|Year : 2021 | Volume
| Issue : 2 | Page : 95-98
Safety and efficacy of Ayurveda interventions in diabetic retinopathy: Protocol for systematic review
Praveen Balakrishnan1, Varsha Sumedhan1, Thekkekkoottumughath P Sinimol1, Azeem Ahmed2, Sridevi Venigalla3, Devarkonda Sudhakar4
1 Regional Ayurveda Research Institute, Thiruvananthapuram, Kerala, India
2 Central Council for Research in Ayurvedic Sciences (CCRAS), New Delhi, India
3 National Center for Indian Medical Heritage, Hyderabad, Telangana, India
4 National Ayurveda Research Institute for Panchakarma, Cheruthuruthy, Kerala, India
|Date of Submission||27-Jul-2021|
|Date of Acceptance||23-Sep-2021|
|Date of Web Publication||23-Dec-2021|
Dr. Praveen Balakrishnan
Regional Ayurveda Research Institute, Poojappura, Thiruvananthapuram 695012, Kerala.
Source of Support: None, Conflict of Interest: None
Introduction: Diabetic retinopathy (DR), a complication of diabetes mellitus, is a leading cause of blindness on a global level. Nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), both with and without diabetic macular edema (DME), are the stages of DR. The conventional treatment strategies for DR include intravitreal injections, laser photocoagulation, and surgical approach. There are quite a few individual studies available in various databases showing the efficacy of Ayurveda intervention in DR. However, a systematic review of these studies is not available to date. The aim of this study is to perform a systematic review of various clinical studies of Ayurveda treatments in DR, along with meta-analysis, if possible. This shall help in providing more precise estimates of the effectiveness of management of DR using Ayurveda interventions. Methods and Analysis: A systematic review of randomized controlled trials (RCTs), quasi-randomized controlled trials (QRCTs), controlled clinical trials (CCTs), multiple arms clinical trials, and single-group studies on DR published/unpublished from January 1990 to November 2020 will be conducted. The database search will be performed using the words with Boolean operators: Ayurveda OR Ayurvedic AND Diabetic Retinopathy as title, abstract, or keyword. Clinical trials of patients fulfilling the diagnostic criteria based on signs and symptoms of DR in any of its stages, irrespective of age and either gender, will be selected. Studies that are based on the Ayurvedic treatments such as Shodhana (purification therapies), Shamana (pacification therapies), Netra Kriyakalpa (topical ophthalmic application of medications), Moordha Taila Prayoga (topical application of medicine on head), Mukha Kriya Kramas (usage of medicine on/in mouth and on face such as Mukhalepa, Kabala, Gandoosha) irrespective of dosage, type, schedule, drug, form, and advised Pathayapathya (lifestyle changes) as intervention or control will be selected. Response to treatment, both subjective and objective, is the primary outcome and onset of serious adverse events is the secondary outcome. Ethics and Dissemination: Ethical approval was obtained from the Institutional Ethics Committee. The results obtained will be published in a peer-reviewed journal. Trial Registration Number: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42019136750.
Keywords: Ayurveda, diabetic retinopathy, efficacy, protocol, safety, systematic review
|How to cite this article:|
Balakrishnan P, Sumedhan V, Sinimol TP, Ahmed A, Venigalla S, Sudhakar D. Safety and efficacy of Ayurveda interventions in diabetic retinopathy: Protocol for systematic review. J Res Ayurvedic Sci 2021;5:95-8
|How to cite this URL:|
Balakrishnan P, Sumedhan V, Sinimol TP, Ahmed A, Venigalla S, Sudhakar D. Safety and efficacy of Ayurveda interventions in diabetic retinopathy: Protocol for systematic review. J Res Ayurvedic Sci [serial online] 2021 [cited 2022 Jan 21];5:95-8. Available from: http://www.jrasccras.com/text.asp?2021/5/2/95/333537
| Introduction|| |
Diabetic retinopathy (DR) is a complication of diabetes mellitus (DM), which is a leading cause of loss of vision on a global scale., There are mainly two stages of DR: nonproliferative DR (NPDR) and proliferative DR (PDR). NPDR is in the initial stage of DR, characterized by increased vascular permeability and capillary occlusion. PDR is an advanced stage of DR characterized by neovascularization. Diabetic macular edema (DME) may or may not be present in both the above stages. The aim of current contemporary treatment strategies for DR is to manage the microvascular complication through intravitreal pharmacological agents, laser photocoagulation, and vitreous surgeries.
The available clinical evidences indicates that Ayurveda has promising results in the treatment of DR. Few published studies proving the efficacy of Ayurveda interventions such as Shodhana (purification therapies), Shamana (pacification therapies), Netra Kriyakalpa (topical ophthalmic application of medications), Moordha Taila Prayoga (topical application of medicine on head), Mukha Kriya Kalpas (usage of medicine in mouth and on face such as Mukhalepa, Kabala, Gandoosha) in subjective and objective improvement of DR are available on various databases. Apart from these, there are also many unpublished studies in the form of dissertation at various universities pan-India. However, we do not find any systematic review (SR) for Ayurveda interventions for DR to date. So, this study was planned to systematically review and analyze the safety and efficacy of Ayurveda interventions in DR from the available published and unpublished data along with meta-analysis, if possible.
| Methods and Design|| |
A systematic search of published and unpublished data of randomized controlled trials (RCTs), quasi-randomized controlled trials (QRCTs), controlled clinical trials (CCTs), multiple arms clinical trials, and single-group studies on safety and efficacy of Ayurvedic interventions on DR from a period of January 1990 to November 2020 will be conducted. Language restrictions will not be imposed in selection of the articles.
Patients fulfilling the diagnostic criteria based on signs and symptoms of DR in any of its stage, all ages, and either gender will be selected.
Ayurveda treatment modalities such as purification therapies, pacification therapies, topical ophthalmic application of medications, topical application of medicine on head, usage of medicine on/in mouth and on face irrespective of dosage, type, schedule, drug, form, and advised Pathayapathya (do's and don'ts regarding diet and lifestyle) as intervention or control will be selected. We will also include no-therapies (wait and watch)/placebo and/or sham therapy and/or any non-Ayurveda interventions as comparators. Patients receiving additional non-Ayurveda intervention in all groups of study irrespective of the time period of administration will also be considered.
Response to treatment (improvement in subjective and/or objective criteria of assessment) is the primary outcome. Serious adverse effects resulting in death or disability or life-threatening complications or those that led to prolonged hospitalization or even withdrawal due to lack of efficacy or inconvenience of therapy/treatment is the secondary outcome.
Timing and effect measures
There will be no restrictions on administration timings. Secondary outcomes either during the study period or up to 1-month post-completion of the study will be considered.
Peer-reviewed articles published on PubMed, Cochrane Library, Clinical Trial Registry of India (CTRI), Clinical trials.gov, DHARA Online, AYUSH Research Portal (Govt. of India), Semantics Scholar, Directory of Open Access Journals (DOAJ), CAMbase, Annotated Bibliography of Indian Medicine (ABIM), Scienceopen, Google Scholar, RGUHS repository, and Libraries of various institutes will be searched. These online databases will be searched using the words Ayurveda OR Ayurvedic AND Diabetic Retinopathy as title, abstract, or keyword. Prior to final analyses, the searches will be re-run to retrieve further studies for inclusion. Unpublished grey literatures will be searched through formal communication to universities and other institutions. Ayurveda Research Database (ARD) published by Gujarat Ayurveda University will also thoroughly searched for collecting details on various dissertations.
Study selection and data extraction
Two separate review authors PB and VS will independently assess the identified title and abstract during the search. The full papers of the potentially eligible articles will be screened and filtered for inclusion based on the eligibility criteria. Data of study setting, population, demographics, baseline characteristics, details of the intervention and control, study methodology, study completion rates, outcomes, and times of measurement will be abstracted from the included studies using a predefined form. PB and VS independently will extract the data of the included studies. Authors of the articles will be contacted either through e-mail or telephone, when more information is required.
Extracted data will then be assessed for its quality of reporting using standard guidelines such as CONSORT (Consolidated Standards of Reporting Trials)-2010 checklist for quality assessment of included parallel-group randomized clinical trial and TREND (Transparent Reporting of Evaluations with Non-randomized Designs)-2004 checklist for quality assessment of included non-randomized trials by all the three authors. Assessment will be done under three categories based on nature of reporting––“Yes,” “No,” and “Incomplete.” Two points shall be given to completely reported items. 1 point for incomplete reporting and no points for “No” reporting. Results will be calculated in percentage.
Risk of bias of the included studies will be then independently assessed by two authors PB and VS. Cochrane tool of risk of bias (RoB 2) will be used for assessing RCTs and non-randomized trials will be assessed with the Rigor Score (The Evidence Project Risk of Bias Tool). Disagreements, if any among the review authors, will be resolved by discussion with the third review, STP, after which the results will be interpreted.
Narrative statistics of count, percentage, and frequency will be used to present the data. Data will be analyzed by PB and VS, and consultant (statistics) as per requirement, using the RevMan 5 software. Relative risks will be used for dichotomous data, arithmetic mean will be used for continuous data, and weighted mean difference will be used for standard deviations at 95% confidence intervals, assuming the data to be distributed normally. A tabular reporting of medians and ranges will deployed. Separate summary effect estimates of studies that meet and did not meet the individual quality criterion will also be generated. Forest plots will be developed using chi-square test with P-value of 0.05. I2 test with a value of 50% will be applied to denote moderate levels of heterogeneity and to look for overlapping confidence intervals. A random-effects model will be used to combine clinically meaningful heterogenous studies, if required. If sufficient trials are abstracted, a sensitivity analysis will be performed to investigate the robustness of the results to the quality components and a funnel plot will be deployed to indicate publication bias, heterogeneity of results or differences in the methodological quality.
A meta-analysis will be performed if sufficient studies are abstracted and included in this review. For individual trials, wherever possible, mean differences (and 95% confidence intervals) will be reported.
| Conclusion|| |
This SR along with meta-analysis, if possible, will be a stepping stone to provide more insights and better estimates of the safety and efficacy of Ayurveda interventions in diabetic retinopathy. If sufficient information can be pooled, this may also help in making health guidelines on a regional, national, or global level. This may also pave wave in understanding the pros and cons of the current protocols, methodologies adopted in research, and publication in DR so as to correct the cons to plan better and disseminate high-quality researches in future.
Financial support and sponsorship
This work is supported by the Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of AYUSH, Government of India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Azari AA, Barney NP. Conjunctivitis: A systematic review of diagnosis and treatment. JAMA 2013;310:1721-9.
Schneider JE, Scheibling CM, Segall D, Sambursky R, Ohsfeldt RL, Lovejoy L. Epidemiology and economic burden of conjunctivitis: A managed care perspective. J Manage Care Med2014;17:78-83.
Hayasaka S, Kodama T, Ohira A. Traditional Japanese herbal (kampo) medicines and treatment of ocular diseases: A review. Am J Chin Med 2012;40:887-904.
Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. J Pharmacol Pharmacother 2010;1:100-7.
] [Full text]
Des Jarlais DC, Lyles C, Crepaz N; Trend Group. Improving the reporting quality of nonrandomized evaluations of behavioral and public health interventions: the TREND statement. American J Public Health 2004;94:361-6.
Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011. Available from: http://www.cochrane-handbook.org. [Last accessed on 22 Sep 2021].
Kennedy CE, Fonner VA, Armstrong KA, Denison JA, Yeh PT, O’Reilly KR, et al
. The evidence project risk of bias tool: Assessing study rigor for both randomized and non-randomized intervention studies. Syst Rev 2019;8:3.