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Introduction. To evaluate the changes of lens antidilatation, antiedema, and antienzymolysis ability after different concentrations of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC-NHS)-induced collagen cross-linking. Methods. Corneal stromal lenticules (n = 100) obtained from small incision lenticule extraction (SMILE) procedures were divided into 5 groups: no treatment (control); EDC/NHS (5%/2.5%); EDC/NHS(5%/5%); EDC/NHS (10%/5%); riboflavin and ultraviolet-A light (UVA). Collagen crosslinking was induced using EDC-NHS and UVA. Biomechanical assessments including inflation test, enzymatic degradation resistance, and light transmittance were evaluated posttreatment. Results. (1) Lenticule apex displacement ranked: control Group > UVA Group > Group (5%/5%) > Group (5%/2.5%) > Group (10%/5%) (Friedman test, p < 0.0001). (2) Light transmittance was significantly higher in the crosslinked groups versus control, with EDC/NHS superior to UVA riboflavin. After 15 minutes in PBS, light transmittance decreased due to swelling; however, crosslinked groups maintained significantly higher transmittance versus control. (3) Following crosslinking, enzymatic resistance improved significantly, with the EDC-NHS crosslinking group was significantly better than the UVA cross-linking group. Conclusions. EDC/NHS crosslinking enhanced lenticule stiffness, antiedema, and enzymatic resistance and without compromising the transparency of the lens. Moreover, EDC/NHS crosslinking efficacy exceeded UVA riboflavin crosslinking in improving lenticule biomechanical properties. [ABSTRACT FROM AUTHOR]

Background and Objectives: Clinical efficacy and safety of pathogen‐reduced platelet concentrates (PR‐PCs) concerning bleeding prevention are still debated despite conclusive real‐world data from multiple countries where PR‐PCs are transfused routinely. We performed a meta‐analysis of randomized controlled trials (RCTs) comparing the clinical efficacy and safety of conventional platelet components (PCs) and PR‐PCs prepared with the amotosalen/ultraviolet A light (INTERCEPT platelet concentrate [I‐PC]) or riboflavin/ultraviolet light (Mirasol platelet concentrate [M‐PC]) technologies, transfused in thrombocytopenic adult patients. Materials and Methods: A literature search was conducted, and 10 RCTs met the criteria for inclusion in this meta‐analysis. Summary odds ratios (ORs) of clinically significant bleeding (World Health Organization [WHO] bleeding grade ≥2), severe bleeding (WHO bleeding score ≥3) and all‐cause mortality were calculated. Results: The use of I‐PC was not associated with an increase in the OR of clinically significant bleeding when compared to non‐treated PCs (OR, 1.12; 95% CI: 0.89–1.41; p = 0.33), whereas transfusions with M‐PC showed an increase in clinically significant bleeding (OR, 1.34; 95% CI: 1.03–1.75; p = 0.03). The OR of severe bleeding did not increase with either I‐PC or M‐PC (OR 0.88; 95% CI: 0.59–1.31; p = 0.52 for I‐PC; OR 1.25; 95% CI: 0.66–2.37; p = 0.49 for M‐PC). In the case of all‐cause mortality, compared to non‐treated PC, I‐PC showed an OR of 0.61 (95% CI: 0.36–1.04; p = 0.07), and M‐PC showed an OR of 3.04 (95% CI: 0.81–11.47; p = 0.1). Conclusion: No differences were observed concerning the clinical efficacy and safety of overall PR‐PCs when compared to non‐treated PCs. However, differences are evident when analysing platelets prepared with the two PR technologies independently. [ABSTRACT FROM AUTHOR]

Little attention has been paid to interactions between electromagnetic radiation and matter in chemistry education, especially due to a lack of conceptually embedded experiments. The three presented experiments demonstrate how fluorescence can be applied as a detection method for reaction components by using the example of photodegradation of the vitamin riboflavin. The orange‐yellow vitamin is extracted from custard powder and identified by its typical yellow fluorescence as well as by forming a non‐fluorescent red complex when silver ions added. Riboflavin degrades into lumichrome when exposed to UV radiation. By thin‐layer chromatography, riboflavin and lumichrome can be distinguished by their characteristic fluorescence colour. Factors influencing riboflavin degradation like temperature and solvent as well as duration and wavelength of radiation are varied and their influence on reaction speed is examined. [ABSTRACT FROM AUTHOR]

Purpose: To study the demographics and clinical profile of keratoconus (KC) presenting in pre-teen children in India.Methods: This was a retrospective case series conducted as a single-institutional study at a tertiary eye center in India. A total of 586 eyes from 294 KC patients (aged 12 years or less) without any active comorbid conditions of the eye were included in the study. Slit-lamp biomicroscopy was used to document the clinical signs of KC. Information on age; gender; reason for consultation; family history; history of allergy, atopy, and eye rubbing; manifest refraction; uncorrected and best-corrected distance visual acuity (UCVA and BCVA, respectively); clinical presentation; and contact lens usage were also analyzed, along with data on types of medical and surgical treatments for KC and their outcomes.Results: The mean age of this pediatric KC patient cohort was 9.3 ± 1.8 years, and there was a male (70%) preponderance. Baseline mean UCVA, BCVA, steep keratometry, and flat keratometry were 0.86 ± 0.58 logMAR, 0.44 ± 0.38 logMAR, 54.82 ± 8.4 D, and 48.21 ± 9.5 D, respectively. Progression, necessitating collagen crosslinking (CXL), was noted in 12.7% eyes. Post-CXL, visual and topographic parameters remained stable without any complications till 6 months posttreatment. However, in eyes that did not undergo CXL, significant progression over time (P < 0.001) was observed. A keratoplasty was required in 2.3% eyes.Conclusion: KC was present at an advanced stage in 25% of the pre-teens in our series, and therefore, it is an important diagnostic entity when a refractive error is diagnosed, even in very young children. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the 5-year results of accelerated corneal collagen crosslinking (CXL) for progressive keratoconus and identify preoperative characteristics predictive of visual and topographic outcomes.Methods: A prospective interventional case series. Nineteen eyes of 19 patients receiving accelerated CXL with settings of 18 mW/cm2 for 5 min were included. Clinical and topographic parameters were assessed. Linear regression and logistic regression were used to compare the R2 and odds ratio (OR), respectively, between baseline characteristics and postoperative outcomes.Results: Corrected distance visual acuity (CDVA) remained stable from 0.28 ± 0.21 to 0.25 ± 0.18 logMAR (P = 0.486). The mean cylindrical refraction was stable (P = 0.119). The maximal keratometry (Kmax) decreased from 61.99 ± 10.37 to 59.25 ± 7.75 D (P < 0.001), flattening in the flattest and steepest meridians and mean keratometry were also observed (P ≤ 0.040). The mean anterior elevation at the apex reduced from 21.42 ± 16.69 to 18.53 ± 12.74 μm (P = 0.013) and changes in posterior elevation were non-significant (P = 0.629). Preoperative Kmax best predicted the postoperative change in Kmax (R2 = 0.55, P < 0.001) compared to the other baseline characteristics (P ≤ 0.028), whereas preoperative CDVA was the only significant predictor of postoperative change in CDVA (R2 = 0.41, P = 0.003). Accelerated CXL is less likely to fail in eyes with a steeper preoperative Kmax (OR = 0.74, P = 0.040) or greater posterior elevation at the apex (OR = 0.91, P = 0.042).Conclusion: Kmax significantly decreased following accelerated CXL. Eyes with worse preoperative CDVA and higher Kmax were more likely to have an improvement in visual acuity and corneal flattening. [ABSTRACT FROM AUTHOR]

The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and its ultraviolet (UV) radiation is much greater than that of other regions in the world. Yellow mushroom (Floccularia luteovirens) is a unique and widely distributed edible fungus on the QTP. However, the molecular mechanism of F. luteovirens's response to strong UV radiation remains unclear. Herein, we reported the 205 environmental adaptation and information processing genes from genome of F. luteovirens. In addition, we assembled the RNA sequence of UV-affected F. luteovirens at different growth stages. The results showed that in response to strong UV radiation, a total of 11,871 significantly different genes were identified, of which 4,444 genes in the vegetative mycelium (VM) stage were significantly different from the young fruiting bodies (YFB) stage, and only 2,431 genes in the YFB stage were significantly different from fruiting bodies (FB) stage. A total of 225 differentially expressed genes (DEGs) were found to be involved in environmental signal transduction, biochemical reaction preparation and stress response pathway, pigment metabolism pathway, and growth cycle regulation, so as to sense UV radiation, promote repair damage, regulate intracellular homeostasis, and reduce oxidative damage of UV radiation. On the basis of these results, a molecular regulation model was proposed for the response of F. luteovirens to strong UV radiation. These results revealed the molecular mechanism of adaptation of F. luteovirens adapting to strong UV radiation, and provided novel insights into mechanisms of fungi adapting to extreme environmental conditions on the QTP; the production the riboflavin pigment of the endemic fungi (Yellow mushroom) in the QTP was one of the response to extreme environment of the strong UV radiation. [ABSTRACT FROM AUTHOR]

Background. Corneal collagen cross-linking (CXL) therapy, a method that uses a combination of riboflavin and ultraviolet-A light (UVA), can promote the formation of covalent cross-linking of amino acid residues of corneal collagen and enhance the hardness of the cornea. In this study, we explored the effects of corneal stromal lens collagen cross-linking regraft on corneal biomechanics. Methods. A total of 15 New Zealand white rabbits were divided into 3 groups: normal control group (group A), SMILE + uncross-linked lens implantation group (Group B), and SMILE + cross-linking lens implantation group (group C). The design parameters of SMILE surgery were as follows: the corneal cap was 120 um thick, the lens diameter was 6.5 mm, and the diopter was -6.0D. Riboflavin and ultraviolet-A (UVA) were used as corneal stromal lens CXL, which was implanted into the allogeneic rabbit corneal stromal bag 24 hours after the operation. Postoperative corneal thickness (CCT), refraction, AS-OCT, and corneal biomechanics were performed before and then at 1 and 3 months after the operation. Results. All corneas appeared transparent and smooth 3 months after surgery. The corneal thicknesses of both group B and group C were lower than those before the operation. The corrected refraction of group B and group C after lens implantation was also lower than the expected corrected power; there was no significant difference between the two groups (P > 0.05). AS-OCT results showed an uneven surface and thickness of the corneal stromal lens in two eyes of group B. Moreover, corneal elastic deformation increased with intraocular pressure in each group; displacement from large to small was group B > group C and > group A. The creep from large to small was group B > group C > group A. The fiberboard layers of groups B and C were disordered, and there were a few autophagosomes in the fibroblasts of group B by transmission electron microscopy (TEM). Conclusions. Allograft graft of corneal stromal lens collagen cross-linked can significantly increase the biomechanical properties of the cornea. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze if the outcome after corneal crosslinking (CXL) in progressive keratoconus patients depends on the stage at which the procedure is performed. This knowledge would help to improve success of CXL and to define surgery indications in those patients.Methods: In this retrospective study, 124 consecutive eyes of 100 patients with progressive keratoconus undergoing corneal CXL at the University Eye Hospital Tübingen were included. The eyes were graded according to modified Krumeich stages depending on induced myopia or astigmatism, corneal radii, minimum corneal thickness, and morphological changes. The observation period covered November 2008 to September 2018. Preoperatively, 12 and 24 months after CXL, the best corrected visual acuity (BCVA) was determined and astigmatism as well as tomographic parameters (Kmax, Kmin, central corneal thickness (CCT), minimum corneal thickness (MCT)) were measured by means of a Scheimpflug camera system.Results: BCVA results showed significant differences between the modified Krumeich stages at 12 months (p = 0.014) and at 24 months postoperatively (p = 0.032). Also, astigmatism differed significantly among the stages at 24 months after CXL (p = 0.023). However, no significant differences regarding astigmatism were detectable after 12 months. In terms of Kmax, Kmin, CCT, and MCT, no significant differences between the Krumeich stages were observed.Conclusions: BCVA showed a significantly higher improvement after CXL in the early stage of keratoconus compared to a higher stage. However, the postinterventional tomographic values did not differ significantly between the different modified Krumeich stages. The significantly higher improvement in BCVA after CXL in the early stage might indicate that earlier intervention provides a higher subjective benefit to the individual. Further studies with larger sample sizes are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: To assess Photo Activated Chromophore for Infective Keratitis-Cross Linking (PACK-CXL) and its efficacy as a treatment modality in managing microbial keratitis.Methods: Single Centre prospective interventional study in infectious keratitis. A total of eleven patients were taken who had corneal thickness (CT) more than 400μm. PACK-CXL was performed according to Dresden's protocol. The response was assessed by slit lamp examination, BCVA and AS-OCT at the time of complete healing.Results: The mean visual acuity at presentation was 1.207logMAR (0.3-3) which improved to mean value of 0.53logMAR (0.3-1). Mean time taken for complete epithelization was 17.45 days (14- 30 days) and that for complete healing was 33.72 days (21- 60 days). Mean CT at the baseline was 650.5± 108μm which reduced on consecutive follow up visits. There was reduction in the symptoms in nine patients except in two. One case reported increase in symptoms with worsening increase in endoexudates and hypopyon, and the other developed drug toxicity due to topical medications.Conclusion: Patients who underwent PACK-CXL showed good and early healing, good remodelling of cornea and improved visual acuity. The recalcitrant cases became responders to the same medications after PACK-CXL. Thus, PACK-CXL works well for both fungal and bacterial keratitis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the clinical outcomes and assess preoperative characteristics that may predict outcomes in keratoconus 1 year after accelerated transepithelial corneal cross-linking (ATE-CXL).Methods: This prospective study included 93 eyes of 84 consecutive keratoconus patients with 1-year follow-up after ATE-CXL. Preoperative characteristics included corneal astigmatism, anterior chamber depth, anterior chamber volume, radius of curvature, posterior elevation, central corneal thickness (CCT), thinnest corneal thickness, steepest meridian keratometry, flattest meridian keratometry, and the maximum keratometry (Kmax). Data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. The patient eyes were grouped into 3 subgroups according to CCT and Kmax values to observe the changes of keratoconus progression.Results: All patients were successfully operated without complications at any follow-up time point. Mean changes of Kmax from baseline at 6 and 12 months were - 0.60 ± 2.21 D (P = 0.011) and - 0.36 ± 1.58 D (P = 0.030), respectively. Eyes with a thinner CCT and higher Kmax values exhibited a tendency for topographic flattening of ≥1.0 D (P = 0.003; P = 0.003). In the subgroup comparison, the Kmax values decreased significantly at 6 and 12 months after ATE-CXL in the group with CCT ≤ 450 μm (P = 0.018 and P = 0.045); the Kmax values of the group with Kmax > 65.0 D decreased significantly at 6 months postoperatively (P = 0.025).Conclusion: ATE-CXL is a safe and effective treatment for keratoconus patients. Patients with thinner CCT and higher Kmax values are more likely to benefit from ATE-CXL. [ABSTRACT FROM AUTHOR]

Purpose: To monitor the changes in the ABCD grading system during a one-year follow-up after a corneal cross-linking (CXL) procedure.Methods: This prospective study included 30 eyes of 25 patients with keratoconus, who received the CXL treatment. The patients with a history of ocular trauma or surgery and other corneal pathology were excluded from the study. The patients were examined at the baseline visit and followed up at 3, 6, and 12 months after the CXL. All the patients underwent a standard CXL procedure with visual acuity and Scheimpflug tomography testing at each visit. The corneal parameters and ABCD grading were monitored throughout the follow-up period.Results: There were no significant changes of parameter A and anterior radius curvature (ARC) in the ABCD grading system. Parameters B and D showed progression postoperatively, with an improvement of parameter D on the final visit. Parameter C showed a statistically significant increase at all three post-CXL visits, but a constant gradual decrease in the value over time.Conclusion: The ABCD grading system can be very useful in monitoring the progression of keratoconus (KC), but it can also help in monitoring the efficacy of corneal cross-linking. The anterior surface parameters in the ABCD grading system did not show progression in the post-CXL period, and parameters C and D showed improvement and stability a year after the procedure. [ABSTRACT FROM AUTHOR]

