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Ophthalmic & Physiological Optics : the... Nov 2017Blue-blocking (BB) spectacle lenses, which attenuate short-wavelength light, are being marketed to alleviate eyestrain and discomfort when using digital devices, improve... (Review)
Review
PURPOSE
Blue-blocking (BB) spectacle lenses, which attenuate short-wavelength light, are being marketed to alleviate eyestrain and discomfort when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. The aim of this review was to investigate the relative benefits and potential harms of these lenses.
METHODS
We included randomised controlled trials (RCTs), recruiting adults from the general population, which investigated the effect of BB spectacle lenses on visual performance, symptoms of eyestrain or eye fatigue, changes to macular integrity and subjective sleep quality. We searched MEDLINE, EMBASE, the Cochrane Library and clinical trial registers, until 30 April 2017. Risk of bias was assessed using the Cochrane tool.
RESULTS
Three studies (with 136 participants) met our inclusion criteria; these had limitations in study design and/or implementation. One study compared the effect of BB lenses with clear lenses on contrast sensitivity (CS) and colour vision (CV) using a pseudo-RCT crossover design; there was no observed difference between lens types (log CS; Mean Difference (MD) = -0.01 [-0.03, 0.01], CV total error score on 100-hue; MD = 1.30 [-7.84, 10.44]). Another study measured critical fusion frequency (CFF), as a proxy for eye fatigue, on wearers of low and high BB lenses, pre- and post- a two-hour computer task. There was no observed difference between low BB and standard lens groups, but there was a less negative change in CFF between the high and low BB groups (MD = 1.81 [0.57, 3.05]). Both studies compared eyestrain symptoms with Likert scales. There was no evidence of inter-group differences for either low BB (MD = 0.00 [-0.22, 0.22]) or high BB lenses (MD = -0.05 [-0.31, 0.21]), nor evidence of a difference in the proportion of participants showing an improvement in symptoms of eyestrain or eye fatigue. One study reported a small improvement in sleep quality in people with self-reported insomnia after wearing high compared to low-BB lenses (MD = 0.80 [0.17, 1.43]) using a 10-point Likert scale. A study involving normal participants found no observed difference in sleep quality. We found no studies investigating effects on macular structure or function.
CONCLUSIONS
We find a lack of high quality evidence to support using BB spectacle lenses for the general population to improve visual performance or sleep quality, alleviate eye fatigue or conserve macular health.
Topics: Circadian Rhythm; Contrast Sensitivity; Eye Pain; Eyeglasses; Humans; Light; Macula Lutea; Randomized Controlled Trials as Topic; Sleep; Sleep Initiation and Maintenance Disorders; Visual Acuity
PubMed: 29044670
DOI: 10.1111/opo.12406 -
The Lancet. Global Health Sep 2017Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment.
METHODS
We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12).
FINDINGS
Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9-65·4) were blind (crude prevalence 0·48%; 80% UI 0·17-0·87; 56% female), 216·6 million (80% UI 98·5-359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34-4·89; 55% female), and 188·5 million (80% UI 64·5-350·2) had mild visual impairment (2·57%, 80% UI 0·88-4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1-1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9-997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9-57·3) in 1990 to 36·0 million (80% UI 12·9-65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (-36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3-270·0) in 1990 to 216·6 million (80% UI 98·5-359·1) in 2015.
INTERPRETATION
There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels.
FUNDING
Brien Holden Vision Institute.
Topics: Blindness; Global Health; Humans; Prevalence; Vision Disorders; Visual Acuity
PubMed: 28779882
DOI: 10.1016/S2214-109X(17)30293-0 -
Ophthalmology Oct 2018Presbyopia prevalence and spectacle-correction coverage were estimated by systematic review and meta-analysis of epidemiologic evidence, then modeled to expand to... (Meta-Analysis)
Meta-Analysis
TOPIC
Presbyopia prevalence and spectacle-correction coverage were estimated by systematic review and meta-analysis of epidemiologic evidence, then modeled to expand to country, region, and global estimates.
CLINICAL RELEVANCE
Understanding presbyopia epidemiologic factors and correction coverage is critical to overcoming the burden of vision impairment (VI) from uncorrected presbyopia.
METHODS
We performed systematic reviews of presbyopia prevalence and spectacle-correction coverage. Accepted presbyopia prevalence data were gathered into 5-year age groups from 0 to 90 years or older and meta-analyzed within World Health Organization global burden of disease regions. We developed a model based on amplitude of accommodation adjusted for myopia rates to match the regionally meta-analyzed presbyopia prevalence. Presbyopia spectacle-correction coverage was analyzed against country-level variables from the year of data collection; variation in correction coverage was described best by a model based on the Human Development Index, Gini coefficient, and health expenditure, with adjustments for age and urbanization. We used the models to estimate presbyopia prevalence and spectacle-correction coverage in each age group in urban and rural areas of every country in the world, and combined with population data to estimate the number of people with near VI.
RESULTS
We estimate there were 1.8 billion people (prevalence, 25%; 95% confidence interval [CI], 1.7-2.0 billion [23%-27%]) globally with presbyopia in 2015, 826 million (95% CI, 686-960 million) of whom had near VI because they had no, or inadequate, vision correction. Global unmet need for presbyopia correction in 2015 is estimated to be 45% (95% CI, 41%-49%). People with presbyopia are more likely to have adequate optical correction if they live in an urban area of a more developed country with higher health expenditure and lower inequality.
CONCLUSIONS
There is a significant burden of VI from uncorrected presbyopia, with the greatest burden in rural areas of low-resource countries.
Topics: Eyeglasses; Global Health; Humans; Presbyopia; Prevalence; Vision Disorders; Visual Acuity; Visually Impaired Persons
PubMed: 29753495
DOI: 10.1016/j.ophtha.2018.04.013 -
European Journal of Cancer (Oxford,... Sep 2021Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based...
BACKGROUND
Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based diagnostic support systems, in particular convolutional neural network (CNN)-based image analysis tools, have shown great potential in medical computer vision. In this systematic review, we summarise recent studies reporting CNN-based approaches for digital biomarkers for characterization and prognostication of gastrointestinal cancer pathology.
METHODS
Pubmed and Medline were screened for peer-reviewed papers dealing with CNN-based gastrointestinal cancer analyses from histological slides, published between 2015 and 2020.Seven hundred and ninety titles and abstracts were screened, and 58 full-text articles were assessed for eligibility.
RESULTS
Sixteen publications fulfilled our inclusion criteria dealing with tumor or precursor lesion characterization or prognostic and predictive biomarkers: 14 studies on colorectal or rectal cancer, three studies on gastric cancer and none on esophageal cancer. These studies were categorised according to their end-points: polyp characterization, tumor characterization and patient outcome. Regarding the translation into clinical practice, we identified several studies demonstrating generalization of the classifier with external tests and comparisons with pathologists, but none presenting clinical implementation.
CONCLUSIONS
Results of recent studies on CNN-based image analysis in gastrointestinal cancer pathology are promising, but studies were conducted in observational and retrospective settings. Large-scale trials are needed to assess performance and predict clinical usefulness. Furthermore, large-scale trials are required for approval of CNN-based prediction models as medical devices.
Topics: Deep Learning; Gastrointestinal Neoplasms; Humans; Treatment Outcome
PubMed: 34391053
DOI: 10.1016/j.ejca.2021.07.012 -
Arthritis Care & Research Jun 2019To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).
OBJECTIVE
To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).
METHODS
Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong.
RESULTS
Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss.
CONCLUSION
This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.
Topics: Arthritis, Juvenile; Biological Products; Consensus; Glucocorticoids; Humans; Immunosuppressive Agents; Ophthalmology; Predictive Value of Tests; Rheumatology; Risk Factors; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Uveitis
PubMed: 31021540
DOI: 10.1002/acr.23871 -
The Cochrane Database of Systematic... Feb 2017Theoretically, autologous serum eye drops (AS) offer a potential advantage over traditional therapies on the assumption that AS not only serve as a lacrimal substitute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Theoretically, autologous serum eye drops (AS) offer a potential advantage over traditional therapies on the assumption that AS not only serve as a lacrimal substitute to provide lubrication but contain other biochemical components that allow them to mimic natural tears more closely. Application of AS has gained popularity as second-line therapy for patients with dry eye. Published studies on this subject indicate that autologous serum could be an effective treatment for dry eye.
OBJECTIVES
We conducted this review to evaluate the efficacy and safety of AS given alone or in combination with artificial tears as compared with artificial tears alone, saline, placebo, or no treatment for adults with dry eye.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), 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 also searched the Science Citation Index Expanded database (December 2016) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 July 2016.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared AS versus artificial tears for treatment of adults with dry eye.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all titles and abstracts and assessed full-text reports of potentially eligible trials. Two review authors extracted data and assessed risk of bias and characteristics of included trials. We contacted investigators to ask for missing data. For both primary and secondary outcomes, we reported mean differences with corresponding 95% confidence intervals (CIs) for continuous outcomes. We did not perform meta-analysis owing to differences in outcome assessments across trials.
MAIN RESULTS
We identified five eligible RCTs (92 participants) that compared AS versus artificial tears or saline in individuals with dry eye of various origins (Sjögren's syndrome-related dry eye, non-Sjögren's syndrome dry eye, and postoperative dry eye induced by laser-assisted in situ keratomileusis (LASIK)). We assessed the certainty of evidence as low or very low because of lack of reporting of quantitative data for most outcomes and unclear or high risk of bias among trials. We judged most risk of bias domains to have unclear risk in two trials owing to insufficient reporting of trial characteristics, and we considered one trial to have high risk of bias for most domains. We judged the remaining two trials to have low risk of bias; however, these trials used a cross-over design and did not report data in a way that could be used to compare outcomes between treatment groups appropriately. Incomplete outcome reporting and heterogeneity among outcomes and follow-up periods prevented inclusion of these trials in a summary meta-analysis.Three trials compared AS with artificial tears; however, only one trial reported quantitative data for analysis. Low-certainty evidence from one trial suggested that AS might provide some improvement in participant-reported symptoms compared with artificial tears after two weeks of treatment; the mean difference in mean change in symptom score measured on a visual analogue scale (range 0 to 100, with higher scores representing worse symptoms) was -12.0 (95% confidence interval (CI) -20.16 to -3.84; 20 participants). This same trial found mixed results with respect to ocular surface outcomes; the mean difference in mean change in scores between AS and artificial tears was -0.9 (95% CI -1.47 to -0.33; 20 participants; low-certainty evidence) for fluorescein staining and -2.2 (95% CI -2.73 to -1.67; 20 participants; low-certainty evidence) for Rose Bengal staining. Both staining scales range from 0 to 9, with higher scores indicating worse results. The mean change in tear film break-up time was 2.00 seconds longer (95% CI 0.99 to 3.01; 20 participants; low-certainty evidence) in the AS group than in the artificial tears group. Investigators reported no clinically meaningful differences in Schirmer's test scores between groups (mean difference -0.40 mm, 95% CI -2.91 to 2.11; 20 participants; low-certainty evidence). None of these three trials reported tear hyperosmolarity and adverse events.Two trials compared AS versus saline; however, only one trial reported quantitative data for analysis of only one outcome (Rose Bengal staining). Trial investigators of the two studies reported no differences in symptom scores, fluorescein staining scores, tear film break-up times, or Schirmer's test scores between groups at two to four weeks' follow-up. Very low-certainty evidence from one trial suggested that AS might provide some improvement in Rose Bengal staining scores compared with saline after four weeks of treatment; the mean difference in Rose Bengal staining score (range from 0 to 9, with higher scores showing worse results) was -0.60 (95% CI -1.11 to -0.09; 35 participants). Neither trial reported tear hyperosmolarity outcomes. One trial reported adverse events; two of 12 participants had signs of conjunctivitis with negative culture that did resolve.
AUTHORS' CONCLUSIONS
Overall, investigators reported inconsistency in possible benefits of AS for improving participant-reported symptoms and other objective clinical measures. There might be some benefit in symptoms with AS compared with artificial tears in the short-term, but we found no evidence of an effect after two weeks of treatment. Well-planned, large, high-quality RCTs are warranted to examine participants with dry eye of different severities by using standardized questionnaires to measure participant-reported outcomes, as well as objective clinical tests and objective biomarkers to assess the benefit of AS therapy for dry eye.
Topics: Adult; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Serum; Sodium Chloride; Tears
PubMed: 28245347
DOI: 10.1002/14651858.CD009327.pub3 -
Acta Ophthalmologica Sep 2017Outdoor time is considered to reduce the risk of developing myopia. The purpose is to evaluate the evidence for association between time outdoors and (1) risk of onset... (Meta-Analysis)
Meta-Analysis Review
Outdoor time is considered to reduce the risk of developing myopia. The purpose is to evaluate the evidence for association between time outdoors and (1) risk of onset of myopia (incident/prevalent myopia); (2) risk of a myopic shift in refractive error and c) risk of progression in myopes only. A systematic review followed by a meta-analysis and a dose-response analysis of relevant evidence from literature was conducted. PubMed, EMBASE and the Cochrane Library were searched for relevant papers. Of the 51 articles with relevant data, 25 were included in the meta-analysis and dose-response analysis. Twenty-three of the 25 articles involved children. Risk ratio (RR) for binary variables and weighted mean difference (WMD) for continuous variables were conducted. Mantel-Haenszel random-effects model was used to pool the data for meta-analysis. Statistical heterogeneity was assessed using the I test with I ≥ 50% considered to indicate high heterogeneity. Additionally, subgroup analyses (based on participant's age, prevalence of myopia and study type) and sensitivity analyses were conducted. A significant protective effect of outdoor time was found for incident myopia (clinical trials: risk ratio (RR) = 0.536, 95% confidence interval (CI) = 0.338 to 0.850; longitudinal cohort studies: RR = 0.574, 95% CI = 0.395 to 0.834) and prevalent myopia (cross-sectional studies: OR = 0.964, 95% CI = 0.945 to 0.982). With dose-response analysis, an inverse nonlinear relationship was found with increased time outdoors reducing the risk of incident myopia. Also, pooled results from clinical trials indicated that when outdoor time was used as an intervention, there was a reduced myopic shift of -0.30 D (in both myopes and nonmyopes) compared with the control group (WMD = -0.30, 95% CI = -0.18 to -0.41) after 3 years of follow-up. However, when only myopes were considered, dose-response analysis did not find a relationship between time outdoors and myopic progression (R = 0.00064). Increased time outdoors is effective in preventing the onset of myopia as well as in slowing the myopic shift in refractive error. But paradoxically, outdoor time was not effective in slowing progression in eyes that were already myopic. Further studies evaluating effect of outdoor in various doses and objective measurements of time outdoors may help improve our understanding of the role played by outdoors in onset and management of myopia.
Topics: Humans; Leisure Activities; Myopia; Time Factors
PubMed: 28251836
DOI: 10.1111/aos.13403 -
American Journal of Ophthalmology Jun 2017To compare the postoperative efficacy, predictability, safety, and visual quality of all major forms of laser corneal refractive surgeries for correcting myopia. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To compare the postoperative efficacy, predictability, safety, and visual quality of all major forms of laser corneal refractive surgeries for correcting myopia.
DESIGN
Systematic review and network meta-analysis.
METHODS
Search of MEDLINE, EMBASE, Cochrane Library, and the US trial registry was conducted up to November 2015. Randomized controlled trials (RCT) reporting in accordance with the eligibility criteria were included in this review. We performed a Bayesian random-effects network meta-analysis.
RESULTS
Forty-eight RCTs were identified. For efficacy (uncorrected visual acuity [UCVA]), there were no statistically significant differences between any pair of treatments analyzed. The SUCRA (surface under the cumulative ranking curve) ranking (from best to worst) was femtosecond-based laser in situ keratomileusis (FS-LASIK), LASIK, small-incision lenticule extraction, femtosecond lenticule extraction (FLEx), photorefractive keratectomy (PRK), laser epithelial keratomileusis (LASEK), epipolis (Epi)-LASIK, transepithelial PRK (T-PRK). For predictability (refractive spherical equivalent [SE]), a statistically significant difference was found when FS-LASIK was compared with LASIK (odds ratio [OR] 2.29, 95% credible interval [CrI] 1.20-4.14), PRK (OR 2.16, 95% CrI 1.15-4.03), LASEK (OR 2.09, 95% CrI 1.08-4.55), and Epi-LASIK (OR 2.74, 95% CrI 1.11-6.20). The SUCRA ranking (from best to worst) was FS-LASIK, T-PRK, LASEK, PRK, LASIK, Epi-LASIK. There were no statistically significant differences in the safety (best spectacle-corrected visual acuity) comparisons. For both postoperative higher-order aberrations (HOAs) and contrast sensitivity (CS), there were no statistically significant differences between any pair of treatments analyzed. The SUCRA ranking results show that some corneal surface ablation techniques (PRK and LASEK) rank highest.
CONCLUSIONS
This network meta-analysis shows that there were no statistically significant differences in either visual outcomes (efficacy and safety) or visual quality (HOAs and CS). FS-LASIK behaved better in predictability than any other type of surgeries.
Topics: Cornea; Humans; Lasers, Excimer; Myopia; Network Meta-Analysis; Photorefractive Keratectomy; Postoperative Period; Refraction, Ocular; Visual Acuity
PubMed: 28336402
DOI: 10.1016/j.ajo.2017.03.013 -
Advances in Therapy Aug 2022A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) at 1 and 2 years, and overall safety and injection frequency of each treatment.
METHODS
An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified protocol was followed by a Bayesian NMA to compare brolucizumab (6 mg q12w/q8w) against sham and all relevant anti-VEGF regimens. Pooled mean injection frequency, serious adverse ocular events, and discontinuation rates were estimated for each treatment regimen.
RESULTS
Nineteen RCTs were included in NMA base-case analysis. Brolucizumab (6 mg q12w/q8w) with loading-phase (LP) demonstrated superior best-corrected visual acuity (BCVA) gains to sham both at year 1 (mean difference 16.8 [95%CrI 13.3, 20.4]) and year 2 (mean difference 21.2 [95%CrI 17.4, 25.0]) and was comparable to other anti-VEGFs. Brolucizumab (6 mg q12w/q8w) also showed superior retinal thickness reduction to most comparators including ranibizumab (0.5 mg q4w; year 1 mean difference - 50.1 [95%CrI - 70.3, - 29.8]; year 2 mean difference - 49.5 [95%CrI - 70.8, - 28.6]), aflibercept (2 mg q8w; year 1 mean difference - 39.7 [95%CrI - 52.9, - 26.4]; year 2 mean difference - 35.0 [95%CrI - 49.1, - 21.4]), and faricimab (6 mg q16w/q8w; year 1 mean difference - 27.6 [95%CrI - 42.3, - 12.8]). Brolucizumab (6 mg q12w/q8w) showed similar rates of treatment discontinuation and serious and overall adverse events (both years). At year 2, pooled annualized injection frequency was lowest for brolucizumab (6 mg q12w/q8w) and highest for ranibizumab (0.5 mg q4w) at 5.7 and 11.5 injections annually, respectively.
CONCLUSION
Among all licensed anti-VEGF treatments, brolucizumab showed superior reduction in retinal thickness and comparable BCVA gains and discontinuation rates, despite having the lowest injection frequency. The current study provides the most up-to-date, robust comparison of treatments for nAMD.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child, Preschool; Humans; Infant; Intravitreal Injections; Macular Degeneration; Network Meta-Analysis; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 35678996
DOI: 10.1007/s12325-022-02193-3 -
The Cochrane Database of Systematic... Sep 2019Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA...
BACKGROUND
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
OBJECTIVES
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); 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 search for trials. We last searched the electronic databases on 16 February 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
AUTHORS' CONCLUSIONS
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Randomized Controlled Trials as Topic
PubMed: 31517988
DOI: 10.1002/14651858.CD010051.pub2