Download Macular Pigment Density in patients with Diabetes compared with

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. Name of the candidate: Dr.Joel Antony Kavalakatt
2. Name of the institution: St.John’s Medical College
John nagar
Bangalore-560034
3. Course: M.S. Ophthalmology
4. Date of admission to the Course:25-04-2012
5. Title of the topic: ”Macular Pigment Density in patients with Diabetes
compared with normative data obtained for a control group”
6. GUIDE:
Dr. MARY VARGHESE
RETINA CONSULTANT SERVICES
ASSOCIATE PROFESSOR
DEPARTMENT OF OPHTHALMOLOGY
7. Brief Resume of intended work:
INTRODUCTION:
The 3 carotenoids lutein, zeaxanthin and meso-zeaxanthin, which account for the 'yellow spot' at
the macula are referred to as macular pigment(MP) , with concentrations that peak at the center
of the fovea. The highest levels of macular pigment in the human body are measured in Henle’s
fibers at the fovea and in the inner nuclear layer in the perifoveal area. Macular carotenoids are
powerful antioxidants which prevent free-radical reactions that can damage cellular function.
MP absorbs light in the harmful short-wave end of the spectrum and dissipates it as heat before it
renders damage to the foveal tissue. MP is not synthesized by the human body but of entirely
dietary origin.
Hyperglycemia and oxidative stress is a major cause in pathophysiology of diabetic retinopathy.
An experimental study has shown decreased oxidative damage post carotenoid supplementation.
Various principles have been explored for measuring MP in vivo.Commonly used techniques for
measuring Macular pigment optical density (MPOD) include heterochromatic ,fundus
reflectometry (via fundus photography) and autofluorescence (AF), which are image-based
methods; and Raman spectroscopy, which is a signal-based test.
7.1NEED FOR THE STUDY:
Diabetic retinopathy is a major cause of blindness in the world.
Some studies have identified macular pigment as a potential modifiable risk factor in age-related
macular degeneration, but there are very few studies on macular pigment among diabetics and
little data in Indians.
Most of the studies have been done using the flicker photometry technique which is a
psychophysical method and studies have shown that they have poor repeatability values1,.
MPOD using single wavelength reflectometry which is an objective method of assessment is
intended to be used.
Various studies have shown that macular pigment density is a modifiable component(post
antioxidants) with resultant reduction in oxidative damage and thus may prevent the progression
of diabetic retinopathy.
7.2 REVIEW OF LITERATURE:
Lima et al found in a study of 43 patients found that Type 2 diabetic patients, with or without
retinopathy, had reduced MPOD when compared with that in non-diabetic patients.They also
found an inverse correlation between HBA1c and MPOD. MPOD was measured with a modified
confocal scanning laser ophthalmoscope and compared among groups2.
The normal value of macular pigment optical density (MPOD) in 300 adult eyes of south Indian
population was assessed by Raman et al3. The MPOD showed an increase from 20 to 39 years of
age and then a decrease. At 40 to 49 years men had higher MPOD than women and at 50-59
vice versa. This seems to be the only study done in Indian population where the author tried to
establish a normative data.
Bour et al found out that fundus photography was a feasible method of studying MPOD in
healthy Pediatric patients by comparing results with other reflectance methods4.
Davies et al found out that lens in diabetics had increased optical density using colour matching
technique5.
Thomas et al found out that reliable MPOD measurements can be made in elderly patients even
with dense cataracts by measuring MPOD before and after cataract surgery6.
Yuzuru et al found out that Cataract, especially its nuclear component, affects MPOD measured
by autofluorescence spectrometry7.
Allessandro et al found out that there was no age related decline in macular pigment density8.
Nolan et al reported an inverse association between MPOD and increasing age in ageing Irish
population9.
Sandberg et al in study of 176 patients found out that MPOD was more in men compared to
women, positively related to serum lutein and inversely related to serum cholestetrol10.
Hammond et al found an inverse relationship between body fat content and MPOD11.
Studies have found slightly lower MPOD in former and current smokers than in persons who
never smoked. Smoking and body mass index showed moderately inverse associations. Martha et
al found that people on lutein supplementation had significantly higher MPOD12.
Kowluru et al. demonstrated that zeaxanthin supplementation in diabetic rats significantly
inhibited diabetes-induced retinal oxidative damage and elevation in vascular endothelial growth
factor and adhesion molecules, which play important roles in the pathogenesis of diabetic
retinopathy13.
The LUXEA study (Lutein Xanthophyll Eye Accumulation), a double blind, randomized,
controlled trial, showed after supplementation with Lutein(L), Zanthophyll(Z), or both MPOD
only increased by 15% on supplementation with L or L and Z14.
7.3 OBJECTIVES OF THE STUDY:
Comparison of MPOD in patients with diabetes with or without diabetic retinopathy(DR) and
healthy controls.
8. MATERIALS AND METHODS:
Study design- This will be a prospective cross sectional comparative study design.
Source of data-Control group: : The control group will be drawn from patients attending the
ophthalmology department who do not have diabetes or other retinal disorders.
Subjects:
The subjects will be enrolled from among diabetic patients who attend the Ophthalmology outpatient clinic of SJMCH.
Sample size: 120 (30 in diabetic patients with DR)
(30 in diabetic patients without DR)
(60 controls for each) based on numbers attending opd.
Inclusion Criteria:
-Patients with an established diagnosis of type 2 diabetes
- with mild and moderate DR.
- without DR
Exclusion Criteria
- Patients with corneal opacity.
- Patients with more than Grade 2 nuclear sclerosis
- Patients with severe non proliferative and proliferative DR
- Patients with macular edema, Age related macular degeneration.
- Patients with previous ocular surgery /trauma/ previous macular laser
- Refusal to give consent for Fundus photography
8.2 Method of collection of data:
Patients with diabetes attending OPD of St.Johns Hospital Bangalore and referred cases for
ophthalmic evaluation having diabetes from September 2012 to August 2014.
A detailed history including demographics, ocular disease, past medical illness(duration of
diabetes) drug history and personal history( esp smoking history in terms of pack years) will be
taken.
Ophthalmic examination will include
-Best corrected visual acuity (BCVA) assessed using illuminated ETDRS Chart and scored with
Log MAR Scale.
-Near vision with Times New Roman chart.
-Colour vision using Ishihara’s chart.
Post dilatationSlit lamp examination will be used to assess the type and the severity of the anterior segment
lens opacities in each eye classified as LOCS classification.
Slit lamp biomicroscopy(90/78d lens) and indirect ophthalmoscopy to assess diabetic
retinopathy status.
Fundus photography
All patients after adequate dilatation will be positioned in front of the fundus camera and
instructed to maintain steady fixation at the red fixation LED and fundus image will be captured
in MPOD mode. MPOD will be measured by fundus photography using a Visucam 500 (Carl
Zeiss) which uses single wavelength reflectometry principle . Three measurements will be
obtained at the same sitting.
HBA1c and lipid levels of all patients will be acquired from records, this being a standard
investigation in all diabetics of St. Johns Medical College.
BMI will be measured in terms of weight in kilograms by height in metre2 and classified into
~19:underweight,19-25:ideal,25-30 overweight,~30:obese,~35:severely obese,~40:morbid
obesity,~50:super obese.
After inclusion, the patients will be divided into three groups.
Group 1 - Nondiabetic patients
Group 2 - Diabetic patients without clinical evidence of retinopathy
Group 3 - Diabetic patients with mild to moderate nonproliferative diabetic retinopathy.
Descriptive and inferential statistics will be done using SPSS version 16. P<0.5 is taken as
significant. ANOVA will be used for calculation.
LIST OF REFERENCES
1de Kinkelder R, van der Veen R L P, Verbaak F D, Faber D J, van Leeuwen, Berendschot T T J
Macular pigment optical density measurements: evaluation of a device using heterochromatic
flicker photometryEye (2011) 25, 105-112doi:10.1038/eye.2010.164; published online 5
November 2010
2. Lima VC, Rosen RB, Maia M, Prata TS, Dorairaj S, Farah ME et al. Macular pigment optical
density measured by dual-wavelength autofluorescence imaging in diabetic and nondiabetic
patients: a comparative study . Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5840-5. Epub 2010
May 26.
3. Raman R, Rajan R, Biswas S, Vaitheeswaran K, Sharma T. Macular pigment optical density
in a South Indian population. Invest Ophthalmol Vis Sci. 2011 Oct 7;52(11):7910-6. doi:
10.1167/iovs.11-7636. Print 2011.
4. Bour LO J,Koo L,Delori FC, Apkarian Patricia and Fulton BA. Fundus Photography for
Measurement of MacularPigment Density Distribution in Children (Invest OphthalmolVis Sci.
2002;43:1450–1455.
5 Davies N P and Morland A B .Color Matching in Diabetes: Optical Density of the Crystalline
Lens and Macular Pigments (Invest Ophthalmol Vis Sci. 2002;43:281–289).
6. Thomas A. Ciulla, Billy R. Hammond, Jr, Chi Wah Yung, and Linda M. Pratt Macular
Pigment Optical Density before and after Cataract Extraction(Invest Ophthalmol Vis Sci.
2001;42:1338–1341)
7 Sasamoto A, Gomi F,Sawa M, Sakaguchi H, Tsujikawa M and Nishida K. Effect of Cataract in
Evaluation of Macular Pigment Optical Density by Autofluorescence Spectrometry (Invest
Ophthalmol Vis Sci. 2011;52:927–932) DOI:10.1167/iovs.10-5664.
8. Iannaccone A,1 Marco Mura, Kevin T. Gallaher, Elizabeth J. Johnson,William Andrew Todd,
Kenyon et al. ABC StudyMacular Pigment Optical Density in the Elderly: Findings in a Large
Biracial Midsouth Population Sample (Invest Ophthalmol Vis Sci. 2007;48:1458–1465)
DOI:10.1167/iovs.06-0438.
9. . Nolan JM, Kenny R, O'Regan C, Cronin H, Loughman J, Connolly EE et al.Macular pigment
optical density in an ageing Irish population: The Irish Longitudinal Study on Ageing S.
Ophthalmic Res. 2010;44(2):131-9. Epub 2010 Jun 2.
10 Sandberg M A, Johnson J E and Berson E.The Relationship of Macular Pigment Optical
Density to Serum Lutein in Retinitis Pigmentosa (Invest Ophthalmol VisSci. 2010;51:1086–
1091) DOI:10.1167/iovs.09-3396.
11 Hammond BR Jr, Ciulla TA, Snodderly DM. Macular pigment density is reduced in obese
subjects. Invest Ophthalmol Vis Sci.2002;43:47–50.
12. Martha Dietzel, Meike Zeimer, Britta Heimes, Birte Claes, Daniel Pauleikhoff and HansWerner Hense. Determinants of Macular Pigment Optical Density and Its Relation to AgeRelated Maculopathy: Results from the Muenster Aging and Retina Study (MARS) (Invest
Ophthalmol Vis Sci. 2011;52:3452–3457) DOI:10.1167/iovs.10-6713
13 Kowluru RA, Menon B, Gierhart DL. Beneficial effect of zeaxanthinon retinal metabolic
abnormalities in diabetic rats.Invest Ophthalmol Vis Sci. 2008;49:1645–1651.
14 Schalch W, Cohn W, Barker FM et al. Xanthophyll accumulation in the human retina during
supplementation with lutein or zeaxanthin-the LUXEA (Lutein Xanthophyll Eye Accumulation)
study.Arch Biochem Biophys.2007;458:128–135.
8.3 Does the study require any investigations or interventions to be conducted on patients
or other humans or animals? If so, please specify:
The tests which have been enumerated as the part of study are well known standard commercial
tests to photograph the fundus. Images captured on the instrument for analysis,will not be
printed, and thus avoiding extra cost of printing the photos
8.4 Was Ethical Clearance obtained from your institution in case of 7.3?
9. SIGNATURE OF THE CANDIDATE:
10. REMARKS OF THE GUIDE: Diabetic retinopathy is one of the leading causes of
blindness. This study will help to establish a correlation between diabetic retinopathy and MPOD
which may help in early diagnosis of diabetic retinopathy. Macular pigment density has also
been postulated to be a modifiable risk factor of DR and thus may help in altering its course.
11. NAME AND DESIGNATION OF
11.1GUIDE: Dr. MARY VARGHESE
RETINA CONSULTANT SERVICES
ASSOCIATE PROFESSOR
DEPARTMENT OF OPHTHALMOLOGY
11.2 SIGNATURE
11.3 HEAD OF THE DEPARTMENT: DR.REJI KOSHY THOMAS
PROFESSOR
DEPARTMENT OF OPHTHALMOLOGY
11.4 SIGNATURE:
11.5 REMARKS OF THE CHAIRMAN AND PRINCIPAL:
11.6 SIGNATURE: