|Year : 2022 | Volume
| Issue : 2 | Page : 166-170
Dry eye disease in patients with alcohol use disorder
Lily Daniel1, Mubeen Taj2
1 Department of Ophthalmology, Karpaga Vinayaga Institute of Medical Sciences and Research Institute, Chennai, Tamil Nadu, India
2 Department of Psychiatry, ACS Medical College, Chennai, Tamil Nadu, India
|Date of Submission||09-Oct-2021|
|Date of Decision||08-Feb-2022|
|Date of Acceptance||09-Feb-2022|
|Date of Web Publication||30-Jun-2022|
No. 211, Annammal Road, Thiruverkadu Co Operative Nagar, Thiruverkadu, Chennai - 600 077, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aim: To study the symptoms and signs of dry eye disease (DED) among individuals with alcohol use disorder (AUD). Subjects and Methods: This case-control study was conducted in the out patient Department of Ophthalmology in a medical college in South India over a period of twelve months, on a total of 172 eyes of 86 participants with 43 cases of alcohol use disorder (AUD) and 43 controls. The cases of AUD were 18 years or older and fulfilled the criteria of diagnosis of AUD as per the Diagnostic and Statistical Manual of Mental Disorders –5th edition (DSM-5). The controls were matched for age and sex with the cases. All cases and controls were subjected to the Ocular Surface Disease Index® (OSDI) questionnaire and Schirmer's test after assessment of their best-corrected visual acuity (BCVA). The cases were further assessed for tear breakup time (TBUT), fluorescein staining, and rose Bengal staining using slit lamp biomicroscopy followed by fundus examination. The Chi-square test, odds ratio, 95% confidence interval were calculated using the Statistical Packages for Social Sciences (SPSS) version 20 software. A P value of <0.05 was considered significant. Results: The mean age of cases was 45+/-11 years. Cases less than 40 years showed the highest proportion (44.2%) of DED with irritation being the most common symptom (24.4%). OSDI scores showed mild type of DED in 39.5% (P < 0.0001). Schirmer's indicated dry eyes in 38.3% (P < 0.0001) with OR of 12.1 in the right eye and 13.4 in the left eye. TBUT revealed marginal grade for dry eye in 44 eyes (51.2%) and definitive dry eye in 35 eyes (40.7%) In AUD, conjunctival and corneal staining with fluorescein were seen in 46 eyes (53.5%) with interpalpebral staining in 22 eyes (25.6%), inferior staining in 14 eyes (16.3%) and a combination of interpalpebral and inferior staining in 10 eyes (11.6%). Conclusion: Alcohol has a deleterious effect on the ocular surface and gives rise to DED. This implicates the necessity of regular ophthalmic screening including staining of the ocular surface to diagnose and treat DED in people with AUD especially in the age group between 18–40 years.
Keywords: Alcohol use disorder, dry eye disease, ocular surface disease
|How to cite this article:|
Daniel L, Taj M. Dry eye disease in patients with alcohol use disorder. TNOA J Ophthalmic Sci Res 2022;60:166-70
| Introduction|| |
Tear Film and Ocular Surface Society Dry Eye Work Shop defined dry eye disease (DED) as a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles. The prevalence of dry eye varies from 7% to 54% from country to country.,, DED is common in elderly, women especially older women,, and can be associated with glaucoma. Imbalance in epidermal growth factors, vitamin A, fibronectin, and neurotrophic actor growth factor may contribute to the pathogenesis of DED. Causes of DED include alcohol consumption, smoking, sleep disturbances, contact lens, and cosmetics. DED, needless to say, impairs the quality of life.
A meta-analysis on alcohol consumption and dry eye disease revealed the many controversies in the association of alcohol and DED though the study itself concluded that alcohol consumption may be a significant risk factor for DED. Literature review revealed the paucity of studies that looked into DED in alcohol use disorder (AUD) in the Indian population. In a study by Sahai et al. on a hospital based population in India, there has been no mention of alcohol as a risk factor for DED.
| Objectives|| |
To study the symptoms and signs of DED in patients diagnosed with AUD as per DSM- 5 criteria.
| Subjects and Methods|| |
This was a case-control study, conducted in the outpatient department of Ophthalmology of a medical college in Chennai, South India between November 2019 and October 2020. This medical college caters to the needs of a semi-urban population. The study adhered to the tenets of Declaration of Helsinki and ethics clearance from the Institutional Ethics committee was obtained. Written consent was obtained from each participant (both cases and controls).
All male patients above the age of 18 years, who attended the outpatient department of Ophthalmology during the study period fulfilling the diagnosis of AUD based on the criteria of DSM–5 were included as cases. The DSM-5 provides the standard language by which clinicians communicate about mental disorders. The manual brought alcohol abuse and alcohol dependence to a single category of alcohol use disorder. A diagnosis of AUD is made when a patient with alcohol abuse manifests two or more of the 11 criteria listed in the manual. The criteria are based on the extent of their alcohol dependence and not on the quantity of alcohol consumed or duration of the disorder.
The patients' attendants, who were free from any ophthalmic disorders and with no history of alcohol abuse, were included as controls. The controls were age and gender matched with cases. Patients who were under alcohol influence during the time of clinical examination, those who had a history of systemic illness that could cause dryness, and lid disorders such as blepharitis which could lead to DED were excluded from the study. A total of 86 participants with 43 cases and 43 controls were included as study participants. The eyes of each patient were studied.
All cases and controls were tested for their best corrected visual acuity (BCVA) and then subjected to Ocular Surface Disease Index questionnaire® (OSDI, Allergan Inc, California, USA) explained in vernacular followed by Schirmer's test. The cases were further assessed for TBUT, fluorescein staining, and rose Bengal staining using slit lamp biomicroscopy followed by fundus examination. Those cases 40 years and above with no corneal punctate erosions underwent applanation tonometry as well. The controls however were subjected to OSDI, Schirmer's, and slit lamp examination only.
Ocular Surface Disease Index (OSDI)
OSDI questionnaire was used to assess the symptoms of DED and correlate them with the severity of DED. The questionnaire has three subscales: ocular symptoms, vision-related function, and environmental triggers. Patients were requested to rate their responses to each of the mentioned parameters on a 0-4 scale, with 0 corresponding to none of the time and four corresponding to all of the time. A final score was calculated which ranges from 0–100, with scores 1–12 representing normal, 13 – 22 representing mild, 23 – 32 representing moderate, and greater than 33 representing severe DED.
Patients were diagnosed with DED based on the presence of both symptoms and one positive sign. These patients diagnosed with DED based on OSDI were further subjected to the following tests.
Schirmer's 1 test: This test measures basic and reflex tearing. It involves measuring the wetting of a Whatman filter paper (5 mm wide and 35 mm long, graduated tear strips, Contacare Ophthalmics and Diagnostics.
Diagnostics, Vadodara, India). This test was done without anesthesia and was considered positive if the wetting of filter paper was less than 5 mm at the end of five minutes. A positive Schirmer's indicated DED due to aqueous tear deficiency.,
Tear-film breakup times (TBUT): An impregnated fluorescein strip (Fluorescein Sodium I.P -1 mg, Contacare Ophthalmics and Diagnostics, Vadodara, India) moistened with non preserved saline was placed in the lower fornix and the patient was asked to blink several times. The tear film was examined under the cobalt flue filter of the slit lamp through 10 × magnification. TBUT was measured as the interval between the last blink and the appearance of the first randomly distributed dry spot on the cornea in seconds., A TBUT of more than 10 seconds was considered as normal, 5 to 10 seconds as marginal, and less than 5 seconds as low and indicative of DED. Reduced tear break up time signified an evaporative type of dry eye.
Fluorescein staining: A normal ocular surface does not stain with fluorescein. We classified the fluorescein staining patterns of the conjunctiva and cornea according to the description by Cosar and Sridhar. The fluorescein staining patterns were examined again using a cobalt blue filter of the slit lamp through 10× magnification. Interpalpebral staining of cornea and conjunctiva and inferior corneal staining indicated DED.,,
Rose Bengal staining: An impregnated rose Bengal strip (Rose Bengal 1.5 mg, Ophtechnis Unlimited, Parwanoo, India) was placed in the lower fornix and the patient was asked to blink. The conjunctiva and corneal staining were examined with a green filter to assess the amount scored according to the Van Bijsterveld scoring system in which the ocular surface was divided into three zones, nasal conjunctival, corneal and temporal conjunctival. In each zone, a staining score in points was used. The minimum is zero andthe maximum is three for each zone. More than three was considered positive. Rose Bengal stains dead and devitalized epithelial cells,
Data analysis was done using Statistical Packages for Social Sciences (SPSS, Inc, Chicago, IL) version 20. Statistical tests like Chi-square test, odds ratio, 95% confidence interval were calculated appropriately and P value of <0.05 was considered as significant.
| Results|| |
From our study population, the majority of the cases were in the younger age group of 18-40 years (44.2%), followed by 41-50 years (37.2%), and age groups of 51-60 years and above 60 years each having 9.3% individuals [Table 1]. The mean age of the participants from the alcoholic group was 45 +/- 11 years. The most common symptom that the cases complained of was irritation in the eye (24.4%), followed by blurring of vision, redness, and congestion [Table 2]. On assessing dry eye based on OSDI score, we deduced that the cases had a greater prevalence of mild dry eye (39.5%) with OSDI score between 13-22, followed by a moderate type of dry eye (32.6%) with the OSDI score 23 – 32. 18.6% of cases had a severe dry eye with an OSDI score of more than 33. Whereas 93% of the control group had normal tear homeostasis. The presence of DED in cases based on OSDI was statistically significant P < 0.0001 [Table 3].
Whereas on assessing dry eye based on Schirmer's test, we again saw a greater proportion of cases having evidence of DED (< than 5 mm of wetting of Whatman) in either eye (37.2% in right eye and 39.5% in left eye) compared to the control group (4.7% in either eye) which was statistically significant with P < 0.0001 [Table 4]. The odds ratio (OR) of DED in individuals from the case group was (12.1 in the right eye and 13.4 in the left eye) as compared to the control group. On performing TBUT amongst the cases, we inferred 91.8% of cases had either form of DED. Most cases had the marginal dry eye of prolonged TBUT between 5 – 10 seconds (55.8% in right eye and 46.5% in left eye), followed by the definitive dry eye of fewer than 5 seconds (37.2% in right eye and 44.2% in left eye) [Table 5] In AUD, 44 eyes (53.5%) had conjunctival and corneal staining in the form of multiple punctate erosions indicative of DED. 22 eyes (25.5%) of eyes had interpalpebral staining of conjunctiva and cornea, 14 eyes (16.3%) of cases had inferior staining and 10 eyes (11.6%) had both interpalpebral and inferior staining. However, there was no superior corneal or conjunctival staining in any of the cases.
[Chart 1]. The rose Bengal staining was negative in all the cases.
| Discussion|| |
In our study, younger age group of less than 40 years of age had a greater association between AUD and DED. This is contrary to the study by Magno et al. who found no difference between the various age groups and alcohol use related dry eye. According to the meta-analysis by Yong-Sheng et al., there was no statistical difference between age and gender groups and occurrence of dry eye amongst patients with AUD. This difference could be attributed to the effect of different ethnic groups and mixed gender groups in the other studies. 24.4% of our patients with AUD had irritation as the commonest symptom in the study group. This is similar to the study conducted by Magno et al., where 30% of the patients with alcohol use disorder had symptomatic dry eye. That irritation was seen only in 24.4% of patients could be explained by the neuropathy that alcohol consumption produces, thereby reducing the symptoms appreciated by these patients. Even though peripheral neuropathy is known to occur in alcohol use, there were only two amongst the cases who had impaired corneal sensation. According to a study by Ferdinandis et al., only heavy drinkers have a greater risk of developing peripheral neuropathy due to alcohol. There has been no universally accepted definition of heavy drinking (The Blue Mountains Eye Study [BMES] 16 and Beaver Dam Eye Study [BDES] 45 defined heavy drinking as more than four drinks per day. In contrast, the Los Angeles Latino Eye Study (LALES) defined heavy drinking as more then five drinks on any day within the past year). Most of the participants with AUD said that they were mostly weekend drinkers and consumed either rum or brandy, one quarter (180 ml) or half a quarter on weekends and denied daily drinking. Only eight of them said that they consumed alcohol every day ranging from 180 ml to 360 ml per day.
The OSDI questionnaire is a validated questionnaire that is used widely to detect the symptoms of DED. Other validated questionnaires are the Women's Health Study questionnaire and the 5-item dry eye questionnaire (DEQ-5). Chatterjee et al. showed a moderate correlation between OSDI and DEQ-5 in the Indian population. While OSDI is widely used to detect symptoms of DED due to various causes, literature search did not reveal any other study that had used OSDI to detect symptoms of DED in AUD. Our case control study detected mild DED in 38.4% of eyes and moderate DED in 33.6% of eyes and severe DED in 18.6% of eyes in AUD.
The DEWS 2 workshop classified DED as aqueous deficient and evaporative types. According to DEWS 2, low blink rate is an intrinsic factor towards an evaporative type of dry eye, and vitamin A deficiency is an extrinsic factor responsible for the evaporative type of dry eye. Alcohol is known to produce both altered blink states and vitamin A deficiency. Chan et al attributed nutritional deficiencies in chronic alcoholics to the altered blink reflexes and Cadaveira et al. stated that electrolyte disturbances and an altered neurotransmitter metabolism among alcoholics may be responsible for the abnormal blink reflexes. The reduced blink rate seen in alcoholics causes evaporation of the aqueous thereby causing aqueous deficiency in the tear film. Chronic alcoholism alters the metabolism of vitamins, most commonly affected are Vitamin A, vitamin B6, and thiamine and folate. Vitamin A deficiency produces goblet cell loss which causes mucin deficiency. Deficiency of mucous layer may also produce aqueous deficiency and evaporative states., Thus alcohol consumption produces both aqueous and evaporative DED. Reduced aqueous causes increased tear osmolarity which causes the accumulation of pro-inflammatory cytokines that in turn causes increased ocular inflammation. Studies by Kim et al. have shown the presence of ethanol in tears in alcoholics.
Ethanol reduces the volume of tears causing increased tear osmolarity further triggering the expression of pro-inflammatory cytokines. Ethanol in tears produces reduced tear break up time and also reduced Shirmer's.
In accordance with these observations, our study showed the presence of aqueous deficiency by positive Schirmer's in 38.3% of cases and evaporative type of dry eye by prolonged TBUT indicative of marginal dry eye in 51.1% of cases and definitive dry eye in 40.7% of cases. Again, very few studies had looked into TBUT in AUD. Thomas et al. evaluated the ocular surface by measuring TBUT, surface staining with fluorescein, conjunctival and corneal sensitivities, and Shirmer's 2 in smokers. The smoker group was found to have lower TBUT. We could not find any study that evaluated TBUT in AUD.
Punctate erosions in the corneal epithelium result from damage to the corneal epithelium due to aqueous and mucin deficiency resulting from the evaporative type of DED. Both inferior and interpalpebral erosions staining with fluorescein are seen in DED,, The punctate staining occurs because the fluorescein dye passes through defective tight junctions between epithelial cells and stains the epithelial defect caused by epithelial shedding. In our study, the interpalpebral staining was seen in 22 eyes and inferior staining was seen in 14 eyes in AUD. Interpalpebral staining is characteristic of DED although inferior staining can also occur.,, The punctate erosions or punctate epitheliopathy of the cornea in DED results from increased tear film osmolarity and resultant inflammation. Long standing epithelial thinning can trigger the intraepithelial terminals of subbasal nerve plexus of the cornea and cause keratoneuralgia.
A total of 53.5% of patients with AUD were found to have fluorescein staining of the ocular surface. This was the major strength of our study as none of the previous studies have correlated the fluorescein staining pattern of dry eye amongst alcoholic patients. This finding could give us a crucial indication to start dry eye management even in the community, where elaborate tests for dry eye evaluation might not be available.
The limitation of our study is that we did not include women with alcohol use disorder in our study, as it is not very common for women in the semi-urban population to consume alcohol due to south Indian culture and customary beliefs. Hence we could not assess the alcohol intake and sex-specific effect on dry eye disaease outcome amongst this population. This was a case control study but the controls were not subjected to TBUT and Fluorescein staining as these were contact-induced and the patients had not consented. This was another limitation in our study. Non-contact methods of studying the tear film would have yielded more conclusive results.
| Conclusion|| |
Alcohol consumption produces an evaporative type of DED that adversely affects the ocular surface and causes tear film instability, giving rise to symptoms and signs of DED. This case control study in a semi-urban population revealed a significantly high association between DED and AUD. The findings of mild and moderate DED as per OSDI score, prolonged TBUT, and punctate fluorescein staining in the interpalpebral and inferior zones of cornea and conjunctiva are significant and are reported in only two other studies. Most of the studies have dealt with the detection of symptoms of DED only.
AUD causes a peripheral neuropathy that may impair corneal sensation causing patients to seek attention late. Once corneal punctate erosions set in and become severe, the resultant neuralgia may cause severe pain which would compound the many struggles of patients with AUD. We recommend subjecting patients with AUD, especially those who are less than 40 years of age not only to a validated questionnaire on DED but also to the study of their tear film by Schirmers's andTBUT and study of their ocular surface with fluorescein staining with slit lamp biomicroscopy to detect DED early and thereby improving their quality of life. Non-invasive study of the tear film and the ocular surface would be the future in detecting DED in AUD.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]