A Comparative Clinical Study of Ocular Surface Disorders in Diabetic and Non-Diabetic Persons

A Comparative Clinical Study of Ocular Surface Disorders in Diabetic and Non-Diabetic Persons

BY

Dr. SHEBA SINGH

Synopsis For Registration of subject for dissertation

to

Rajiv Gandhi University of Health ScienceS

Karnataka, Bangalore

In Partial Fulfillment of Regulationsfor the award of

Masters Degree in OPHTHALMOLOGY

Department of OPHTHALMOLOGY

M.S. RAMAIAH MEDICAL COLLEGE , BANGALORE-560007

Rajiv Gandhi University of Health ScienceS

Karnataka, Bangalore

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE CANDIDATE AND ADDRESS (in block letters)

1. NAME OF THE INSTITUTION

1. COURSE OF STUDY AND SUBJECT

1. DATE OF ADMISSION TO THE COURSE

1. TITLE OF THE TOPIC

1. BRIEF RESUME OF THE INTENDED WORK

6.1 NEED FOR STUDY

• It is well known that diabetic individuals are vulnerable to many sight threatening disorders, the most widely known of which is diabetic retinopathy. However, diabetic patients have also been found to have symptoms indicative of dry eye .These symptoms include foreign body sensation, itching, blurred vision, and photophobia. There is, thus, an implication of a correlation between diabetes mellitus and tear film abnormalities. Therefore, a study of the pre-corneal tear film in diabetic patients is important in order to obtain a better understanding of the underlying mechanisms of dry eye.
• This study aims to evaluate the correlation between diabetes mellitus and abnormalities of the pre-corneal tear film by comparing the tear film in diabetics and non diabetics.
• Ocular surface disease causes increased morbidity in Diabetics thus leading to an increased economic burden on the population. Hence it is important to investigate the damage of ocular surface caused by diabetes mellitus which in turn would provide the guidelines for an appropriate treatment protocol.
• REVIEW OF LITERATURE

•Diabetes Mellitus is one of the most common diseases worldwide

•Diabetes mellitus can lead to many complications in the eye such as diabetic retinopathy, cataract, refractive errors, diabetic keratopathy and ocular surface disorders.1

•The ocular surface consists of the tear film, the epithelia of the cornea and conjunctiva. The diseases impairing the structure and function of ocular surface are called ocular surface diseases2.

•Diabetic patients frequently complain of typical dry eye symptoms, such as burning and foreign body sensation or sand gritty feeling.3

•In more severe cases, the combination with diabetic neurotrophic keratopathy would help to explain the absence of symptoms or apparent tolerance to dryness and epitheliopathy4

•In initial and mild cases, transient visual acuity reduction due to tear film instability may be also present4

•The most frequent and measurable clinical findings are reduced tear secretion, tear film instability, higher grade of conjunctival squamous metaplasia, lower goblet cell density and reduced corneal sensation, but diabetes mellitus also reduces the lipid layer of the tear film5

6.3 OBJECTIVES OF THE STUDY

• To document the damage of ocular surface in both groups.
• To study the magnitude of tear film dysfunction.
• To compare results between both groups.

1. MATERIALS AND METHODS

7.1 SOURCE OF DATA:

All Patients attending OPD at M.S Ramaiah Medical College and Teaching Hospital during the period October 2013 to May 2015.

7.2 METHOD OF COLLECTION OF DATA

This study will be conducted prospectively to investigate the relationship between diabetes mellitus and tear film abnormalities by enrolling normal persons and diabetics after taking due consent. They will be assigned to age and gender matched groups

A detailed history, general physical examination, detailed ophthalmologic examination and relevant investigations as mentioned below will be done for each patient enrolled in the study.

The Ocular surface will be studied by the following tests :

(1)The Schirmer test

(2)Lissamine Green staining test

(3)Tear film Break Up Time ( BUT)

(4)Impression cytology of the conjunctival surface

Schirmer’s test

Most commonly used test and measures the basal secretion in an eye which is anaesthetized to eliminate reflex tearing. A 5 mm x 30mm filter paper strip is folded 5 mm from the end. The folded end is placed gently over the lower palpebral conjunctiva at its lateral one-third. The patient keeps the eye open and looks upward. Blinking is permissible. 6

After 5 min, the strips are removed and the amount of the wetting is measured from the folded end of the strip. It is commonly accepted that <5 mm of wetting in 5 minutes is a sign of dry eye6.

Lissamine Green staining test

Lissamine Greenis used to indirectly ascertain the presence of reduced tear volume by the detection of damaged epithelial cells. Lissamine Greendye is instilled in each conjunctival sac, Dead or dying cells of the corneal epithelium take up Lissamine Greenin the exposed interpalpebral area6.

A positive test will show a triangular stipple staining of the nasal and temporal bulbar conjunctiva in the inter-palpebral area.

Tear film Break Up Time (BUT)

Sterile Fluorescein 2% dye is instilled into the lower fornix of the eye and the patient is asked to blink. The cornea is scanned under low slit lamp magnification using blue cobalt filtered light. The patient is instructed to blink once or twice and then stare straight ahead without blinking.6

The time of appearance of the first dry spot formation from the last blink measures the tear film BUT. A BUT of less than 10 seconds is abnormal.6

Impression cytology

This is a non invasive test. Conjunctival impressions are obtained using millipore cellulose acetate paper strips (3 x 10 mm size with a diagonal edge) under topical anaesthesia. A speculum is inserted and the lacrimal lake at the inner canthus and dried with a swab. A blunt smooth edged forceps is used to grasp the filter paper strip at one end and the paper is applied on the temporal bulbar conjunctiva. A smooth glass rod is used to press the paper gently. The paper strip is then removed with a peeling motion after 2-3 seconds. The strips are dropped into a bottle containing fixative solution, (ethyl alcohol, formaldehyde and glacial acetic acid in 20:1:1 volume ratio).6

After staining the slides are examined under the light microscope. Impression cytology specimens are graded as normal or abnormal based on epithelial cell morphology and goblet cell density.

Rationale for Sample Size : 104 (52 in each group)

A study by Ortiz et al has observed that the area and density of goblet cells was area values ​​and average density of goblet cells were 580.46 ± 370μm2in Diabetes Mellitus and 235.58 ± 109.03 cél.goblet / mm2 in Non Diabetics.

In the present study expecting similar results with 95% confidence, 80% power and considering minimum difference between the groups of 150μm2 as clinically significant.

The study requires minimum of 52 subjects in each group.

Statistical methods : Descriptive statistics of area and density of goblet cells and tear film will be analysed and presented in terms of mean and standard deviation.

Independent T test would be used to compare the goblet cells and tear films between the 2 groups.

Inclusion Criteria:

(1)Known diabetic patients (52) with h/o DM for more than 5yrs

(2)Non diabetic patients as control group (52)

Exclusion Criteria:

• Patients on any drug treatment , Topical (Betaxolol, Olapatidine, Naphazoline, Miotics or Mydriatics , Ketorolac) or Systemic (Beta blockers anti-hypertensives, anti-histaminics , Anti-psycotics) which produces dry eye.5
• Patient having under gone any ocular surgery (Cataract , Refractive surgery, pterygium excision)5
• Patients with any other ocular disorder known to produce dry eye (Allergic eye disease, Vit A deficiency, Post Steven Johnsons, Vernal keratoconjuctivitis, Post ocular chemical burns) .
• Systemic diseases associated with dry eye other than diabetes mellitus (RA , SLE , CVD, Thyroid disordes)

PATIENT PROFORMA

COMPARATIVE STUDY OF OCULAR SURFACE DISORDERS

IN DIABETIC AND NON-DIABETIC PERSONS

S. No HOSPITAL NUMBER DATE

NAME A/S OCCUPATION

Past history

Diabetic status NIDDM/ IDDM

Duration of DM

Blood Sugar level

HbA1C

Diabetes treatment

Personal history

Tobacco/ Alcohol/ Smoking/ Computer use/ others

Ophthalmic Examination

1. Vision RELE

1. Ocular examination

RELE

RE LE

Slit lamp Examination

RE LE

Syringing

Corneal sensation

Refraction

RE LE

Fl stain

Lissamine Green staining test

Schirmer’s test

Tear break up time

Impression cytology

The data collected will be statistically analyzed using T tests

7.3D OES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? (IF SO DESCRIBE BRIEFLY).

The study will involve the following non-invasive investigations on humans :

-Best Corrected Visual Acuity done with Snellen's chart.

-Slit lamp bio-microscopy and dilated fundus examination

-Fluorescein stain

-Lissamine Green staining test

-Schirmer’s test

-Tear Break Up Time

-Impression cytology

7.4HAS THE ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
YES

LIST OF REFERENCES

1. 5. Ronaldo M, Zierhut M .The ocular surface and tear film and their dysfunction in dry eye disease. Surv ophthalmol .2001;45(Suppl 2 ):S203-10.
2. 6. Abdel-Khaled LMR. Morphological changes in the human conjunctival epithelium in KCS. Br J ophthalmol 1978; 62:80-83.
3. 20. Bron Aj. Eyelids, Conjunctiva and Lacrimal apparatus. Wolff’s Anatomy of the eye and Orbit .London Chapman &Hall Mdical, 1997: pp 30-84.
4. 20. Bron Aj. Eyelids, Conjunctiva and Lacrimal apparatus. Wolff’s Anatomy of the eye and Orbit .London Chapman &Hall Mdical, 1997: pp 30-84.
5. 12. Seifart U, Stremp . The dry eye and diabetes mellitus Ophthalmology. 1994 Apr; 91(2):235-9.
6. Labbé A . Ocular surface investigations in dry eye . J Fr Ophtalmol. 2007 Jan; 30(1):76-97

1. SIGNATURE OF THE CANDIDATE

Dr. SHEBA SINGH

10.REMARKS OF THE GUIDE:

Dry eye is a common problem after 40 years of age and the incidence is more common in Diabetics. In severe cases it can even be vision threatening in it’s presentation. Hence this is an appropriate and needful study to help timely treatment and better yet prevent the same.

11.NAME AND DESIGNATION OF THE

11.1GUIDE: Dr. MALAVIKA. KRISHNASWAMY

PROFESSOR AND HEAD OF DEPARTMENT

DEPARTMENT OF OPHTHALMOLOGY

M.S. RAMAIAH MEDICAL COLLEGE,

BANGALORE – 560054

11.2SIGNATURE

11.3CO-GUIDE IF ANY : NONE

11.4SIGNATURE

11.5HEAD OF THE DEPARTMENT :

Dr.MALAVIKA. KRISHNASWAMY

PROFESSOR AND HEAD OF DEPARTMENT

DEPARTMENT OF OPHTHALMOLOGY

M.S. RAMAIAH MEDICAL COLLEGE,

BANGALORE – 560054

11.6SIGNATURE

12.1REMARKS OF THE CHAIRMAN AND PRINCIPAL

12.2SIGNATURE

Dr. A.C. ASHOK

Ph.no: 080-23605190

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