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The British Journal of Dermatology Jan 2018We undertook a Cochrane review of randomized controlled trials (RCTs) evaluating the effects of light-based interventions for acne vulgaris. We searched the Cochrane... (Meta-Analysis)
Meta-Analysis
We undertook a Cochrane review of randomized controlled trials (RCTs) evaluating the effects of light-based interventions for acne vulgaris. We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and grey literature sources (September 2015). We used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach to assess the quality of evidence (QoE). We included 71 RCTs (4211 participants, median sample size 31). Results from a single study (n = 266, low QoE) showed little or no difference in effectiveness on participants' assessment of improvement between 20% aminolaevulinic acid (ALA) photodynamic therapy (PDT), activated by blue light, vs. vehicle plus blue light, whereas another study (n = 180) comparing ALA-PDT (red light) concentrations showed that 20% ALA-PDT was no more effective than 15% ALA-PDT but better than 10% and 5% ALA-PDT. Pooled data from three studies (n = 360, moderate QoE) showed that methyl aminolaevulinate PDT, activated by red light, had a similar effect on changes in lesion counts vs. placebo cream with red light. Several studies compared yellow light with placebo or no treatment, infrared light with no treatment, gold microparticle suspension with vehicle and clindamycin/benzoyl peroxide (C/BPO) combined with pulsed dye laser with C/BPO alone. None of these showed any clinically significant effects. Most studies reported adverse effects, but inadequately, with scarring reported as absent, and blistering only in studies on intense pulsed light, infrared light and PDT (very low QoE). Carefully planned studies, using standardized outcome measures and common acne treatments as comparators, are needed.
Topics: Acne Vulgaris; Adult; Aminolevulinic Acid; Female; GRADE Approach; Gold Compounds; Humans; Infrared Rays; Male; Photochemotherapy; Photosensitizing Agents; Phototherapy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28338214
DOI: 10.1111/bjd.15495 -
World Journal of Gastroenterology Feb 2017To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma. (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.
METHODS
Included studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the statistic.
RESULTS
Ten studies ( = 402) that met inclusion criteria were included in this analysis. The for χ heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.
CONCLUSION
In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.
Topics: Aged; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Intrahepatic; Biliary Tract Surgical Procedures; Cholangiocarcinoma; Cholangitis; Drainage; Female; Humans; Male; Middle Aged; Models, Statistical; Odds Ratio; Palliative Care; Photochemotherapy; Prospective Studies; Quality of Life; Research Design; Stents; Treatment Outcome
PubMed: 28275308
DOI: 10.3748/wjg.v23.i7.1278 -
International Journal of Cancer Jul 2017A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment... (Review)
Review
A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.
Topics: Female; Human Papillomavirus DNA Tests; Humans; Neoplasm Recurrence, Local; Papillomaviridae; Papillomavirus Infections; Photochemotherapy; Risk Factors; Uterine Cervical Dysplasia
PubMed: 28124442
DOI: 10.1002/ijc.30623 -
Photodiagnosis and Photodynamic Therapy Jun 2017For deep carious lesions, a more conservative treatment modality ("selective caries removal") has been proposed, where only the heavily contaminated dentine is removed.... (Meta-Analysis)
Meta-Analysis Review
For deep carious lesions, a more conservative treatment modality ("selective caries removal") has been proposed, where only the heavily contaminated dentine is removed. In this regard, effective adjuncts for cavity disinfection such as the antimicrobial photodynamic therapy (aPDT) can be valuable clinically prior to definitive restoration. Therefore, the aim of this study was to systematically assess clinical studies on the effectiveness of aPDT as a supplementary tool in the treatment of deep caries lesions. Searches were performed in four databases (PubMed, EMBASE, ISI Web of Science, ClinicalTrials.gov) from 1st January, 2011 until 21st June, 2016 for search terms relevant to the observed parameters, pathological condition, intervention and anatomic entity. The pooled information was evaluated according to PRISMA guidelines. At first, 1651 articles were recovered, of which 1249 full-text articles were evaluated, 270 articles thereof were reviewed for eligibility and finally 6 articles met all inclusion criteria. The aPDT protocols involved Methylene Blue, Toluidine Blue and aluminium-chloride-phthalocyanine as photosensitizers and diode lasers, light-emitting diodes and halogen light-sources. The data from five reports, utilizing both culture-dependent and -independent methods, disclosed significant reduction of cariogenic bacterial load after mechanical caries removal with adjunct aPDT. As these studies exhibit some methodological limitations, e.g. lack of positive controls, this systematic review can support the application of aPDT to a limited extent only in terms of reducing the microbial load in deep carious lesions before restorative treatment.
Topics: Bacterial Infections; Bacterial Load; Combined Modality Therapy; Dental Caries; Disinfection; Evidence-Based Medicine; Humans; Photochemotherapy; Photosensitizing Agents; Prevalence; Risk Factors; Treatment Outcome
PubMed: 28099873
DOI: 10.1016/j.pdpdt.2017.01.005 -
Actas Dermo-sifiliograficas May 2017Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the... (Meta-Analysis)
Meta-Analysis Review
Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the procedure is time-consuming, can be very painful, and requires infrastructure. These shortcomings led to the emergence of daylight PDT. To obtain a global estimate of efficacy, we undertook a systematic literature review and performed a meta-analysis of the available evidence on the efficacy and safety of daylight PDT as compared to conventional PDT in the treatment of actinic keratosis and/or field cancerization. The conclusion is that the difference in efficacy is clinically negligible (global estimate of the mean response rate difference, -3.69%; 95% CI, -6.54% to -0.84%). The adverse effects of daylight PDT are mild and localized (79% of patients report no discomfort), and patients report less pain (P<.001). Daylight PDT gives good to excellent cosmetic results in more than 90% of patients, and patient satisfaction is greater (P<.001).
Topics: Carcinoma, Squamous Cell; Clinical Trials, Phase III as Topic; Esthetics; Humans; Keratosis, Actinic; Neoplasms, Radiation-Induced; Oxidation-Reduction; Pain; Patient Satisfaction; Photochemistry; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Sunlight; Ultraviolet Rays
PubMed: 28063524
DOI: 10.1016/j.ad.2016.09.020 -
The Cochrane Database of Systematic... Dec 2016Choroidal neovascularisation (CNV) is a common complication of pathological myopia. Once developed, most eyes with myopic CNV (mCNV) experience a progression to macular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Choroidal neovascularisation (CNV) is a common complication of pathological myopia. Once developed, most eyes with myopic CNV (mCNV) experience a progression to macular atrophy, which leads to irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) therapy is used to treat diseases characterised by neovascularisation and is increasingly used to treat mCNV.
OBJECTIVES
To assess the effects of anti-vascular endothelial growth factor (anti-VEGF) therapy for choroidal neovascularisation (CNV), compared with other treatments, sham treatment or no treatment, in people with pathological myopia.
SEARCH METHODS
We searched a number of electronic databases including CENTRAL and Ovid MEDLINE, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP). We did not use any date or language restrictions in the electronic searches for trials. Electronic databases were last searched on 16 June 2016.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs comparing anti-VEGF therapy with another treatment (e.g. photodynamic therapy (PDT) with verteporfin, laser photocoagulation, macular surgery, another anti-VEGF), sham treatment or no treatment in participants with mCNV.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two authors independently screened records, extracted data, and assessed risk of bias. We contacted trial authors for additional data. We analysed outcomes as risk ratios (RRs) or mean differences (MDs). We graded the certainty of the evidence using GRADE.
MAIN RESULTS
The present review included six studies which provided data on the comparison between anti-VEGF with PDT, laser, sham treatment and another anti-VEGF treatment, with 594 participants with mCNV. Three trials compared bevacizumab or ranibizumab with PDT, one trial compared bevacizumab with laser, one trial compared aflibercept with sham treatment, and two trials compared bevacizumab with ranibizumab. Pharmaceutical companies conducted two trials. The trials were conducted at multiple clinical centres across three continents (Europe, Asia and North America). In all these six trials, one eye for each participant was included in the study.When compared with PDT, people treated with anti-VEGF agents (ranibizumab (one RCT), bevacizumab (two RCTs)), were more likely to regain vision. At one year of follow-up, the mean visual acuity (VA) in participants treated with anti-VEGFs was -0.14 logMAR better, equivalent of seven Early Treatment Diabetic Retinopathy Study (ETDRS) letters, compared with people treated with PDT (95% confidence interval (CI) -0.20 to -0.08, 3 RCTs, 263 people, low-certainty evidence). The RR for proportion of participants gaining 3+ lines of VA was 1.86 (95% CI 1.27 to 2.73, 2 RCTs, 226 people, moderate-certainty evidence). At two years, the mean VA in people treated with anti-VEGFs was -0.26 logMAR better, equivalent of 13 ETDRS letters, compared with people treated with PDT (95% CI -0.38 to -0.14, 2 RCTs, 92 people, low-certainty evidence). The RR for proportion of people gaining 3+ lines of VA at two years was 3.43 (95% CI 1.37 to 8.56, 2 RCTs, 92 people, low-certainty evidence). People treated with anti-VEGFs showed no obvious reduction (improvement) in central retinal thickness at one year compared with people treated with PDT (MD -17.84 μm, 95% CI -41.98 to 6.30, 2 RCTs, 226 people, moderate-certainty evidence). There was low-certainty evidence that people treated with anti-VEGF were more likely to have CNV angiographic closure at 1 year (RR 1.24, 95% CI 0.99 to 1.54, 2 RCTs, 208 people). One study allowed ranibizumab treatment as of month 3 in participants randomised to PDT, which may have led to an underestimate of the benefits of anti-VEGF treatment.When compared with laser photocoagulation, there was more improvement in VA among bevacizumab-treated people than among laser-treated people after one year (MD -0.22 logMAR, equivalent of 11 ETDRS letters, 95% CI -0.43 to -0.01, 1 RCT, 36 people, low-certainty evidence) and after two years (MD -0.29 logMAR, equivalent of 14 ETDRS letters, 95% CI -0.50 to -0.08, 1 RCT, 36 people, low-certainty evidence).When compared with sham treatment, people treated with aflibercept had better vision at one year (MD -0.19 logMAR, equivalent of 9 ETDRS letters, 95% CI -0.27 to -0.12, 1 RCT, 121 people, moderate-certainty evidence). The fact that this study allowed for aflibercept treatment at 6 months in the control group might cause an underestimation of the benefit with anti-VEGF.People treated with ranibizumab had similar improvement in VA recovery compared with people treated with bevacizumab after one year (MD -0.02 logMAR, equivalent of 1 ETDRS letter, 95% CI -0.11 to 0.06, 2 RCTs, 80 people, moderate-certainty evidence).Of the included six studies, two studies reported no adverse events in either group and two industry-sponsored studies reported both systemic and ocular adverse events. In the control group, there were no systemic or ocular adverse events reported in 149 participants. Fifteen people reported systemic serious adverse events among 359 people treated with anti-VEGF agents (15/359, 4.2%). Five people reported ocular adverse events among 359 people treated with anti-VEGF agents (5/359, 1.4%). The number of adverse events was low, and the estimate of RR was uncertain regarding systemic serious adverse events (4 RCTs, 15 events in 508 people, RR 4.50, 95% CI 0.60 to 33.99, very low-certainty evidence) and serious ocular adverse events (4 RCTs, 5 events in 508 people, RR 1.82, 95% CI 0.23 to 14.71, very low-certainty evidence). There were no reports of mortality or cases of endophthalmitis or retinal detachment.There was sparse reporting of data for vision-related quality of life (in favour of anti-VEGF) in only one trial at one year of follow-up. The studies did not report data for other outcomes, such as percentage of participants with newly developed chorioretinal atrophy.
AUTHORS' CONCLUSIONS
There is low to moderate-certainty evidence from RCTs for the efficacy of anti-VEGF agents to treat mCNV at one year and two years. Moderate-certainty evidence suggests ranibizumab and bevacizumab are equivalent in terms of efficacy. Adverse effects occurred rarely and the trials included here were underpowered to assess these. Future research should be focused on the efficacy and safety of different drugs and treatment regimens, the efficacy on different location of mCNV, as well as the effects on practice in the real world.
Topics: Angiogenesis Inhibitors; Bevacizumab; Choroidal Neovascularization; Humans; Laser Coagulation; Macula Lutea; Myopia, Degenerative; Photochemotherapy; Photosensitizing Agents; Porphyrins; Randomized Controlled Trials as Topic; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Verteporfin
PubMed: 27977064
DOI: 10.1002/14651858.CD011160.pub2 -
Acta Ophthalmologica May 2017Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal... (Meta-Analysis)
Meta-Analysis Review
Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE and Cochrane databases were searched for all studies examining the effects of standard, trans-epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (±1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Ultraviolet Rays
PubMed: 27678078
DOI: 10.1111/aos.13224 -
Gastrointestinal Endoscopy Jun 2016Previous estimates of incidence of intestinal metaplasia (IM) recurrence after achieving complete remission of IM (CRIM) through endoscopic therapy of Barrett's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Previous estimates of incidence of intestinal metaplasia (IM) recurrence after achieving complete remission of IM (CRIM) through endoscopic therapy of Barrett's esophagus (BE) have varied widely. We performed a systematic review and meta-analysis of studies to estimate an accurate recurrence risk after CRIM.
METHODS
We performed a systematic search of multiple literature databases through June 2015 to identify studies reporting long-term follow-up after achieving CRIM through endoscopic therapy. Pooled incidence rate (IR) of recurrent IM, dysplastic BE, and high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) per person-year of follow-up after CRIM was estimated. Factors associated with recurrence were also assessed.
RESULTS
We identified 41 studies that reported 795 cases of recurrence in 4443 patients over 10,427 patient-years of follow-up. This included 21 radiofrequency ablation studies that reported 603 cases of IM recurrence in 3186 patients over 5741 patient-years of follow-up. Pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC after radiofrequency ablation were 9.5% (95% CI, 6.7-12.3), 2.0% (95% CI, 1.3-2.7), and 1.2% (95% CI, .8-1.6) per patient-year, respectively. When all endoscopic modalities were included, pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC were 7.1% (95% CI, 5.6-8.6), 1.3% (95% CI, .8-1.7), and .8% (95% CI, .5-1.1) per patient-year, respectively. Substantial heterogeneity was noted. Increasing age and BE length were predictive of recurrence; 97% of recurrences were treated endoscopically.
CONCLUSIONS
The incidence of recurrence after achieving CRIM through endoscopic therapy was substantial. A small minority of recurrences were dysplastic BE and HGD/EAC. Hence, continued surveillance after CRIM is imperative. Additional studies with long-term follow-up are needed.
Topics: Adenocarcinoma; Argon Plasma Coagulation; Barrett Esophagus; Catheter Ablation; Cryotherapy; Electrocoagulation; Endoscopic Mucosal Resection; Esophageal Neoplasms; Esophagoscopy; Humans; Laser Therapy; Photochemotherapy; Precancerous Conditions; Recurrence
PubMed: 26902843
DOI: 10.1016/j.gie.2016.02.009 -
Medical and surgical interventions for the treatment of usual-type vulval intraepithelial neoplasia.The Cochrane Database of Systematic... Jan 2016Usual-type vulval intraepithelial neoplasia (uVIN) is a pre-cancerous condition of the vulval skin. Also known as high-grade VIN, VIN 2/3 or high-grade vulval squamous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Usual-type vulval intraepithelial neoplasia (uVIN) is a pre-cancerous condition of the vulval skin. Also known as high-grade VIN, VIN 2/3 or high-grade vulval squamous intraepithelial lesion (HSIL), uVIN is associated with high-risk subtype human papilloma virus (HPV) infection. The condition causes distressing vulval symptoms in the majority of affected women and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of uVIN. High morbidity and recurrence rates associated with surgical treatments make less invasive treatments highly desirable.
OBJECTIVES
To determine which interventions are the most effective, safe and tolerable for treating women with uVIN.
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8 2015, MEDLINE and EMBASE (up to 1 September 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that assessed medical and surgical interventions in women with uVIN. If no RCTs were available, we included non-randomised studies (NRSs) with concurrent comparison groups that controlled for baseline case mix in multivariate analysis.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodology with two review authors independently extracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random-effects methods. Network meta-analysis was not possible due to insufficient data.
MAIN RESULTS
We included six RCTs involving 327 women and five NRSs involving 648 women. The condition was variously named by investigators as uVIN, VIN2/3 or high-grade VIN. Five RCTs evaluated medical treatments (imiquimod, cidofovir, indole-3 carbinol), and six studies (one RCT and five NRSs) evaluated surgical treatments or photodynamic therapy. We judged two RCTs and four NRSs to be at a high or unclear risk of bias; we considered the others at relatively low risk of bias. Types of outcome measures reported in NRSs varied and we were unable to pool NRS data. Medical interventions: Topical imiquimod was more effective than placebo in achieving a response (complete or partial) to treatment at five to six months post-randomisation (three RCTs, 104 women; risk ratio (RR) 11.95, 95% confidence interval (CI) 3.21 to 44.51; high-quality evidence). At five to six months, a complete response occurred in 36/62 (58%) and 0/42 (0%) women in the imiquimod and placebo groups, respectively (RR 14.40, 95% CI 2.97 to 69.80). Moderate-quality evidence suggested that the complete response was sustained at one year (one RCT, nine complete responses out of 52 women (38%)) and beyond, particularly in women with smaller VIN lesions. Histologically confirmed complete response rates with imiquimod versus cidofovir at six months were 45% (41/91) and 46% (41/89), respectively (one RCT, 180 women; RR 1.00, 95% CI 0.73 to 1.37; moderate-quality evidence). Twelve-month data from this trial are awaited; however, interim findings suggested that complete responses were sustained at 12 months. Only one trial reported vulval cancer at one year (1/24 and 2/23 in imiquimod and placebo groups, respectively). Adverse events were more common with imiquimod than placebo and dose reductions occurred more frequently in the imiquimod group than in the placebo group (two RCTs, 83 women; RR 7.77, 95% CI 1.61 to 37.36; high-quality evidence). Headache, fatigue and discontinuation were slightly more common with imiquimod than cidofovir (moderate-quality evidence). Quality of life scores reported in one trial (52 women) were not significantly different for imiquimod and placebo. The evidence of effectiveness of topical treatments in immunosuppressed women was scant. There was insufficient evidence on other medical interventions. Surgical and other interventions: Low-quality evidence from the best included NRS indicated, when data were adjusted for confounders, that there was little difference in the risk of VIN recurrence between surgical excision and laser vaporisation. Recurrence occurred in 51% (37/70) of women overall, at a median of 14 months, and was more common in multifocal than unifocal lesions (66% versus 34%). Vulval cancer occurred in 11 women (15.1%) overall at a median of 71.5 months (9 to 259 months). The risk of vulval cancer did not differ significantly between excision and laser vaporisation in any of the NRSs; however, events were too few for robust findings. Alternative surgical procedures that might be as effective include Cavitron ultrasonic surgical aspiration (CUSA) and loop electrosurgical excision (LEEP) procedures, based on low- to very low-quality evidence, respectively. Very low-quality evidence also suggested that photodynamic therapy may be a useful treatment option.We found one ongoing RCT of medical treatment (imiquimod) compared with surgical treatment.
AUTHORS' CONCLUSIONS
Topical treatment (imiquimod or cidofovir) may effectively treat about half of uVIN cases after a 16-week course of treatment, but the evidence on whether this effect is sustained is limited. Factors predicting response to treatment are not clear, but small lesions may be more likely to respond. The relative risk of progression to vulval cancer is uncertain. However, imiquimod and cidofovir appear to be relatively well tolerated and may be favoured by some women over primary surgical treatment.There is currently no evidence on how medical treatment compares with surgical treatment. Women who undergo surgical treatment for uVIN have about a 50% chance of the condition recurring one year later, irrespective of whether treatment is by surgical excision or laser vaporisation. Multifocal uVIN lesions are at a higher risk of recurrence and progression, and pose greater therapeutic dilemmas than unifocal lesions. If occult cancer is suspected despite a biopsy diagnosis of uVIN, surgical excision remains the treatment of choice. If occult cancer is not a concern, treatment needs to be individualised to take into account the site and extent of disease, and a woman's preferences. Combined modalities may hold the key to optimal treatment of this complex disease.
Topics: Adult; Aminoquinolines; Antineoplastic Agents; Carcinoma in Situ; Cidofovir; Cytosine; Disease Progression; Female; Humans; Imiquimod; Indoles; Laser Therapy; Neoplasm Recurrence, Local; Organophosphonates; Photochemotherapy; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Vulvar Neoplasms
PubMed: 26728940
DOI: 10.1002/14651858.CD011837.pub2 -
The Cochrane Database of Systematic... Dec 2015Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy.
OBJECTIVES
To compare the relative effectiveness of interventions for central serous chorioretinopathy.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model.
MAIN RESULTS
We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked.The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC.Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) -0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted.Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD -0.10 logMAR, 95% CI -0.18 to -0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted.Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI -0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants).Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD -0.20 logMAR, 95% CI -0.30 to -0.11; 45 participants). There were no significant adverse effects noted.Other comparisons were largely inconclusive.We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified.
AUTHORS' CONCLUSIONS
CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials.
Topics: Carbonic Anhydrase Inhibitors; Central Serous Chorioretinopathy; Helicobacter Infections; Helicobacter pylori; Humans; Laser Therapy; Photochemotherapy; Propranolol; Randomized Controlled Trials as Topic; Remission, Spontaneous; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Watchful Waiting
PubMed: 26691378
DOI: 10.1002/14651858.CD011841.pub2