RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
- Name of the candidate: Dr. ShwetaSarveshPandey
- Name of the institution: St.John’s Medical College
John nagar
Bangalore-560034
3. Course: M.S. Ophthalmology
- Date of admission to the Course: 24-05-2012
5.Title of the topic--Correlation of Retinal nerve fiber layer thickness and macular thickness using optical coherence tomography with visual parameters in non glaucomatous optic neuropathy.
6. Brief Resume of intended work:
INTRODUCTION:
Optic neuropathy is a common end point finding of pathologies affecting the anterior visual pathway anywhere between the retinal ganglion cells up to the lateral geniculate body. Optic atrophy is a misnomer.1 Optic atrophy should not be considered a diagnosis; it is a pathological end point that is clinically discernible but does not imply cause.Optic neuropathy refers to damage to the optic nerve due to any cause. Damage and death of nerves leads to characteristic features like loss of vision, visual field loss, colour vision abnormalities and a pale disc.
Light incident from the ophthalmoscope undergoes total internal reflection through the axonal fibers, and subsequent reflection from the capillaries on the disc surface gives rise to the characteristic pink color of a healthy optic disc.Degenerated axons lose this optical property which explains the pallor in optic atrophy.Alternatively, the loss of capillaries which supply the optic disc may be the cause of disc pallor.
Lesions anterior to optic chiasmaresult in unilateral changes while those involving thechiasma and optic tract result in bilateral changes. Common causes of optic nerve head(ONH) structural changes are due to primary, post neuritic,consecutive, ischemic and glaucomatous optic atrophy; etiology of this could be any of the following conditions: optic neuritis, papilloedema, compression by tumors, toxic and nutritional neuropathies, hereditary neuropathies and trauma.
In optic nerve disease, visual loss can be quantified with reliable and validated measures of visual function which includes central visual acuity, field of vision and colour vision testing. The structural damage can be quantified using OCT.
The gold standard for testing optic nerve function is Perimetry using visual field(VF) analyzer. Each point in the VF reflects the visual sensitivity of the corresponding point in the retina.Static threshold perimetry records visual function at each retinal location qualitatively and semi-quantitatively by measuring the weakest perceptible light spot.2 In optic neuropathy, visual field changes can include enlargement of the blind spot, caeco- central scotoma, arcuatescotomas, altitudinal defects, hemianopic defects and peripheral constriction of fields.
Since the ganglion cells and retinal nerve fibrelayer(RNFL) contribute to retinal thickness in the macula, it is expected to be reduced to some degree in the macula and peripapillary region in eyes with chronic optic nerve dysfunction.Optical coherence tomography (OCT), first described in 1991 by Huang et al3 is a high-resolution, cross-sectional imaging technique that allows in vivo measurements of the retinal nerve fiber layer (RNFL). The third-generation machine, Stratus OCT (Carl ZeissMeditec, Dublin, CA), is able to quantify the thickness of the RNFL at a resolution of approximately 8 to 10 μm.
6.1 NEED FOR THE STUDY
Visual field analysis is the most common investigation used to assess the optic nerve function but perimetry is a subjective test requiring patient comprehension and cooperation for a considerable period of time, which may not be possible in patients with poor vision and in some neurological diseases. They may also not have good dexterity.
Optical Coherence Tomography on the other hand is a non invasive imaging which measures the retina nerve fibre layer thickness in a cross sectional manner with high accuracy.It may be assumed that the reduced visual sensitivity in any given visual field area should be proportionate to the amount of ganglion cell loss in corresponding area.2
So, if we can prove that the above two parameters correlate, we could use more objective RNFL thickness measured using OCT in the assessment and follow up of patients with visual pathway defects.It is also important to differentiate subtle or early changes from normal variants. For example—optic neuritis in multiple sclerosis is often subclinical. An early diagnosis is needed to prevent further visual loss where ever possible.
The purpose of the study is to investigate the spatial correlation between loss of VFS(measured with SAP) and focal RNFL thinning(measured with OCT) in patients with optic nerve disorders.
6.2 REVIEW OF LITERATURE:
1. In a study conducted by Soltan-sanjari et al 35 eyes of 28 patients were studied.The Retinal nerve fiber thickness was measured using OCT and visual fields using a Humphrey field analyzer.2
Mean global RNFL thickness was 44.9±27.5 μm which was significantly correlated with mean deviation score on automated perimetry (r=0.493, P=0.003).However,no significant correlation was observed between visual field pattern standard deviation and the corresponding quadrantic RNFL thickness.In a similar manner, no significant association was found between visual acuity and RNFL thickness.
2. Padmavathy et al conducted a study in whichpatients were grouped; 25 patients (50 eyes) with temporal pallor and visual acuity less than 6/12 in group 1; 20 patients (39 eyes) with segmental pallor and visual acuity of 6/6- 6/9 in Group 2;and 25 patients (50 eyes) with normal fundus and visual acuity were taken as controls in Group 3.
The RNFL in the temporal quadrant and retinal thickness at macula were significantly lower in both Group 1 and 2 when compared with group 3.On examining the correlation between vision and temporal pallor there is a decrease in RNFL thickness with decrease in vision.4
3.In a study conducted by Kanamori et al on 34 eyes of 18 patients with band atrophy, it was found that retinal nerve fiber layer thickness decreased in all OCT parameters and the degree of decrease in RNFL thickness correlated with that of visual field defects.5
4.Fisher et al conducted a study on 72 eyes of 36 patients with multiple sclerosis to measure their RNFL thickness using OCT and visual function/low-contrast letter acuity using sloan charts.It was concluded that scores for low-contrast letter acuity correlated with RNFL thickness.6
5.Kusuhara et al conducted a study on 22 eyes of patients with unilateral optic atrophy reported that macular thinning with the preserved foveal thickness is a hallmark of eyes with optic atrophy. Together with no correlation between foveal thickness and BCVA, this finding would help in differentiating macular and optic nerve diseases.7
6.In a similar study conducted by William et al on 276 eyes of 276 patients,it was reported that RNFL thickness can be used to predict visual field loss.8
6.3 OBJECTIVES OF THE STUDY
Primary Objective: To correlate Retinal nerve fiber layer (RNFL) thickness and macular thickness in patients with non-glaucomatous optic neuropathy with visual acuity and visual fields.
7. MATERIALS AND METHODS:
Study design-This will be a prospective, cross sectional, observational study
7.1Source of data--Patients with various optic nerve disorders attending Ophthalmology department of St.JohnsMedical College Hospital Bangalore from September 2012 to August 2014
Sample size-50
Inclusion Criteria
- Age>18 years
-clinically diagnosed optic nerve disease.
- best corrected visual acuity better than 6/60
Exclusion Criteria
-Acute phase of inflammatory disorders of the optic nerve.
-Acute phase of disc edema (increase in RNFL thickness due to axoplasmic stasis)
-Glaucoma
- IOP>20 mm of Hg.
-Patients in whom visual fields cannot be done
-Patients in whom fundus evaluation cannot be done
-Media opacities like >grade 2 Nuclear Sclerosis
-Refractive error more than +/- 5D
-Retinal diseases- diabetic retinopathy, hypertensive retinopathy
- Anaemia
7.2 Method of collection of data:
Patients with various optic nerve disorders attending Ophthalmology department of St.JohnsMedical College Hospital Bangalore from September 2012 to August 2014.
Informed consent will be taken.
A detailed history including demographics, ocular disease, past medical illness,history of neurological disease, family history and personal history will be taken.
Ophthalmological examination will include:
-A complete anterior segment examination, include examination of pupillary reactions and intraocular pressure measurements.
-Best corrected visual acuity assessed using illuminated ETDRS Chart and scored with Log MAR Scale,
- Near vision with Times New Roman chart
-Colour vision using ishihara's chart
-Contrast sensitivity using Pelli-Robson’s chart.
- Fundus evaluation using direct ophthalmoscope and with indirect ophthalmosope and +90/+78D lens slit lamp biomicroscopy.
-Visual fields/ perimetry 24-2 SITA standard using Humphrey Visual Field analyzer 745i. A reliable visual field test is defined as one with fewer than 20% fixation losses, 33%false-positive responses, or false-negative responses.
-Retinal nerve fiber thickness and Macular thickness using CirrusTM HD Spectral Domain Optical coherence tomography(4000-1720) version 4.5.1.11.It will be performed through a dilated pupil. Internal fixation will be used and a circular 3.4 mm scan centered on the optic disc will be obtained. Macular scans will also be obtained.Three of the best obtained scans will be selected.OCT will be repeated when the obtained scans are not appropriate due to poor focusing or inadequate centration. The patient will be excluded if repeat scans are also unsatisfactory.Finally, the selected OCT scans will be analyzed using the Average Retinal Nerve Fiber Layer Thickness program.Mean RNFL thickness will be recorded globally and separately for the superior, inferior,nasal and temporal quadrants. Mean macular thickness will be calculated using the automated programme Macular cube 512x128.
Pearsons correlation analysis will be used to evaluate the correlation between mean deviation on Humphrey visual field and global RNFL thickness.Association between macular thickness and BCVA also will be evaluated by Pearsons correlation analysis.
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please specify:
Yes.
Visual field analysis and RNFL analysis.
The tests which have been enumerated are routinely used in the evaluation of patients with optic nerve disorders.
No interventions are carried out as part of the study
7.4 Was Ethical Clearance obtained from your institution in case of 7.3?
Yes.
8. LIST OF REFERENCES
1. Sadeen AA. Optic atrophy and papilloedema. In: Albert DM, Miller JH(ed.) Albert and Jakobiec’s Principles and Practice of Ophthalmology. Third edition. Saunders, Boston;2008;281:3861-3870
2.Soltan-Sanjari M, Parvaresh M M, Maleki A et al ,Correlation between Retinal Nerve Fiber Layer Thickness by Optical Coherence Tomography and Perimetric Parameters in of Optic Atrophy. Journal of ophthalmic and vision research 2008; Vol. 3, No. 2:91-94.
3. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography.Science. 1991;254: 1178–1181.
4.Maharajan P, Pal B P, Kunnatur R et al. Analyze RNFL Thickness in Patients of Segmental Pallor by OCT and Analyze Thickness with Visual Acuity, AIOS; 2010
5. Kanamori A, Nakamura M, Matsui N et al. Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs. Ophthalmology 2004;111:2278-2283
6 . Fisher J,Jacobs D, Markowitz C et al.Relation of Visual Function to Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis. Ophthalmology 2006;113:324-332
7. Kusuhara S, Nakamura M, Nagai-Kusuhara A et al.Macular thickness reduction in eyes with unilateral optic atrophy detected with optical coherence tomography. Eye (2006);20:882–887
8. Williams ZY, Schuman JS, Gamell L et al. Optical coherence tomography measurement of nerve fiber layer thickness and the likelihood of a visual field defect.Am J Ophthalmol 2002;134:538-546
9. Schuman JS, Pedut-Kloizman T, Hertzmark E et al. Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103:1889-1898.
10. Monteiro ML, Moura FC, Medeiros FA et al. Diagnostic ability of optical coherence tomography with a normative database to detect band atrophy of the optic nerve.Am J Ophthalmol 2007;143:896-899.
11. Jones AL, Sheen NL, North RVetal.The Humphrey optical coherence tomography scanner: quantitative analysis and reproducibility study of thickness measurement by use of optical coherence tomography. Br J Ophthalmol 2001;85:673-676.
9. SIGNATURE OF THE CANDIDATE:
10. REMARKS OF THE GUIDE:
Axonal damage of the optic nerve manifests as RNFL defects, which are structural changes and can be objectively quantified using OCT. Visual field analysis using Humphrey visual field analyzer measures the functional sensitivity of the retinal points.
There is a need to correlate the functional tests and structural tests in patients with non-glaucomatous neuropathy, so that when functional tests cannot be performed due to poor patient cooperation; they can be managed and followed up depending on the structural changes in the RNFL thickness.
OCT measurement of RNFL which is the most proximal region of the afferent visual pathway is important in neuroophthalmic disorders. This may become useful especially in the management of patients with multiple sclerosis in whom RNFL thickness may become a marker of previous subclinical optic neuritis.
11. NAME AND DESIGNATION OF
11.1GUIDE: DR.MARY JOSEPH
ASSOCIATE PROFESSOR
DEPARTMENT OF OPHTHALMOLOGY
11.2 SIGNATURE:
11.3 C0-GUIDE
11.4 SIGNATURE:
11.5 HEAD OF THE DEPARTMENT:
DR.REJI KOSHY THOMAS
PROFESSOR
DEPARTMENT OF OPHTHALMOLOGY
11.6 SIGNATURE:
12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL:
12.2 SIGNATURE: