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1.
Safety and efficacy of riboflavin-assisted collagen cross-linking of cornea in progressive keratoconus patients: A prospective study in North East India.
Bhattacharyya, A, Sarma, P, Das, K, Agarwal, B, Medhi, J, Das Mohapatra, SS
Indian journal of pharmacology. 2019;(3):157-167
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Abstract
INTRODUCTION Riboflavin- and ultraviolet (UV)-A-mediated collagen cross-linking of the cornea is a frequently used therapeutic measure for the treatment of progressive keratoconus (PK). First, riboflavin increases cross-linking and second, it serves as a protective shield to other deep ocular structures. However, pharmacogenomic variation in riboflavin efficacy is reported. As the Northeast Indian population represents a genetically diverse group of population compared to mainstream India, we have assessed the efficacy of the procedure in a northeastern population with PK. METHODS In this study, 78 eyes with PK were included (n = 39 in the treatment arm and n = 39 in the control arm). The primary objective was to evaluate the effect of corneal collagen cross-linking using riboflavin (C3R) (epithelium off) on maximum keratometry. The secondary objectives were evaluation of change in corneal topography parameters, i.e., minimum keratometry (Kmin), simulated keratometry (Sim K), subjective refraction (cylinder power, spherical power, and spherical equivalent [SE]), uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and contrast sensitivity (CS) and safety (intraocular pressure, endothelial cell density, and percentage hexagonality) at 1, 3, and 6 months following C3R procedure. RESULTS Statistically significant improvement was noted in Kmin (6 months), Sim K (3 and 6 months), cylinder power (3 and 6 months), spherical power (3 and 6 months), SE (3 and 6 months), BCVA (6 months), and UCVA (1, 6 months) in the C3R group (n = 39) when compared to the control group (n = 39). The mean CS decreased at 1 month and gradually improved to achieve statistically significant value at 6 months in the C3R group (P < 0.05). CONCLUSION Riboflavin-assisted C3R treatment showed promising efficacy in the treatment of PK patients in our population. As the collagen turnover rate of cornea is 2-3 years and the progression of PK is highly variable, we need long-term studies to evaluate the efficacy of C3R over time, requirement of repeat therapy, and safety of repeat cross-linking.
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Riboflavin Concentrations at the Endothelium During Corneal Cross-Linking in Humans.
Seiler, TG, Batista, A, Frueh, BE, Koenig, K
Investigative ophthalmology & visual science. 2019;(6):2140-2145
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Abstract
PURPOSE To determine the riboflavin concentration in the posterior corneal stroma, Descemet's membrane, and endothelium prior to UV irradiation in corneal cross-linking (CXL) in humans. METHODS Five human deepithelialized cadaver corneas were mounted into artificial anterior chambers. After the establishment of stable physiological hydration, two-photon imaging with a certified multiphoton tomograph was used to determine fluorescence intensity and second harmonic generation signals from collagen throughout each cornea by optical sectioning, with a step size of 2.5 μm. Afterward, 0.1% riboflavin solution was applied to the anterior corneal surface, similar to the standard CXL protocol. To determine the absolute riboflavin concentration immediately before UV irradiation, corneas were measured by two-photon imaging just at the end of the riboflavin imbibition and after riboflavin saturation. RESULTS The topical application of 0.1% riboflavin results in a riboflavin concentration that decreases to 0.035% in the posterior stroma. Inside Descemet's membrane and endothelium, the concentration drops further to only approximately 0.015% at the endothelial level. Local riboflavin distribution indicates a predominantly paracellular passive diffusion of riboflavin into the anterior chamber. CONCLUSION The experimentally determined riboflavin concentration of 0.015% at the endothelium shows a substantial discrepancy of a factor of 1.7 to the previously theoretically calculated 0.025%. A lower riboflavin concentration at the endothelium may enable higher radiant exposures and further improve the efficacy of CXL.
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Beer yeast-derived fluorescent carbon dots for photoinduced bactericidal functions and multicolor imaging of bacteria.
Gao, Z, Zhao, CX, Li, YY, Yang, YL
Applied microbiology and biotechnology. 2019;(11):4585-4593
Abstract
Beer yeast-modified fluorescent carbon dots were synthesized via a one-step strategy for photoinduced bactericidal functions and bio-imaging in bacterial viability assessment. The proposed carbon dots (CDs) were used as an visible light-triggered antibacterial material, and the antimicrobial activities of the CDs against Gram-negative model bacterial species (Escherichia coli) were evaluated under conditions of varying other experimental parameters including CDs concentrations and treatment times. The result showed that the CDs have excellent antibacterial performance of bactericidal effect within 120 min of under visible-light irradiation. And the bactericidal efficiency increased with the increasing concentration of CDs and visible-light illumination time. Moreover, the CDs with high quantum yield (21%) possess highly negative zeta potential (- 41.7 mV) and low cytotoxicity, the CDs could serve as an efficient dye for bacterial viability evaluation, they could selectively stain dead E. coli rather than live ones, which make dead E. coli be viewed with multicolor fluorescence under different excitation wavelengths.
