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Materials (Basel, Switzerland) Jan 2020Sinus augmentation can be performed with or without grafting biomaterials, and to date, there is no quality evidence regarding the augmentation of the sinus floor using... (Review)
Review
BACKGROUND
Sinus augmentation can be performed with or without grafting biomaterials, and to date, there is no quality evidence regarding the augmentation of the sinus floor using only platelet concentrates, which can improve the healing period and enhance bone regeneration by stimulating angiogenesis and bone formation. The main objective of this paper was to assess the effect of the sole use of platelet concentrates in sinus augmentation in terms of newly formed bone, augmented bone height, and clinical outcomes and to assess the additional beneficial effects of platelet-rich fibrin (PRF) in combination with other grafting biomaterials.
METHODS
A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Pooled analyses were performed with the Review Manager software.
RESULTS
For sinus elevation only using platelet concentrates, 11 studies met the inclusion criteria and were included for qualitative synthesis. Only one study was a clinical trial, which reported improved outcomes for the allograft group compared to the titanium-PRF (T-PRF) group. A total of 12 studies where PRF was used in addition to grafting biomaterials met eligibility criteria and were included in the review. Results from meta-analyses provided no additional beneficial effects of PRF in sinus augmentation in terms of bone height and percentage of soft tissue area. There was a statistically significant lower percentage of residual bone substitute material in the PRF (+) group compared to the PRF (-) group. The percentage of newly formed bone was slightly higher in the PRF (+) group, but this was not statistically significant.
CONCLUSION
There is no robust evidence to make firm conclusions regarding the beneficial effects of the sole use of platelet concentrates in sinus augmentation. However, studies have shown favorable outcomes regarding implant survival, bone gain, and bone height. The use of PRF with other grafting biomaterials appears to provide no additional beneficial effects in sinus lift procedures, but they may improve the healing period and bone formation. Well-conducted randomized clinical trials (RCTs) are necessary to confirm the available results to provide recommendations for the clinical practice.
PubMed: 32019255
DOI: 10.3390/ma13030622 -
Arthroscopy, Sports Medicine, and... Oct 2021To evaluate clinical outcomes after intraosseous injection for knee osteoarthritis systematically with available clinical evidence. (Review)
Review
PURPOSE
To evaluate clinical outcomes after intraosseous injection for knee osteoarthritis systematically with available clinical evidence.
METHODS
A systematic search methodology of the PUBMED, EMBASE, and CINAHL databases was conducted in November 2020. The search workflow was in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The following inclusion criteria were adopted: clinical trials of any level of evidence, reporting clinical outcomes following intraosseous injections of bone substitutes or biologic agents, and mesenchymal stem cells or platelet-rich plasma into the knee as treatment modalities for osteoarthritis. Duplicate data and articles not written in English were excluded from this review.
RESULTS
Six studies were identified and included in this review, with a total of 167 patients. Two studies used subchondroplasty CaP injections, while 4 studies used intraosseous injections of platelet-rich plasma. Two studies provided Level II evidence, 2 studies provided Level III evidence, and a further 2 provided Level IV evidence. Five out of 6 studies reported data using the visual analog scale, 4 studies used the Knee Injury and Osteoarthritis Outcome Score, while 3 studies used the Western Ontario and McMaster Universities Osteoarthritis Index. Clinical improvements in pain and functionality were documented in all trials, with only a few patients experiencing adverse events.
CONCLUSION
Intraosseous injections for knee osteoarthritis are safe and effective. However, multiple pertinent variables such as safety, cost of treatment, and performance against placebos and other treatment modalities require further evaluation before intraosseous injections can be considered as standard treatment for patients presenting with osteoarthritis of the knee.
PubMed: 34712993
DOI: 10.1016/j.asmr.2021.06.006 -
Heliyon Sep 2020To assess clinical studies that compare synthetic or enriched natural materials to autologous osseous grafts among individuals with cleft lip and palate to determine... (Review)
Review
Evaluation of density, volume, height and rate of bone resorption of substitutes of autologous bone grafts for the repair of alveolar clefts in humans: A systematic review.
