, thus achieving the ultimate goal of improving the bonding performance of deep caries. This paper summarizes recent progress of research on PA for the treatment and repair of deep caries, including the promotion of dentin remineralization and antibacterial activity as well as the improvement in dentin bonding and acid etching effect, to provide a more comprehensive reference for treating and restoring deep caries in clinical practice.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry / 浙江大学学报·医学版

OBJECTIVES@#To design and prepare silk fibroin/hyaluronic acid composite hydrogel.@*METHODS@#The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope.@*RESULTS@#The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good.@*CONCLUSIONS@#The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.

Repetibilidade do estudo tomográfico da córnea com Scheimpflug rotacional, em olhos normais, olhos com ceratocone e olhos com ceratocone operados por crosslinking / Repeatability of the tomographic study of the cornea with a rotational Scheimpflug in normal eyes, eyes with keratoconus and eyes with crosslinking for keratoconus

RESUMO Objetivo Avaliar a precisão da tomografia corneana com imagens de Scheimpflug (Pentacam® AXL, OCULUS, Wetzlar, Alemanha) nos padrões de escaneamento com 25 e 50 imagens, verificando sua repetibilidade e reprodutibilidade em olhos normais, com ceratocone e com ceratocone após crosslinking. Métodos Estudo prospectivo, transversal, misto, no qual foram incluídos os pacientes que tinham córneas normais, ou com ceratocone; e não tinham realizado cirurgias corneanas, com exceção do crosslinking. Foram excluídos os pacientes que tivessem realizado outras cirurgias, como implante de anel intracorneano ou transplante de córnea. Foram realizadas três medidas com 25 imagens e três medidas com 50 imagens em cada olho incluído no estudo. Resultados O estudo avaliou 54 olhos de 41 pacientes. Destes, dez (18,52%) olhos eram com córneas normais e sem cirurgia ocular prévia aleatoriamente selecionados de 5 pacientes; 22 (40,74%) olhos aleatoriamente selecionados de 18 pacientes com ceratocone, sem cirurgia ocular prévia; e 22 (40,74%) olhos com ceratocone de 18 pacientes operados por crosslinking. No estudo da repetibilidade, percebemos uma maior variação de valores em todos os índices nos pacientes com ceratocone comparados aos de pacientes com olhos normais, em grande parte dos parâmetros analisados. Conclusão Não houve diferença significativa entre os métodos de escaneamento por 25 e 50 imagens, sendo o escaneamento por 25 imagens mais conveniente. A presença de ceratocone teve impacto negativo na repetibilidade de ambos os tipos de exame, e foi grande a concordância entre os métodos nos três grupos estudados. O coeficiente de repetibilidade permite considerar a relevância clínica dos dados para avaliar a progressão de ceratocone.

ABSTRACT Objective To evaluate the accuracy of corneal tomography with Scheimpflug images (Pentacam® AXL, OCULUS, Wetzlar, Germany) in scanning patterns with 25 and 50 images, by analyzing their repeatability and reproducibility in normal eyes, eyes with keratoconus and with keratoconus after crosslinking. Methods Prospective, cross-sectional, mixed study including patients who had normal corneas, or who had keratoconus, who had not undergone corneal surgery, with the exception of crosslinking. Patients who had undergone surgery for intracorneal ring implantation or corneal transplantation were excluded. Three measurements were performed with 25 images and three measurements were performed with 50 images on each eye included in the study. Results The study evaluated a total of 54 eyes of 41 patients. Of these, 10 (18.52%) eyes had normal corneas, without previous eye surgery, 22 (40.74%) were eyes with keratoconus, without previous eye surgery, and 22 (40.74%) were eyes with keratoconus, with crosslinking for keratoconus. In the study of repeatability, we noticed a greater variation of values in all indices in patients with KC compared to those with normal eyes, in most of the parameters analyzed. Conclusion There is no significant difference between the scanning methods with 25 and 50 images. However, 25 scans has advantages that make it the main method suggested. The presence of keratoconus has a negative impact on the repeatability of both types of examination, and there is great agreement between the methods in the three groups studied. The high repeatability coefficient in some parameters suggests that these data should be used with care in the assessment of keratoconus progression.

Corneal epithelial remodeling following stromal lenticule addition keratoplasty combined with corneal collagen cross-linking for the treatment of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the epithelial remodeling of femtosecond laser-assisted stromal lenticule addition keratoplasty combined with corneal collagen cross-linking(SLAK-CXL)in patients with progressive keratoconus, investigate the remodeling rules of corneal epithelial and influencing factors, and provide clinical data for further refractive correction.METHODS: Retrospective and observational study. A total of 28 keratoconus patients(29 eyes)who received SLAK-CXL from September 2020 to October 2021 were included. Preoperative and postoperative visual acuity, intraocular pressure(IOP), diopter, keratometry and corneal epithelial thickness(CET)were recorded. The trend of CET change was observed. The factors affecting CET were analyzed according to the thickness and depth of the lenticule.RESULTS: Flattest meridian keratometry(Kf)and steepest meridian keratometry(Ks)at 1mo postoperatively were significantly larger than those preoperatively(P&#x003C;0.05). The thinnest corneal thickness(TCT)at 1, 2, 6mo and 1a postoperatively were significantly larger than preoperative(P&#x003C;0.05). The CET changed with time, with the central CET showing a larger variation tendency. The CET of superior, superior nasal, nasal, superior temporal in paracentral area were thinned, the CET of superior, temporal, superior temporal in midperipheral area were thinned, while the CET of superior nasal was thickened in peripheral area at 1, 2, 6mo and 1a postoperatively. The variation of CET was not correlated with the thickness or depth of lenticule at 1a postoperatively(P&#x003E;0.05).CONCLUSIONS: It is firstly found that the corneal morphology has changed after SLAK-CXL. CET decreases and then increases and then decreases again. At 1a postoperatively, the CET of the central and paracentral areas is thinner, while the CET of the midperipheral and peripheral areas is thicker. The degree of epithelial remodeling is not correlated with lenticule thickness or depth.