Purpose: To find the intraocular lens (IOL) power calculation changes before and after isotonic collagen cross-linking (CXL) in keratoconus patients.Methods: : Thirty-five eyes of 25 patients who underwent isotonic CXL were included. The cases included conventional CXL (n = 16), accelerated CXL (n = 7), contact lens-assisted CXL (CACXL) (n = 9), accelerated CACXL (n = 3). All underwent ocular biometry (IOL master), corneal topography (Orbscan II), and simulated keratometry (Orbscan II) preoperatively and 1-year post CXL. Change in best-corrected visual acuity (BCVA), axial length (AL), simulated keratometry (Sim K), anterior chamber depth (ACD), and IOL power were analyzed in the overall data and then grouped based on flattening (Group A) and no flattening (Group B) of Sim K value post CXL procedure.Results: For the overall data, there was no significant change in IOL power (P = 0.05) at the end of 1 year, BCVA showed a significant increase (P < 0.01), and Sim K reading showed a statistically significant flattening (P = 0.001); ACD and AL showed insignificant change. In intergroup comparison, there was no statistically significant change in IOL power. However, in Group A, a significant change in BCVA and Sim K values was observed. In both groups (Group A and Group B), IOL power was found to be negatively correlated with AL and Sim K values.Conclusion: Isotonic CXL did not affect IOL power calculation at the end of 1 year. However, significant change in BCVA and sim K reading was noted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of CXL in treating fungal keratitis as an adjuvant therapy.Methods: Detailed clinical examination microbiological investigation was performed. Twenty fungal keratitis patients were recruited and randomized into two groups: group 1 (n= 11, standard antifungal), group 2 (n=9, corneal collagen crosslinking with standard antifungal). Corneal scraping and tear samples collected were subjected to real-time PCR targeting ITS, TLR analysis and cytokine analysis.Results: The mean time for complete resolution of ulcer for group 2 was significantly shorter compared to group 1 and the final mean BCVA was better for group 2. Expression of IL-1β, IL-8, IFN-γ significantly decreased immediately post CXL in group 2 patients. Significant downregulation of TLR 6, TLR-3, TLR-4 was observed 3-days post CXL compared to group 1 patients.Conclusion: Adjuvant effect of CXL was significant in treating fungal keratitis compared to standalone antifungal treatment. [ABSTRACT FROM AUTHOR]

Background: There is a global increase in whole blood usage and at the same time, emerging pathogens give cause for pathogen reduction technology (PRT). The Mirasol PRT has shown promising results for plasma and platelet concentrate products. Treatment of whole blood with subsequent platelet survival and recovery analysis would be of global value.Study Design and Methods: A two-arm, open-label laboratory study was performed with 40 whole blood collections in four groups: non-leukoreduced non-PRT-treated, non-leukoreduced PRT-treated, leukoreduced non-PRT-treated, and leukoreduced PRT-treated. Leukoreduction and/or PRT-treatment was performed on the day of collection, then all WB units were stored at room temperature for 24 h. Sampling was performed after hold-time and after 24-h storage in RT. If PRT-treatment or leukoreduction, samples were also taken subsequently after treatment. Thirteen healthy volunteer blood donors completed the in vivo study per protocol. All WB units were non-leukoreduced and PRT-treated. Radioactive labeling of platelets from RT-stored, PRT-treated whole blood, sampling of subjects, recovery, and survival calculations were performed according to the Biomedical Excellence for Safer Transfusion Collaborative protocol.Results: In vitro characteristics show that PRT-treatment leads to increased levels of hemolysis, potassium, and lactate, while there are decreased levels of glucose, FVIII, and fibrinogen after 24 h of storage. All values are within requirements for WB. In vivo recovery and survival of platelets were 85.4% and 81.3% of untreated fresh control, respectively.Conclusions: PRT-treatment moderately reduces whole blood quality but is well within the limits of international guidelines. Recovery and survival of platelets are satisfactory after Mirasol treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to test a method for estimating corneal rigidity before and after cross-linking (CXL) using a Schiøtz tonometer.Methods: The study was performed in the Kyiv City Clinical Ophthalmological Hospital "Eye Microsurgical Center", Ukraine. This was a prospective, consecutive, randomized, masked, case-by-case, clinical study. Corneal rigidity, indicated by the gradient (G) between lg applied weight and corresponding lg scale reading during Schiøtz tonometry, were obtained by increasing (A-mode) then reducing (D-mode) weights by two operators [A] in keratoconus, post-CXL and control subjects for estimation of (i) interoperator and (ii) intersessional errors, (iii) intergroup differences; [B] before and after CXL. Central corneal thickness CCT was measured by scanning slit pachymetry. ANOVA, t tests, linear regression were the statistical tools used.Results: Average interoperator difference (ΔG) was -0.120 (SD = ±0.294, 95%CI = -0.175 to -0.066). A significant correlation between ΔG and the mean of each pair of G values was found (r = -0.196, n = 112, P = 0.038). Intersessional differences in mean G values were insignificant (P > 0.05). There was a significant correlation between G at first session (X1) and difference between sessions (ΔG) [Operator 1, ΔG = 0.598x1-0.461, r = 0.601, n = 27, P = 0.009]. Significant intergroup differences in G were found (Operator 1, one-way ANOVA, F = 4.489, P = 0.014). The difference (Δ) between the pre-(X2) and post-CXL treatment G values was significantly associated with the pre-CXL treatment value (Operator 1, Δ = 1.970x2-1.622, r = 0.642, n = 18, P = <.001). G values were correlated with CCT in keratoconus and post-CXL.Conclusion: Corneal rigidity (G) estimated using the Schiøtz tonometer can be useful for detecting changes after CXL. However, G values are linked to CCT, can vary from time-to-time and the procedure is operator dependent. [ABSTRACT FROM AUTHOR]

Background: Bacterial contamination of platelet concentrates (PCs) is the predominant cause of infectious transfusion reactions. The Pathogen Inactivation Mirasol system was implemented at the King Faisal Specialist Hospital (Saudi Arabia) to reduce the risk of transfusing contaminated PCs. This pilot study evaluated the effectiveness of Mirasol against Klebsiella pneumoniae, a pathogen associated with transfusion reactions, in whole blood-derived PCs.Study Design and Methods: Whole blood (WB) units inoculated with one of six K. pneumoniae strains (five clinical isolates and ATCC-700603) at a concentration of 3-38 CFU/unit, were processed using the platelet-rich plasma (PRP) method. Each spiked PC was pooled with four unspiked units. The pooled PC was split into three Mirasol storage bags: an untreated unit (control), and two units treated with Mirasol at 26 and 32 h post-WB collection, respectively. PC samples obtained before and after Mirasol treatment were used for BacT/ALERT cultures and determination of bacteria quantification. Each experiment was repeated three independent times.Results: Five strains were detected prior to PC treatment (24 h post-WB spiking), while one clinical isolate was not detected. Mirasol treatment after 26 h of WB collection resulted in complete inactivation of all K. pneumoniae strains. However, treatment 32 h post-WB collection resulted in the breakthrough of one clinical isolate in two of the three replicates with ~7.8 log10 CFU/unit detected on day 5 of PC storage.Conclusion: Delayed Mirasol treatment from 26 to 32 h post-WB collection, resulted in one breakthrough. These results highlight the importance of minimizing the time between WB collection and PI treatment. [ABSTRACT FROM AUTHOR]

Objective: During the COVID-19 era, a reliable method for tracing aerosols and droplets generated during otolaryngology procedures is needed to accurately assess contamination risk and to develop mitigation measures. Prior studies have not investigated the reliability of different fluorescent tracers for the purpose of studying aerosols and small droplets. Objectives include (1) comparing vitamin B2, fluorescein, and a commercial fluorescent green dye in terms of particle dispersion pattern, suspension into aerosols and small droplets, and fluorescence in aerosolized form and (2) determining the utility of vitamin B2 as a fluorescent tracer coating the aerodigestive tract mucosa in otolaryngology contamination models. Methods: Vitamin B2, fluorescein, and a commercial fluorescent dye were aerosolized using a nebulizer and passed through the nasal cavity from the trachea in a retrograde-intubated cadaveric head. In another scenario, vitamin B2 was irrigated to coat the nasal cavity and nasopharyngeal mucosa of a cadaveric head for assessment of aerosol and droplet generation from endonasal drilling. A cascade impactor was used to collect aerosols and small droplets ≤14.1 µm based on average aerodynamic diameter, and the collection chambers were visualized under UV light. Results: When vitamin B2 was nebulized, aerosols ≤5.4 µm were generated and the collected particles were fluorescent. When fluorescein and the commercial water tracer dye were nebulized, aerosols ≤8.61 µm and ≤2.08 µm respectively were generated, but the collected aerosols did not appear visibly fluorescent. Endonasal drilling in the nasopharynx coated with vitamin B2 irrigation yielded aerosols ≤3.30 µm that were fluorescent under UV light. Conclusion: Vitamin B2's reliability as a fluorescent tracer when suspended in aerosols and small droplets ≤14.1 µm and known mucosal safety profile make it an ideal compound compared to fluorescein and commercial water-based fluorescent dyes for use as a safe fluorescent tracer in healthcare contamination models especially with human subjects. [ABSTRACT FROM AUTHOR]