OBJECTIVE
To assess clinical studies that compare synthetic or enriched natural materials to autologous osseous grafts among individuals with cleft lip and palate to determine which would be the substitute to autologous bone graft for alveolar cleft repair in humans.
MATERIALS AND METHODS
Randomized and controlled clinical trials on alveolar clefts treated with synthetic bone substitutes and autogenous bone grafts combined with osteoinductive factors compared with autogenous bone grafts alone (with ≥4-month follow-up and reporting clinical/radiographic data) were considered eligible. MEDLINE, EMBASE, and Central databases were searched for articles published until February 2020.
RESULTS
Of 73 eligible articles, 15 were included. Some inductive factors along with iliac crest bone decreased bone reabsorption, preserved the generated bone height/width, and reduced the required autologous bone graft volume. Bone morphogenetic protein (BMP2) as an autologous bone graft substitute, demonstrated satisfactory alveolar defect healing, by avoiding autograft use. Many materials did not yield better outcomes than did autologous grafts; however, hydroxyapatite and collagen complex, hydroxyapatite agarose composite gel, acellular dermal matrix film, fibrin glue, platelet-rich plasma, and deproteinized bovine bone showed similar bone healing outcomes, being an alternative alveolar defect treatment.
CONCLUSIONS
BMP2, as an osteoinductive factor along with a synthetic matrix, yields satisfactory bone healing and avoids the need for autologous bone grafts. However, high-quality RCTs are necessary to determine the most effective and safe concentration and protocol of BMP2 utilization as a substitute for the autologous iliac crest bone grafting.
PubMed: 32954025
DOI: 10.1016/j.heliyon.2020.e04646 -
Cornea Sep 2022The purpose of this study was to assess short-term efficacy and safety of tear promotion eye drops (biological tear substitutes and topical secretagogues) for treating... (Meta-Analysis)
Meta-Analysis
PURPOSE
The purpose of this study was to assess short-term efficacy and safety of tear promotion eye drops (biological tear substitutes and topical secretagogues) for treating dry eye disease.
METHODS
Randomized controlled trials comparing short-term effects of biological tear substitutes or topical secretagogues versus placebo or other topical dry eye treatments in adults with dry eye disease were identified from the MEDLINE, Embase, Scopus, ClinicalTrials.gov , and World Health Organization International Clinical Trials Registry Platform databases. Pairwise meta-analysis and network meta-analysis were performed. Outcomes were ocular symptoms, ocular surface staining, tear break-up time, Schirmer test, and adverse events. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach.
RESULTS
Thirty-nine randomized controlled trials (3693 patients) were eligible. Using artificial tears as a reference, autologous platelet lysate was the most effective treatment for lowering ocular surface disease index (unstandardized mean difference [USMD] -31.85; 95% confidence interval [CI]: -43.19 to -20.51) and platelet rich plasma showed the most reduction in corneal fluorescein staining scores (standardized mean difference -2.52; 95% CI: -3.23 to -1.82). Cord blood serum was the most effective treatment for increasing tear break-up time (USMD 2.67; 95% CI: 0.53-4.82), and eledoisin was superior to others in improving Schirmer scores (USMD 2.28; 95% CI: 0.14-4.42). Most interventions did not significantly increase ocular adverse events compared with artificial tears.
CONCLUSIONS
Biological tear substitutes, including autologous serum, autologous platelet lysate, platelet rich plasma, and cord blood serum, might be the most effective treatment among tear promotion eye drops in relieving dry eye symptoms without increasing adverse events. However, there remains uncertainty around these findings because of low/very low certainty of evidence.
Topics: Adult; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Network Meta-Analysis; Secretagogues; Tears
PubMed: 34924549
DOI: 10.1097/ICO.0000000000002943 -
Digestive Diseases and Sciences May 2020Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress-or lack thereof-in improving outcomes of type 1 HRS over time.
METHODS
We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019.
RESULTS
Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4-43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2-51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94-1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96-1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95-1.20, p = 0.26) and 0.97 (95% CI 0.85-1.12, p = 0.70).
CONCLUSION
Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.
Topics: Adult; Albumins; Anti-Bacterial Agents; Dopamine; Drug Therapy, Combination; Female; Hepatorenal Syndrome; Humans; Male; Middle Aged; Midodrine; Norepinephrine; Octreotide; Plasma Substitutes; Randomized Controlled Trials as Topic; Regression Analysis; Survival Rate; Terlipressin; Treatment Outcome; Vasoconstrictor Agents; Young Adult
PubMed: 31571102
DOI: 10.1007/s10620-019-05858-2 -
British Journal of Anaesthesia Oct 2021Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in critically ill patients have raised questions regarding the safety of this product. Our aim in this meta-analysis was to evaluate the safety and efficacy of 6% HES during surgery and in trauma.
METHODS
This systematic review and meta-analysis was registered at PROSPERO (CRD42018100379). We included 85 fully published articles from 1980 to June 2018 according to the protocol and three additional recent articles up to June 2020 in English, French, German, and Spanish reporting on prospective, randomised, and controlled clinical trials applying volume therapy with HES 130/0.4 or HES 130/0.42, including combinations with crystalloids, to patients undergoing surgery. Comparators were albumin, gelatin, and crystalloids only. A meta-analysis could not be performed for the two trauma studies as there was only one study that reported data on endpoints of interest.
RESULTS
Surgical patients treated with HES had lower postoperative serum creatinine (P<0.001) and showed no differences in renal dysfunction, renal failure, or renal replacement therapy. Although there was practically no further difference in the colloids albumin or gelatin, the use of HES improved haemodynamic stability, reduced need for vasopressors (P<0.001), and decreased length of hospital stay (P<0.001) compared with the use of crystalloids alone.
CONCLUSIONS
HES was shown to be safe and efficacious in the perioperative setting. Results of the present meta-analysis suggest that when used with adequate indication, a combination of intravenous fluid therapy with crystalloids and volume replacement with HES as colloid has clinically beneficial effects over using crystalloids only.
Topics: Colloids; Critical Illness; Crystalloid Solutions; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Length of Stay; Perioperative Care; Randomized Controlled Trials as Topic
PubMed: 34330414
DOI: 10.1016/j.bja.2021.06.040 -
The Cochrane Database of Systematic... Mar 2021Retained placenta is a common complication of pregnancy affecting 1% to 6% of all births. If a retained placenta is left untreated, spontaneous delivery of the placenta... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retained placenta is a common complication of pregnancy affecting 1% to 6% of all births. If a retained placenta is left untreated, spontaneous delivery of the placenta may occur, but there is a high risk of bleeding and infection. Manual removal of the placenta (MROP) in an operating theatre under anaesthetic is the usual treatment, but is invasive and may have complications. An effective non-surgical alternative for retained placenta would potentially reduce the physical and psychological trauma of the procedure, and costs. It could also be lifesaving by providing a therapy for settings without easy access to modern operating theatres or anaesthetics. Injection of uterotonics into the uterus via the umbilical vein and placenta is an attractive low-cost option for this. This is an update of a review last published in 2011.
OBJECTIVES
To assess the use of umbilical vein injection (UVI) of saline solution with or without uterotonics compared to either expectant management or with an alternative solution or other uterotonic agent for retained placenta.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (14 June 2020), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing UVI of saline or other fluids (with or without uterotonics), either with expectant management or with an alternative solution or other uterotonic agent, in the management of retained placenta. We considered quasi-randomised, cluster-randomised, and trials reported only in abstract form.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We assessed the certainty of the evidence using the GRADE approach. We calculated pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs), and presented results using 'Summary of findings' tables.
MAIN RESULTS
We included 24 trials (n = 2348). All included trials were RCTs, one was quasi-randomised, and none were cluster-randomised. Risk of bias was variable across the included studies. We assessed certainty of evidence for four comparisons: saline versus expectant management, oxytocin versus expectant management, oxytocin versus saline, and oxytocin versus plasma expander. Evidence was moderate to very-low certainty and downgraded for risk of bias of included studies, imprecision, and inconsistency of effect estimates. Saline solution versus expectant management There is probably little or no difference in the incidence of MROP between saline and expectant management (RR 0.93, 95% CI 0.80 to 1.10; 5 studies, n = 445; moderate-certainty evidence). Evidence for the following remaining primary outcomes was very-low certainty: severe postpartum haemorrhage 1000 mL or greater, blood transfusion, and infection. There were no events reported for maternal mortality or postpartum anaemia (24 to 48 hours postnatal). No studies reported addition of therapeutic uterotonics. Oxytocin solution versus expectant management UVI of oxytocin solution might slightly reduce in the need for manual removal compared with expectant management (mean RR 0.73, 95% CI 0.56 to 0.95; 7 studies, n = 546; low-certainty evidence). There may be little to no difference between the incidence of blood transfusion between groups (RR 0.81, 95% CI 0.47 to 1.38; 4 studies, n = 339; low-certainty evidence). There were no maternal deaths reported (2 studies, n = 93). Evidence for severe postpartum haemorrhage of 1000 mL or greater, additional uterotonics, and infection was very-low certainty. There were no events for postpartum anaemia (24 to 48 hours postnatal). Oxytocin solution versus saline solution UVI of oxytocin solution may reduce the use of MROP compared with saline solution, but there was high heterogeneity (RR 0.82, 95% CI 0.69 to 0.97; 14 studies, n = 1370; I² = 54%; low-certainty evidence). There were no differences between subgroups according to risk of bias or oxytocin dose for the outcome MROP. There may be little to no difference between groups in severe postpartum haemorrhage of 1000 mL or greater, blood transfusion, use of additional therapeutic uterotonics, and antibiotic use. There were no events for postpartum anaemia (24 to 48 hours postnatal) (very low-certainty evidence) and there was only one event for maternal mortality (low-certainty evidence). Oxytocin solution versus plasma expander One small study reported UVI of oxytocin compared with plasma expander (n = 109). The evidence was very unclear about any effect on MROP or blood transfusion between the two groups (very low-certainty evidence). No other primary outcomes were reported. For other comparisons there were little to no differences for most outcomes examined. However, there was some evidence to suggest that there may be a reduction in MROP with prostaglandins in comparison to oxytocin (4 studies, n = 173) and ergometrine (1 study, n = 52), although further large-scale studies are needed to confirm these findings.
AUTHORS' CONCLUSIONS
UVI of oxytocin solution is an inexpensive and simple intervention that can be performed when placental delivery is delayed. This review identified low-certainty evidence that oxytocin solution may slightly reduce the need for manual removal. However, there are little or no differences for other outcomes. Small studies examining injection of prostaglandin (such as dissolved misoprostol) into the umbilical vein show promise and deserve to be studied further.
Topics: Anti-Bacterial Agents; Bias; Blood Transfusion; Female; Humans; Injections, Intravenous; Oxytocics; Oxytocin; Placenta, Retained; Plasma Substitutes; Pregnancy; Prostaglandins; Randomized Controlled Trials as Topic; Sodium Chloride; Umbilical Veins
PubMed: 33705565
DOI: 10.1002/14651858.CD001337.pub3 -
Cardiology Journal 2022Fluid resuscitation is a fundamental intervention in patients with hypovolemic shock resulting from trauma. Appropriate fluid resuscitation in trauma patients could... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fluid resuscitation is a fundamental intervention in patients with hypovolemic shock resulting from trauma. Appropriate fluid resuscitation in trauma patients could reduce organ failure, until blood components are available, and hemorrhage is controlled. We conducted a systematic review and meta-analysis assessing the effect of hypertonic saline/dextran or hypertonic saline for fluid resuscitation on patient outcomes restricted to adults with hypovolemic shock.
METHODS
We conducted a search of electronic information sources, including PubMed, Embase, Web of Science, Cochrane library and bibliographic reference lists to identify all randomized controlled trials (RCTs) investigating outcomes of crystalloids versus colloids in patients with hypovolemic shock. We calculated the risk ratio (RR) or mean difference (MD) of groups using fixed or random-effect models.
RESULTS
Fifteen studies including 3264 patients met our inclusion criteria. Survival to hospital discharge rate between research groups varied and amounted to 71.2% in hypertonic saline/dextran group vs. 68.4% for isotonic/normotonic fluid (normal saline) solutions (odds ratio [OR] = 1.19; 95% confidence interval [CI] 0.97-1.45; I2 = 48%; p = 0.09). 28- to 30-days survival rate for hypertonic fluid solutions was 72.8% survivable, while in the case of isotonic fluid (normal saline) - 71.4% (OR = 1.13; 95% CI 0.75-1.70; I2 = 43%; p = 0.56).
