Effect of Ayurvedic Treatment protocol in the management of Madhumehajanya Timira w.s.r to Diabetic Retinopathy-A Clinical Study

The frame of the present research work entitled Effect of Ayurvedic Treatment protocol in themanagement of Madhumehajanya Timira w.s.r. to DiabeticRetinopathy-A Clinical Studyhasbeen disposed into following sections:

 1.      Introduction

2.      Conceptualstudy-Ayurvedic & Modern review

3.      Drugreview- Pharmacognostical &Analytical Study

4.      Procedurereview

5.      Clinicalstudy

6.      Discussion

7.      Summaryand Conclusion

1) Introduction:

In Introduction part,the gravity and incidence of the disease has been discussed. Its hypothesis in Ayurvedicliterature regarding concept of the disease, treatment and selection of therapyafter reviewing the previous research works done has been explained thoroughly.The plan of study with the selected aims and objectives was also given in briefin this portion. Hypothesis regarding selection of procedures was made upon thefacts that in Madhumeha, there is Rakta vitiation due to Kledaand Kapha Vargiya Dravyas causing damage to Rasayanis. Laterthere will bederangement of Kapha causing Pitta Dushtiand further leads to a condition similar to Raktapitta. Based upon thishypothesis Koshtashodhana was adopted. Takradhara which checksbleeding, acts on relieving stress and nourishes the Shira Marma wasadopted along with Nasya which is having sense organ stimulant, Srotoshodhakaand Raktapittahara properties. Rasayana Yoga was consistingof all Pramehahara and Chakshushya drugs and was selected on thebasis ofhypothesis that it affects both Madhumehameha as well asMadhumehajanya Timira.

Aimsand objectives

1.     Tounderstand Madhumehajanya Timira inthe light of Diabetic Retinopathy – various ocular complications of Diabetesmellitus.

2.     Toevaluate the clinical efficacy of the adopted treatment approach in DiabeticRetinopathy

Hypothesis

Null Hypothesis (H0)

The adoptedAyurvedic treatment is not effective in managing Diabetic Retinopathy.

Alternative Hypothesis (H1)

The adoptedAyurvedic treatment is effective in managing Diabetic Retinopathy.

2) ConceptualStudy:

 a) Ayurvedicreview

 MadhumehajanyaTimira is a Drishtigata Roga. The term Drishti hasbeen used bothfunctionally and structurally in our classics. After acomprehensive review regarding this term, it has been concluded that eyeball asa whole along with structures directly involved in visual process starting withtear film, central cornea, lens, retina as a whole and optic tract can be takenas Drishti with selectivity as percontexts. In Prameha Pidika, Rasayani Daurbalya concept has come whichoccurs due to Kleda and Kapha Bahulya as well as due to Apana andVyana Vayu Dushti in the body due toimproper/no treatment of Pramehaand continuation of etiological factors. Also another fact that Rasayani Daurbalyais present since the starting phase of the disease but manifested as fundusfindings later and visual symptoms still later came into consideration whilereviewing the literature.

 On comparing the etiological factors a greatsimilarity between etiological factors of Prameha as well as Netra Rogaswere found.  Moreover medievalperiod book, Netraprakashika hasa direct reference of Netra Rogas due to Prameha. By taking allthese concepts the study was planned. The modern review of the disease wastaken from different text books, peer review journals and internet. Thepathogenesis involved in is Rasayani Daurbalya (vascular damageconsisting endothelial cell damage, pericyte loss etc.) was analysed in both Ayurvedicand Modern perspectives.

 b) Modern Review

 As the major structureevident to be involved in Diabetic retinopathy is Retina, due importance hasbeen given to retina and its anatomy has been dealt with in detail. In diseasereview, detailed description regarding etiology, pathogenesis, classificationand treatment have been dealt.

 3) Drug Review:

 Drug review  deals  with the  detailed  description of  selected  formulations i.e.  Drugs of Takradhara, Durvadi Ghrita which was used for Marsa andPratimarsha Nasya and Rasayana Yoga and the logic/ reasonbehind the selection of formulations.

 Under Drug Review,Pharmacognostical as well as Analytical study of the drugs were given in detailwith their main physico- chemical parameters.