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Photodynamic Therapy of Psoriasis Using Photosensitizers of Vegetable Origin.
Bruschi, ML, da Silva, JB, Rosseto, HC
Current pharmaceutical design. 2019;(20):2279-2291
Abstract
Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can decrease the patients' morbidity and improving their life quality. The aim is to achieve disease control, minimize the adverse drug effects, and tailor the treatment to individual patient factors. Photodynamic therapy (PDT) is based on local or systemic administration of a non-toxic photosensitizer followed by irradiation with a particular wavelength to generate reactive oxygen species (ROS), mainly highly cytotoxic singlet oxygen (1O2). The generation of these species results in the attack to substrates involved in biological cycles causing necrosis and apoptosis of affected tissues. Photosensitizers are found in natural products and also obtained by partial syntheses from abundant natural starting compounds. They can be isolated at low cost and in large amounts from plants or algae. Therefore, this manuscript reviews the use of molecules from vegetal sources as photosensitizer agents for the PDT of psoriasis. Psoriasis pathogenesis, management and treatment were reviewed. PDT principles, fundamentals and utilization for the treatment of psoriasis were also discussed. Photosensitizers for PDT of psoriasis are also reviewed focusing on those from vegetal sources. Despite the PDT is utilized for the treatment of psoriasis, very little amount of photosensitizers from plant sources are utilized, such as chlorophyll derivatives and hypericin; however, other natural photosensitizers such as curcumin, could also be investigated. They could constitute a very important, safe and cheap alternative for the successful photodynamic treatment of psoriasis.
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Effect of Toxic Metal Ions on Photosensitized Singlet Oxygen Generation for Photodegradation of Polyaromatic Hydrocarbon Derivatives and Inactivation of Escherichia coli.
Herschmann, JR, Ali, A, Harris, M, McClinton, M, Zamadar, M
Photochemistry and photobiology. 2019;(3):823-832
Abstract
Here, we report an experimental study of the effect of toxic metal ions on photosensitized singlet oxygen generation for photodegradation of PAH derivatives, Anthracene-9,10-dipropionic acid disodium salt (ADPA) and 1,5-dihydroxynapthalene (DHN) and photoinactivation of Escherichia coli bacteria by using cationic meso-tetra(N-methyl-4-pyridyl)porphine tetrachloride (TMPyP) as a singlet oxygen photosensitizer. Three s-block metals ions, such as Na+ , K+ and Ca2+ and five toxic metals such as Cd2+ , Cu2+ , Hg2+ , Zn2+ and Pb2+ were studied. The s-block metal ions showed no change in the rate of photodegradation of ADPA or DHN by TMPyP, whereas a dramatic change in the photodegradation of ADPA and DHN was observed in the presence of toxic metals. The maximum photodegradation rate constants of ADPA and DHN were observed for Cd2+ ions [(3.91 ± 0.20) × 10-3 s-1 and (7.18 ± 0.35) × 10-4 s-1 , respectively]. Strikingly, the photodegradation of ADPA and DHN was almost completely inhibited in the presence of Hg2+ ions and Cu2+ ions. A complete inhibition of growth of E. coli was observed upon visible light irradiation of E. coli solutions with TMPyP and toxic metal ions particularly, Cd2+ , Hg2+ , Zn2+ and Pb2+ ions, except for Cu2+ ions where a significantly slow inhibition of E. coli's growth was observed.
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Corneal crosslinking: Current protocols and clinical approach.
Beckman, KA, Gupta, PK, Farid, M, Berdahl, JP, Yeu, E, Ayres, B, Chan, CC, Gomes, JAP, Holland, EJ, Kim, T, et al
Journal of cataract and refractive surgery. 2019;(11):1670-1679
Abstract
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.
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Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma.
Keyal, U, Bhatta, AK, Zhang, G, Wang, XL
Journal of the American Academy of Dermatology. 2019;(3):765-773
Abstract
Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. Surgery remains the main stay of treatment, but some patients are not eligible for surgery and, more importantly, lesions at critical sites need nonsurgical approaches for tissue preservation. In this context, photodynamic therapy (PDT) has been extensively studied as noninvasive or minimally invasive treatment, and studies have shown promising results in terms of safety, efficacy, and cosmetic outcome. Also, studies have proposed different mechanism for its efficacy. However, human studies demonstrating its efficacy are limited in terms of sample size and tumor depth of invasion. Good results are mainly seen in case reports of microinvasive SCC, which is defined as SCC limited to papillary dermis. This inadequacy is due to inadequate penetration of topically applied photosensitizers through keratinized tumor surfaces. To overcome these hurdles, pretreatment with lasers or microneedles and encapsulation of photosensitizers into nanoparticles have been tried. Hence, the present article will discuss studies that have demonstrated the efficacy and safety of PDT for cutaneous SCC, studies that have postulated the mechanism of action of PDT, agents that have been used as PDT enhancers, and finally, the recent use of adjuvant therapy in combination with PDT.
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Randomized Study of Collagen Cross-Linking With Conventional Versus Accelerated UVA Irradiation Using Riboflavin With Hydroxypropyl Methylcellulose: Two-Year Results.
Hagem, AM, Thorsrud, A, Sandvik, GF, Drolsum, L
Cornea. 2019;(2):203-209
Abstract
PURPOSE To compare the clinical outcome 2 years after corneal collagen cross-linking (CXL) with conventional and accelerated ultraviolet A (UVA) irradiation using riboflavin with hydroxypropyl methylcellulose. METHODS Prospective randomized controlled study. Forty patients with keratoconus (40 eyes) were randomized to either CXL using conventional 3 mW/cm UVA irradiation for 30 minutes (CXL30 group) or accelerated 9 mW/cm UVA irradiation for 10 minutes (CXL10 group). In both groups, a solution of 0.1% riboflavin with 1.1% hydroxypropyl methylcellulose (methylcellulose-riboflavin) was used. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and Scheimpflug tomography were performed at baseline and after 24 months. RESULTS Both groups had statistically significant improvement in CDVA and maximum keratometric reading compared with baseline; however, with no statistically significant difference in the change between the 2 groups. No significant changes in flattest, steepest and mean keratometry (K1, K2 and K mean) were found in either of the groups. There were no statistically significant changes in ECD in either group after 2 years or in the difference in the change between the 2 groups. A literature review showed comparative clinical outcome after accelerated CXL compared with conventional CXL; however, in several studies, there was a tendency for less pronounced corneal flattening after accelerated CXL. CONCLUSIONS Improvement in visual acuity and maximum keratometric reading 2 years after CXL was found after both conventional and accelerated UVA irradiation using methylcellulose-riboflavin. This suggests that when using riboflavin with methylcellulose, the less time-consuming accelerated protocol is a valuable and effective option in CXL treatment.
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Role of photodynamic therapy in the treatment of esophageal cancer.
Wu, H, Minamide, T, Yano, T
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2019;(5):508-516
Abstract
Photodynamic therapy (PDT), a treatment of choice for cancer, induces a photochemical reaction, thereby eradicating tumor cells. This is achieved through the administration of a photosensitizer drug, which is activated with a laser after localization to the tumor mass, and is an approved curative endoscopic ablative treatment for superficial esophageal squamous cell carcinoma (ESCC) in Japan. PDT has been approved for dysplastic Barrett's esophagus and as a palliative treatment for patients with symptomatic obstructive esophageal cancer in US. However, its adverse events and complicated procedure and the development of alternative endoscopic procedures such as endoscopic submucosal dissection, radiofrequency ablation and cryotherapy, have largely limited the practice of PDT in esophageal cancer worldwide. Recently, owing to the invention of second-generation PDT using talaporfin sodium and diode laser, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. As a salvage treatment for patients with local failure after chemoradiotherapy (CRT), PDT has shown promising complete response with less phototoxicity and shorter sun shade period. In addition, the efficacy and safety of PDT in patients with local failure of ESCC after CRT were shown in several clinical trials. The direction of the study interest of the next-generation PDT is the safety and potential expansion of the indications for its application in the future. This review covers the PDT for the treatment of ESCC and dysplastic Barrett's esophagus, with special focus on the role of PDT in practice for esophageal cancer.
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Do Thiazide Diuretics Increase the Risk of Skin Cancer? A Critical Review of the Scientific Evidence and Updated Meta-Analysis.
Bendinelli, B, Masala, G, Garamella, G, Palli, D, Caini, S
Current cardiology reports. 2019;(9):92
Abstract
PURPOSE OF REVIEW We reviewed the hypothesised mechanisms of skin cancerogenesis for thiazide diuretics; conducted an updated meta-analysis of studies focusing on their association with skin cancer risk; critically appraised the quality of available studies and identified knowledge gaps; and discussed implications for health professionals and patients. RECENT FINDINGS Thiazide diuretics possess well-described photosensitizing properties and a causal association with skin cancer is biologically plausible. The epidemiological evidence is stronger for squamous cell cancer; however, diversity in design among studies, methodological concerns potentially affecting the validity of results, and scarcity of data on dose-relation relationship suggest caution in drawing conclusions. Only few, unbalanced, and/or heterogeneous data exist to date for melanoma and basal cell cancer. Patients effectively treated with thiazide diuretics are currently not advised to stop treatment, but encouraged to limit exposure to sunlight and regularly check their skin. While endorsing these recommendations, we believe that well-designed studies are urgently needed to overcome persistent knowledge gaps.