title: In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma.
abstract: OBJECTIVE
  To evaluate the effects at 1 year of preservative-free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters.
  
  
  METHODS
  Forty patients with primary open-angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age-matched controls. Clinical tests (IOP, Schirmer I test, and lacrimal film break-up time BUT) and in vivo conjunctival confocal microscopy (IVCM) were performed in all patients at baseline and after 12 months. IVCM (HRT II Rostock Cornea Module; Heidelberg Engineering GmbH, Heidelberg, Germany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial regularity.
  
  
  RESULTS
  IVCM and clinical parameters were similar in the three groups at baseline. After 12 months, intra-epithelial goblet cell density was significantly lower in the preserved (48.25 ± 7.70) than in the preservative-free beta-blocker group (86.83 ± 22.17, p < 0.001) and controls (88.9 ± 18.33, p < 0.001). The epithelial layer was significantly more regular in the preserved beta-blocker medication group than in the preservative-free beta-blocker group (p < 0.001) and the control group (p < 0.001). A significant reduction in both Schirmer I and BUT was found in the group of preserved timolol (respectively, 11.3 ± 2.97 and 8.12 ± 0.99) compared with preservative-free timolol (16.8 ± 1.83 and 11.27 ± 1.27, p < 0.001) and controls (17.8 ± 1.87 and 12.10 ± 1.28, p < 0.001).
  
  
  CONCLUSIONS
  Based on our IVCM data, preservative-free beta-blocker gel induces less changes at ocular surface than preserved beta-blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma.
authors.affiliation: Department of Surgery, Ophthalmology Unit, University of Siena, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Frezzotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Fogagnolo
authors.forename: Gentiana
authors.initials: G
authors.lastname: Haka
authors.forename: Ilaria
authors.initials: I
authors.lastname: Motolese
authors.forename: Michele
authors.initials: M
authors.lastname: Iester
authors.forename: Simone A
authors.initials: SA
authors.lastname: Bagaglia
authors.forename: Pietro
authors.initials: P
authors.lastname: Mittica
authors.forename: Cristina
authors.initials: C
authors.lastname: Menicacci
authors.forename: Luca
authors.initials: L
authors.lastname: Rossetti
authors.forename: Eduardo
authors.initials: E
authors.lastname: Motolese
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001548:Benzalkonium Compounds / Q000627:therapeutic use*; D002452:Cell Count; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005782:Gels; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D004364:Pharmaceutical Preparations; D011310:Preservatives, Pharmaceutical / Q000627:therapeutic use*; D013666:Tears / Q000378:metabolism; D013999:Timolol / Q000627:therapeutic use*; D014065:Tonometry, Ocular
chemical_list: D000319:Adrenergic beta-Antagonists; D001548:Benzalkonium Compounds; D005782:Gels; D004364:Pharmaceutical Preparations; D011310:Preservatives, Pharmaceutical; D013999:Timolol
keywords: antiglaucoma drugs; conjunctival modification; in vivo confocal microscopy; toxicity