@article {341636,
	title = {Effects of corneal nerve density on the response to treatment in dry eye disease.},
	journal = {Ophthalmology},
	volume = {122},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {662-8},
	abstract = {PURPOSE: To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment. DESIGN: Phase IV, double-masked, randomized clinical trial. PARTICIPANTS: Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls. METHODS: Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5\%, or loteprednol etabonate 0.5\%/tobramycin 0.3\% twice daily for 4 weeks. At baseline, in\&nbsp;vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups. MAIN OUTCOME MEASURES: Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer{\textquoteright}s test, and SNFL. RESULTS: In patients with DED, baseline SNFL (17.06{\textpm}5.78 mm/mm(2)) was significantly lower than in controls (23.68{\textpm}3.42 mm/mm(2), P\&nbsp;= 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (\&lt;16.84 mm/mm(2)), subjects with near-normal baseline SNFL (>=16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P \&lt; 0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL. CONCLUSIONS: Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients{\textquoteright} response to DED therapy.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.11.006},
	author = {Kheirkhah, Ahmad and Dohlman, Thomas H and Amparo, Francisco and Arnoldner, Michael A and Jamali, Arsia and Hamrah, Pedram and Dana, Reza}
}
