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March 2008 Saikumar et al. - OCT in <strong>Pre</strong>-permetric <strong>Glaucoma</strong> 39<br />

<strong>Diagnosis</strong> <strong>of</strong> <strong>Pre</strong>-<strong>perimetric</strong> <strong>Glaucoma</strong><br />

<strong>using</strong> <strong>Optical</strong> Coherence Tomography<br />

Dr. S J. Saikumar MS, Dr. Saphy Jose, Dr. Savita Bhat MS, Dr. Mahesh G. MS, FRCS, Dr. A. Giridhar MS<br />

Abstract<br />

Introduction<br />

Objective: To study the efficacy <strong>of</strong> <strong>Optical</strong> Coherence Tomography in pre <strong>perimetric</strong><br />

glaucoma.<br />

Methods: 76 glaucoma suspects with normal or borderline white on white visual fields<br />

underwent RNFL analysis with <strong>Optical</strong> Coherence Tomography (Stratus OCT version 4).<br />

Outcome measure: Borderline or definite RNFL thinning in the inferior or superior<br />

quadrants was taken as the main outcome measure.<br />

Results: Six out <strong>of</strong> seventy six glaucoma suspects showed RNFL changes in OCT suggestive<br />

<strong>of</strong> glaucoma giving the test a specificity <strong>of</strong> 92 %. All six patients had cup disc ratio <strong>of</strong> 0.6 or<br />

more and five out <strong>of</strong> six patients had IOP <strong>of</strong> 18 or more and positive family history <strong>of</strong> glaucoma.<br />

Conclusion: <strong>Optical</strong> Coherence Tomography is an useful tool for diagnosis <strong>of</strong> pre perimetry<br />

glaucoma especially in the presence <strong>of</strong> other risk factors like raised IOP, enlarged cup and<br />

family history <strong>of</strong> glaucoma.<br />

<strong>Glaucoma</strong> is an optic neuropathy characterized by a<br />

specific and progressive injury to the optic nerve and<br />

retinal nerve fiber layer 1 . Because the injury due to<br />

glaucoma is irreversible, early detection and prevention<br />

<strong>of</strong> glaucomatous RNFL loss is <strong>of</strong> vital importance.<br />

Examination <strong>of</strong> the optic nerve head and its surrounding<br />

nerve fiber layer is considered essential in both<br />

detection and monitoring <strong>of</strong> glaucoma. Damage to the<br />

RNFL has been shown to precede visual field loss. Upto<br />

30-50 % nerve fibre loss might have occurred before<br />

the first detectable field defect 2 . Hence, objective<br />

Giridhar Eye Institute, Ponneth Temple Road, Kadavanthra, Cochin 682 020<br />

E-mail: girieye@vsnl.com<br />

ORIGINAL<br />

ARTICLE<br />

methods <strong>of</strong> measuring these structures will aid<br />

ophthalmologists in making an accurate diagnosis.<br />

<strong>Optical</strong> Coherence Tomography (OCT) which was first<br />

described in 1991, is a high resolution cross sectional<br />

imaging technique that allows accurate measurement<br />

<strong>of</strong> the retinal nerve fiber layer 3 . With the ability to<br />

quantify the thickness <strong>of</strong> the RNFL with a resolution <strong>of</strong><br />

8 to 10 microns, clinicians potentially have a more objective<br />

tool in helping to diagnose glaucoma much earlier than<br />

visual fields. However, white on white perimetry is still<br />

considered the gold standard for diagnosis <strong>of</strong> glaucoma.<br />

AAO <strong>Pre</strong>ferred Practice Patterns still mentions that the<br />

diagnosis <strong>of</strong> glaucoma is based on appearance <strong>of</strong> the<br />

optic disc and standard achromatic perimetry 4 . In this<br />

current study glaucoma suspects who had normal or


40 Kerala Journal <strong>of</strong> Ophthalmology Vol. XX, No. 1<br />

borderline visual fields were subjected to RNFL analysis<br />

<strong>using</strong> <strong>Optical</strong> Coherence Tomography.<br />

Materials and Method<br />

The sudy was designed as a retrospective observational<br />

case series which included glaucoma suspects attending<br />

a tertiary care glaucoma centre.<br />

Study Population: 103 glaucoma suspects who<br />

underwent RNFL analysis on <strong>Optical</strong> Coherence<br />

Tomography were initially enrolled, out <strong>of</strong> which 76<br />

eyes <strong>of</strong> 76 patients fulfilled all criteria and were finally<br />

included in the study. Only one eye per person was<br />

included in the study. If one eye had abnormal fields<br />

and the other eye normal, the normal eye was included<br />

in the study. If both eyes were normal or both were<br />

borderline, the eye with the better PSD value on HFA<br />

was selected and assigned to the study.<br />

Complete ophthalmic examination including visual<br />

acuity, intraocular pressure, gonioscopy and optic disc<br />

evaluation was performed. All patients initially<br />

underwent either 30-2 full threshold or SITA - standard<br />

white on white perimetry. The time gap between<br />

perimetry and OCT was not more than two weeks.<br />

Patients with spherical refractive errors <strong>of</strong> more than<br />

6D, astigmatism more than 3 Dioptres, visual acuity<br />

worse than 6/12 were excluded from the study. Other<br />

exclusion criteria were secondary causes <strong>of</strong> raised IOP,<br />

abnormal disc appearance such as tilted discs and<br />

suspected neurological diseases which are likely to<br />

affect the field testing. Those patients with extensive<br />

peripapillary atrophy were also excluded from the study.<br />

Definition <strong>of</strong> glaucoma suspect: For the purpose<br />

<strong>of</strong> this study a glaucoma suspect was defined as the<br />

presence <strong>of</strong> an abnormal disc appearance consistent<br />

with glaucoma as determined by an experienced<br />

clinician. Disc asymmetry <strong>of</strong> 0.2 or more was also<br />

included in the definition <strong>of</strong> glaucoma suspect.<br />

Observation procedures: All selected patients had<br />

a reliable visual field on Humphrey Visual Field<br />

Analyzer. Reliable fields were defined as fixation loss<br />

rate <strong>of</strong> less than 33 % and false positive and false negative<br />

error rates <strong>of</strong> less than 20 %. Normal and borderline<br />

definitions were based on the glaucoma hemi field test.<br />

OCT measurements: The test was performed after<br />

dilation <strong>of</strong> the pupil to at least 5 millimetre. Three<br />

measurements were performed for each eye. Only<br />

measurements with signal strengths <strong>of</strong> six or more were<br />

accepted as reliable for this study.<br />

Outcome Measures: Definite RNFL thinning (shaded<br />

as red) or borderline RNFL thinning (shaded as yellow)<br />

in either the inferior or superior portion <strong>of</strong> the disc<br />

was taken as the main outcome measure. Charts with<br />

only temporal or nasal thinning were excluded from<br />

the study.<br />

Statistical Analysis: The Fisher exact test was used to<br />

assess the statistical significance <strong>of</strong> glaucomatous<br />

changes in OCT in the presence <strong>of</strong> other risk factors<br />

like raised IOP, family history <strong>of</strong> glaucoma and enlarged<br />

cup-disc ratio. Odds ratio was also calculated for the<br />

above mentioned risk factors.<br />

Results<br />

After all exclusions, 76 eyes <strong>of</strong> 76 patients were enrolled<br />

in the study, <strong>of</strong> which 51 were males and 25 were<br />

females. The age group distribution is shown in Figure1.<br />

Fig. 1. Age group distribution <strong>of</strong> the study population<br />

A total <strong>of</strong> 6 patients had abnormal OCT among the<br />

76 patients enrolled in the study.15 patients had a<br />

positive family history <strong>of</strong> glaucoma in either their first<br />

degree or second-degree relative and out <strong>of</strong> these 5<br />

had abnormal OCT. Only one person with abnormal<br />

OCT had no family history <strong>of</strong> glaucoma. The difference<br />

between the positive family history group and the<br />

negative family history group was statistically<br />

significant (p value 0.001, Fisher exact test). The odds<br />

<strong>of</strong> having an abnormal OCT was 36 times in persons<br />

having a positive family history <strong>of</strong> glaucoma.<br />

A total <strong>of</strong> 47 persons had a CD ratio <strong>of</strong> 0.6 or more, out<br />

<strong>of</strong> which 17 had CDR <strong>of</strong> more than 0.8 (Figure 2).<br />

5 out <strong>of</strong> 6 OCT positive persons had a CDR <strong>of</strong> 0.8 or<br />

more, and one had a CDR <strong>of</strong> 0.7. When a CDR <strong>of</strong> 0.6<br />

was taken as the cut-<strong>of</strong>f, the chance for having an


March 2008 Saikumar et al. - OCT in <strong>Pre</strong>-permetric <strong>Glaucoma</strong> 41<br />

abnormal OCT was not statistically significant (p value<br />

0.0768, Fisher exact test). But when CDR <strong>of</strong> 0.8 was<br />

taken as the cut-<strong>of</strong>f, the chances <strong>of</strong> having an abnormal<br />

OCT was statistically significant (p value 0.0017, Fisher<br />

exact test). Persons with a CDR <strong>of</strong> 0.8 or more are<br />

22 times more likely to have an abnormal OCT,<br />

compared to those having a CDR <strong>of</strong> 0.7 or less.<br />

The mean IOP <strong>of</strong> the 76 eyes enrolled in the study was<br />

16.29. 26 patients had an IOP <strong>of</strong> 18 or more, out <strong>of</strong><br />

which only 7 eyes had an IOP <strong>of</strong> 22 mm Hg or more<br />

(Figure 3). 5 out <strong>of</strong> the 6 patients who had an abnormal<br />

OCT had IOP more than 18 mm Hg. With 18 mm Hg as<br />

the cut-<strong>of</strong>f, the chance <strong>of</strong> having an abnormal OCT was<br />

statistically significant (p value 0.0161, Fisher exact<br />

Fig. 2. Distribution <strong>of</strong> cup disc ratio in the study population<br />

test). The odds <strong>of</strong> having an abnormal OCT was 11<br />

times more in persons with an IOP <strong>of</strong> more than 18<br />

when compared to those with IOP <strong>of</strong> 17 or less.<br />

OCT in glaucoma is a very effective tool in identifying<br />

the true negatives. It shows that 70 out <strong>of</strong> 76 eyes was<br />

proven as not having glaucomatous damage. This gives<br />

the test a specificity <strong>of</strong> 92 %.<br />

Fig. 3. Distribution <strong>of</strong> IOP in the study population<br />

4 eyes had inferior thinning and 2 had superior thinning.<br />

No biarcuate thinning was seen in any <strong>of</strong> the six cases.<br />

5 eyes out <strong>of</strong> 6 had definite thinning <strong>of</strong> RNFL (shaded as<br />

red) and I had borderline thinning (shaded as yellow).<br />

In the 70 persons with normal OCT, mean RNFL<br />

thickness was 119.3 and 124 in the superior and inferior<br />

quadrants respectively. Compared to this, the same<br />

Table 1 showing mean superior and inferior RNFL<br />

thickness in patients with normal and abnormal OCT<br />

values were 79 and 75.33 respectively in the 6 patients<br />

with abnormal OCT. (Table 1)<br />

Discussion<br />

Mean superior Mean inferior<br />

RNFL thickness RNFL thickness<br />

(in microns) (in microns)<br />

Patients with 119.3 124<br />

normal OCT<br />

Patients with 79 75.33<br />

abnormal OCT<br />

We have studied 76 eyes <strong>of</strong> 76 patients who were<br />

clinically found to have some suspicion <strong>of</strong> <strong>Glaucoma</strong>.<br />

The numbers were slightly smaller compared to a few<br />

other studies 5, 6 . Ours was an observational study and<br />

there was no control group, which were used in other<br />

studies 5, 6 . In the study by Kanamori et al 6 normal<br />

population, glaucoma suspects, ocular Hypertensives<br />

and glaucoma patients were included in the study and<br />

compared. We were only studying the ability <strong>of</strong> the<br />

OCT in picking up <strong>Pre</strong> <strong>perimetric</strong> glaucoma in suspected<br />

cases.<br />

The role <strong>of</strong> family history has been highlighted in many<br />

studies 7,8,9 although the incidence <strong>of</strong> MYOC mutation<br />

among Indian primary open angle glaucoma patients<br />

has been found to be lower compared to certain other<br />

parts <strong>of</strong> the world 10 . In our study, in glaucoma suspects<br />

with normal fields, those with positive family history<br />

<strong>of</strong> glaucoma are 36 times more likely to have an<br />

abnormality in OCT when compared to those with no<br />

family history <strong>of</strong> glaucoma.<br />

Cup – disc ratio has been used to define glaucoma<br />

suspects in many other studies 11 . Lalezary et al 11 have


42 Kerala Journal <strong>of</strong> Ophthalmology Vol. XX, No. 1<br />

used stereo photographs to classify the study<br />

population into normal and glaucoma suspects. In our<br />

study the classification has been done by an experienced<br />

glaucoma specialist by <strong>using</strong> 78 D lens biomicroscopy.<br />

In our study, the specificity was a healthy 92 %, which<br />

means the OCT is a good tool to rule out disease.<br />

Sensitivity was not calculated in our study since this<br />

requires a normal age-matched control group. Budenz<br />

et al showed a sensitivity <strong>of</strong> 84 % and a specificity <strong>of</strong><br />

98 % in their study on <strong>perimetric</strong> glaucomas 12 .<br />

As expected the mean RNFL thickness in the inferior<br />

and superior quadrant was significantly lower in the<br />

abnormal OCT group compared to the normal OCT group.<br />

Kanamori et al have studied the temporal and nasal<br />

thickness also along with the superior and inferior 6 .<br />

We felt that many errors may crop up if the nasal and<br />

temporal thickness was included. Also the inferior and<br />

superior poles were the first affected in early glaucoma.<br />

The normal OCT showed the characteristic double-hump<br />

pattern which is in agreement with other human 6 and<br />

histologic studies 13 .<br />

Self assessment <strong>of</strong> this study – STARD<br />

guidelines<br />

Standards for Reporting <strong>of</strong> Diagnostic Accuracy<br />

(STARD) is an internationally accepted method <strong>of</strong><br />

assessing a study conducted on a diagnostic equipment.<br />

A recent report on the quality <strong>of</strong> reporting <strong>of</strong> diagnostic<br />

accuracy was conducted with 30 published articles. The<br />

STARD guideline consists <strong>of</strong> 25 points which are to be<br />

fulfilled for a good diagnostic study 14 . In this meta<br />

analysis only 26 % <strong>of</strong> the papers reported more than<br />

half <strong>of</strong> the STARD items. Our study has reported<br />

11 out <strong>of</strong> the 25 STARD items, and this compares well<br />

with many published articles on diagnostic accuracy <strong>of</strong><br />

OCT in diagnosis <strong>of</strong> early glaucoma.<br />

Conclusion<br />

<strong>Optical</strong> Coherence Tomography is a useful tool for pre<br />

<strong>perimetric</strong> diagnosis <strong>of</strong> glaucoma. The usefulness <strong>of</strong><br />

this tool increases in the presence <strong>of</strong> other risk factors<br />

like family history <strong>of</strong> glaucoma, large cup disc ratio<br />

and high intra ocular pressure. The specificity <strong>of</strong> this<br />

tool in our study was 92 % which makes it a good tool<br />

to rule out those who do not have glaucoma.<br />

Comparative studies with the other imaging tools like<br />

HRT and GDx are needed in our population to<br />

determine which is the best tool for diagnosis <strong>of</strong> early<br />

glaucoma.<br />

References<br />

1. Sommer A, Miller NR, Pollack I et al. The nerve fiber<br />

layer in the diagnosis <strong>of</strong> glaucoma. Arch Ophthalmol<br />

1977; 95: 2149-2156.<br />

2. Quigley HA, Addicks EM, Green R. Optic nerve damage<br />

in human <strong>Glaucoma</strong>. III: Quantitative correlation <strong>of</strong><br />

nerve fiber loss and visual field defect in glaucoma.<br />

Arch Ophthalmol 1982; 100: 135-146.<br />

3. Huang D, Swanson EA, Lin CP et al. <strong>Optical</strong> Coherence<br />

Tomography. Science 1991; 254: 1178-81.<br />

4. American Academy <strong>of</strong> Ophthalmology <strong>Pre</strong>ferred<br />

Practice Patterns Committee, <strong>Glaucoma</strong> Panel. Primary<br />

Open Angle <strong>Glaucoma</strong> Suspect. San Francisco. 2002.<br />

5. Nouri-Mahdavi K, H<strong>of</strong>fman D, Tannenbaum DP et al.<br />

Identifying early glaucoma with <strong>Optical</strong> Coherence<br />

Tomography. Am J Ophthalmol 2004; 137: 228-235.<br />

6. Kanamori A, Nakamura M, Escano MFT et al. Evaluation<br />

<strong>of</strong> the <strong>Glaucoma</strong>tous damage on Retinal Nerve Fiber<br />

Thickness measured by <strong>Optical</strong> Coherence Tomography.<br />

Am J Ophthalmol 2003; 135: 513-520<br />

7. McNought AI, Allen JG, Healy DL et al. Accuracy and<br />

implications <strong>of</strong> a reported family history <strong>of</strong> glaucoma.<br />

Experience from the <strong>Glaucoma</strong> Inheritance study. Arch<br />

Ophthalmol 2000 July; 118(7): 900-904.<br />

8. Wu J, Hewitt AW, Green CM et al. Disease severity <strong>of</strong><br />

familial glaucoma compared with sporadic glaucoma.<br />

Arch Ophthalmol 2006 July 124 (7): 950-954.<br />

9. Leske MC, Wu SY, Hennis A et al. Risk factors for<br />

incident glaucoma – The Barbados Eye Study.<br />

Ophthalmology July 2007.<br />

10. Sripriya S, Uthra S, Sangeetha R et al. Low frequency<br />

<strong>of</strong> MYOC mutations in Indian POAG patients. Clin Genet<br />

2004 Apr; 56 (4): 333-337.<br />

11. Lalezary M, Medeiros FA, Weinreb RN et al. Baseline<br />

<strong>Optical</strong> Coherence Tomography predicts the development<br />

<strong>of</strong> <strong>Glaucoma</strong>tous change in <strong>Glaucoma</strong> Suspects. Am J<br />

Ophthalmol 2006; 142:576 e1 – 576 e8.<br />

12. Budenz DL, Michael A, Chang RT et al. Sensitivity and<br />

Specificity <strong>of</strong> the Stratus OCT for Perimetric <strong>Glaucoma</strong>.<br />

Ophthalmology 2005; 112: 3-9.<br />

13. Varma R, Skaf M, Barron E. Retinal nerve fiber thickness<br />

in normal human eyes. Ophthalmology 1996; 103:<br />

2114-2119.<br />

14. Johnson ZK, Siddiqui MAR, Azuara-Blanco A. The<br />

Quality <strong>of</strong> reporting <strong>of</strong> Diagnostic Accuracy studies <strong>of</strong><br />

<strong>Optical</strong> Coherence Tomography studies in <strong>Glaucoma</strong>.<br />

Ophthalmology 2007; 114: 1607-1612.

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