Dr.Shipra Singh, S17480, Dr. Perwez Khan
CORRESPONDING AUTHOR-DR. SHIPRA SINGH
ROOM NO. 34
P.G. GIRLS HOSTEL,
GANESH SHANKER VIDHYARTHI MEMORIAL MEDICAL COLLEGE, KANPUR, UTTAR PRADESH
INDIA
CONTACT NO. 8756380604
Email id- shipra.aquarious@gmail.com
PERWEZ KHAN, MS *
SHIPRA SINGH, MS**
LUBNA KHAN, MD***
PRIYANKA GUPTA, MS****
*Associate Professor, Department of ophthalmology, Ganesh Shankar Vidhyarthi Memorial Medical College, Kanpur.
**Post graduation resident, Ganesh Shankar Vidhyarthi Memorial Medical College, Kanpur.
***Associate Professor, Department of Pathology, Ganesh Shankar Vidhyarthi memorial medical college, Kanpur.
****Senior resident,Ganesh Shankar Vidhyarthi Memorial Medical College, Kanpur.
KEYWORDS: AGE RELATED MACULAR DEGENERATION, GUTKHA.
WORD COUNT: 1637
TOTAL TABLES : 5
TOTAL REFERENCES : 23
GUTKHA- A SLOW POISON .TURNING EYES BLIND.
ABSTRACT
INTRODUCTION/ BACKGROUND
Gutkha use is a growing public health problem in India. It is an extremely popular herbal concoction sold throughout subcontinent. It is commonly used as mouth freshener and causes addiction. It has a lot of harm but most people are unaware of it.
Purpose
The aim of this study was to investigate the relationshipbetween smokeless tobacco (gutkha) and risk for developing Age related macular degeneration (AMD).
MATERIALS AND METHOD
A cross sectional study was conducted to assess the role of gutkha in causation of AMD in individuals above 50yrs of age who consumed gutkha for more than 10 years.102 gutkha chewers were compared with 146 controls. All subjects underwent detailed ocular examination. AMD was defined as presence of geographic atrophy and Choroidal neovascularization (CNVM) on Fundus fluorescein angiography(FFA).
RESULTS
Total 4262 patients were screened, among them 1278 were taking gutkha. 102 gutkha chewers were diagnosed having AMD. 38% males consuming gutkha for >40 years was significantly higher than female. Only 146 people who had no addiction were diagnosed as AMD. A significant association was found between AMD and gutkha usage (p= 0.0001); odds ratio was 1.68(95% CI 1.414 to 1.946) among gutkha chewers as compared to nongutkha chewers.In gutkha chewers hospital based prevalence of AMD was 7.9% as compared to nongutkha chewers (4.8%).
CONCLUSION
Strong association between AMD and gutkha usage was observed.
INTRODUCTION
Age-related macular degeneration (AMD) is a common, chronic, progressive degenerative disorder of the macula that affects older individuals and features central visual loss as a result of drusen deposition, geographical atrophy, serous detachment of the retinal pigment epithelium, and neovascularization.It is the leading cause of irreversible visual impairment among the elderly population worldwide, affecting 30–50 million individualsand ranked as the third leading cause globally[1-4].Risk factors can be classified as modifiable and non modifiable.A variety of risk factors for AMD have been described like advanced age, Caucasian race, certain genetic polymorphisms, higher body mass index, hypertension, cardiovascular risk factors, hyperlipidemia, dietary factors, excessive alcohol consumption and a history of smoking are proven risk factors in the development of AMD [5,6].
MATERIALS AND METHODS
A cross sectional study for the duration of one year from December 2013 to December 2014 was conducted in the department of ophthalmology. Informed consent was taken and study was done in accordance with Declaration of Helsinki. Records were analyzed with respect to age, sex, demographical profile and history of any substance abuse.
Inclusion criteria: Patient more than 50 years of age and those who were taking gutkha for more than 10 years.
Exclusion criteria:
- Cases and controls with evidence of other inflammatory or retinovascular disease such as retinal vessel occlusion, diabetic retinopathy, or chorioretinitis that could contribute to the development or confound the diagnosis of maculopathy.
- History of any other addiction.
All patients were subjected to detailed ocular & fundus examination,FFA and OCT was done as and when required.
RESULTS:
Total 4262 patients were screened and they were again categorized as gutkha chewers and non gutkha chewers who had no history of any addiction. Among 1278 gutkha chewers 102 patients were diagnosed as cases of AMD, who chewed gutkha for more than 10 years. They were compared with 146 patients who had no any other addiction taken as controls and were suffering from AMD.
AMD was found to be more common in gutkha chewers (7.9%) as compared to non gutkhachewers (4.8%). This difference is statistically significant with p<0.0001. Odds ratio was 1.68(95% CI 1.414 to 1.946) among gutkha chewers as compared to non gutkha chewers (Table 1).
Table 1
Prevalence of AMD among gutkha chewers and nongutkha chewers.
| DISEASE ARMD
PRESENT |
DISEASE ARMD
ABSENT |
TOTAL | |
| GUTKHA CHEWERS | 102(7.9%) | 1176(92%) | 1278 |
| NON GUTKHA CHEWERS | 146(4.8%) | 2838(95%) | 2984 |
| TOTAL | 248 (5.8%) | 4014(94.18%) | 4262 |
Out of 248 patients, maximum number of patients 93(37.5%) were in the age group of 51-60 years of age. 148(59.6%) were males and 100(40.3%) were females.
Among 102gutkhachewers, maximum number of patients 53 (51.9%) were in the age group of 51-60 years of age. Prevalence of gutkha was more common among males (71.5%) than females (28.4%).Among 146 non gutkha chewers , maximum number of patients 49 (33.5%) were in the age group of 61-70 years of age.( Table 2)
Table 2
Age and sex distribution among gutkha and non gutkha chewers
| Age | GUTKHA CHEWERS
Male Females |
|
NON GUTKHA
CHEWERS Males Females |
TOTAL | ||||
| 51 – 60 | 39(53.42%) | 14(48.2%) | 15(20%) | 25(35.2%) | 93(37.5%) | |||
| 61 – 70 | 23(31.5%) | 12(41.3%) | 25(33.3%) | 24(33.8%) | 84(33.8%) | |||
| 71 – 80 | 09(12.3%) | 02(6.8%) | 29(38.6%) | 18(25.3%) | 59(23.7%) | |||
| >80 | 02(2.7%) | 01(3.4%) | 06(8%) | 04(5.6%) | 12(4.8%) | |||
| TOTAL | 73(71.5%) | 29(28.4%) | 75(51.36%) | 71(48.6%) | 248 | |||
Out of 102 gutkha chewer cases, majority of patients 67( 65.68% ) were taking gutkha for more than 30 years of duration out of which 54( 72%) were males and 13(44.8%) were females . Only 8.2% males and 17.2% females were taking gutkha for ten to twenty years duration.17.8% males and 37.9% females chewed gutkha for duration of twenty to thirty years. (Table 3)
Table 3
Duration of gutkha intake
| DURATION OF GUTKHA INTAKE
( IN YEARS) |
CASES
(MALES) |
CASES(FEMALES) | TOTAL |
| 10-20 | 6 (8.2%) | 5 (17.2%) | 11(10.7%) |
| 20-30 | 13(17.8%) | 11 (37.9%) | 24(23.5%) |
| >30 | 54(72%) | 13(44.8%) | 67(65.68%) |
| TOTAL | 73 | 29 | 102 |
Among 102 gutkha chewer cases, maximum number of patients 44(43.13%) were taking more than four pouches of gutkha per day.9 (12.3%) males and 8(27.5%) females were having less than two pouches per day.29 (39.7%) males and 12(41.3%) females were taking two to four pouches per day.35 (47.9%) males and 9(31%) females were taking more than four pouches per day.(Table 4)
Table 4
Number of pouches of gutkha used per day
| NUMBER OF POUCHES USED PER DAY | MALES | FEMALES | TOTAL |
| <2 | 9 (12.3%) | 8 (27.5%) | 17(16.6%) |
| 2-4 | 29 (39.7%) | 12 (41.3%) | 41(40.1%) |
| >4 | 35 (47.9%) | 9 (31%) | 44(43.13%) |
| TOTAL | 73 | 29 | 102 |
Among both gutkha chewers and non gutkhachewers, maximum number of patients 175(70.5%) were having bilateral involvement of eyes as compared to 73(29.4%) of unilateral cases. Out of 102 gutkha chewer patients 34(33.3%) were having unilateral AMD and 68(66.6%) had bilateral AMD. Similarly among 146 non gutkha chewers 39 (26.7%) were having unilateral AMD and 175 (70.5%) had bilateral ARMD.(Table 5).
Table 5
Laterality in gutkha and non gutkha chewers
| LATERALITY | UNILATERAL (ARMD) | BILATERAL (ARMD) | TOTAL CASES |
| GUTKHA CHEWERS | 34(33.3%) | 68(66.6%) | 102 |
| NON GUTKHA CHEWERS | 39(26.7%) | 107(73.2%) | 146 |
| TOTAL | 73(29.4%) | 175 (70.5%) | 248 |
DISCUSSION:
Age related macular degeneration (AMD) is a macular neurodegenerative disease that has recently emerged as one of the main socio-economical health issues worldwide afflicting the elderly population aged above 50 years due to increased life span [3,4,7]
Early AMD is characterized by the presence of soft drusen( small < 63 um ,intermediate>63um, <=125um; large>125um) ,areas of hyperpigmentation or hypopigmentation associated with drusen. Visual acuity is not used to define AMD because advanced changes may be present without anatomically affecting fovea.Advanced AMDis more severe, with Geographic atrophy(GA) and/or Choroidal neovascularization (CNV)[8].The World Health Organization (WHO) estimated in 2002 that 8.7% of the world’s blindness was due to AMD rendering 14 million persons worldwide blind or severely visually impaired from AMD [7].
Oxidative stress is a major factor in the pathogenesis. Retinal pigment epithelial (RPE) cells are prone to reactive oxygen species (ROS) arising during the stress due to intense oxygen metabolism and a high oxygen pressure [9-11]. Nicotine itself promotes angiogenesis in experimental models due to its vasculogenic properties [12-14] and may also induce catecholamine release increasing platelet aggregability. Platelets contribute to the growth of plaque through the accretion of thrombus, as well as through the release of growth factors (such as platelet-derived growth factor (PDGF)) that induce vascular smooth muscle cell proliferation. Nicotine also exerts a vasoconstrictive action via α-adrenergic stimulation which may impair blood flow through the choroid [15].
Gutkhais a dry, relatively nonperishable commercial preparation containing areca nut, slaked lime, catechu, condiments and powdered tobacco. The same mixture without tobacco is called pan masala[16].
Chemical analysis of gutkha showed the presence of polyaromatic hydrocarbons, nitrosamines, and toxic metals such as arsenic, lead, cadmium , nickel, polyaromatic hydrocarbons and residual pesticides, with wide variation between different brands[16,17].
Cigarette smoking and smokeless tobacco ( gutkha) more or less has same ill effects on health.
Gutkha usage is common among all age groups and acceptable by both the genders of the society in Indian subcontinent.
This study showed that the prevalence of AMD was more common among gutkha chewers (7.9%)as compared to non gutkhachewers (4.8%) and developing at earlier age. Similar to smoking this smokeless tobacco product (gutkha) also has a causal risk for developing AMD.
The areca nut is considered to be the fourth most commonly used psychoactive substance after the tobacco, alcohol and caffeine and it has been suggested that approximately 10% of the World’s population chew it regularly [18].
The areca nut contains several psychoactive compounds. Arecoline, the principal alkaloid in areca nut, acts as an agonist primarily at muscarinic acetylcholine receptors, acts as a stimulant of the central and autonomic nervous system, and causes increases in the levels of monoamines such as noradrenaline, as well as acetylcholine at higher doses. This leads to subjective effects of increased well-being, alertness and stamina. Arecaidine, another active ingredient, may have anxiolytic properties through inhibition of gamma-amino butyric acid (GABA) reuptake. Thus areca nut use by itself and more so with tobacco additives, is associated with the development of a dependence syndrome [19].
It is well known that Areca-nut chewing habit has been associated with oral diseases including oral cancer, oral submucous fibrosis and periodontal disease; however, some authors have reported that the Areca nut chewing abuse may also jeopardize the systemic health among its users.[15-20]
Some studies also showed that areca nut chewing has a relationship with metabolic syndrome21. It is also associated with hypertension, diabetes and cardiovascular complication22 , which by themselves are independent risk factors for the development of AMD.
Studies have showed that chronic gutkha usage due to continued nicotine stimulated catecholamine secretion may raise blood cholesterol levels and also hampers the maintenance of blood glucose level by insulin.
Presence of toxic metals like arsenic, cadmium, lead and nickel in gutkha ,may have deleterious effects on retina, Raj et al (2013)23studied toxic effect of the metal mixture ( Arsenic, cadmium and lead ) at human relevant doses, on developing rat astrocytes. They observed modulation in the levels of myelin and axon proteins, such as myelin basic protein ( MBP), proteolipid protein, 2’-3’ cycle – nucleotide-3’ phosphodiesterase, myelin associated glycoprotein and neurofilatment ( NF) in the brain of developing rats. They concluded that exposure to Arsenic, cadmium and lead mixture impairs myelin and axon development in rat brain; optic nerve and retina.
In our study , a significant association was found between AMD and gutkha usage ( p=0.001) with odd ratio 1.68 ( 95% CI 1.414 to 1.946) as compared to non-gutkha chewers.
Gutkha contains higher concentration of nicotine as well as areca nut which causes dependency syndrome making difficult to quit as compared to quitting cigarettes. This fact has been demonstrated in our study as maximum number of patients were chewing gutkha 67(65.68%) for more than thirty years and also 43.13% were taking more than four pouches of gutkha per day.Inspite of realizing the harmful effects of gutkha , many people used it as mouth freshener after meals. It is popular among all age groups and commonly used by both the genders as it is cheaply available and sweet in taste and also due to forceful misleading advertisements.
All the above mentioned factors and the toxic effects of different constituents present in the gutkha played a role in the development of AMD.
CONCLUSION
Strong association between AMD and gutkha usage was observed. To the best of our knowledge till date, no study has been attempted to analyze the effect of gutkha on causation of AMD. The truth is that tobacco in any form remains the most dangerous consumer product in the world in the 21st century which kills half its patrons and its very existence is a bane to mankind. People are not aware of the dangers of gutkha usage and find it difficult to quit because of the addictive nature of the chemical nicotine. Hence it is emphasized that usage of gutkha should be discouraged.
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