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Accelerated Pulsed High-Fluence Corneal Cross-Linking for Progressive Keratoconus.
Gore, DM, Leucci, MT, Koay, SY, Kopsachilis, N, Nicolae, MN, Malandrakis, MI, Anand, V, Allan, BD
American journal of ophthalmology. 2021;:9-16
Abstract
PURPOSE To report on 2-year results of accelerated corneal collagen cross-linking (CXL) in progressive ectasia using the Avedro KXL system. DESIGN Prospective interventional case series. METHODS A total of 870 patients (1,192 eyes) attending Moorfields Eye Hospital after CXL were included. All patients undergoing CXL had progressive keratoconus. Corneas with a minimum stromal thickness <375 μm were excluded. Riboflavin 0.1% soak duration was 10 minutes. High-fluence pulsed UVA was delivered at 30 mW/cm2 for 4 minutes, with a 1.5-second on/off cycle (total energy 7.2 J/cm2). Subjective refractive, corneal tomography, and specular microscopy were performed at baseline, 6, 12, and 24 months postoperatively. The primary outcome measure was a change in maximum keratometry (Kmax) at 24 months. RESULTS Twelve- and 24-month follow-up data were available on 543 and 213 patients, respectively (mean age 25.4 ± 6.6 years). In mild cones (Kmax < 55 diopter [D]), mean keratometry remained unchanged at 24 months. In more advanced disease, we observed modest corneal flattening compared to baseline (Kmax 63.2 ± 6.5 D vs 61.9 ± 8.1 D, P = .02), but no significant changes in central keratometry (K1 or K2). Keratometric stabilization was confirmed in 98.3% of eyes. Mean CDVA, manifest refraction and endothelial cell density did not change. Overall, 2.7% of eyes lost more than 2 lines of CDVA. CONCLUSION Accelerated pulsed CXL is a safe, effective, and refractively neutral intervention (at 2 years) to halt disease progression in keratoconus.
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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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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.
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Low light visual function after accelerated corneal Cross-Linking Protocols: 18 mW/cm2 vs. 9 mW/cm2.
Asgari, S, Hashemi, H, Jafarzadehpur, E, Mohamadi, A, Mehravaran, S, Fotouhi, A
Romanian journal of ophthalmology. 2018;(4):270-276
Abstract
Objective. To compare one-year results of vision, corneal aberrometry and contrast sensitivity (CS) in low light conditions between 5- and 10-minute accelerated cross-linking (CXL) protocols. Methods. Thirty eyes were evaluated in each studied group. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity by the SC-2000 Snellen chart, corneal higher order aberrations using the OPD Scan III and CS using MonCv3System was tested under mesopic (20 lux) and scotopic (0.5 lux) light conditions at pre-CXL and 6 and 12 months post-CXL. Results. At 12 months, a mean improvement of 0.06±0.22 (22.2%) and 0.02±0.25 logMAR (7.9%) in mesopic UDVA and 0.01±0.13 (14.3%) and 0.07±0.13 logMAR (87.9%) in mesopic CDVA was observed in the 5- and 10-minute groups, respectively. Mean decline in scotopic UDVA was 0.01±0.16 (1.0%) and 0.03±0.17 logMAR (11.9%) and mean improvement in scotopic CDVA was 0.03±0.10 (35.5%) and 0.02±0.07 logMAR (22.2%), respectively. Inter-group differences in the decrease of corneal aberrations were not statistically significant. Among CS variables, only inter-group changes in corrected CS 0.5 to 2.2 was significantly different (all P<0.050). The linear regression analysis showed that these differences were related to baseline values not CXL protocols; corrected CS 0.5 (Pgroup=0.261 and Pbaseline value<0.001), CS 1.1 (Pgroup=0.250 and Pbaseline value<0.001), and CS 2.2 (Pgroup=0.101 and Pbaseline value=0.054). Conclusions. Changing the intensity of UV in cross-linking from 18mW/ cm2 to 9mW/ cm2 does not affect the visual function under low-light conditions.
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Primary photodynamic therapy with verteporfin for small pigmented posterior pole choroidal melanoma.
Fabian, ID, Stacey, AW, Papastefanou, V, Al Harby, L, Arora, AK, Sagoo, MS, Cohen, VM, ,
Eye (London, England). 2017;(4):519-528
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Abstract
PurposeThe purpose of the study was to investigate the outcomes of primary photodynamic therapy (PDT) for small pigmented posterior pole choroidal melanoma.Patients and methodsProspective interventional consecutive case series of 15 patients with small pigmented posterior pole choroidal melanoma, who were treated with three sessions of PDT and followed-up thereafter. Risk factors for failure were assessed and outcome measures at presentation were compared to those at last follow-up visit.ResultsTumor control was achieved in 12 (80%) patients in a median follow-up time of 15 months (mean 14, range 8-18). Three patients failed treatment, diagnosed in a median time of 5 months (mean 4, range 3-6), after first PDT. In all failed cases, lesions were 100% pigmented; de novo melanoma rather than transformed nevi and showed a radial growth pattern rather than increased thickness. All failed cases were subsequently successfully treated with radiotherapy. In this cohort, subretinal fluid (SRF) was significantly reduced (P<0.001), vision did not deteriorate (P=0.11) and even improved in patients with subfoveal SRF at presentation (P=0.018), tumor height significantly decreased (P=0.037) and no complications were recorded.ConclusionPrimary PDT was found to be a safe and efficient treatment modality for small pigmented posterior pole choroidal melanoma, achieving short-term tumor control in 80% of patients. PDT offers patients the opportunity to preserve vision by avoiding the retinopathy associated with conventional radiation treatments for choroidal melanoma. However, the long-term local control of these tumors remains uncertain.
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A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer.
Yano, T, Kasai, H, Horimatsu, T, Yoshimura, K, Teramukai, S, Morita, S, Tada, H, Yamamoto, Y, Kataoka, H, Kakushima, N, et al
Oncotarget. 2017;(13):22135-22144
Abstract
Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period. This study aimed to evaluate the safety and efficacy of PDT using second generation photosensitizer, talaporfin sodium for local failure after CRT. This was the multi-institutional non-randomized phase II study. Patients with histologically proven local failure limited within the muscularis propria after 50Gy or more radiotherapy (RT) for esophageal cancer were eligible. We set the primary endpoint as local complete response (L-CR) per patients. And, secondary endpoints were confirmed L-CR, local progression free survival (L-PFS), progression free survival (PFS), overall survival (OS), L-CR per lesions (Lesion L-CR), and confirmed Lesion L-CR. The PDT procedure commenced with intravenous administration of a 40 mg/m2 dose of talaporfin sodium followed by diode laser irradiation at a 664 nm wavelength. 26 eligible patients were enrolled and all were treated with PDT. Twenty three patients with 25 lesions were assessed L-CR after PDT; the L-CR rate per patients was 88.5% (95% CI: 69.8%-97.6%). No skin phototoxicity was observed, and no grade 3 or worse non-hematological toxicities related to PDT were observed. PDT using talaporfin sodium and a diode laser is a safe and curative salvage treatment for local failure after CRT or RT for patients with esophageal cancer.
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U.S. Multicenter Clinical Trial of Corneal Collagen Crosslinking for Treatment of Corneal Ectasia after Refractive Surgery.
Hersh, PS, Stulting, RD, Muller, D, Durrie, DS, Rajpal, RK, ,
Ophthalmology. 2017;(10):1475-1484
Abstract
PURPOSE To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of corneal ectasia after laser refractive surgery. DESIGN Prospective, randomized, multicenter, controlled clinical trial. PARTICIPANTS One hundred seventy-nine subjects with corneal ectasia after previous refractive surgery. METHODS The treatment group underwent standard CXL, and the sham control group received riboflavin alone without removal of the epithelium. MAIN OUTCOME MEASURES The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry (K), comparing treatment with control groups. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. RESULTS In the crosslinking treatment group, the maximum K value decreased by 0.7 diopters (D) from baseline to 1 year, whereas there was continued progression in the control group (1.3 D difference between treatment and control, P < 0.0001). In the treatment group, the maximum K value decreased by 2.0 D or more in 14 eyes (18%) and increased by 2.0 D or more in 3 eyes (4%). The CDVA improved by an average of 5.0 logarithm of the minimum angle of resolution (logMAR) letters. Twenty-three eyes (32%) gained and 3 eyes (4%) lost 10 or more logMAR letters. The UDVA improved 4.5 logMAR letters. Corneal haze was the most frequently reported crosslinking-related adverse finding. CONCLUSIONS Corneal collagen crosslinking was effective in improving the maximum K value, CDVA, and UDVA in eyes with corneal ectasia 1 year after treatment, with an excellent safety profile. CXL is the first approved procedure to diminish progression of this ectatic corneal process.
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United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment.
Hersh, PS, Stulting, RD, Muller, D, Durrie, DS, Rajpal, RK, ,
Ophthalmology. 2017;(9):1259-1270
Abstract
PURPOSE To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus. DESIGN Prospective, randomized, multicenter, controlled clinical trial. PARTICIPANTS Patients with progressive keratoconus (n = 205). METHODS The treatment group underwent standard CXL and the sham control group received riboflavin alone without removal of the epithelium. MAIN OUTCOME MEASURES The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry value, comparing treatment with control group. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. RESULTS In the CXL treatment group, the maximum keratometry value decreased by 1.6 diopters (D) from baseline to 1 year, whereas keratoconus continued to progress in the control group. In the treatment group, the maximum keratometry value decreased by 2.0 D or more in 28 eyes (31.5%) and increased by 2.0 D or more in 5 eyes (5.6%). The CDVA improved by an average of 5.7 logarithm of the minimum angle of resolution (logMAR) units. Twenty-three eyes (27.7%) gained and 5 eyes lost (6.0%) 10 logMAR or more. The UDVA improved 4.4 logMAR. Corneal haze was the most frequently reported CXL-related adverse finding. There were no significant changes in endothelial cell count 1 year after treatment. CONCLUSIONS Corneal collagen crosslinking was effective in improving the maximum keratometry value, CDVA, and UCVA in eyes with progressive keratoconus 1 year after treatment, with an excellent safety profile. Corneal collagen crosslinking affords the keratoconic patient an important new option to decrease progression of this ectatic corneal process.
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Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes.
Caruso, C, Ostacolo, C, Epstein, RL, Barbaro, G, Troisi, S, Capobianco, D
Cornea. 2016;(2):145-50
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PURPOSE To report the clinical outcomes with 24-month follow-up of transepithelial cross-linking using a combination of a D-alpha-tocopheryl polyethylene-glycol 1000 succinate (vitamin E-TPGS)-enhanced riboflavin solution and abbreviated low fluence UV-A treatment. METHODS In a nonrandomized clinical trial, 25 corneas of 19 patients with topographically proven, progressive, mild to moderate keratoconus over the previous 6 months were cross-linked, and all patients were examined at 1, 3, 6, 12, and 24 months. The treatments were performed using a patented solution of riboflavin and vitamin E-TPGS, topically applied for 15 minutes, followed by two 5-minute UV-A treatments with separate doses both at fluence below 3 mW/cm(2) that were based on preoperative central pachymetry. RESULTS During the 6-month pretreatment observation, the average Kmax increased by +1.99 ± 0.29 D (diopter). Postoperatively, the average Kmax decreased, changing by -0.55 ± 0.94 D, by -0.88 ± 1.02 D and by -1.01 ± 1.22 D at 6, 12, and 24 months. Postoperatively, Kmax decreased in 19, 20, and 20 of the 25 eyes at 6 months, 12 months, and 24 months, respectively. Refractive cylinder was decreased by 3 months postoperatively and afterward, changing by -1.35 ± 0.69 D at 24 months. Best spectacle-corrected visual acuity (BSCVA) improved at 6, 12, and 24 months, including an improvement of -0.19 ± 0.13 logarithm of the minimum angle of resolution units at 24 months. There was no reduction in endothelial cell count. No corneal abrasions occurred, and no bandage contact lenses or prescription analgesics were used during postoperative recovery. CONCLUSIONS Transepithelial cross-linking using the riboflavin-vitamin E solution and brief, low-dose, pachymetry-dependent UV-A treatment safely stopped keratoconus progression.
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Evaluation of a novel high-resolution magnifying videoendoscope that is capable of photodynamic diagnosis and therapy for gastric cancer.
Nakamura, T, Oinuma, T, Yamagishi, H, Masuyama, H, Terano, A
Photodiagnosis and photodynamic therapy. 2015;(1):115-22
Abstract
OBJECTIVE To evaluate the usefulness of a novel high-resolution magnifying videoendoscope called the XG-0001 (Fujifilm, Tokyo, Japan) that is capable of PDD and PDT in experimental and clinical situations. MATERIALS AND METHODS The fluorescences of three photosensitizers (i.e., porfimer sodium (Photofrin), protoporphyrin IX and talaporfin sodium (Laserphyrin)) were studied experimentally via excitation with a purple diode laser (VDL, wavelength 405nm). Five consecutive patients with superficial early gastric cancer not indicated for surgery or other curative endoscopic treatment due to complicated serious diseases were enrolled in this study. After close endoscopic examinations, 2mg/kg of Photofrin were intravenously injected into the patients for PDT, and 5-aminolevulinic acid (ALA; 15-20mg/kg) was orally taken for PDD. PDD using VDL and PDT using an excimer-dye laser (630nm, 4mJ, 60Hz) were performed with the XG-0001. RESULTS Photofrin and Laserphyrin had experimentally the lowest and highest fluorescence intensities, respectively. The five patients comprised four men and one woman with a mean age 75.2 year and an age range of 56-83 years. Two additional cancerous lesions were newly detected by magnifying pharmacoendoscopy. In each patient, PDD was successfully performed. PDT could also safely performed and CR was obtained in 71.4% (5/7) of the cancerous lesions in five patients, and no serious complications were encountered. CONCLUSION The XG-0001, which is based on a simultaneous videoendoscopy method that uses an RGB color chip CCD, proved extremely useful in routine use and also in PDD and PDT for gastric cancer.
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Effects of antimicrobial photodynamic therapy and surgical endodontic treatment on the bacterial load reduction and periapical lesion healing. Three years follow up.
Garcez, AS, Arantes-Neto, JG, Sellera, DP, Fregnani, ER
Photodiagnosis and photodynamic therapy. 2015;(4):575-80
Abstract
Besides the advances in endodontics, there are situations in which surgery is necessary to retain a tooth that otherwise would be extracted. This study analyzes the microbial reduction after conventional periapical surgery followed by antimicrobial photodynamic therapy (aPDT) in 3 years follows up. Twenty-eight teeth needing periapical surgery were enrolled in this study. Microbiological samples were taken after: (1) accessing the lesion, (2) surgical procedure, and (3) aPDT. The teeth received a full mucoperiosteal flap, osteotomy with a high-speed bur, manual curettage of lesion and of the root, root-end resection and retrograde cavities prepared using ultrasonic retro-tips. After the conventional procedure the cavities received an aqueous solution of methylene blue (60 μM, 3 min) and were irradiated with a diode laser λ=660 nm (6 min, 15 J). After aPDT, a retrograde filling with mineral trioxide aggregate, flap re-positioning, and sutures conventionally ended the procedure. In all the cases, a periapical X-ray exam was taken before and after the surgical procedure. The microbiological samples showed an overall significant reduction, surgical procedure achieved a mean reduction of about 3.5 log while aPDT achieved a 5 log reduction. After 36 months of follow up the patients had, in average a reduction of 78% of the periapical lesion area. It appears that surgical endodontic treatment associated with antimicrobial photodynamic therapy highly improves the microbial reduction compared to the traditional technique and this could directly affect the treatment prognosis and periapical lesion healing.