<i>Background & Objectives</i>: Dry eye disease (DED) has become very prevalent, with the increased usage of internet and video terminals. The present study was carried out to compare the efficacy of tear substitutes in enhancing the signal strength of measurements of optic nerve head, retinal nerve fiber layer and macula by Optical coherence tomography (OCT), and resultant change in image quality. Thus proving the role of artificial tear substitutes in increasing the diagnostic accuracy of Optical coherence tomography (OCT) measurements. <i>Methods</i>: A double blinded randomized control trial was performed on one hundred and fifty patients needing optical coherence tomography. They were randomly allocated into three groups to receive any one of the three tear substitutes Group 1 –Sodium hyaluronate (Molecular Weight M Wt 799.6g/mol) Group 2 – Poly ethylene glycol (Molecular Weight M Wt 400g/mol), Group -3 Hydroxy Propyl Methyl cellulose (Molecular Weight M Wt 1261.4 g/mol); Measurement of signal strength for optic nerve head, retinal nerve fiber thickness RNFL and sub foveal thickness SFT was done before and after instillation of tear substitutes. Data was analyzed using the Statistical Package for Social Sciences SPSS 22 version software. P value <0.05 was considered statistically significant. <i>Results</i>: The groups were comparable with respect to mean age and gender distribution. The mean signal strength (SS) of Optic Nerve Head (ONH) evaluation improved in all the groups in both eyes. The increase was the highest in Group II in both eyes. The increase in retinal nerve fiber layer thickness [RNFL] was seen in both eyes in all the groups. Improvement in macular evaluation sub foveal thickness (SFT) was seen in Group II of both eyes and group III in the Left eye. <i>Interpretation and Conclusion</i>: All tear substitutes improved the quality of the image but the improvement varied with regard to the parameters measured, thus proving artificial tear application is an essential for Optical coherence tomography OCT measurements in persons prone to dry eye This reduces the scope for error due to bad images and thereby the possibility of misdiagnosis of ophthalmic disease.
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