 4) Procedure Review:

 Procedure review introduces the detailed descriptionof selected procedures i.e Koshtashodhana Karma, Shirashodhana, Takradhara, Marsaand Pratimarsha Nasya for thepresent clinical study.

 5) Clinical Study:

 Clinical study section deals with the need and planof study in detail, aims and objectives, material and methods, criteria forselection of patients in the study and exclusion criteria, Grouping, treatmentschedule, assessment criteria and observations in tabular form along with thestatistical analysis of results obtained.

1.      Thestudy was approved by Institutional ethics committee letter no. PGT/7A/Ethics/2015-16/2625 dated 11/12/15.

 2.      TheClinical trial was registered under CTRI with CTRI No. CTRI/2016/04/006803registered on 07/04/2016.

 AClinical Research Proforma was designed consisting of examination of thepatient, various investigations etc. Based on the assessment criteria andobservations, the effects and results of the therapy were assessed. Thepatients were selected by SIMPLE RANDOM SAMPLING METHOD & were divided into2 groups:

 GroupA: (Trial Group) – 70 patients

 GroupB :( Control Group) – 30 patients

The study was conducted in black box design.

InclusionCriteria

Ø Patientswilling for the treatment.

Ø Patientsof 30-70 years having Type 2(Non insulin dependent) diabetes with or withoutvisual disturbances, but with detectable ophthalmoscopic features of DR.

Ø Patientof Type 2(Non insulin dependent) diabetes with blood sugar level, FBS- 126 to220 mg/dl or PPBS-180 to 300 mg/dl with ongoing treatment.

ExclusionCriteria

Ø Patientswho are extremely debilitating and those who are not able to withstandtreatment procedures.

Ø Patientsof Type-1 Diabetes or the patients of Type-2 Diabetes taking Insulin.

Ø HighRisk DR or those requiring emergency intervention.

Ø Patientsof DR with media opacities like cataract, vitreous degeneration etc. whichinterfere with ophthalmoscopical findings.

Ø Patientshaving other ocular pathologies like glaucoma, high myopia etc.

Ø HypertensiveRetinopathy and DR associated with pregnancy.

Ø Patientswhose BCVA is less than 6/60

  A total of 100 patientsdiagnosed to have diabeticretinopathy with symptoms and/or signs wereselected for the study. 10 patients dropped out were later excluded from thestudy. The selected patients were assigned randomly into two groups (A &B),group A having 62 and group B having 28 patients. Each group was subjected tothe treatment in the following method.

STUDY DESIGN(GROUPING):

 Group A:(Treatment Group)

Preparatory Stage:

1)                 Deepana Pachana with ShivaksharaPachana Churna/ Chitrakadi Vati/      AmapachanaVati/ Trikatu Churna 5-10 gms/ 1 tablet  with lukewarm water      orally twice daily for 5-7 days according to the Koshtaof patients.

2)                 KoshtaShodhana with *ErandaBrishta Hareetaki/ Avipattikara Churna -*5-10gms with lukewarm water orally in  morning for 3-5 days according to the Koshtaand             Prakriti ofpatients.

3)                 Shirashodhanawith Anu Taila– 8-10 drops into each nostril for 7 days.

Treatment phase:

1)*MarshaNasya with Durvadi Ghrita-*8-10 drops into each nostril for 7 days followedby Pratimarsha Nasya with same. Total three sitting of Marsha Nasyawas done.

2. Takradharaby Siddha-Takra as medium 30 minutesdaily for 15 days in morning. Total three sitting of Takradhara was done.

3.        Oral Medication (Anubhuta Rasayana Yoga) - 3 gmat bed timewith 3gm Madhu and 6 gm Ghrita.

Allthe above therapies were continued along with Anti-hyperglycemic treatment asadvised by the treating physician.

GroupB: (Control Group)

Diagnosed cases of DM having DR changes were includedand kept under observation till the whole therapy period. They were continuedwith their anti-hyperglycemic and anti-DR treatment, if any.

Durationof Therapy and Follow up:

The therapy was continued for 90 days.

Follow up study was done for 1 month at 15 daysinterval.

Theeffect of treatment was assessed on the basis of both subjective criteria andobjective criteria; since the improvements in both patients’ vision andophthalmoscopic features are necessary in Diabetic Retinopathy to say if theexisting stage of retinopathy regressed or maintained. Specialized scoring pattern for subjective criteriawas adopted. Whereas for objective assessment of therapy Best Corrected Visualacuity, Ophthalmoscopy, Fundus photography, Fundus Fluorescein Angiography and Opticalcoherence tomography was adopted. Laboratoryinvestigations - FBS, PPBS, HbA1C, S. Cholesterol, Hb, S.G.O.T, S.G.P.T, Urea, S.Creatinineand Urine sugar were also taken  for assessment.Results were assessed in terms of percentage relief andstatistical evaluations.

 Observations (Demographic data)

 Maximum number ofpatients was of age group between 61-70years. Majority of the patients weremale i.e. 57(57.00%) and rest patients were female i.e. 43(43.00%). Majority ofpatients were Hindus i.e. 94(94.00%) and 06(06.00%) patients were Muslim. Majorityi.e. 98 (98.00 %) patients were married. 38(38.00%) patients were house wivesfollowed by 25(25.00 %) patients retired. Maximum patients (51.00%) were uneducated.Majority of the patients i.e. 47.00% belonged to middle class. In this study100.00% belonged to Jangala Desha. Maximum (91.00%) of patients wereVegetarian. Maximum i.e. 84.00% patients were having good appetite. Maximum82.00% patients were having sound sleep. Itwas observed that 64.00% were having Mridu Koshta.Maximum (92.00%) patients were having normal micturition. It wasobserved that 11.00% patients were addicted to Tobacco. It was observed that84.00% of patients had moderate built. Maximum female patients, i.e 86.04 %were in menopausal period. It was observed that 86.00% were using spectacles. InAharaja Nidana, 20.00% were having excessive use of curd. In Viharaja Nidana, 15.00% patients were having mental stress and 15.00 %patients were having daysleeping. Maximum i.e. 66.00% of patients were taking Madhura Rasa dominantdiet. Also 55.00% of patients were taking Snigdha Guna dominant diet.

It was observed that 63.00%patients were of Pittakapha Prakriti, 37.00 % patients were of Rajasik Prakriti, 95.00% patients werehaving Madhyama Satva, 93.00% patients were found to have *Madhyama Sara,*95.00 % of patients were having Madhyama Samhanana, 95.00% ofpatients were having Madhyama Pramana, 95.00% were having Madhyama**Satmya, 94.00 % of patients were having Madhyama *Ahara Shakti,*92.00   %   of  patients   were   having  moderate exercises, 61.00% were in the Madhyama age group and 95.00% patients were having MadhyamaVikruti.

Observations on Disease.

All (100.00%) of patientswere having complaints of diminished vision, followed by 18.00 % of patientshaving complaints of blurriness of vision. No patients had complaints offrequent changes in presbyopic glasses, perception of flashes of light,floaters and problem for dark adaptation. In this study 95.00% of patients had NPDR, 05.00% had PDR and 04.00%had DME. Majority of patients 73.00% were having dot blot haemorrhages.Superficial Haemorrhages were seen in 49.00 % patients. 60.00% patients werehaving hard exudates. In the study, 96.00% patients had gradual onset of ocularcomplaints and 04.00% had sudden onset. In the study 63.00 % were having chronicityof 0-1 year whereas 30.00 % patients were having chronicity of 2 –5 years. Maximumnumber of the patients, i.e.48.00% was having history of Diabetes up to 5years. 27.00 %reported onset of Diabetes 6-10 years ago. It was observed that 97.00%patients were having regular control of Blood sugar level. Positive family history was reported in23.00% and 77.00% had no family history of DM. Also 41.00 % were foundto be hypertensive.

 A detailed description of effect of therapy wasgiven on the basis of subjective criteria, objective parameters and labinvestigations. In brief the comparative results of both the groups can beexplained like this-

 a) Comparative Effects in both Groups

 On Symptoms- Onsymptoms like defective vision and blurred vision, both the groups hadstatistically insignificant result.

 **On Signs-**Treatmenton Group A was more effective in reducing dot-blot haemorrhages, superficialhaemorrhages, hard exudates and BCVA.

