Marijuana smoking and cataract

Summary

Background. –

Cigarette smoking is a well-known risk factor for cataract and other ailments, including heart disease, lung cancer, and chronic obstructive pulmonary disease. Cannabis smoke, like tobacco smoke, contains a comparable variety of carcinogenic and toxic compounds.

Purpose. –

In the present study, we analyzed UK Biobank data to determine whether smoking cannabis, like cigarettes, might be related to cataract.

Methods. –

Our analysis included all UK Biobank subjects with cataracts and information on cannabis and cigarette smoking habits. The diagnosis of cataract was ascertained using the 10th Revision of the International Classification of Diseases (ICD10), H25. The age at diagnosis of cataract was obtained from UK Biobank data field 4700. Cannabis information was recorded in UK Biobank category 143, data field 20453, ever taken cannabis.

Results. –

Subjects who used cannabis 11–100 times or more were significantly younger (4–5 years) when they developed cataract than subjects who never used cannabis. To determine the relationship of current cigarette smoking to cannabis use and age at cataract, the univariate general linear model of SPSS was used, dependent variable age at cataract, fixed factor cannabis use, random factor pack years of cigarettes smoked. Cannabis use was significantly related to age at cataract diagnosis (P < 0.001) and independent of the effect of pack-years of cigarettes smoked (P = 0.008). Linear regression revealed an insignificant relationship between pack-years of cigarette smoking and age at cataract diagnosis (P = 0.073). To further evaluate the relationship of cannabis to cataract, propensity score matching was performed. We identified 28,432 subjects with cataract. Current cigarette smoking and age were covariates; cannabis use (yes/no) was the indicator variable. Current cigarette smoking was significantly associated with a 1.2 odds ratio for cataract. Cannabis use was not significantly associated with the odds ratio for cataract.

Conclusion. –

Like tobacco smoke, cannabis smoke contains thousands of organic and inorganic chemical compounds. Cannabis tar is chemically similar to tar found in tobacco smoke, and over fifty known carcinogens have been identified in cannabis smoke, including nitrosamines, reactive aldehydes, and polycyclic hydrocarbons. Thus, the association of cannabis with cataract that we report here is not entirely surprising. Further studies are warranted.

The most common cause of blindness is age-related cataract (ARC). According to the World Health Organization’s (WHO) most recent estimation, ARC is responsible for 51% of global blindness in over 20 million people. Even though cataracts can be surgically removed and replaced with an artificial intraocular lens to restore vision, many people are still blind because of cataracts due to a lack of surgical services and high surgery costs. Cataract-induced visual impairment and blindness are becoming more common as the population ages and are becoming a major social issue around the world [1].

Preventing cataracts or slowing the progression of vision loss has the potential to provide enormous advantages and could markedly reduce the financial and clinical burden of cataracts. Therefore, recognizing modifiable risk factors for cataract is critical and may aid in the development of preventive strategies. Several factors related to an elevated risk of ARC, such as age, sunlight exposure, and cigarette smoking, have already been investigated [2].

Cigarette smoking is a well-known risk factor for cataract and other ailments, including heart disease, lung cancer, and chronic obstructive pulmonary disease (COPD). Tobacco smoke contains a variety of chemicals, including nicotine, free radicals, and carbon monoxide, all of which can cause oxidative stress and play a role in the development of ARC. Several previous epidemiologic studies have linked smoking to an increased incidence of ARC, particularly nuclear cataract (NC) [3,4].

Cannabis smoke, like tobacco smoke, contains a comparable variety of carcinogenic and toxic compounds. Concerns about the respiratory effects of inhaling cannabis smoke are heightened by awareness of the harm caused by tobacco smoke and the various ways in which cannabis is smoked. When compared to tobacco, cannabis requires a longer and deeper inhalation, as well as a shorter butt length and a higher combustion temperature. Cannabis inhalation causes a fivefold rise in carboxyhemoglobin concentration, a fourfold increase in tar inhaled, and a one-third increase in tar retention in the lower airway [5].

In the present study, we analyzed UK Biobank data to determine whether smoking cannabis, like cigarettes, might be related to cataract.

Methods

The UK Biobank is a large prospective observational study of men and women. Participants were recruited from across 22 centers located throughout England, Wales, and Scotland between 2006 and 2010 and continue to be longitudinally followed for capture of subsequent health events [6]. This methodology is like that of the ongoing Framingham Heart Study [7], with the exception that the UKB program collects postmortem samples, which Framingham did not.

Our UK Biobank application was approved as UKB project 57245 (S.L., P.H.R.). Our analysis included all subjects with cataracts and cannabis smoking information. Cataract diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD10), H25. Age cataract diagnosed was from data field 4700. Cannabis information was recorded in UKB category 143, data field 20453, ever taken cannabis. A touch screen posed the question, “Have you taken CANNABIS (marijuana, grass, hash, ganja, blow, draw, skunk, weed, spliff, dope), even if it was a long time ago?” Answers were no, yes 1–2 times, yes 3–10 times, yes 11–100 times, yes more than 100 times.

Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai. We used the UK Biobank Data Parser (ukbb parser), a python-based package that allows easy interfacing with the large UK Biobank dataset [8]. Statistical analysis was done with SPSS 25 and R.

Results

Age of subjects was 56 ± 8 (mean ± SD), 54% were female, 46% were male, 95% were white British.

Cannabis use and age at cataract of 2358 subjects are shown in Table 1. The variability is significant (P < 0.001, one way Anova). Subjects who used cannabis 11–100 times or more were significantly younger (4–5 years) when they developed cataract than subjects who never used cannabis (P = 0.05, Tukey B post hoc test).

Table 1.

Cannabis use and age at cataract of 2358 subjects. The variability is significant (P < 0.001, one way Anova). Subjects who used cannabis 11–100 times or more were significantly younger when they developed cataract than subjects who never used cannabis (P = 0.05, Tukey B post hoc test).

Cannabis use	n	Age		SD
None	1942	57.55	±	10.03
1—2 times	208	55.72	±	10.99
3—10 times	104	55.95	±	8.855
11—100 times	71	52.24	±	9.013
More than 100 Times	33	53.3	±	9.386
Total	2358

Linear regression revealed an insignificant relationship between pack-years cigarette smoking and age when cataract developed (P = 0.073).

To determine the relationship of current cigarette smoking to cannabis use and age at cataract, the univariate general linear model of SPSS was used, dependent variable age at cataract, fixed factor cannabis use, random factor pack years of cigarettes smoked. Cannabis use was significantly related to age at cataract (P < 0.001) and independent of the effect of pack years of cigarettes smoked (P = 0.008).

To further evaluate the relationship of cannabis to cataract, propensity score matching was performed. We identified 28,432 subjects with cataract using ICD10 H25. Current cigarette smoking and age were covariates, cannabis use (yes/no) was the indicator variable. No covariate exhibited a large imbalance (i.e., standardized mean difference > 25). A line plot of standardized mean differences (Cohen’s d) before and after matching is in Fig. 1. The figure demonstrates that covariate balance was greatly improved in the matched sample. The results of logistic regression without/with weighting are in Table 2. Current cigarette smoking was significantly associated with odds ratio of cataract 1.2. Cannabis use was not significantly associated with odds ratio of cataract.

Figure 1.

Propensity score matching, line plot of standardized mean differences (Cohen’s d) before (All Data) and after matching (Matched Data). The two upper lines represent the covariates, cigarette smoking and age. The lower line represents propensity scores. The figure shows that covariate balance was greatly improved in the matched sample.

Table 2.

Propensity score matching, cataract (yes/no) dependent variable, results of logistic regression without/with treatment weighting, O.R. odds ratio, L.B. lower bound, U.B. upper bound. Current cigarette smoking was significantly associated with odds ratio of cataract 1.2. Cannabis use was not significantly associated with odds ratio of cataract.

	Unweighted
	95% L.B.	O.R.	95% U.B.	P value
Cannabis	0.881	0.961	1.047	0.356
Age	1.145	1.154	1.163	<0.001
Current smoke	1.067	1.202	1.355	0.003
Weighted
Cannabis	0.886	0.966	1.053	0.429
Age	1.144	1.153	1.162	<0.001
Current smoke	1.087	1.225	1.381	0.001

Discussion

Inhaling cannabis smoke is injurious to the eye, but in the case of cataract is different than inhaled tobacco smoke eye damage. Cannabis accelerates cataract development but does not increase risk of cataract. Cigarette smoking increases risk of cataract but does not significantly accelerate cataract formation. Apparently, remote use of cannabis leads to development of cataract earlier, whereas current tobacco use increases the risk of cataract. The situation resembles breast cancer and hormone replacement therapy (HRT). Women on HRT had earlier age at breast cancer diagnosis, yet the relative risk of breast cancer was significantly increased only among current HRT users but not among past users [9].

Tobacco smoke contains high levels of toxic heavy metals including cadmium, lead, and copper, which accumulate in the lens and contribute to cataract development [10]. The same heavy metals contaminate cannabis, limiting its pharmacologic use [11].

Pesticides are another toxic component of cannabis. Cannabis is susceptible to pests, fungi, and bacterial infections, just like other plants. Growers are more likely to utilize plant growth stimulators and pesticides to boost and speed cannabis production because of its growing popularity, particularly in countries and jurisdictions where cannabis is now legal for both medicinal and recreational purposes. But pesticide use, even on legal cannabis crops, is not being monitored, and there is a paucity of knowledge about how pesticides that have been pyrolyzed in cannabis harm the user. Few studies have attempted to bridge the gap between observed residue levels and pesticide internal dosages resulting from the use of cannabis. There are currently no approved or confirmed procedures for testing cannabis for pesticides, and there is a scarcity of information available on the subject [12].

Pesticides are implicated in eye problems. Multiple animal species have shown ocular toxicity from pesticide exposure and reveal a dose-response relationship. Pesticides have pathological effects on the conjunctiva, cornea, lens, retina, and optic nerve [13].

A weakness in our study is our inability to identify cataract type. Smoking cigarettes has a 3-fold increase on the risk for nuclear cataract development, as noted above, and some effect on posterior subcapsular cataract, but little or no association with cortical cataract [3]. UK Biobank does not characterize cataracts by type.

Like tobacco smoke, cannabis smoke contains thousands of organic and inorganic chemical compounds. Cannabis tar is chemically similar to tar found in tobacco smoke, and over fifty known carcinogens have been identified in cannabis smoke, including nitrosamines, reactive aldehydes, and polycyclic hydrocarbons [14]. Thus, the association of cannabis with cataract that we report here is not entirely surprising. Further studies are warranted.