1.
Corneal collagen cross-linking for bacterial infectious keratitis.
Davis, SA, Bovelle, R, Han, G, Kwagyan, J
The Cochrane database of systematic reviews. 2020;(6):CD013001
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Abstract
BACKGROUND Infectious keratitis is an infection of the cornea that can be caused by bacteria, viruses, fungi, protozoa, or parasites. It may be associated with ocular surgery, trauma, contact lens wear, or conditions that cause deficiency or loss of corneal sensation, or suppression of the immune system, such as diabetes, chronic use of topical steroids, or immunomodulatory therapies. Photoactivated chromophore for collagen cross-linking (PACK-CXL) of the cornea is a therapy that has been successful in treating eye conditions such as keratoconus and corneal ectasia. More recently, PACK-CXL has been explored as a treatment option for infectious keratitis. OBJECTIVES To determine the comparative effectiveness and safety of PACK-CXL with standard therapy versus standard therapy alone for the treatment of bacterial keratitis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 7); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 8 July 2019. SELECTION CRITERIA We included randomized controlled trials (RCTs), quasi-RCTs, and controlled clinical trials (CCTs) of PACK-CXL for bacterial keratitis. We included quasi-RCTs and CCTs as we anticipated that there would not be many RCTs eligible for inclusion. DATA COLLECTION AND ANALYSIS Two review authors working independently selected studies for inclusion in the review, assessed trials for risk of bias, and extracted data. The primary outcome was proportion of participants with complete healing at four to eight weeks. Secondary outcomes included visual acuity, morphology, adverse events, and treatment failure at four to eight weeks. MAIN RESULTS We included three trials (two RCTs and one quasi-RCT) in this review for a total of 59 participants (59 eyes) with bacterial keratitis. Trials were all single-center and were conducted in Egypt, Iran, and Thailand between 2010 and 2014. It is very uncertain whether PACK-CXL with standard antibiotic therapy is more effective than standard antibiotic therapy alone for re-epithelialization and complete healing (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.88 to 2.66; participants = 15). We judged the certainty of the evidence to be very low due to the small sample size and high risk of selection and performance bias. The high risk of selection bias reflects the overall review. Masking of participants was not possible for the surgical arm. No participant had a best-corrected visual acuity of 20/100 or better at eight weeks (very low certainty evidence). There is also no evidence that use of PACK-CXL with standard therapy results in fewer instances of treatment failure than standard therapy alone (RR 0.50, 95% CI 0.05 to 4.98; participants = 32). We judged the certainty of evidence to be low due to the small sample size and high risk of selection bias. There were no adverse events reported at 14 days (low certainty evidence). Data on other outcomes, such as visual acuity and morphological characteristics, could not be compared because of variable time points and specific metrics. AUTHORS' CONCLUSIONS The current evidence on the effectiveness of PACK-CXL for bacterial keratitis is of low certainty and clinically heterogenous in regard to outcomes. There are five ongoing RCTs enrolling 1136 participants that may provide better answers in the next update of this review. Any future research should include subgroup analyses based on etiology. A core outcomes set would benefit healthcare decision-makers in comparing and understanding study data.
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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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Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron.
Ito, H, Nishio, Y, Hara, T, Sugihara, H, Tanaka, T, Li, XK
European journal of pharmacology. 2018;:25-33
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Abstract
Heme oxygenase-1 (HO-1) is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance through affecting the differentiation of dendritic cells. The aim of this study is to determine whether the combination of 5-aminolevulinic acid (ALA) and iron induces HO-1 expression in healthy human peripheral blood mononuclear cells (PBMC). The study was an open labeled, non-randomized, non-placebo-controlled trial using healthy male adults and consisted of three parts. Study A aimed to find the peak HO-1 expression at 0, 1, 2, 3, 4, 6, 8, 12, 16, and 24 h after administration. Study B aimed to examine HO-1 dose dependency at 150, 300, and 600 mg of ALA and the need for iron supplementation. Study C aimed to investigate HO-1 changes during a three-day, repetitive administration of ALA and iron. The combination of ALA 600 mg and sodium ferrous citrate (SFC) 942 mg upregulated HO-1 in PBMC at 8 h after administration while sole administration of ALA or SFC was unable to induce HO-1. HO-1 in blood myeloid and plasmacytoid dendritic cells was also upregulated with ALA+SFC. Clear dose dependency of ALA+SFC was not detected, and a slight tendency towards a cumulative effect of HO-1 after three-day, repetitive administration was observed. ALA, which is already approved for use in several countries as a diagnosis agent for cancer, has the potential to become a novel therapeutic drug for diseases stemming from unwanted immune response such as autoimmune diseases and the rejection response following organ transplantation.