Contact lens-assisted corneal cross-linking (CACXL) was introduced by Jacob et al. in 2012 for treating thin keratoconic corneas using riboflavin soaked soft contact lens to artificially increase the functional corneal thickness. It is advantageous over other thin corneal cross-linking techniques as it works independent of swelling properties of the cornea, is an epi-off technique and does not require additional time, additional expensive equipments or special solutions. The only additional requirement as compared to all other techniques is a UV barrier-free soft contact lens (SoflensTM, B&L) which is easily available and inexpensive. Advantages include simplicity, easy adaptability, early visual rehabilitation, good visual outcomes, safety, and efficacy. Progression rates are acceptable and the need for re-treatment has been low. CACXL can help regularize corneal shape and may be used in isolation or synergistically with Intracorneal ring segments (ICRS) or Corneal allogenic intrastromal ring segments (CAIRS). It gives about 70% stiffening as compared to standard Dresden protocol CXL in less ideal porcine eye studies. Murine eye models that closely mimic thin corneas and show greater cross-linking effect as compared to porcine eyes may be a better model for evaluation of CACXL, however further studies are needed. Care should be taken in selecting the right kind of contact lens. Proper technique should be followed, especially by confirming thinnest functional pachymetry to be above 400 microns intra-operatively before application of UV-A. The sub-contact lens riboflavin film should be avoided as also an excessively thick supra-contact lens riboflavin film and too many re-applications. [ABSTRACT FROM AUTHOR]

The past two decades have witnessed an unprecedented evolution in the management of keratoconus that demands a holistic approach comprising of inhibiting the ectatic progression as well as visual rehabilitation. The advent of corneal cross-linking (CXL) in the late 1990s resulted in long-term stabilization of the ectatic cornea along with limited reduction in corneal steepening and regularization of corneal curvature. However, CXL as a standalone procedure does not suffice in rehabilitating the functional vision especially in patients who are unwilling or intolerant towards contact lenses. The concept of "CXL plus" was proposed which incorporates adjunctive use of refractive procedures with CXL in order to overcome the optical inefficiency due to corneal irregularity, decrease the irregular astigmatism, correct the residual refractive error and improve functional visual outcome in keratoconus. Several refractive procedures such as conductive keratoplasty (CK), photorefractive keratectomy (PRK), transepithelial phototherapeutic keratectomy (t-PTK), intrastromal corneal ring segments (ICRS) implantation, phakic intraocular lens (PIOL) implantation and multiple other techniques have been combined with CXL to optimize and enhance the CXL outcome. This review aimed to summarize the different protocols of CXL plus, provide guidelines for selection of the optimum CXL plus technique and aid in decision-making for the comprehensive management of cases with primary keratoconus in addition to discussing the future and scope for innovations in the existing treatment protocols. [ABSTRACT FROM AUTHOR]

Background: Pathogen reduction technology has become an accepted method for limiting transfusion‐transmitted infections (TTIs). Riboflavin and ultraviolet light (RUV) treatment of platelets (PLTs) is an optional means of pathogen inactivation owing to its safety, effectiveness, and ease of use. However, the literature on effects of ultraviolet (UV) light spectra and doses on pathogen reduction is still contradictory. Methods: We tested the effectiveness of killing Escherichia coli following RUV exposure with one broad‐spectrum and two narrow‐spectrum light sources centered at 311 and 365 nm and at successively higher doses by limited dilution survival assays. After comparing the effectiveness of E coli and phage inactivation (n = 6) and the changes in PLT count and metabolism caused by RUV treatment with optimized UV light at increasing doses, we confirmed our results by using four model virus systems that represent common TTIs, as well as PLT function and activation assays at an optimized light dose. Results: The narrow‐spectrum UV, centered at 311 nm, optimally reduced the E coli titer with a light dose ≥8.11 J/mL, resulting in the same trend of E coli and phage reduction at different light doses. At 8.11 J/mL, 311‐nm narrow‐spectrum UV had a good inactivation effect on E coli and phages, eliminating many viruses, and resulted in acceptable PLT quality after RUV treatment and during storage for 4 days. Conclusions: Our data suggest restricting exposure to narrow‐spectrum UV centered at 311 nm can increase E coli elimination and potentially optimize virus titer reduction without significantly compromising PLT quality. [ABSTRACT FROM AUTHOR]

Purpose: To compare the corneal densitometry changes after transepithelial pulsed (t-ACXL), epithelium-off continuous (c-ACXL) and epithelium-off pulsed (p-ACXL), accelerated corneal crosslinking for patients with progressive keratoconus.Methods: Prospective, interventional case series at a university hospital tertiary referral center. Forty eyes received t-ACXL, 40 eyes received c-ACXL, and 40 eyes received p-ACXL. Corneal tomography, densitometry and visual acuity were evaluated preoperatively and at 1, 3, 6, 12 and 24 months postoperatively.Results: Total densitometry values of the total layer over the annular diameters 0-12 mm expressed in grayscale units (GSU) showed no significant change after t-ACXL and p-ACXL but increased significantly after c-ACXL at 1 month (16.76 ± 2.38, P value < 0.01) and 3 months (16.12 ± 2.22, P value 0.04), returning to baseline levels at month 6 (14.97 ± 2.13, P value 0.99) and remained stable until final follow-up. At 1 month, the mean change in total densitometry value of the t-ACXL group (-0.53 ± 2.08) was significantly lower than the p-ACXL (0.70 ± 1.96 P value 0.04) and c-ACXL (1.97 ± 2.65 P value < 0.01). There was no statistical difference in the mean change in total densitometry between the three groups from 6 to 24 months. In the c-ACXL group, a higher degree of CXL-induced corneal haze at 1 month was observed in patients with steeper preoperative keratometry readings and in individuals where a greater flattening effect was achieved at 24 months.Conclusions: Continuous epithelium-off accelerated cornea crosslinking appears to induce more corneal haze than pulsed epithelium-off and transepithelial pulsed cornea crosslinking in the early postoperative period. Differences resolve by six-months. [ABSTRACT FROM AUTHOR]

Background: This study evaluated blood components processed by the platelet rich plasma (PRP) method from fresh whole blood (FWB) treated with a pathogen reduction technology (PRT). The effects of storage temperature on PRT treated platelet concentrates (PCs) were also examined.Study Design and Methods: PRT was performed using riboflavin and ultraviolet light on FWB in citrate phosphate dextrose anticoagulant. Following PRT, red blood cells (RBCs), PCs, and plasma for fresh frozen plasma (FFP), were isolated by sequential centrifugation. RBCs were stored at 4°C, FFP at -80°C, and PC at 22°C or at 4°C. Components were assayed throughout their storage times for blood gases, chemistry and CBC, hemostatic function as well as platelet (PLT) and RBC integrity.Results: Component processing following PRT resulted in a significant drop in platelet recovery. Most PRT-PC bags fell below AABB guidelines for platelet count. PRT-PC also showed a decrease in clot strength and decreased aggregometry response. Platelet caspases were activated by PRT. Storage at 4°C improved platelet function. In PRT-FFP, prothrombin time and partial thromboplastin time (PT and aPTT) were prolonged; factors V, VII, VIII, and XI, protein C, and fibrinogen were significantly decreased. Free hemoglobin was elevated two-fold in PRT-RBC.Conclusion: Blood components isolated by the PRP method from PRT-treated WB result in a high percentage of PC that fail to meet AABB guidelines. FFP also shows diminished coagulation capacity. However, PRT-RBC are comparable to control-RBC. PRT-WB retains acceptable hemostatic function but alternatives to the PRP method of component separation may be more suitable. [ABSTRACT FROM AUTHOR]

Pathogen reduction technologies have been under development for more than two decades and phase III randomized clinical trials (RCTs) using pathogen reduced (PR) blood components have been performed.[1] To date, two PR platelet products have been evaluated using the RCT design: PR platelets prepared by UV illumination in the presence of amotosalen (Intercept Blood System, Cerus) and PR platelets treated with riboflavin plus UV illumination (Mirasol Pathogen Reduction Technology, Terumo BCT). The number of transfusions per patient receiving PR platelets was greater than controls in five amotosalen RCTs[[3], [6], [8]] and in all three riboflavin RCTs (Tables and). All patients were thrombocytopenic with mean pre-platelet transfusion platelet counts ranging from 10 to 18 x 10 SP 9 sp /L. The CCIs in the PR group were lower than in control patients at both 1 and 24 hours following transfusion of amotosalen platelets and riboflavin platelets (Tables and). Four RCTs[[3], [5], [10]] included some patients with solid tumors, where the incidence, nature and duration of bleeding might be different from patients with hematologic malignancies, so this adds some complexity to interpretation of results. [Extracted from the article]

Purpose: To investigate the corneal epithelial thickness profiles in patients with a confirmed diagnosis of stable and progressive keratoconus.Setting: Studio Italiano di Oftalmologia, Rome, Italy.Design: Observational study.Methods: 86 patients with either stable (n = 52) or progressive (n = 34) keratoconus and 182 healthy controls were enrolled in the study. Disease progression was confirmed by repeated corneal topographies over 1 year follow-up before inclusion in the study. All subjects had full corneal and epithelial thickness mapping taken by spectral domain optical coherence tomography (SD-OCT). The full corneal mapping was investigated by evaluating the central corneal thickness, the thinnest point, the superonasal-inferotemporal thickness difference and the minimum-median thickness difference. The epithelial mapping was investigated by assessing the 2 mm central thickness, the inferior paracentral (2-5 mm) thickness, and the minimum-maximum thickness difference.Results: No significant differences in full corneal mapping were found between stable and progressive keratoconic eyes. Of note, the inferior paracentral region of the corneal epithelium was significantly thinner in progressive (50 ± 3 μm) than stable (53 ± 4 μm) keratoconus (P < 0.001).Conclusions: The SD-OCT corneal epithelial mapping was valuable for detecting local thickness changes in eyes with keratoconus. Monitoring the corneal epithelial changes across the inferior area in patients with keratoconus could be worthy for assessing disease progression. [ABSTRACT FROM AUTHOR]

Members of the ASCRS Cornea Clinical Committee performed a review of the current literature on the corneal crosslinking (CXL) procedure for treating corneal ectasia. The members explored the data on the techniques currently in use and under investigation, including their advantages, safety profiles, risks, and cost analyses, compared with data on corneal transplantation. They concluded that CXL limits the progression of keratoconus, thus reducing the need for transplantation. They also found that compared with permitting the disease to progress naturally, CXL techniques carry significant and long-term cost and safety benefits, primarily by reducing the need for corneal transplantation. Studies of various CXL techniques (eg, epithelium-on treatment, changes in ultraviolet light parameters, riboflavin composition) continue with the ultimate goal of improving the procedure's safety and efficacy. [ABSTRACT FROM AUTHOR]

Pathogen reduction technologies are implemented to increase the safety of blood products. We previously showed that the UVB alone significantly contributes to the storage lesions observed in platelets treated with riboflavin/UVB using a home-made illuminator. The present study aims at confirming these observations using the commercial Mirasol® technology. A three-arm study (untreated, UV−, Mirasol®-treated platelets) was conducted to investigate the platelet storage lesions throughout storage (n = 4). A two-arm study was then designed to compare Intersol and T-PAS+ additive solutions (n = 3). Phenotype and functional platelet characteristics were assessed using flow cytometry, aggregometry, antioxidant assays and metabolic parameters. Mirasol®-treated platelets exhibit enhanced storage lesions compared to controls (increase of activation markers and glycolysis rate, lower hypotonic shock and double-agonist activation responses, and decrease of total antioxidant capacity). Here, we also confirmed that the UV radiation alone is causing platelet lesions. Riboflavin tends to have an intracellular protective role while it decreases the extracellular antioxidant defenses. Furthermore, benefits of platelet additive solutions containing potassium and magnesium were confirmed as it reduces the extent of storage lesions. The photosensitizer, UV illumination and composition of the platelet additive solutions are key parameters influencing the platelet storage lesion. The clinical relevance of these findings is not fully understood and recent published clinical studies could not show increase in bleeding in patients receiving Mirasol-treated platelets. New developments in storage solutions might help to improve storage conditions of PRT-treated platelets and should be prioritised as research subject in the future. [ABSTRACT FROM AUTHOR]

Introduction: The demarcation line (DL) observed since the pioneering crosslink (CLX) protocol at the posterior edge of the cross-linked stroma has been universally accepted as a therapeutic milestone of treatment. Numerous laboratory and clinical CXL studies demonstrate that a deeper DL is associated with a higher amount and saturation level of crosslinks, a more pronounced stiffening effect, and a more durable ectasia stability. Areas covered: A critical revision of laboratory, clinical, and analytical studies on the DL depth supports the significance of the DL as an evaluator of the performance of CLX procedures in terms of biomechanical efficacy and safety avoiding extensive experiments. A mechanical approach based on experimental data shows that the DL depth obtained with different CXL protocols relates with an asymptotic non-linear increasing function to the modified biomechanical corneal stiffness (elastic modulus). Expert opinion: The strong connection between the depth of the DL and the increase of the biomechanical efficacy can be explained by means of UV cross-linking chemical investigations demonstrating that only a limited amount of free reactive collagen residues is involved in the short-wave UV-mediated CXL. Thus, the CXL density can rise only up to an upper boundary value, i.e. the saturation value. [ABSTRACT FROM AUTHOR]

Purpose: To compare the subclinical inflammatory response (as measured by anterior chamber flare) induced after standard (3 mW/cm2, 30 min) and accelerated (18 mW/cm2, 5 min) corneal cross-linking (CXL). Methods: In this comparative, non-randomized study, patients with progressive keratoconus who underwent standard or accelerated CXL were studied. Laser flare photometery (FM-600; Kowa, Tokyo, Japan) was used to measure anterior chamber flare preoperatively and at 1 week, 1 month, 3 months, and 6 months after the procedure. Results: Sixty eyes of 60 patients were studied; 30 eyes in each group. Mean baseline flare values were 4.15 ± 1.19 and 4.57 ± 2.17 ph/ms in standard and accelerated groups, respectively (p = 0.228).and after surgery increased in all follow-up measurements in the both groups similarly (P > 0.05). Conclusion: Both standard and accelerated CXL results in induction of a subclinical inflammatory response that persists up to 6 month. The response was similar between the two groups. [ABSTRACT FROM AUTHOR]

Flavins are cofactors in several light‐activated enzymes and therefore their excited states are found to involve in many photobiological processes. Excited state dynamics of flavin compounds corresponding to their first singlet state (S1) has been studied using a plethora of techniques, whereas studies related to highly absorbing ultraviolet excited states are lacking. Here, we study the ultrafast excited state dynamics of riboflavin and flavin mononucleotide using resonance Raman intensity analysis upon photoexcitation into their most intense absorption band centered at 266 nm. Resonance Raman cross sections of each flavin band are quantitatively measured across the 266‐nm absorption band (257–280 nm), and Raman excitation profiles are constructed. We have used Lee and Heller's time‐dependent wave packet theory to simulate the experimental Raman cross sections in a self‐consistent manner. The simulation results in instantaneous structural changes along with solvation dynamics, through linewidth broadening within tens of femtoseconds following photoexcitation. Major structural changes were observed through contraction and elongation of several ring stretching coordinates, affecting at a different site when compared with the S1 excitation. The value of the total reorganization energy was determined to be 1,665 cm−1 (and 1,602 cm−1 for flavin mononucleotide) with a contribution of 1,310 cm−1 from the inertial response of water. We find upon excitation, the first solvation shell inertially responds with an ultrafast timescale of <30 fs for both the molecules. Our results can be useful to determine the structure and dynamics of flavoenzymes by using flavin as a probe following excitation within their 266‐nm absorption band. Herein, we report the quantitative measurement of resonance Raman cross sections upon UV excitations within the absorption band centered around 266 nm of riboflavin and flavin mononucleotide. Further, these experimental cross sections along with quantum chemical computations were modeled using Lee–Heller's time‐dependent theory of resonance Raman scattering. The results from these simulations shed light on the structural and solvation dynamics of flavins within few tens of femtoseconds after photoexcitation. [ABSTRACT FROM AUTHOR]

Purpose: To compare the 24 month visual, refractive, topographic and aberrometric results of the accelerated and standard corneal collagen cross-linking (CXL) in pediatric keratoconus patients.Methods: 87 eyes of 64 consecutive keratoconus patients under 18 years old with 24 month follow-up period following standard or accelerated CXL were included. 38 eyes received standard CXL (3 Mw/cm2, 30 min), while 49 eyes had accelerated CXL (9 mW/cm2, 10 min). Changes in the uncorrected (UCVA) and best corrected visual acuity (BCVA), spherical equivalent (SE), manifest astigmatism (MA), corneal topographic parameters, and corneal aberrations such as spherical aberration (SA), high order aberrations (HOAs), horizontal and vertical coma were evaluated. Corneal haze was graded and progression rate was assessed.Results: The difference between baseline and 24 months postoperative UCVA, BCVA, SimK (keratometry)-1, SimK-2, Kmax, and the corneal aberrations were not significantly different between the two groups (p > 0.05 for all). The mean reduction in thinnest corneal pachymetry from baseline to 24 months after CXL was higher in accelerated CXL group (p = 0.007). The progression rate was 13.1% in standard and 16.3% in accelerated group (p = 0.754). There were no differences in the grade of corneal haze between the two groups (p = 0.249). No complications were observed in the both groups.Conclusion: The 24 month results of accelerated and standard CXL revealed that, the efficacy and safety of accelerated CXL were the same with standard CXL in pediatric keratoconus patients. As being a rapid procedure, accelerated CXL appears to be more benefical for pediatric patients. [ABSTRACT FROM AUTHOR]

Abstract Objectives Transfusion of hemocomponents is essential for clinical and surgical procedures and therefore their safety has increased. An option for pathogen reduction includes the combination of riboflavin and UV light. To our knowledge, there are no studies in Latin America that demonstrate the effectiveness of the pathogen reduction in hemocomponents. The objective of this work was to evaluate the efficiency of a pathogens reduction system in platelets concentrates (PC) and plasma. Materials and methods PC and plasma were contaminated with Escherichia coli , Klebsiella pneumoniae , Streptococcus pyogenes and Staphylococcus epidermidis at 104 to 106 CFU and subjected to bacterial reduction. After bacterial reduction, hemocomponents were subjected to cultivation of surviving bacteria by automated method and classical colonies quantification. Additionally, quality control testing was performed in order to confirm the integrity of platelets and coagulation laboratory values in plasma before and after bacterial reduction. Results The bacterial death in PC/plasma was expressed by Logarithmic Reduction Value as follows: for both strains (E. coli and S. pyogenes) 4/4, 5/5 and 6/6; for K. pneumoniae 2.54/2.23, 2.94/2.22 and 3.44/2.98, for S. epidermidis 4/4, 3.11/5 and 3.23/4.19, for 104, 105 and 106 CFU, respectively. In PC and plasma, platelet count, pH (at 22 °C), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, factor VIII and total proteins (TP) were slightly modified. Conclusions UV light with riboflavin is able to reduce an important number of pathogens in hemocomponents; however, the bacterial reduction is influenced by the nature and quantity of the pathogen. [ABSTRACT FROM AUTHOR]

Background: Pathogen reduction technology (PRT) enhances blood component safety, but its implementation is hampered by loss of blood quality and cost.Study Design and Methods: A retrospective study was conducted to investigate the efficacy, safety, and cost of 9673 riboflavin and ultraviolet light-treated platelet (PLT) transfusions given to 1211 patients during a 3-year period. The results were compared with the efficacy, safety, and cost of 6424 nontreated PLT transfusions administered to 1500 patients during a 3-year comparison period before PRT implementation.Results: Despite a similar PLT transfusion dose per unit for both periods (pre-PRT period 3.26 vs. PRT period 3.19), the mean number of PLT concentrates per patient (4.2 vs. 7.8; p = 0.006) and the total dose of PLTs received by patients were higher in the PRT period (13.6 vs. 24.8; p = 0.0002). Hematology and medical and surgical patient categories had the highest PLT use per patient. However, febrile (2.5% vs. 1.2%; p = 0.02) and allergic (0.16% vs. 0.08%; p = 0.01) reactions were lower during the PRT period. The blood center saved €284,805.58 due to a reduction of outdated PLTs from 16.8% to 0.72% after PRT implementation.Conclusions: Although PRT can improve PLT safety, it can increase the amount of PLTs required for transfusion in some patient categories. The cost of PRT can be partially offset by the savings associated with a lower rate of PLT outdates. This cost reduction can be a key factor in settings where inventory management is challenged by a high percentage of wasted PLTs due to outdating. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate corneal biomechanics before and after collagen crosslinking (CXL) in patients with progressive keratoconus. Materials and Methods: In this prospective study, CXL was performed under topical anesthesia after removal of the epithelium (epi-off technique) by applying ultraviolet A (UVA) light at a wavelength of 365 nm and power of 3 mW/cm² or 5.4 joule/cm². Isoosmolar 0.1% riboflavin solution was administered before and during UVA irradiation. In addition to ophthalmologic examination, ocular response analyzer measurements were performed pre- and postoperatively. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated intraocular pressure (IOPcc), Goldmann-correlated intraocular pressure (IOPg), and central corneal thickness (CCT) were recorded. Results: The study included 35 eyes of 30 patients with progressive keratoconus. The mean age was 28.2±6.5 years and postoperative follow- up time was 20.2±14.7 months (range: 6-74 months). The mean CH was 8.60±1.23 mmHg preoperatively, 8.96±2.05 mmHg in the early postoperative period (1-6 months), (p=0.28) and 8.96±1.28 mmHg in the late postoperative period (10-29 months) (p=0.48). Mean CRF was 7.13±1.50 mmHg preoperatively, 8.48±2.16 mmHg in the early postoperative period (p=0.009), and 7.71±1.29 mmHg in the late postoperative period (p=0.40). Mean IOPcc was 12.78±2.34 mmHg preoperatively, 15.38±4.21 mmHg in the early postoperative period (p=0.12) and 13.68±3.61 mmHg in the late postoperative period (p=0.48). Mean IOPg was 9.56±2.73 mmHg preoperatively, 13.01±4.45 mmHg in the early postoperative period (p=0.046), and 10.86±3.47 mmHg in the late postoperative period (p=0.44). Mean CCT was 484.43±41.26 µm preoperatively, 474.16±64.74 µm in the early postoperative period (p=0.70), and 470.38±33.64 µm in late postoperative period (p=0.71). Conclusion: CXL is a treatment modality believed to affect corneal biomechanics in keratoconus, but the results of larger patient series with longer follow-up periods may enable a better evaluation. [ABSTRACT FROM AUTHOR]

Repeatability and agreement of a new scheimpflug device and a Hartmann-Shack aberrometer with a ray-tracing aberrometer in normal, keratoconus, and CXL groups. CXL is known to have complications such as post-CXL haze or scar, sterile infiltrates, failure, excessive flattening, and endothelial damage, among a few others. Corneal collagen -cross-linking (CXL) as we know is a procedure to enhance the biomechanical strength of the cornea, thereby, halting the progression of corneal weakening in Keratoconus (KC). [Extracted from the article]

Keywords: Collagen cross-linking; corneal fluorescein angiography; deep corneal neovascularization; herpetic stromal keratitis; keratoconus EN Collagen cross-linking corneal fluorescein angiography deep corneal neovascularization herpetic stromal keratitis keratoconus 1156 1158 3 06/02/20 20200601 NES 200601 A 22-year-old male who underwent collagen cross-linking (CXL) in both eyes elsewhere 3 years ago for keratoconus presented with symptomatic blurring of vision and redness in the left eye. Herpetic keratitis after corneal collagen cross-linking with riboflavin and ultraviolet-A for progressive keratoconus. Collagen cross-linking, corneal fluorescein angiography, deep corneal neovascularization, herpetic stromal keratitis, keratoconus. [Extracted from the article]

Aim. To evaluate two different techniques of cross-linking: standard epithelium-off (CXL epi-off) versus transepithelial (CXL epi-on) cross-linking in patient with progressive keratoconus. Methods. Forty eyes from 32 patients with progressive keratoconus were prospectively enrolled from June 2014 to June 2015 in this nonblinded, randomized comparative study. Twenty eyes were treated by CXL epi-off and 20 by CLX epi-on, randomly assigned, and followed for 2 years. All patients underwent a complete ophthalmologic testing that included uncorrected and best corrected visual acuity, central and peripheral corneal thickness, corneal astigmatism, simulated maximum, minimum, and average keratometry, corneal confocal microscopy, Schirmer I and break-up time (BUT) tests, and the Ocular Surface Disease Index. Intra- and postoperative complications were recorded. The solution used for CXL epi-off comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), whereas the solution for CXL epi-on (Ricrolin TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with a UV-X system at 3 mW/cm2. Results. In both groups, a significant improvement in visual function (Group 1: baseline 0.36 ± 0.16 logMAR, two-year follow-up 0.22 ± 0.17 logMAR, p=0.01; Group 2: baseline 0.32 ± 0.18 logMAR, 2-year follow-up 0.27 ± 0.19 logMAR, p=0.01) was recorded. Keratometry remained unchanged in both groups. The mean corneal thickness showed a significant reduction (mean difference of corneal thickness: −55 micron and −71 micron, resp.). One-month after treatment, OSDI© reached 13.56 ± 2.15 in Group 1 (p=0.03) and 11.26 ± 2.12 in Group 2 (p=0.04). At confocal microscopy, abnormal corneal nerve alterations were found in both groups. Fibrotic reaction (43.75%) and activated keratocyte (62.6%) were more commonly recorded in Group 1 than in Group 2 (25.0% and 18.75%), with p=0.668 and 0.356, respectively. Conclusion. Our findings demonstrate that both procedures are able to slow keratoconus progression. Both treatment modalities are equivalent in terms of results and related complications. CXL epi-on technique is preferable to CXL epi-off since it preserves the corneal thickness and improves visual acuity, also reducing the postoperative ocular discomfort during the study period. [ABSTRACT FROM AUTHOR]

Purpose. To investigate whether the protection of corneal limbus from riboflavin exposure during collagen cross-linking (CXL) prevents limbal epithelial stem cell (LESC) loss. Methods. Ten New Zealand white rabbits received an epithelium-off CXL using an accelerated protocol. Seven days before procedure, 5-bromo-2-deoxyuridine (BrdU) was intraperitoneally injected. During procedure, riboflavin was applied to the corneal surface within a 9 mm diameter retention ring in 5 rabbits, thereby preventing the limbus from riboflavin exposure. In other 5 rabbits, riboflavin was instilled every 2 min, allowing the spillover to the limbus. One day after UVA irradiation, corneas were subjected to histological and molecular assays. Results. There were no differences in corneal thickness and epithelial healing between the groups. The numbers of BrdU-labelled and p63+ limbal epithelial cells were markedly reduced in the group without a ring, but significantly increased when a ring was used. Robust expression of CK3/12 was observed in the limbal epithelium in the group with a ring. The mRNA levels of ABCG2, FGF2, IL-1β, and IL-6 were significantly increased in the corneas with a ring. Conclusions. Protection of limbus from riboflavin during CXL was effective in preserving LESCs. However, inflammation was increased in the cornea treated with riboflavin using a ring. [ABSTRACT FROM AUTHOR]

Purpose: To review the application of the PACK-CXL and to identify different treatment protocols according to the pathogens associated with keratitis.Methods: A systematic review of 21 articles. The primary outcome was the healing of a corneal ulcer, defined as epithelization, blocking corneal melting. The secondary end-point was the recovery of visual acuity.Results: We studied a total of 145 eyes. Infectious keratitis was associated with bacteria in 80 eyes (55.55%), fungus in 24 eyes (16.67%), and protozoa in 13 (8.97%). In 26 (18%), the microbiological culture was negative or not performed. The mean time of re-epithelization was 25.70±29.83days (1-180). A total of 27 patients needed corneal transplantation. The overall probability of blocking corneal melting was 84.13%. Three different protocols for each group of pathogens have been proposed.Conclusion: PACK-CXL still has a limit in its spread. In the future, we hope that each pathogen will be treated with the most efficient and least invasive protocols available. [ABSTRACT FROM AUTHOR]

To evaluate ocular fundus biological changes after scleral collagen cross-linking (CXL) with riboflavin/ ultraviolet A (UVA) on rhesus monkeys in vivo by analyzing retina and choroid biological parameters. Six 3-year-old male rhesus monkeys (12 eyes) were observed in this study, with scleral CXL procedures applied on superior temporal equatorial sclera on random eyes of all rhesus. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) examination were performed before and 1 week, 1 month, 3 months and 6 months after CXL. The thickness of retina and choroid and the flow density of retinal superficial vascular networks were analyzed respectively in different regions after CXL. As for retina thickness and flow density of retinal superficial vascular networks, no statistical difference was noted between CXL eyes and control eyes at 1 day, 1week, 1 month, 3 months and 6 months (P>0.05). Among choroid parameters, the choroidal thickness in 1500μm temporal to the fovea center of CXL eyes revealed a significant reduction in 1 week postoperatively (P<0.05), but it subsequently increased from 1 month postoperatively, and no statistical difference was found between two groups in the following periods (P>0.05). The choroidal thickness nearby crosslinked region may change temporarily following scleral CXL, and it might recover gradually after 1 month postoperatively. The vascular flow density and thickness of retina were not affected by scleral CXL. Further study should be performed to evaluate the potential adverse effects at the direct vicinity of the application site and the long-term effect of scleral CXL in clinical application. [ABSTRACT FROM AUTHOR]

Background: The aim was to assess one-year changes in uncorrected and corrected contrast sensitivity (CS) and glare under scotopic conditions after accelerated cross-linking (CXL) using the 18 mW/cm2 protocol for the treatment of progressive keratoconus and compare results with unoperated controls.Methods: In this non-randomised clinical trial, 30 eyes were enrolled in the CXL group and 30 were assigned to the control group. Scotopic CS at spatial frequencies (SFs) of 0.5, 1.1, 2.2, 3.4, 7.1 and 15 cycles per degree (cpd) were assessed using the MonCv3System (Metrovision, Pérenchies, France) under scotopic conditions (0.5 lux) at baseline and at six and 12 months.Results: The mean ages of the participants in the CXL and control groups were 24.32 ± 5.17 and 30.93 ± 7.43 years, respectively (p < 0.001). After adjusting for age, changes in uncorrected and corrected CS and glare were similar in the two groups (all p > 0.05) except for corrected CS at SF 7.1 cpd (1.45 ± 4.31 versus 3.21 ± 4.69 dB, p = 0.010) and 15 cpd (1.12 ± 4.63 versus 3.03 ± 5.48 dB, p = 0.007), which were reduced as an effect of CXL. Based on covariate analyses, among corrected CS indices, corrected CS7.1 and CS15 were related to CXL and their baseline values (all p < 0.050). Uncorrected CS in all SFs and uncorrected and corrected glare were related to their pre-operative values (all p < 0.001).Conclusion: Accelerated CXL can reduce scotopic corrected CS at SFs higher than 7.0 cpd in cases with better baseline values of these parameters. Changes in uncorrected CS and glare are only a factor of baseline values and the indices reduce in cases with better baseline values after one year. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and efficiency of Riboflavin and Ultraviole A (UVA) supported corneal collagen crosslinking treatment (CXL) in the keratoconic eyes. Materials and Methods: One hundred nineteen eyes of 71 patients with progressive keratoconus were included in this prospective study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, slit lamp examination, corneal topography, contrast sensitivity,central corneal thickness (CCT) with ultrasound pachymeter were evaluated at baseline and at 1,3,6 and 12 months follow-up. Results: The mean age of the patients was 19.4±3.5 years. There was a mean of 1 snellen line improvement in both UDVA and CDVA (P=0.01). No patient lost 2 or more snellen lines of CDVA. At month-12 follow-up, mean manifest refraction spherical equivalent and mean keratometry readings showed a significant decrease of 1.13 and 0.41 diopters (P=0.04). The CCT decreased significantly during the first 3 months (P<0.05). Sight threatening complications were not encountered in any patient eye. Conclusion: Corneal collagen crosslinking seems to be safe and effective in keratoconic eyes. The visual acuity may increase and progression was not encountered during 1 year follow-up. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to investigate the efficacy of minimally invasive repetitive UVA irradiation along with riboflavin treatment on sclera collagen cross-linking in rabbits. Method. Forty-eight healthy adult New Zealand white rabbits were randomly divided into four groups: pseudosurgery group (group I), single-irradiation group (group II), duplicate-irradiation group (group III), and triplicate-irradiation group (group IV), with 12 rabbits in each group. For the single-irradiation group, a specially made LED light source was inserted through a minimally invasive conjunctival incision to gain close contact with the sclera for irradiation, and for the repetitive irradiation groups, the above experimental procedure was repeated once or twice every other week. Biomechanical parameters of the sclera including ultimate stress (σ) and 8% Young’s modulus (E) were compared among the groups. Results. In comparison with control group I, the ultimate stress of group II, group III, and group IV increased by 80.1%, 107.9%, and 182.1%, respectively, and their 8% Young’s modulus increased by 106.1%, 159.5%, and 208.5%, respectively, one day after surgery (P<0.01). Conclusion. Repetitive minimally invasive UVA irradiation with riboflavin significantly increased biomechanical strength of the sclera in the irradiated area, and biomechanical strength increased with repeated times of irradiation. [ABSTRACT FROM AUTHOR]

In order to study Staphylococcus epidermis and Staphylococcus aureus in vitro viability after the exposure to ultraviolet (UV) light and riboflavin, twelve strains of Staphylococcus epidermis and twelve strains of Staphylococcus aureus were isolated from patients with bacterial keratitis. The growth situation of Staphylococcus epidermidis and Staphylococcus aureus under different experimental conditions was qualitatively observed. The number of colonies surviving bacteria was counted under different UV light power and different exposure time. The experiment showed that there was no inhibition effect on the growth of bacteria using riboflavin alone. In UV alone group and UV-riboflavin group, inhibition effect on the bacteria growth was found. The UV-riboflavin combination had better inhibition effect on bacteria than UV irradiation alone. The amount of bacteria in the UV-riboflavin group was decreased by 99.1%~99.5% and 54.8%~64.6% in the UV alone group, when the UV light power was 10.052 mW/cm2 and the irradiation time was 30 min. Moreover, with the increase of the UV power or irradiation time, the survival rates of bacteria were rapidly reduced. Compared with Staphylococcus aureus, Staphylococcus epidermis was more easily to be killed under the action of UV light combined with riboflavin. [ABSTRACT FROM AUTHOR]

ABSTRACT In the present study, we optimized the ultraviolet-A (UVA)/riboflavin crosslinking for the collagen-based artificial cornea for the first time to resolve the lack of donor cornea for corneal disease. We found that the crosslinking conditions, including irradiation time and irradiation intensity, played important roles on the property of the sample. At the optimal condition (with the irradiation time of 30 min and the irradiation intensity of 5 mW/cm2), the sample exhibited excellent crosslink degree and mechanical property while keeping good light transmittance. Meanwhile, the sample showed improved enzyme tolerance capacity and thermal stability. This developed artificial cornea also had good biocompatibility to human corneal epithelial cells in vitro. In vivo lamellar keratoplasty results showed that the developed sample could promote complete epithelialization in about 4 weeks, and the transparency is restored quickly in the first 6 weeks. Corneal rejection reaction and keratoconus are not observed. This optimized UVA/riboflavin crosslinking method would have great potential for collagen-based artificial cornea in clinic. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45226. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of ascorbic acid (vitamin C), the main antioxidant agent in the cornea on transepithelial corneal cross-linking (CXL) where the main mechanism is oxidation.Methods: Twenty eyes of 20 rabbits were divided into 3 groups: Group 1 (7 eyes) had transepithelial corneal CXL after being fed with normal diet; Group 2 (7 eyes) had corneal CXL after once-daily subcutaneous injections of 200 mg of ascorbic acid in addition to normal diet; and the control group (6 eyes) was fed with normal diet but did not have corneal CXL performed. Ascorbic acid levels were measured in aqueous humor and plasma, and biomechanical measurements were applied to the cornea.Results: There was a significant difference in ascorbic acid levels of plasma (P = 0.008) and aqueous humor (P = 0.006) between group 1 and 2. The Young's modulus values of group 1 and 2 were similar (P = 0.741) and were significantly higher than the control group (P = 0.02 and P = 0.01). The increase rate in Young's modulus values was 37.3% in group 1 and 43.9% in group 2 compared to control group. The ultimate strain values in group 1 and 2 were similar (P = 0.632) and were significantly higher than control group (P = 0.04, P = 0.03). The ultimate stress values in group 1 and 2 were similar (P = 0.836) and were significantly lower than control group (P = 0.001, P = 0.001).Conclusions: Systemic vitamin C does not appear to decrease effectiveness of transepithelial corneal CXL. Therefore, there is no reason to stop or reduce vitamin C supplementation before corneal CXL therapy. [ABSTRACT FROM AUTHOR]

The combination of saccharides and UV sensitive chemical molecules in the solution form has been in the interest of medicine for treating medical complications and imaging techniques due to their remarkable properties under UV radiation. Therefore, two samples of dextrin based riboflavin solutions containing 10 wt% of dextrin content and 0.1 wt% of UV sensitive riboflavin content were prepared at the room temperature. In order to understand how UV radiation affects the viscosity of prepared solutions at various temperatures, one of the prepared samples was protected from light while another sample was radiated to UV at a biologically harmless wavelength where the absorbance peaks are obtained by UV/visible spectroscopy. Dynamic viscosity measurements of UV-radiated and un-radiated solutions for different temperatures were performed with constant velocity where the most reliable torque is shown. It was understood that application of UV radiation increased the viscosity value of radiated sample at the room temperature, however; it did not alter the fluid types of test samples. Fluid type of all test solutions was found to be non-Newtonian dilatant fluids as the shear stress vs. shear rate curves of solutions reliably obeyed Ostwald-de-Waele equation. Flow type of all solutions was classified as shear thickening fluids (STF) since power law consistency coefficient ( n ) of Ostwald-de-Waele equation was found to be > 1 ( n > 1). Based on this experimental outcome, the effect of UV radiation on shear thickening behavior of the solutions which include low viscous biocompatible solutions was studied for the first time. Thermal behavior of all test solutions was mathematically modeled via Arrhenius viscosity equation. The degree of STF increased and viscosity of dextrin based riboflavin solutions was found to be slightly greater than other test samples at increasing temperature values after UV radiation. As expected, viscosity values of all test samples decreased at elevated temperatures. [ABSTRACT FROM AUTHOR]

Background: The platelet (PLT) storage lesion is in part caused by the collection and/or production process. Pathogen inactivation (PI) further accelerates its development leading to a reduced in vitro PLT functionality and hence quality. Although the treatment of PLT concentrates (PCs) with riboflavin and ultraviolet light PI should occur within 22 hours of collection, in this study the impact of treatment timing on in vitro PLT quality was investigated.Study Design and Methods: Apheresis PCs were PI treated on the day of production or on Days 1, 3, or 4 of storage or left untreated as control. A panel of in vitro variables was used to monitor quality throughout 7-day storage, including metabolism, PLT activation, and release of microparticles. Changes in phosphorylation profiles of proteins in the lysate and levels of PLT factor 4, thrombospondin, and epidermal growth factor (EGF) in the releasate were analyzed by immunoblots or enzyme-linked immunosorbent assay.Results: By Day 7 of storage, units illuminated on Day 4 showed a smaller impact of the PI process than units treated on the day of production or one day after on PLT quality such as PLT activation; metabolic activity; microvesicle and EGF release; and phosphorylation of p38, ERK, and HSP27. PCs treated on Day 3 of storage displayed an intermediate effect.Conclusion: The timing of PI treatment of PCs influences in vitro PLT quality. Based on these results, timing recommendations should be reconsidered. If PI is applied, inventory management in blood banks might improve with a more flexible collection and treatment regime. [ABSTRACT FROM AUTHOR]

Background: Pathogen reduction technologies (PRTs) are considered for the implementation of safer platelet (PLT) transfusion. PRT treatment involves the addition of a photosensitizer to a blood component followed by ultraviolet (UV) light irradiation. However, the effects of PRT treatment on PLT thrombus formation and thrombus stability have not been satisfactorily clarified.Study Design and Methods: Leukoreduced PLT concentrates (PCs) were treated with riboflavin and UV light (Mirasol PRT). PLT thrombus formation on collagen was evaluated by the microchannel method, by which the total amount of PLTs deposited was measured as indices of thrombus formation and thrombus stability. Using a cone-plate shear-induced PLT aggregometer, PLT reactivity in blood flow was examined in a wide range of shear stresses of 6 to 108 dyn/cm2 .Results: There was no significant difference in surface coverage between PRT-treated PLTs and control PLTs on collagen. On the other hand, the total amount of PRT-treated PLTs deposited was higher than that of control PLTs. The promotive effect of PRT treatment on PLT deposition completely disappeared in the presence of tirofiban, a potent integrin αIIbβ3 inhibitor. The percentage of the dissociation of PRT-treated PLTs on collagen was lower than that of control PLTs after flushing with phosphate-buffered saline. PRT treatment significantly inhibited PLT aggregation under high-shear-stress conditions.Conclusion: Riboflavin-based PRT treatment of PCs leads to the enhancement of PLT thrombus formation and thrombus stability on collagen. However, it does not enhance the reactivity of PLTs not in contact with collagen under high-shear-stress conditions. [ABSTRACT FROM AUTHOR]

Background and Objectives Staphylococcus epidermidis forms surface-attached aggregates (biofilms) in platelet concentrates ( PCs), which are linked to missed detection during PC screening. This study was aimed at evaluating the efficacy of riboflavin- UV treatment to inactivate S. epidermidis biofilms in buffy coat ( BC) PCs. Materials and Methods Biofilm and non-biofilm cells from S. epidermidis ST-10002 and S. epidermidis AZ-66 were individually inoculated into whole blood ( WB) units (~106 colony-forming units ( CFU)/ ml) ( N = 4-5). One spiked and three unspiked WB units were processed to produce a BC- PC pool. Riboflavin was added to the pool which was then split into two bags: one for UV treatment and the second was untreated. Bacterial counts were determined before and after treatment. In vitro PC quality was assessed by flow cytometry and dynamic light scattering. Results Bacterial counts were reduced during BC- PC production from ~106 CFU/ ml in WB to 103-104 CFU/ ml in PCs ( P < 0·0001). Riboflavin- UV treatment resulted in significantly higher reduction of S. epidermidis AZ-66 than strain ST-10002 (≥3·5 log reduction and 2·6-2·8 log reduction, respectively, P < 0·0001). Remaining bacteria post-treatment were able to proliferate in PCs. No differences in S. epidermidis inactivation were observed in PCs produced from WB inoculated with biofilm or non-biofilm cells ( P > 0·05). Platelet activation was enhanced in PCs produced with WB inoculated with biofilms compared to non-biofilm cells ( P < 0·05). Conclusion Riboflavin- UV treatment was similarly efficacious in PCs produced from WB inoculated with S. epidermidis biofilm or non-biofilm cells. Levels of biofilm-derived S. epidermidis ≥103 CFU/ ml were not completely inactivated; however, further testing is necessary with lower (real-life) bacterial levels. [ABSTRACT FROM AUTHOR]