The efficacy of oral Zinc supplement in young adult patients of dry eye disease associated with acne vulgaris- A Randomized controlled study

Dry eye is an ocular surface disease that is characterized by symptoms including irritation and discomfort of the ocular surface caused by abnormal tear film and ocular surface inflammation. Tear film hyperosmolarity, increased ocular surface staining, ocular surface remodeling and increased inflammation have all been observed in the pathology of dry eye syndromes. Oxidative stress has been reported as one of the mechanisms in dry eyes and normally plays a physiologic role in cell signaling. Excessive oxidative stress damages DNA, RNA, or cell proteins, causing cell death and inducing inflammation.[Dry eye is an ocular surface disease that is characterized by symptoms including irritation and discomfort of the ocular surface caused by abnormal tear film and ocular surface inflammation. Tear film hyperosmolarity, increased ocular surface staining, ocular surface remodeling and increased inflammation have all been observed in the pathology of dry eye syndromes. Oxidative stress has been reported as one of the mechanisms in dry eyes and normally plays a physiologic role in cell signaling. Excessive oxidative stress damages DNA, RNA, or cell proteins, causing cell death and inducing inflammation.

Acne vulgaris is a disease of sebaceous gland and Mebomian gland is a modified sebaceous gland. Androgens represent the most important of all hormones regulating sebum production. As of puberty, androgens stimulate sebum production and acne formation in both sexes.[2]

Zinc is essential for the maintenance of the corneal and conjunctival epithelium. Zn also functions as a modulator of the immune response through its availability. Chronic zinc deficiency increases immune dysfunctions, increased oxidative stress, increased generation of inflammatory cytokines, ocular surface inflammation and delayed wound healing.[3] Zinc also suppresses the proliferation of androgen receptor (AR) and functioned as a negative growth regulator for the AR.

Role of Zinc

1.    Zinc (Zn) is an essential trace element for humans and it is the second most abundant trace metal in humans after iron.

2.    Immune modulators

3.    Anti-inflammatory property

4.    Anti-oxidant property

5.    Healing property of cells epithelium

6.    Anti-androgenic property

SAMPLE SELECTION CRITERIA

Inclusion criteria

All young adult patients [18 years to 30 years], presented with dry eye disease and also having concurrent Acne vulgaris and providing written consent for voluntary participation would be recruited for this study.

Exclusion criteria

A detailed history and clinical examination would be conducted to exclude the subjects with any known systemic illnesses like diabetes mellitus, thyroid disorders and auto-immune disorders. Subjects with history of smoking, alcohol consumption, or any other drugs like isotretonion, anti-histaminic, anti-cancer and beta-blockers would be excluded.  Subjects with Computer work or mobile use of more than four hours in a day would also be excluded from the study.

 FLOW OF THE STUDY

1. After institute ethical clearance, patients fulfilling the inclusion criteria will be selected.

2. Informed and written consent will be taken

3.  After Randomization:

 Method of Randomization

We will distribute the patients into two groups randomly.

·         Group I (Standard Treatment): Eye drop Carboxymethyly cellulose 0.5%, 1 drop 4-6 times a day with anti acne medications

·         Group II (Intervention Group I):  Eye drop Carboxymethyly cellulose 0.5%, 1 drop 4-6 times a day plus oral Zinc(50mg) 1 tablet twice daily for 3 months along with anti acne medications.

5. Blinding

The study will be triple blinded. The patient, surgeon, the data collector, as well as data analyzer will be blinded in the study. The surgery will be performed by a single surgeon i.e Principal Investigator, who will also be responsible for data collection.

The nursing officer will load the 3mL syringe with the solution as per the randomization sequence and covered by an opaque surgical tape ensuring triple blinding i.e blinding of the patient, surgeon, data collector, and data analyzer.

6.  Sample size-  60

This would use a convenience sample with defined inclusion and exclusion criteria for this study.

1.    Ophthalmic examination:

All patients will undergo visual acuity, intraocular pressure, colour vision, fundus examination, Schirmer I & II, TBUT, TFH and corneal fluorescin staining score [FSS score] to see ocular surface changes. Longer TBUT represents the stable tear film and shorter TBUT is considered as the unstable tear film. FSS is defined as the degree of punctate keratitis and higher score is considered as more severe FSS. Eyelid margin hyperemia indicates the inflammation of eyelid and higher score represents the inflammation of eyelid. Tear secretion will be measured using the Schirmer strip test with (II) and without anesthesia (I). A fine strip paper was placed inside the lower conjunctival sac and the wet part will be measured. A modified standardized patient evaluation of eye dryness (SPEED) questionnaire will be used to assess the frequency and severity of each symptom, including dryness, foreign body sensation (FBS), coldness, eye fatigue, pain, and photophobia for frequency of symptoms. The SPEED questionnaire was scored for both frequency of symptoms (0 = no symptoms, 1 = sometimes, 2 = often, and 3 = constant) and severity of symptom/impact on daily life (0 = no symptoms, 1 = tolerable but not uncomfortable, 2 = uncomfortable but does not interfere with my day, 3 = bothersome and interferes with my day, and 4 = intolerable and unable to perform my daily tasks).

Visual analogue pain scale (VAS) will be used to asses to measure ocular pain intensity [where 0 = no discomfort and 10 = maximal discomfort]. The survey will be conducted using the ocular surface disease index (OSDI) questionnaire. OSDI was calculated after patient OSDI questionnaire completion for measuring dry eye symptoms severity. OSDI is scored on a scale of 0–100 with greater scores representing greater disability.

 9.  Follow-up will be done on second week, fourth week and after second & third months.

10. Review of data and data analysis

11. Result calculation