 On Lab Parameters- onlab investigations like FBS and S. Cholesterol, Group A was better than Group Bwhereas on PPBS, Hb, HbA1C and urine sugar both the groups were showing more orless same results which was statistically insignificant. It could also beconcluded that there was no statistically significant change in SGOT, SGPT,Urea and S. creatinine in Trial group. Thus there was no change in liverfunction and renal function tests in patients of trial group after taking Rasayana yoga.

 b) OverallEffect of Therapy

 Â·        In Group A, out of 62 patients, 04(06.45%) got moderate improvement after the completion of treatment, 23(37.09%)got mild improvement, 35 (56.45%) remained unchanged. No eye showedprogression.

 

• In Group B, out of 28 patients, 02 (07.14%) got moderate improvement after the completion of treatment, 06 (21.42%) got mild improvement, 18 (64.28 %) remained unchanged and 02(7.14 %) showed worsening in condition.
• Thus it may be concluded that Group A where Ayurvedic treatment were also given with modern-counterpart showed over all better effect.

 6)Discussion:

 A detailed discussionwas done on selection of disease, conceptual part, and selection of proceduresand drug with their probable modes of action, clinical study and effect oftherapy on all the selected patients. Some important discussion on results are-

  â€¢ Group A (TreatmentGroup) was effective in reducing dot blot haemorrhages and superficialhaemorrhages. This can be said that Group A indicates towards improving healthof retinal vasculature in this short duration of treatment with a significantimprovement in hemorrhages by reducing the Kledain blood and improving the other Dushyas,and by virtue of Rasayana Yoga, Takradhara and Nasya theRasayani daurbalya is countered,thereby the structural health ofthe body vasculature is strengthened. That’s why no fresh haemorrhage wasobserved.

ʉۢ Group A was more effective in lowering FBS andS.cholesterol showing that integrated approach in DM gives a better FBS andS.cholesterol control. It is reflecting that treatment by Takradhara,Pratimarsha Nasya and Rasayana therapy after Koshtashodhana ingroup A was helpful in blood sugar and S. cholesterolcontrol along withits maintenance for a long period.

•                    There was no statistically significantchange in SGOT, SGPT, Urea and S. creatinine in Trial group. Thus there was nochange in liver function and renal function tests in patients of trial groupafter taking Rasayana Yoga.

 Koshtashodhana byvirtue of its Kledaharana, Pitta Shodhana, Rakta Prasadana actions;Sirasodhana due to its Urdhwasrota Shodhana effect; Durvadi GhritaMarsa and Pratimarshanasya by its Rakta Sthambhaka and senseorganrejuvenating properties, Takradhara due to its Raktha Sthambhaka, Kledaharana,Sophaharana and mental relaxant effect and all drugs used in Rasayanayoga by their Chakshushya and Pramehahara properties havetheir role in combatingthe pathogenesis of Madhumehajanya TimiraDR. Thus by these virtues the holistic Ayurvedic approach is helpful ingiving a complimentary treatment protocol to the    DRpatients.

 Secondary outcome of the study: Allpatients reported betterment in their physicaland mental well beingwhich suggests that Holistic approach is improving the Quality of life andvision. Some reported attainment of good sleep following Takradhara which verifies its soothing and mental relaxing effect.

 Adverse reactions:No adverse reactions were reported in any of the patients duringtheentire study period and follow up

 CONCLUSION

 From the present study following conclusionsare drawn:

 â€¢   Group A (Treatment Group) showed betterresults on Dot blot haemorrhages, Superficial haemorrhages, hard Exudates,BCVA, FBS and S. cholesterol.

 â€¢ Boththe groups showed almost similar effects in PPBS, Hb , HbA1C and urine sugarwhich was statistically insignificant.

 â€¢ Therewas no statistically significant change in SGOT, SGPT, Urea and S. creatininein Trial group showing the safety of Anubhuta**Rasayana Yoga.

 â€¢ Therewas no statistically significant change in symptoms like defective vision andblurred vision in both groups.

   The better results in the treatment group(Group A)may be due to the improved health status of whole body vasculature speciallymicrovasculature in retina i.e Rasayanis, which prevented furtherexudations thereby decreasing retinal oedemaleading to improved visual status.Hence the null hypothesis was rejected and alternate hypothesis ie,†Theadopted Ayurvedic treatment is effective in managing DiabeticRetinopathy†has been proved.