Journal of Research in Ayurvedic Sciences

REVIEW ARTICLE
Year
: 2021  |  Volume : 5  |  Issue : 2  |  Page : 69--79

Management strategies and critical appraisal of age-related macular degeneration (AMD): A systematic review


Bandahalli Madhusudhana Rao Bhavya, Shashidhar H Doddamani, Rajendra Kumar 
 Central Ayurveda Research Institute (Central Council for Research in Ayurvedic Sciences, Ministry of AYUSH, Govt. of India), Bengaluru, India

Correspondence Address:
Dr. Bandahalli Madhusudhana Rao Bhavya
Central Ayurveda Research Institute (Central Council for Research in Ayurvedic Sciences, Ministry of AYUSH, Govt. of India), # 12, Uttarahalli Manavarthe Kaval, Uttarahalli (Hobli), Bangalore South (Tq.), Kanakapura Main Road, Talaghattapura Post, Bengaluru 560109.
India

Abstract

INTRODUCTION: Age-related macular degeneration (AMD) is a degenerative disease of macula associated with aging. It is the most leading cause of the central vision loss and blindness in the developed countries above the age of 55 years. OBJECTIVES: The aim of this article is to critically analyze and to provide quality evidence in view of safety, efficacy, and effectiveness of Ayurveda interventions. MATERIALS AND METHODOLOGY: The study reviewed randomized controlled trials (RCTs), non-RCTs, and case studies on the management of AMD in Ayurveda. They were retrieved through Ayurveda research databases and Medical Journal databases such as MEDLINE, SCOPUS, Web of Science, and other directories of open access journals. Hand searching was done using predefined search terms. The search was limited to articles published till July 2021. Study selection followed the symptomatology of AMD. The data were documented and extracted using study ID and design, sample size, duration, interventions, outcomes, and result. The quality and the risk of bias assessment were done using available tools. Quantitative synthesis was not attempted as we aimed at only systematic review. RESULTS: There were 28 screened records of which 6 fulfilled pre-defined criteria. Most commonly adopted therapeutics include four studies on Nasya (medication through nose), five on Tarpana (lubrication of eye), and two studies focussing on Basti (therapeutic enema) as primary management. The results were categorized under Shodhana (purification therapy) and Shamana (palliative). Overall studies show a significant improvement in subjective parameters assessed through gradation index. Panchakarma combined with eye treatment showed better relief. CONCLUSION: The study outcome yielded considerable improvement in vision and also assisted in maintaining existing vision which is greatly appreciable in addressing the subject’s quality of life by controlling further progression of the disease.



How to cite this article:
Bhavya BM, Doddamani SH, Kumar R. Management strategies and critical appraisal of age-related macular degeneration (AMD): A systematic review.J Res Ayurvedic Sci 2021;5:69-79


How to cite this URL:
Bhavya BM, Doddamani SH, Kumar R. Management strategies and critical appraisal of age-related macular degeneration (AMD): A systematic review. J Res Ayurvedic Sci [serial online] 2021 [cited 2022 Jan 21 ];5:69-79
Available from: http://www.jrasccras.com/text.asp?2021/5/2/69/333540


Full Text



 Introduction



Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world and presents with two forms: “dry” or atrophic and “wet” or exudative. The atrophic form is more common than the exudative form, with about 90% of patients being diagnosed with atrophic age-related macular degeneration. The exudative form of the disease usually leads to more serious vision loss and is responsible for 90% of the blindness due to this disease. AMD is common in people over 65 years of age and among whites and females.[1] In 2015, it affected 6.2 million people globally. In 2013, it was the fourth most common cause of blindness after cataracts, preterm birth, and glaucoma.[2] The modern management of this disease is aimed at reducing the risk or halting the progression of degeneration using low vision aids, antioxidants, and other supplements and surgeries to prevent further loss of vision.

Owing to the lack of proper management in conventional health sciences, this review study was initiated to provide quality evidence of interventions involved in the management of both dry and wet forms of the AMD. It is a known fact that Ayurveda interventions are being used since time immemorial in managing various age-related diseases including eye using Kriyakalpas (Ayurveda ophthalmic formulations), Rasayanas (antioxidants), etc. Besides, there are also various research works available which were carried out to study the effectiveness and efficacy of various treatment modalities involved in managing AMD through Ayurveda. Thus the scope of the study can be well understood which has been undertaken to critically analyze and to provide quality evidence in view of safety, efficacy, and effectiveness.

 Materials and Methods



Eligibility criteria

The studies included cases of age group 40–70 years of any gender, based on symptomatology of AMD; using Ayurveda interventions, dietary restrictions and lifestyle modifications with or without non-Ayurveda interventions in the study group and/or placebo therapy and/or non-Ayurveda interventions were used as comparators/controls. The study excluded review studies, conceptual studies, newsletters, book chapters, supplementary articles, conference reports, abstracts, and non-full text articles.

Outcome measures were assessed based on efficacy and safety indicators such as

Efficacy: Improvement in signs and symptoms of AMD and/or objective criteria.

Improvement in the participant’s health-related quality of life.

Safety: Serious adverse event/adverse effect/withdrawal of the treatment due to dissatisfaction or inconvenience of therapy/treatment.

Information sources

Search methods for identification of studies were grouped under headings of:

Electronic searches

We searched the following Ayurveda and Medical Journal databases such as AYUSH Research Portal, DHARA (Digital Helpline for Ayurveda Research Abstracts), MEDLINE via PubMed and CAM on PubMed, PubMed Central, Cochrane Library (Cochrane Central Register of Controlled Trials), NISCAIR Online Periodicals Repository (NOPR), Cochrane Complementary Medicine trial register, Web of Science, Scopus, Embase, Directory of Open Access Journals (DOAJ), Google Scholar, Open Access Databases, Free Medical Journals database, for ongoing trials clinical trial registry of India, World Health Organization.

Hand searching

Hand search was done for those which are not indexed in any electronic database using Ayurveda Research Database (ARD), thesis works, conference proceedings, newsletters, bibliographies, and souvenirs.

Search strategy

Searching the database through PICO strategy (Population, Intervention, Control/Comparison, and Outcome) was done, and it is described in [Table 1]. MeSH terms, keywords, and filters after the PICOS search were used which included the following: AND randomized controlled trial OR non randomized controlled trial OR clinical trial OR clinical studies OR case series OR case studies. The search was limited to articles published till July 2021.{Table 1}

Selection process

The study reviewed randomized controlled trials (RCTs), non-RCTs, case studies, and case series. This review was performed as per the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.[3] The first author independently screened the titles and abstracts to see if it is eligible or unclear. The full report of all potentially relevant studies was read by the first author to evaluate for inclusion if they fulfilled the inclusion and exclusion criteria. Then we scrutinized for multiple publications by BMB and SHD from the same data. All authors (BMB, SHD, and RP) documented the excluded studies with reason for their exclusion. The reference lists, bibliographies of included studies, and excluded systematic reviews were also screened. A total of 22 studies which were not eligible for inclusion were identified. Any disagreements in this were resolved by a third investigator (RP) by discussion.

Data collection process

Data collected under the following processes, titles, and abstracts were screened for eligibility. The full report of relevant studies was read to evaluate for inclusion and exclusion criteria. Excluded studies were documented with reasons for their exclusion. The reference lists, bibliographies of included studies, and excluded studies were also screened. All clinical outcomes and variations of reporting were included. The data were documented using study id and design, sample size, duration, interventions, dosage, outcomes, and result.

Data items

Data were extracted using domains such as study id and design, sample size, duration, dosage schedule, intervention, outcome measures; results were summarized on a data extraction form and later tabulated.

Two reviewers (BMB and SHD) summarized the data from the included studies and elaborated on a data extraction form and later tabulated. Any disagreements were resolved by the third investigator (RP). The authors declare that no funding was received.

Study risk of bias assessment

Assessment of risk of bias in the included studies (ROB) for non-RCTs was done using the ROBINS-I tool (Risk of Bias in Non-Randomized Studies of Interventions).[4] We independently performed risk of bias assessment in the eligible studies.

Effect measures

The timing and effect measures varied from 3 months to 3 years or more as different treatment procedures and interventions are included.

Synthesis methods

The main purpose of this systematic review was to report and summarize the current evidence on Ayurveda interventions for glaucoma. Hence they were measured using efficacy and safety outcomes. A meta-analysis was not attempted due to methodological heterogeneity between studies.

Reporting bias assessment

Risk of bias due to missing results in a synthesis was assessed based on the information provided in the published trial report.

Certainty assessment

All the reviewers independently checked each selected article for quality to minimize bias and later discussion was done. The details of the reported data were analyzed using the TREND Statement (Transparent Reporting of Evaluations with Nonrandomized Designs) by giving two points for each item reporting completely, one point for incomplete reporting, and no point for “No” reporting.[5] As there was no randomized controlled study involved in this article, CONSORT (Consolidated Standards of Reporting Trials) statement-2010 checklist was not used.[6]

 Results



Study selection

Out of the 28 studies identified through the database, 22 were excluded as they were not matching the inclusion criteria of the study. A total of 06 eligible studies were selected for qualitative synthesis. These six studies comprised five non-RCTs (NRCTs) and one case study. The study settings are summarized as per “Preferred reporting items for systematic reviews and meta-analyses (PRISMA-P)” in [Figure 1].{Figure 1}

Study characteristics

A brief description of the included studies is elaborated in [Table 2].{Table 2}

Risk of bias in studies

Assessment of risk of bias was done using ROBINS-I tool (Risk of Bias in Non-Randomized Studies of Interventions).[4] Based on this assessment, none of the articles published information on confounding factors and missing data; most of the studies had serious and critical ROB with few giving low and moderate bias for assessing. The domains of assessment were not properly addressed and few improperly reported, for example, there was no proper reporting of interventions status and co-interventions, there were observed deviations from intended interventions, and there was complete lack of information for confounding factors, missing data, and most of the times unclear description of measurement of the outcomes. Hence, they were labeled as serious and critical ROB. Very few studies yielded low and moderate assessment. These assessments are tabulated in [Table 4] based on information published by the authors, and after discussion with co-authors final judgment was presented.{Table 3} {Table 4}

Results of individual studies

It is briefly elaborated in [Table 4].

Results of syntheses

On assessing eligible studies, it was found that the most commonly reported efficacy outcome was improvement in visual acuity, Amsler’s grid aberrations, and color fundus photography.[6],[8],[9] Furthermore, few studies also included Ishihara color vision testing,[6],[7],[11] OCT,[6],[7],[11] and FFA.[6] While reporting toxic or adverse effects,[2] measuring vitals, assessment using Ayurveda parameters,[6] and routine laboratory tests are used to measure the safety outcomes.[6],[7],[8],[10] Improvement in subjective symptoms such as diminished vision and distorted vision is observed in almost all the studies identified.[6],[7],[8],[10],[13] While only one study reported case of vision, remaining were stable (32.5%) and deteriorating (5%).[6] Studies which included treatment using Nasya, Tarpana, and Basti reported significant result in adaptation with dim light (P < 0.001)[7],[11] and perception of flashes of light.[7] There was very little evidence to prove efficacy in terms of drusen and pigmentary changes.[10]

Reporting biases

Bias in selection of the reported result and missing data are considered serious for assessment and are depicted in [Table 4].

Certainty of evidence

The details of reported data were analyzed using TREND Statement (Transparent Reporting of Evaluations with Nonrandomized Designs)—2004 Checklist[4] by giving two points for each item reporting completely, one point for incomplete reporting, and no point for “No” reporting.[4] All the reviewers independently checked each selected article for quality to minimize bias and later discussion was done. Based on the assessment, it was decided that all the articles were incompletely reported.

 Discussion



This systematic review evaluated the management strategies for AMD. The aim was to compare the available evidence in view of safety, efficacy, and effectiveness of Ayurveda interventions, to clinically review and critically analyze the therapeutic modalities presently available for both atrophic and wet forms of the AMD.

Although in Ayurveda there is no definite correlation of AMD, in one instance, it is mentioned by Acharya Sharangadhar Samhita that due to normal aging process vision becomes poor in the sixth decade of life which is similar to the modern medicine in which AMD and other age-related diseases occur due to aging process and oxidative stress of day-to-day life processes.[14] Apart from this, the authors, based on the symptoms (clinical features) exhibited, described it under various terms such as Trutiya-Chaturtha Patalagata Dosha and Hriswajadya,[11] type of eye diseases,[9],[11] where visual disturbances and distorted and central vision are the prominent features; Pitta Vidagdha Drishti is manifesting with Pitta-Vata dominant features.[8] It is an acute manifestation of Pittaja eye disease in which the vitiated Pitta is confined to the third Patala and causes impairment of function of Alochaka pitta which is responsible for normal vision. Some also framed the treatment principle based on the features of Vatika Timira as aging is a Vata dominant process involving degeneration of tissues due to toxins present in blood and blood plasma. Similar pathology happens in AMD, in which vitiation of Prana and Apana Vayu leading to disturbances in the normal homeostasis at the level of chorio-capillaries may cause further obstruction in circulatory channels related to eye.[15] It is a degenerative age-related disease and hence sometimes labeled under vitiated Vata diseases.[12] Few also termed it under the broad heading of Timira where visual disability being the prominent presenting symptom.[10],[12]

Furthermore, it is a known fact that the pathogenesis of disease and Dosha involved is Vata and the subject is geriatric population, which is always associated with the predominance of Vata Dosha. Hence as the disease progresses, there may be involvement of other Doshas such as Rakta, Pitta, and Kapha. Hence, the common management strategies involved are based on the principles of Vata-pitta Shamakachikitsa (palliative), Sroto-Shodhaka (detoxifying minute channels), along with Rasayana (rejuvenating) drugs to nourish the body, to bring the abnormal Doshas back to normalcy and to regenerate the body tissues to some extent. Therefore, the applied topical eye procedures include Tarpana and Putapaka (topical eye procedure through lubrication of eyes using medicated ghee and solutions): Panchakarma procedures in the form of Nasya (instillation of medication through nose) and Basti (therapeutic enema). As mentioned in various contexts, Anulomana (normal movement of Vayu) of Dosha should be the prioritized treatment in the form of Basti in order to remove obstruction in channels.

According to various Acharyas, in the context of eye treatment, it is mentioned that Timira and Adhimantha are eye diseases which can be cured with Basti Chikitsa.[16],[17] While describing the importance of Basti Chikitsa, it is rejuvenating and nutrient-rich to eyes.[18] This indicates that the pharmacological action of Basti can penetrate through the blood retinal barrier and may result in vision improvement by subsiding the aggravated Dosha. Hence, Basti can be administered with the drugs predominantly possessing antioxidant, immunomodulatory, anti-inflammatory, Rasayana, and Vatahara properties.

The Nasya Karma is also one of the preferred procedures in this disease. It can be done with drugs which provide strength to the sense organs and does cleansing of channels. Kriyakalpas (ocular procedures) like Tarpana, Putapaka, Anjana, etc. are applied along with purification procedures to maintain homeostasis and ocular strength as they are considered the foremost treatment procedure mentioned for eye disorders and are also based on clinical experiences.

Oral medicines such as Saptamritalauha, Triphlaghrita, Mahatriphlaghrita, Patoladighrita, Jivantyadighrita, Triphla Churna, Shatavari Churna, Amalaki Churna, and Rasayana Churna can be taken as mentioned in various studies. Apart from these, there is also mentioning of beneficial food items for eye care and nutrition in some studies which are very essential as AMD is a swabavabalaroga which occurs as age advances.[19] Under this, it mainly includes Purana Ghrita (old ghee), Yava (barley), Mudga (green gram), Patola (snake gourd), Karavella (bitter gourd), Karkatoka (spiny gourd), Amalaki (Indian gooseberry), Shatavari (Asparagus racimosa), Vastuka (Eclipta alba), Godhuma (wheat), Shastikashali (brown rice), Triphala decoction, Saindhava (rock salt), pomegranate, Mulaka (radish), drumsticks, etc. and that which possesses sweet and bitter taste.[13],[20],[21],[22]

Thus the treatment approaches are determined based on the clinical stages of the disease and it is mentioned in [Table 5]. The palliative medicines used should have basically Chakshushya (conducive to eyes) properties and that which alleviates Vata, Pitta, and Kaphadosha together with rejuvenating and antioxidant features.{Table 5}

In fact, even in modern ophthalmology while mentioning about the stages of AMD, late AMD is further divided into two subtypes based on the types of damage such as geographic atrophy and wet AMD (also called neovascular AMD),[2] which makes the hypothesis of Dosha involvement at various stages of disease more clear. Even though the review was conducted in a systematic manner, it is substantially possible that some studies may have been missed and some may not be retrieved due to unexplained incidences. The study also included observational studies as there were few clinical studies conducted and so this could also add to the review positively.

The primary objective of all the included studies was to evaluate the efficacy of Ayurveda interventions in AMD with various Ayurveda disease nomenclatures. The secondary objective varied from study to study with prime focus to study the disease conceptually and to assess any untoward effect if seen any. While summarizing the potential effects of Ayurveda interventions reported in the management of AMD in [Table 2], it observed similarities in the clinical outcomes included. Even though there is lack of standardization in the methodology, the clinical overview can be drawn appropriately to some extent as there is improvement in the subjective features in all the studies involved.

Improvement in subjective symptoms such as diminished vision and distorted vision are observed in almost all the studies identified, but the viability of maintenance is not specified as the study duration is of short period. Studies involving multiple interventions such as Nasya, Tarpana, and Basti showed a significant improvement in the clinical features as the interventions are targeting the pathogenesis of the disease and help in pacifying the aggravated Doshas due to their predefined rejuvenating, anti-inflammatory, neuroprotective Vayasthapaka and also help to inhibit tissue degeneration, and this further assists in delaying further progression of the disease. Quality of evidence assessed through the TREND Statement decided that all the articles were incompletely reported as there was need of standardization in terms of reporting trials.

The assessment of risk of bias was done using ROBINS-I tool as there were only NRCT and case studies and most of the domains were not addressed and few improperly reported; for example, there was no proper reporting of interventions status, co-interventions, deviations from intended interventions and there was complete lack of information for confounding factors, missing data, and most of the times unclear description of measurement of the outcomes. Hence, they were labeled as serious and critical ROB. Very few studies yielded low and moderate assessment.

It was challenging to draw a meaningful scientific validity due to lack of proper randomization, methodological insufficiency, short study period, improper sample sizes, high risk of biases, and so there is a need for high-quality studies. However, owing to the disease progressiveness, subjects being affected are elderly where there is potential degeneration of macula and most importantly there is lack of proper management in conventional health sciences, which makes it comfy to consider this study as a primary or add-on management in AMD. Moreover, the study outcome yielded considerable improvement in vision and also assisted in maintaining existing vision which is greatly appreciable in addressing the subject’s quality of life. Hence, this treatment modality is encouraging in controlling further progression of the disease.

 Conclusion



The multiple factors involved in the management of this disease such as chronic degenerative nature of disease, vulnerable age group population, complexity of the pathogenesis of disease, and the predominant Dosha afflicted being Vayu make it difficult to cure or incurable. Thus the outcome measured will be less appreciable and therefore high-quality studies with trials done are needed for longer duration which are valid and reliable in efficacy and sustenance of treatment. However, globally there is increased interest for evidence-based medicine in identifying potent antioxidant, rejuvenating, and anti-aging activity with low or no untoward effects. Ayurveda being potentially proven, time-tested, efficacy-based, and evidence-based medicine makes it easily accessible to the exploring science.

Financial support and sponsorship

The authors declare that no sources of financial or non-financial support for the review were received.

Conflicts of interest

The authors declare that there are no competing interests of review authors.

[INLINE:1]

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