CONCLUSIONS
This systematic review and meta-analysis, which included only evidence from RCTs hypertonic saline/dextran or hypertonic saline compared with isotonic fluid did not result in superior 28- to 30-day survival as well as in survival to hospital discharge. However, patients with hypotension who received resuscitation with hypertonic saline/dextran had less overall mortality as patients who received conventional fluid.
Topics: Adult; Humans; Saline Solution, Hypertonic; Dextrans; Saline Solution; Critical Illness; Randomized Controlled Trials as Topic; Shock; Resuscitation
PubMed: 33140397
DOI: 10.5603/CJ.a2020.0134 -
Cartilage Dec 2021To systematically review the available clinical evidence regarding the safety and efficacy of knee intraosseous injections for the treatment of bone marrow lesions in...
OBJECTIVE
To systematically review the available clinical evidence regarding the safety and efficacy of knee intraosseous injections for the treatment of bone marrow lesions in patients affected by knee osteoarthritis.
DESIGN
A literature search was carried out on PubMed, Embase, and Google Scholar databases in January 2020. The following inclusion criteria were adopted: (1) studies of any level of evidence, dealing with subchondral injection of bone substitute materials and/or biologic agents; (2) studies with minimum 5 patients treated; and (3) studies with at least 6 months' follow-up evaluation. All relevant data concerning clinical outcomes, adverse events, and rate of conversion to arthroplasty were extracted.
RESULTS
A total of 12 studies were identified: 7 dealt with calcium phosphate administration, 3 with platelet-rich plasma, and 2 with bone marrow concentrate injection. Only 2 studies were randomized controlled trials, whereas 6 studies were prospective and the remaining 4 were retrospective. Studies included a total of 459 patients treated with intraosseous injections. Overall, only a few patients experienced adverse events and clinical improvement was documented in the majority of trial. The lack of any comparative evaluation versus subchondral drilling alone is the main limitation of the available evidence.
CONCLUSIONS
Knee intraosseous injections are a minimally invasive and safe procedure to address subchondral bone damage in osteoarthritic patients. They are able to provide beneficial effects at short-term evaluation. More high-quality evidence is needed to confirm their potential and to identify the best product to adopt in clinical practice.
Topics: Bone Substitutes; Calcium Phosphates; Humans; Injections, Intra-Articular; Osteoarthritis, Knee; Platelet-Rich Plasma; Treatment Outcome
PubMed: 32959675
DOI: 10.1177/1947603520959403 -
The Cochrane Database of Systematic... Mar 2021Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or paracentral cornea, irregular corneal scarring, or corneal perforation. Disease onset usually occurs in the second to fourth decade of life, periods of peak educational attainment or career development. The condition is lifelong and sight-threatening. Corneal collagen crosslinking (CXL) using ultraviolet A (UVA) light applied to the cornea is the only treatment that has been shown to slow progression of disease. The original, more widely known technique involves application of UVA light to de-epithelialized cornea, to which a photosensitizer (riboflavin) is added topically throughout the irradiation process. Transepithelial CXL is a recently advocated alternative to the standard CXL procedure, in that the epithelium is kept intact during CXL. Retention of the epithelium offers the putative advantages of faster healing, less patient discomfort, faster visual rehabilitation, and less risk of corneal haze.
OBJECTIVES
To assess the short- and long-term effectiveness and safety of transepithelial CXL compared with epithelium-off CXL for progressive keratoconus.
SEARCH METHODS
To identify potentially eligible studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature database (LILACS); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not impose any date or language restrictions. We last searched the electronic databases on 15 January 2020.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which transepithelial CXL had been compared with epithelium-off CXL in participants with progressive keratoconus.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We included 13 studies with 723 eyes of 578 participants enrolled; 13 to 119 participants were enrolled per study. Seven studies were conducted in Europe, three in the Middle East, and one each in India, Russia, and Turkey. Seven studies were parallel-group RCTs, one study was an RCT with a paired-eyes design, and five studies were RCTs in which both eyes of some or all participants were assigned to the same intervention. Eleven studies compared transepithelial CXL with epithelium-off CXL in participants with progressive keratoconus. There was no evidence of an important difference between intervention groups in maximum keratometry (denoted 'maximum K' or 'Kmax'; also known as steepest keratometry measurement) at 12 months or later (mean difference (MD) 0.99 diopters (D), 95% CI -0.11 to 2.09; 5 studies; 177 eyes; I = 41%; very low certainty evidence). Few studies described other outcomes of interest. The evidence is very uncertain that epithelium-off CXL may have a small (data from two studies were not pooled due to considerable heterogeneity (I = 92%)) or no effect on stabilization of progressive keratoconus compared with transepithelial CXL; comparison of the estimated proportions of eyes with decreases or increases of 2 or more diopters in maximum K at 12 months from one study with 61 eyes was RR 0.32 (95% CI 0.09 to 1.12) and RR (non-event) 0.86 (95% CI 0.74 to 1.00), respectively (very low certainty). We did not estimate an overall effect on corrected-distance visual acuity (CDVA) because substantial heterogeneity was detected (I = 70%). No study evaluated CDVA gain or loss of 10 or more letters on a logarithm of the minimum angle of resolution (logMAR) chart. Transepithelial CXL may result in little to no difference in CDVA at 12 months or beyond. Four studies reported that either no adverse events or no serious adverse events had been observed. Another study noted no change in endothelial cell count after either procedure. Moderate certainty evidence from 4 studies (221 eyes) found that epithelium-off CXL resulted in a slight increase in corneal haze or scarring when compared to transepithelial CXL (RR (non-event) 1.07, 95% CI 1.01 to 1.14). Three studies, one of which had three arms, compared outcomes among participants assigned to transepithelial CXL using iontophoresis versus those assigned to epithelium-off CXL. No conclusive evidence was found for either keratometry or visual acuity outcomes at 12 months or later after surgery. Low certainty evidence suggests that transepithelial CXL using iontophoresis results in no difference in logMAR CDVA (MD 0.00 letter, 95% CI -0.04 to 0.04; 2 studies; 51 eyes). Only one study examined gain or loss of 10 or more logMAR letters. In terms of adverse events, one case of subepithelial infiltrate was reported after transepithelial CXL with iontophoresis, whereas two cases of faint corneal scars and four cases of permanent haze were observed after epithelium-off CXL. Vogt's striae were found in one eye after each intervention. The certainty of the evidence was low or very low for the outcomes in this comparison due to imprecision of estimates for all outcomes and risk of bias in the studies from which data have been reported.
AUTHORS' CONCLUSIONS
Because of lack of precision, frequent indeterminate risk of bias due to inadequate reporting, and inconsistency in outcomes measured and reported among studies in this systematic review, it remains unknown whether transepithelial CXL, or any other approach, may confer an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to further progression of keratoconus, visual acuity outcomes, and patient-reported outcomes (PROs). Arrest of the progression of keratoconus should be the primary outcome of interest in future trials of CXL, particularly when comparing the effectiveness of different approaches to CXL. Furthermore, methods of assessing and defining progressive keratoconus should be standardized. Trials with longer follow-up are required in order to assure that outcomes are measured after corneal wound-healing and stabilization of keratoconus. In addition, perioperative, intraoperative, and postoperative care should be standardized to permit meaningful comparisons of CXL methods. Methods to increase penetration of riboflavin through intact epithelium as well as delivery of increased dose of UVA may be needed to improve outcomes. PROs should be measured and reported. The visual significance of adverse outcomes, such as corneal haze, should be assessed and correlated with other outcomes, including PROs.
Topics: Adult; Bias; Collagen; Corneal Pachymetry; Cross-Linking Reagents; Dextrans; Disease Progression; Epithelium, Corneal; Female; Humans; Iontophoresis; Keratoconus; Male; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Therapy; Visual Acuity; Young Adult
PubMed: 33765359
DOI: 10.1002/14651858.CD013512.pub2