2. ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY

3. BY PROF. SYED IMTIAZ ALI SHAH PROFESSOR & HEAD DEPARTMENT OF OPHTHALMOLOGY CHANDKA MEDICAL COLLEGE LARKANA PAKISTAN

4. INTRODUCTION
Vitamin A, the first discovered fat soluble vitamin and chemically a retinol, is the Immediate precursor of two very important metabolites
1. Retinal and 2. Retinoic acid
Retinal is a very important component of rhodopsin which is mandatory for functioning of photoreceptors.
Retinoic acid has a vital role to play as messenger during transcription of a number of genes.

5. NATURAL AVAILABILITY
Vitamin A is present in animal source particularly in the liver, beef, chicken, eggs and whole milk.
Plants are devoid of vitamin A as such but do contain provitamin A like beta-carotene which is converted into retinol in intestinal mucosa during digestion.
Plant source include carrots, mango, orange fruits, sweet potato and spinach.

6. FUNCTIONS OF VITAMIN A
As it is important part of visual purple of both rods and cones, it serves both night and day vision. As the rods are affected first, night blindness has become a famous feature of vitamin A deficiency
It Maintains epithelia of skin and mucous membranes all over the body
Its immune strengthening function has led to the popularity of this vitamin as anti-infective.

7. FUNCTIONS OF VITAMIN A
Reproductive function includes its need in spermatogenesis and female reproductive cycle.
Skeletal development and maintenance is achieved by its need in the functioning of osteoblasts and osteoclasts.

8. DEFICIENCY STATES
Blindness occurs as a result of photoreceptor dysfunction, xerophthalmia and keratomalacia.
Increased fatigue.
Increased risk of respiratory infections
Increased risk of gastrointestinal infections

9. DEFICIENCY STATES Increased risk of infertility
Increased mortality rate particularly in children due to infectious diseases like measles
Abnormality in bone growth particularly in skull leading to compressive neuropathy including blindness due to optic nerve compression
Elevated intracranial pressure due to inadequate absorption of CSF through meninges

10. BIOAVAILABILITY
Retinol esterifies into retinyl esters and the retinyl esters of animal and plant origin are carried through micelles in the lymph to the blood and finally liver where 50 to 80% of vitamin A is stored by binding with the cellular RBP (retinol binding protein).
In the blood, vitamin A is transported in bound form with retinol binding protein (RBP) which is in turn bound to transthyretin.

11. BIOAVAILABILITY
Retinol binding protein, with normal serum levels of mcg/dl, is synthesized in the liver in presence of amino acids and zinc.
Therefore decreased levels of zinc, iron and RBP are strong reflection of vitamin A deficiency.

12. BIOAVAILABILITY
Vitamin A supplementation alone is not effective in the treatment of vitamin A deficiency states when associated iron deficiency is present. This reflects the importance of associated iron and zinc deficiency.

13. 5000 IU of Vitamin A are required by an adult per day
VITAMIN A REQUIREMENT
5000 IU of Vitamin A are required by an adult per day
Requirement is increased in sick children particularly suffering from measles

14. CAUSES OF DEFICIENCY
Decreased ingestion and absorption, increased requirement and altered metabolism are actual mechanisms operative in vitamin A deficiency.
Malnourishment particularly lack of animal protein as only 40-60% of beta-carotene from plant sources is absorbed by human body, whereas 90% of retinol and retinol esters from animal protein are absorbed by human body.

15. CAUSES OF DEFICIENCY
Patients with sprue, pancreatic insufficiency, inflammatory bowel disease, small intestinal bypass surgery and cystic fibrosis are among the causes of deficiency due to defective absorption.

16. CAUSES OF DEFICIENCY
Alcoholism causes deficiency by altering vitamin A metabolism.
Normally enzyme alcohol dehydrogenase converts retinol to retinaldehyde. Oxidation of retinaldehyde produces retinoic acid.
In alcoholism, ethanol metabolism is given priority by alcohol dehydrogenase resulting in hampered vitamin A metabolism.

17. SIGNS OF VITAMIN A DEFICIENCY REPORTED ALREADY IN LITERATURE
Bitot spots, xerophthalmia, keratomalacia, dry skin, dry hair, broken fingernails, hypertrophy of periosteal bone, mucous membrane keratinization, zinc deficiency and iron deficiency anemia are reported in literature as reflection of vitamin A deficiency.

18. BITOT SPOTS

19. XEROPHTHALMIA

20. KERATOMALACIA

21. DRY SKIN

22. DRY HAIR

23. BROKEN FINGERNAILS

24. HYPERTROPHY OF PERIOSTEAL BONE

25. SIGNS OF VITAMIN A DEFICIENCY REPORTED ALREADY IN LITERATURE
These signs develop when vitamin A levels fall in the blood as low as 0.70 umol/L. (WHO/UNICEF. Indicators for assessing vitamin A deficiency and their application in monitoring and evaluating intervention programmes. Geneva: WHO/NUT/94.1,1994.

26. NORMAL VITAMIN A LEVELS IN BLOOD
Normal range of vitamin A in adults is ug/100ml.
Normal range of vitamin A in infants is ug/100ml.
The normal range for carotene is
ug/100ml.
(Clinical Laboratory Methods: John D. Bauer, Philip G. Ackermann, Gelson Toro. Mosby, Eighth Ed. 1974, )

27. METHODS OF LABORATORY ASSESSMENT OF VITAMIN A
Serum retinol level (vitamin A level) is very costly and not available in many countries including PAKISTAN.
Serum RBP level is relatively less costly but not available in many countries including PAKISTAN.

28. METHODS OF LABORATORY ASSESSMENT OF VITAMIN A
Serum iron level
Serum zinc level (not available in many countries including PAKISTAN)
Serum albumin level
Dark adaptation threshold
LFT
X-ray of long bones to determine excessive deposition of periosteal bone.

29. METHODS OF LABORATORY ASSESSMENT OF VITAMIN A
These studies are costly, time consuming but were performed on selected patients with positive IMTIAZ SIGN.
All the patients with positive IMTIAZ SIGN had subnormal parameters for vitamin A levels in the body.

30. MATERIAL & METHODS
THE STUDY WAS CONDUCTED FROM SEPTEMBER 1999 TO SEPTEMBER 2006 AT OPHTHALMOLOGY DEPARTMENT CHANDKA MEDICAL COLLEGE AND SYED EYE CLINIC LARKANA PAKISTAN. 300 PATIENTS, 70 MALES AND 230 FEMALES WERE IDENTIFIED CLINICALLY AS CASES OF HYPOVITAMINOSIS A ON THE BASIS OF PRESENCE OF “IMTIAZ SIGN” DURING THIS PERIOD.

31. MATERIAL & METHODS
ASSOCIATED SYMPTOMS AND SIGNS OF VITAMIN A DEFICIENCY WERE NOTED. PATIENTS WERE GIVEN THERAPEUTIC DOSES OF VITAMIN A ORALLY AND IMPROVEMENT OBSERVED. PATIENTS WITH LIVER DISEASE AND MALABSORPTION SYNDROME WERE NOT INCLUDED IN THE STUDY.

32. ASSOCIATED EVIDENCE OF VITAMIN A DEFICIENCY
AGE IN YEARS
EVIDENCE
MALE
FEMALE
5-10
11-20
IRON DEFICIENCY
LOW ALBUMIN 4 9 5 8
21-30
31-40
DISTURBED LFT 2 1 3

33. ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY
IMTIAZ SIGN IS THE STAINING OF A DOT OR FEW DOTS OF CONJUNCTIVA WITH SURMA OR KAJAL.
THESE DOTS APPEAR BLACK AND ARE A CAUSE OF CONCERN FOR THE PATIENT.
THESE STAINED AREAS OF CONJUNCTIVA ARE THE EARLIEST SIGN OF VITAMIN A DEFICIENCY.

34. ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY

35. ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY
The rough areas of conjunctiva produced as a result of sub clinical deficiency of vitamin A get this natural stain of kajal or surma used for cosmetic or religious purpose.
These patients often confirm the difficulty in vision in dim light reacting to a leading question which indicates forthcoming nyctalopia.

36. ASSESSMENT OF IMTIAZ SIGN IN VITAMIN A DEFICIENCY
Administration of dietary or therapeutic supplements of vitamin A quickly resolves these stained areas and also resolves associated symptoms of vitamin A deficiency like problem in working in dim light, fatigue, recurrent respiratory infections and GIT upsets in addition to skin and hair effects.

37. TREATMENT
Treatment includes promotion of vitamin A rich diet and 2000 IU to 8000 IU daily in children and IU daily in adults
Resolution of signs and symptoms of vitamin A deficiency is also taken as a therapeutic test.

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