Oral Alcohol Administration Disturbs Tear Film and Ocular Surface 2012.6 초독회 Oral Alcohol Administration Disturbs Tear Film and Ocular Surface Ophthalmology 2012;119:965–971 R4 이민규/Pf.정성근

Introduction Dry eye syndrome is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface Osmolarity reflect the balance of the input and output of tear dynamics. the most effective single measure of dry eye syndrome Alcohol is reportedly excreted through breath, sweat, and urine Whether oral alcohol consumption disturbs the tear film and ocular surface in humans and whether this model can serve as a tear lipid layer-deficient dry eye model. 삼투질농도 단위 용매에 녹아있는 용질의 입자수

Patients and Methods 20 healthy male volunteers 20~25 years of age. normal BMI : 20~25 kg/m2. neither medication nor eye drops. Exclusion Criteria : Hx. of liver disease or ophthalmic surgery, Dry eye Sx. within the previous 6 months -> randomly divided into 2 groups : the alcohol group(10) and the control group(10)

TBUT : Tear film break-up time Soju, 19.5% ethanol (0.75 g/kg) Sleep s wash up s eye drop PM 6 AM 12 AM 6 AM 8 PM 8 Tear osmolarity Subjective symptoms Schirmer’s test TBUT fluorescein staining Corneal sensitivity Tear osmolarity Subjective symptoms Schirmer’s test TBUT fluorescein staining Corneal sensitivity Tear osmolarity Subjective symptoms Schirmer’s test TBUT fluorescein staining Corneal sensitivity Tear & serum ethanol Tear osmolarity Subjective symptoms Schirmer’s test TBUT fluorescein staining Corneal sensitivity Tear & serum ethanol TBUT : Tear film break-up time

Tear Osmolarity Measurement A microcapillary glass tube (Marienfeld, Germany) - on the lower outer conjunctival sac - To avoid reflex tearing, asked to gaze supranasally. A total of 30㎕ of tear samples - centrifugation at 3000 rpm for 3 min, supernatants were obtained. - stored at -80°C - a Multi-OSMETTE 2430 (Precision Systems, Inc., Natick, MA)

Tear and Serum Ethanol Concentration - Ethanol assay kit (BioVision, Mountain View, CA) Serum - isolated after centrifugation at 3000rpm for 5 minutes. - COBAS Integra 800 (Roche, Berlin, Germany) for the diagnostic reagent (EtOH2; Roche, Berlin, Germany)

Subjective Symptoms Visual Analog Pain Scale (VAS) - The scale range : 0 (absence of pain) ~ 10 (maximal pain).

Schirmer’s Tear Secretion Test Represents the basal tear secretion of subjects Topical anesthesia using 0.5% proparacaine hydrochloride (Alcaine; Alcon, Fort Worth, TX) was instilled into the conjunctival sac residual tears were removed using a cotton swab. Filter papers (Color Bar; EagleVision, Memphis, TN) - in the lateral canthus for 5 minutes

Fluorescein Staining corneal punctuate erosion staining - recorded using a standardized grading system - 0 to 3 for each of the 5 areas

Measurement of Corneal Sensitivity Whether alcohol drinking can induce corneal hypesthesia a Cochet-Bonnet esthesiometer (Luneau, France) - Apply the tip of the nylon filament perpendicularly to the surface of the central cornea - The length of the fiber was decreased gradually until a blink reflex was observed. The length was recorded. 촉각계

Statistical Analyses Wilcoxon signed-rank test & Mann–Whitney U test : compare tear film & ocular surface changes Repeated-measures analysis of variance (ANOVA) : assess the impact of orally administrated alcohol on tear film & ocular surface over time

Results

Tear and Serum Ethanol Concentration concentration of ethanol in tears seemed to be approximately half that in serum

Tear Osmolarity

Tear Film Break-up Time

Fluorescence Staining Visual Analog Pain Scale Fluorescence Staining

No significant change was shown in either corneal sensitivity or Schirmer’s test results in either group

Discussion Hyperosmolarity has been suggested to be the primary causative mechanism in dry eye syndrome Mechanisms for ethanol in tears causing a dry tear film & ocular surface 1. act as a hyperosmolar agent 2. act as an organic solvent for the lipid layer 3. disturb cytokine production through various pathways, such as the thromboxane pathway ocular surface is in contact with open air, whereas the blood circuit is a closed loop. Alcohol in tears may evaporate because alcohol is volatile serum alcohol concentrations were measured using an automatic machine, and ethanol concentrations in tears were determined using an ethanol assay kit. -> Although the alcohol concentrations in tears were low, they could induce cellular toxicity

Orally administered alcohol was found in tears. Ethanol concentrations in tears were half those in serum Tear film was unstable to the next morning, when alcohol in the blood was not detected in this study : Alcohol drinking reduces dopamine levels in the CNS -> alter the blinking pattern that can contribute to tear film unstability -> Reduced blinking rate may aggravate the evaporation of tear film Corneal erosion can be caused by tear depletion -> inflammation. Ocular inflammation aggravates dry eye symptoms and increases tear osmolarity, which creates a vicious cycle Schirmer’s tear test and corneal sensitivity showed no significant changes in either group. -> no effect of alcohol administration on tear secretion

Limitation - small sample size - fixed dose of ethanol (0.75 g/kg) : dose–response relationship was not evaluated Oral alcohol administration induced transient dry eye syndrome in healthy individuals. -> Alcohol consumption may aggravate symptoms and signs of dry eye syndrome Can serve as a tear lipid layer-deficient dry eye model