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1.
Epithelial remodeling after corneal crosslinking using higher fluence and accelerated treatment time.
Haberman, ID, Lang, PZ, Broncano, AF, Kim, SW, Hafezi, F, Randleman, JB
Journal of cataract and refractive surgery. 2018;(3):306-312
Abstract
PURPOSE To evaluate changes in regional corneal epithelial thickness after corneal crosslinking (CXL) using higher fluence (7.2 J/cm2) and accelerated treatment time (4 minutes) in eyes with progressive keratoconus using spectral-domain optical coherence tomography (SD-OCT) and to correlate focal epithelial and focal anterior curvature changes. SETTING Academic medical center in the United States. DESIGN Prospective case series. METHODS Patients had anterior segment SD-OCT (RTVue-100) with focal stromal and epithelial measurements and Scheimpflug imaging before and 1, 3, 6, and 12 months after accelerated CXL. RESULTS Twenty-seven eyes from 20 patients were evaluated. Before the accelerated CXL, the epithelium was thinnest in the inferior inner and outer temporal regions, whereas at 12 months postoperatively, the epithelium was significantly thinned in multiple inferior and nasal regions by 1.1 to 3.2 μm (P < .05, all measurements), with no significant changes from 6 to 12 months. Epithelial thickness standard deviation across the central 6.0 mm was significantly reduced by 3 months (1.4 μm, P = .09) and remained stable at 12 months (P = .009). Change in epithelial thickness was poorly correlated to change in anterior curvature (r = -0.035). CONCLUSIONS Significant epithelial remodeling occurred after accelerated CXL in eyes with progressive keratoconus, with improved regularity across the central 6.0 mm, by 6 months after treatment. There was poor correlation between focal epithelial thickness and anterior curvature changes, with wide variability between patients. Establishing the pattern of epithelial remodeling after CXL might help optimize future custom treatment protocols.
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2.
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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3.
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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4.
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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5.
Sequential Intracorneal Ring Segment Implantation and Corneal Transepithelial Collagen Cross-Linking in Keratoconus.
Elsaftawy, HS, Ahmed, MH, Saif, MY, Mousa, R
Cornea. 2015;(11):1420-6
Abstract
PURPOSE To assess the clinical outcomes after sequential surgical implantation of intracorneal ring segments and transepithelial corneal collagen cross-linking (TE-CXL) in keratoconic eyes. METHODS In this consecutive randomized study, 40 eyes of 29 patients with progressive mild to moderate keratoconus were included and were randomly divided into two groups. Group 1 included 20 eyes that underwent Keraring implantation, and group 2 included 20 eyes that underwent Keraring insertion followed by TE-CXL 1 month later. In both groups, channel creation was performed manually. Visual, refractive, and topographic outcomes were measured preoperatively and 1, 3, and 6 months postoperatively. RESULTS There was statistically significant improvement in both groups regarding uncorrected distance visual acuity (P < 0.001) and corrected distance visual acuity (P < 0.001), with a significant reduction in the refractive error and keratometric values (P < 0.001). There was no statistically significant difference between both groups regarding changes in uncorrected distance visual acuity, corrected distance visual acuity, and refractive error (P > 0.05). However, group 2 revealed a more statistically significant reduction in spherical refraction after 3 months (P = 0.04) and highly significant improvement after 6 months (P = 0.004). CONCLUSIONS Intracorneal ring segment implantation is an effective procedure for visual and refractive improvement in keratoconic eyes. The addition of TE-CXL to the procedure compensates for residual superficial irregularities, disrupts the progression of the disease, and provides greater improvements in spherical values. The process is simply a deep stretch with superficial lamellar stiffness.
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6.
Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting.
Said, DG, Elalfy, MS, Gatzioufas, Z, El-Zakzouk, ES, Hassan, MA, Saif, MY, Zaki, AA, Dua, HS, Hafezi, F
Ophthalmology. 2014;(7):1377-82
Abstract
PURPOSE To investigate the efficacy and safety of corneal collagen cross-linking (CXL) with photoactivated riboflavin (photoactivated chromophore for infectious keratitis [PACK]-CXL) in the management of infectious keratitis with corneal melting. DESIGN Prospective clinical trial. PARTICIPANTS Forty eyes from 40 patients with advanced infectious keratitis and coexisting corneal melting. METHODS Twenty-one patients (21 eyes) underwent PACK-CXL treatment in addition to antimicrobial therapy. The control group consisted of 19 patients (19 eyes) who received only antimicrobial therapy. MAIN OUTCOME MEASURES The slit-lamp characteristics of the corneal ulceration, corrected distance visual acuity, duration until healing, and complications were documented in each group. The Mann-Whitney U test was used for statistical analysis. P values less than 0.05 were considered statistically significant. RESULTS The average time until healing was 39.76 ± 18.22 days in the PACK-CXL group and 46.05 ± 27.44 days in the control group (P = 0.68). After treatment and healing, corrected distance visual acuity was 1.64 ± 0.62 in the PACK-CXL group and 1.67 ± 0.48 in the control group (P = 0.68). The corneal ulceration's width and length was significantly bigger in the PACK-CXL group (P = 0.004 and P = 0.007). Three patients in the control group demonstrated corneal perforation; infection recurred in 1 of them. No serious complications occurred in the PACK-CXL group. CONCLUSIONS Corneal CXL with photoactivated riboflavin did not shorten the time to corneal healing; however, the complication rate was 21% in the control group, whereas there was no incidence of corneal perforation or recurrence of the infection in the PACK-CXL group. These results indicate that PACK-CXL may be an effective adjuvant therapy in the management of severe infectious keratitis associated with corneal melting.
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7.
Characteristics influencing outcomes of corneal collagen crosslinking for keratoconus and ectasia: implications for patient selection.
Greenstein, SA, Hersh, PS
Journal of cataract and refractive surgery. 2013;(8):1133-40
Abstract
PURPOSE To determine preoperative patient characteristics that may predict topography and visual acuity outcomes of corneal collagen crosslinking (CXL). SETTING Cornea and refractive surgery practice. DESIGN Cohort study. METHODS Crosslinking was performed in eyes with keratoconus or corneal ectasia. Multiple regression and odds ratio analyses were performed to determine independent predictors of changes in topography-derived maximum keratometry (K) and corrected distance visual acuity (CDVA) 1 year postoperatively. Preoperative characteristics included sex, age, uncorrected distance visual acuity (UDVA), CDVA, maximum keratometry (K), corneal thickness, corneal haze, disease group, and cone location. Postoperative improvement in maximum K was defined as flattening of 2.0 diopters (D) or more and worsening as steepening of 1.0 D or more. Improvement in CDVA was defined as a gain of 2 lines or more and worsening as a loss of 1 line or more. RESULTS The study comprised 104 eyes (66 keratoconus; 38 corneal ectasia). Eyes with a preoperative CDVA of 20/40 or worse were 5.9 times (95% confidence interval [CI], 2.2-6.4) more likely to improve 2 Snellen lines or more. Eyes with a maximum K of 55.0 D or more were 5.4 times (95% CI, 2.1-14.0) more likely to have topographic flattening of 2.0 D or more. No preoperative characteristics significantly predicted worsening of visual acuity or corneal topography. CONCLUSIONS Patients with worse preoperative CDVA and higher K values, particularly with a CDVA of 20/40 or worse or a maximum K of 55.0 D or more, were most likely to have improvement after CXL. No preoperative characteristics were predictive of CXL failure.
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8.
Phase II clinical study on intraoperative photodynamic therapy with talaporfin sodium and semiconductor laser in patients with malignant brain tumors.
Muragaki, Y, Akimoto, J, Maruyama, T, Iseki, H, Ikuta, S, Nitta, M, Maebayashi, K, Saito, T, Okada, Y, Kaneko, S, et al
Journal of neurosurgery. 2013;(4):845-52
Abstract
OBJECT The objective of the present study was to perform a prospective evaluation of the potential efficacy and safety of intraoperative photodynamic therapy (PDT) using talaporfin sodium and irradiation using a 664-nm semiconductor laser in patients with primary malignant parenchymal brain tumors. METHODS In 27 patients with suspected newly diagnosed or recurrent primary malignant parenchymal brain tumors, a single intravenous injection of talaporfin sodium (40 mg/m(2)) was administered 1 day before resection of the neoplasm. The next day after completion of the tumor removal, the residual lesion and/or resection cavity were irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm(2) and a radiation energy density of 27 J/cm(2). The procedure was performed 22-27 hours after drug administration. The study cohort included 22 patients with a histopathologically confirmed diagnosis of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%) were newly diagnosed glioblastomas multiforme (GBM). RESULTS Among all 22 patients included in the study cohort, the 12-month overall survival (OS), 6-month progression-free survival (PFS), and 6-month local PFS rates after surgery and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which could be attributable to the administration of talaporfin sodium, were noted in 7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1 case). Skin photosensitivity test results were relatively mild and fully disappeared within 15 days after administration of photosensitizer in all patients. CONCLUSIONS Intraoperative PDT using talaporfin sodium and a semiconductor laser may be considered as a potentially effective and sufficiently safe option for adjuvant management of primary malignant parenchymal brain tumors. The inclusion of intraoperative PDT in a combined treatment strategy may have a positive impact on OS and local tumor control, particularly in patients with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026 (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862).
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9.
UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study.
Makdoumi, K, Mortensen, J, Sorkhabi, O, Malmvall, BE, Crafoord, S
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2012;(1):95-102
Abstract
BACKGROUND The aim of this work as to investigate the photochemical interaction used in corneal crosslinking (CXL) as the primary therapy for bacterial keratitis. METHODS A prospective non-randomized study was conducted including 16 patients with a clinical diagnosis of bacterial keratitis. No patient had any prior antibiotic treatment for the current infection. Photography and microbial culturing of the infected cornea were performed. Riboflavin was topically administered for 20 min and ultraviolet light (UVA) exposure settings for treatment of keratoconus were used. After the procedure, clinical examinations were done at least once daily until signs of improvement had been established. The frequency of examinations was thereafter reduced. Antibiotic therapy was initiated if infectious progression was suspected. The trial was registered at ISCRTN.org (no: 21432643). RESULTS All eyes responded to the photochemical treatment with improvement in symptoms and signs of reduced inflammation. Epithelial healing was achieved in all cases. Antibiotic administration was necessary in two cases. One patient required a human amniotic membrane transplant. CONCLUSIONS This trial illustrates that photosensitization of riboflavin using UVA at 365 nm has the potential to induce healing in patients with microbial keratitis. The results from the treatment of these 16 patients with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a controlled study in order to assess its efficacy and safety compared to antibiotics.
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10.
Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer.
Yano, T, Muto, M, Yoshimura, K, Niimi, M, Ezoe, Y, Yoda, Y, Yamamoto, Y, Nishisaki, H, Higashino, K, Iishi, H
Radiation oncology (London, England). 2012;:113
Abstract
BACKGROUND Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer. METHODS This phase I, laser dose escalation study used a fixed dose (40 mg/m²) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm², with an escalation plan to 75 J/cm² and 100 J/cm². RESULTS 9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT. CONCLUSIONS PDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm².