AIM: To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS: A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6mo and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time (FTBUT), Schirmer’s I test, ocular surface staining scores and ocular surface disease index score (OSDI)], central corneal sensation (Cochet Bonnett aesthesiometer), central subbasal nerve fiber layer density (SBNFLD) by confocal microscopy. RESULTS: The mean values in the glaucoma cases and control groups respectively were as follows: OSDI score (35.89±16.07/6.02±3.84; P=0.001), Schirmer’s I test score (7.63±2.64 mm/12.86±1.93 mm; P=0.001), FTBUT (9.44±2.76s/11.8±1.88s; P=0.001), corneal (5.7±2.33/ 1.1±0.58; P=0.001) and conjunctival staining score (5.06±1.94/0.84±0.46; P=0.001), corneal sensitivity (4.68±0.44/5.07±0.37; P=0.076), mean subbasal nerve fiber number (3.58±0.99/5.40±1.70; P=0.001), SBNFL length (1101.44±287.56 μm/1963.70±562.56 μm; P=0.001) and density (6883.94±1798.03 μm/mm2/12 273.15±3516.04 μm/mm2; P=0.001). Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal (R2=0.86) and conjunctival staining (R2=0.71) and OSDI score (R2=0.67) showed statistically significant negative correlation with central corneal SBNFLD while FTBUT (R2=0.84), corneal sensitivity (R2=0.52) showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. CONCLUSION: Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications.