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Transfusion-transmitted malaria is a frequent but neglected adverse event in Ghana. We did a randomised controlled clinical trial to assess the efficacy and safety of a whole blood pathogen reduction technology at preventing transfusion transmission of Plasmodium spp parasites. For this randomised, double-blind, parallel-group clinical trial, eligible adult patients (aged ≥18 years) with blood group O+, who required up to two whole blood unit transfusions within 3 days of randomisation and were anticipated to remain in hospital for at least 3 consecutive days after initial transfusion, were enrolled from Komfo Anokye Teaching Hospital in Kumasi, Ghana. The main exclusion criteria were symptoms of clinical malaria, antimalaria treatment within 7 days before randomisation, fever, and haemorrhage expected to require transfusion with up to two units of whole blood during the 3 days following study entry. Eligible patients were randomly assigned 1:1 by computer-generated permuted block randomisation (block size four) list to receive transfusion with either pathogen-reduced whole blood (treated) or whole blood prepared and transfused by standard local practice (untreated). Patients, health-care providers, and data collectors were masked to treatment allocation. Patients in both groups received up to two whole blood unit transfusions that were retrospectively tested for parasitaemia. Pre-transfusion and post-transfusion blood samples (taken on days 0, 1, 3, 7, and 28) were tested for presence and amount of parasite genome, and assessed for haematological and biochemical parameters. The primary endpoint was the incidence of transfusion-transmitted malaria in non-parasitaemic recipients exposed to parasitaemic whole blood, defined as two consecutive parasitaemic post-transfusion samples with parasite allelic matching, assessed at 1–7 days after transfusion. Secondary endpoints included haematological parameters and a safety analysis of adverse events in patients. This study is registered with ClinicalTrials.gov, number NCT02118428, and with the Pan African Clinical Trials Registry, number PACTR201406000777310. Between March 12, 2014, and Nov 7, 2014, 227 patients were enrolled into the study, one of whom was subsequently excluded because she did not meet the inclusion criteria. Of the 226 randomised patients, 113 were allocated to receive treated whole blood and 113 to receive standard untreated whole blood. 223 patients (111 treated and 112 untreated) received study-related transfusions, whereas three patients (two treated and one untreated) did not. 214 patients (107 treated and 107 untreated) completed the protocol as planned and comprised the per-protocol population. Overall, 65 non-parasitaemic patients (28 treated and 37 untreated) were exposed to parasitaemic blood. The incidence of transfusion-transmitted malaria was significantly lower for the pathogen-reduced (treated) patients (1 [4%] of 28 patients) than the untreated group (8 [22%] of 37 patients) in this population (p=0·039). Overall, 92 (41%) of 223 patients reported 145 treatment-related emergent adverse events during the conduct of the study, with a similar incidence of adverse events between groups receiving untreated or treated whole blood. No transfusion-related deaths occurred in the trial. Treatment of whole blood with the Mirasol pathogen reduction system for whole blood reduced the incidence of transfusion-transmitted malaria. The primary endpoint of the study was achieved in the population of non-parasitaemic patients receiving parasitaemic whole blood. The safety profile and clinical outcomes were similar across the two treatment groups. Terumo BCT Inc.

Objectives To compare the clinical efficacy of epithelium-off and transepithelial accelerated corneal collagen crosslinking (ACXL) in adolescent keratoconus. Methods In this prospective observational study with a 1-year follow-up, 60 patients aged 16–26 years (60 eyes) with keratoconus were assigned to two groups: the epithelium-off ACXL group (30 patients, 30 eyes) and the transepithelial ACXL group (30 patients, 30 eyes). Patients were evaluated preoperatively and at 7 days, 1 month, 3 months, 6 months, and 12 months post-treatment. The measurements included visual acuity, corneal parameters, and corneal endothelium parameters. Baseline data and treatment effect were compared using the t-test or Wilcoxon rank-sum test for continuous variables and the chi-square test for categorical variables. Within-group comparisons used paired t-tests or paired rank-sum tests. Results At 12 months postoperatively, the treatment groups showed statistically significant differences in central corneal thickness (IOLMaster), thinnest point corneal thickness (topography), thickness (topography), central corneal thickness, corneal thickness on optical coherence tomography, deformation amplitude (DA), first applanation time, first applanation velocity, second applanation time, second applanation velocity, peak distance (PD), high-contrast acuity, stiffness parameter at the first applanation, and comprehensive refraction ( p  < 0.001). No differences were observed between the groups in any other parameters before or after treatment. Conclusions Both epithelium-off and transepithelial ACXL effectively treat keratoconus. Transepithelial ACXL is slightly inferior to epithelium-off ACXL in maximum corneal curvature but superior in improving corneal thickness and DA parameters. Further studies are necessary to verify the efficacy, safety, and long-term stability of transepithelial ACXL in treating keratoconus.

AimsA blind, randomised, prospective, bilateral study to investigate the efficacy of riboflavin/ultraviolet A corneal collagen cross-linkage to halt the progression of keratoconus.Methods24 patients with early/moderate bilateral keratoconus with recent progression were recruited. One eye was randomly assigned to undergo collagen cross-linkage following epithelial removal with riboflavin 0.1% and ultraviolet A (370 nm at 3 mW/cm2). The other remained untreated as a control. The follow-up was 18 months in 22 patients.ResultsAt 18 months, Orbscan II 3 mm, 5 mm keratometry and simulated astigmatism and cone apex power and wave-front measurements (Keraton Scout), including root mean square, coma and pentafoil showed significant reductions from baseline in treated compared with untreated eyes (p=0.04). In treated eyes at 18 months, the best spectacle-corrected acuity improved (p=0.01), and Orbscan II-simulated keratometry (p<0.001), 3 mm keratometry (p=0.008), simulated astigmatism (p=0.007), cone apex power (p=0.002), root mean square, coma, spherical aberration, secondary astigmatism and pentafoil (p=0.05) decreased from baseline. One treated eye experienced transient recurrent corneal erosions; otherwise there were no complications attributable to the treatment.ConclusionsCorneal collagen cross-linkage appears to be an effective and safe modality to halt the progression of keratoconus. Improvements in visual and topographic parameters are seen in some eyes.

Purpose To evaluate the efficacy and safety of accelerated corneal cross-linking (A-CXL) while preserving the epithelium over the central 3 mm of the cornea compared to epithelium removal CXL in cases of paracentral keratoconus. Methods In this prospective comparative study, 140 eyes of 77 patients were randomized to receive either A-CXL with preservation of the central 3 mm of corneal epithelium or A-CXL with removal of whole corneal epithelium over a central disk area with a diameter of 9 mm. Patients were observed regularly for 1 year after the procedure. The primary outcome measures were to compare early uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), corneal haze, pain, and discomfort in the first week between the two groups. The secondary outcome measure was keratoconus progression after 12 months of follow-up, measured by the maximum keratometry (Kmax) value. Results A significant difference was found between the two groups regarding early postoperative CDVA, corneal haze, pain, and discomfort, with more favorable results in the ACXL with preservation of the central 3 mm of corneal epithelium group. At 12 months of follow-up, a significant improvement in UDVA, CDVA, and Kmax was noticed among patients of the same group, with better final vision and a reduction in Kmax as compared to the preoperative values. Conclusions Preserving the epithelium over the central 3 mm of the cornea during A-CXL in cases with paracentral keratoconus can provide the benefits of immediate early postoperative visual rehabilitation, less corneal haze, less pain, good efficacy, and prevention of keratoconus progression. [J Refract Surg. 2025;41(5):e492–e500.]

This prospective, randomized, controlled trial aims to provide evidence in relation to the efficacy and safety of corneal collagen cross-linking (CXL) in the management of progressive keratoconus. Eligible eyes were separately randomized into either treatment or control groups. Collagen crosslinking was performed using 0.1% riboflavin (in 20% dextran T500) and ultraviolet A (UVA) irradiation (370 nm, 3 mW/cm2, 30 min) in accordance with a previously published protocol. At each review, a full clinical ophthalmic examination was performed including endothelial cell count and confocal microscopy. To date, 66 eyes of 49 patients with documented progression of keratoconus have been enrolled and randomized. Interim analysis of treated eyes showed a flattening of the steepest simulated keratometry value (K-max) by an average of 0.74 diopters (D) (P = .004) at 3 months, 0.92 D (P = .002) at 6 months, and 1.45 D (P = .002) at 12 months. A trend toward improvement in best spectacle-corrected visual acuity was also observed. In the control eyes, mean K-max steepened by 0.60 D (P = .041) after 3 months, by 0.60 D (P = .013) after 6 months, and by 1.28 D (P < or = .0001) after 12 months. Best spectacle-corrected visual acuity decreased by logMAR 0.003 (P = .883) over 3 months, 0.056 (P = .092) over 6 months, and 0.12 (P = .036) over 12 months. No statistically significant changes were found for spherical equivalent or endothelial cell density. Preliminary results of this randomized controlled trial suggest a temporary stabilization of all treated eyes after CXL.

Background and Objectives: The aim of this study is to evaluate and compare changes in corneal densitometry after standard (30 min exposure time of 3 mW/cm2 UVA) and accelerated (10 min exposure time of 9 mW/cm2 UVA) protocols of corneal cross-linking (CXL) in patients with progressive keratoconus. Materials and Methods: This study included a total of 38 eyes of 38 patients divided into two equal-sized subgroups. CXL was performed in one group according to the standard epithelium-off protocol (30 min, 3 mW/cm2 UVA) and in the other group according to an accelerated epithelium-off protocol (10 min, 9 mW/cm2 UVA). Scheimpflug imaging was used to evaluate corneal densitometry in the anterior, central, and posterior corneal layers in three concentric zones (0–2 mm, 2–6 mm, and 6–10 mm) at baseline and 1, 3, and 9 months after surgery. Results: This study included 38 patients divided into two subgroups of 19. One group of patients underwent standard and the other accelerated CXL protocol. Participants in the accelerated group were significantly older (p < 0.001). 9 months after CXL treatment, the accelerated group showed higher central and posterior corneal densitometry values, but, after adjusting for age and baseline values, ANCOVA analysis revealed no significant intergroup differences. Both protocols led to overall reductions in corneal densitometry over time. Conclusions: Both the standard and accelerated CXL protocols induce transient corneal haze, which can be objectified by increased corneal densitometry values in first three months post-CXL. The dynamics of the onset and recovery of postoperative corneal haze are comparable and similar in both protocols.

Purpose To investigate the impact of oxygen delivery on the clinical outcomes of accelerated transepithelial corneal cross-linking (A-TE CXL). Methods Fifty-seven eyes of 44 progressive keratoconus (KCN) patients were randomly separated into two age–sex-matched groups. Twenty-nine eyes of 23 KCN patients that underwent oxygen-supplemented A-TE CXL formed the study group and 28 eyes of 21 patients treated with the same procedure but under room air conditions formed the control group. All patients were examined preoperatively, one, six and twelve months after the procedure. The logMAR spectacle-corrected distance visual acuity (CDVA), maximum keratometry (Kmax), mean keratometry, apical posterior keratometry, cylindrical power, minimum central corneal thickness, keratoconus vertex front and back, ocular aberrations, endothelial cell density (ECD), demarcation line depth (DLD) and proportion measures were recorded for statistical analysis. Results The preoperative, 1st, 6th and 12th months mean Kmax values of the study group were 55.14 ± 3.99D, 54.85 ± 3.82D, 54.37 ± 3.84D and 54.40 ± 3.86, respectively, and 54.47 ± 3.17D, 54.52 ± 2.97D, 54.25 ± 2.95D and 54.20 ± 2.97 in the control group. The mean Kmax value was decreased significantly more in the oxygen-supplemented group after 12 months compared to the control group ( p  = 0.019). The mean DLD was also significantly deeper in the study group (320 ± 17 µm) compared to the control group (269 ± 19 µm). There was no significant difference between the two groups in terms of ECD alterations at any of the time intervals ( p  > 0.05). Conclusion Keratoconus progression was significantly halted in both groups 12 months after the treatment. In addition, oxygen supplementation during A-TE CXL further significantly increased clinical outcomes compared to room air conditions without any significant change in ECD measures.

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.

Background Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. Methods We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. Discussion The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient’s cornea may stop the progression of keratoconus and result in flattening of the cornea. Trial registration This study was prospectively registered at ClinicalTrials.gov on August 31 st , 2020, the identifier of the study is NCT04532788.

Infant DNA methylation profiles are associated with their mother's periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials. We designed a novel drink powder based on determinants of plasma homocysteine in the target population and tested it in a three-arm, randomised, controlled trial. Nonpregnant women aged between 18 and 45 from the West Kiang region of The Gambia were randomised in a 1:1:1 allocation to 12 weeks daily supplementation of either (a) a novel drink powder (4 g betaine, 800 μg folic acid, 5.2 μg vitamin B12, and 2.8 mg vitamin B2), (b) a widely used multiple micronutrient tablet (United Nations Multiple Micronutrient Preparation [UNIMMAP]) containing 15 micronutrients, or (c) no intervention. The trial was conducted between March and July 2018. Supplementation was observed daily. Fasted venepuncture samples were collected at baseline, midline (week 5), and endline (week 12) to measure plasma homocysteine. We used linear regression models to determine the difference in homocysteine between pairs of trial arms at midline and endline, adjusted for baseline homocysteine, age, and body mass index (BMI). Blood pressure and pulse were measured as secondary outcomes. Two hundred and ninety-eight eligible women were enrolled and randomised. Compliance was >97.8% for both interventions. At endline (our primary endpoint), the drink powder and UNIMMAP reduced mean plasma homocysteine by 23.6% (-29.5 to -17.1) and 15.5% (-21.2 to -9.4), respectively (both p < 0.001), compared with the controls. Compared with UNIMMAP, the drink powder reduced mean homocysteine by 8.8% (-15.8 to -1.2; p = 0.025). The effects were stronger at midline. There was no effect of either intervention on blood pressure or pulse compared with the control at endline. Self-reported adverse events (AEs) were similar in both intervention arms. There were two serious AEs reported over the trial duration, both in the drink powder arm, but judged to be unrelated to the intervention. Limitations of the study include the use of a single targeted metabolic outcome, homocysteine. The trial confirms that dietary supplements can influence metabolic pathways that we have shown in previous studies to predict offspring DNA methylation. Both supplements reduced homocysteine effectively and remain potential candidates for future epigenetic trials in pregnancy in rural Gambia. Clinicaltrials.gov Reference NCT03431597.