title: Evaluation of the Safety and Tolerability of Conjunctival Ring for Posterior Segment of the Eye.
abstract: To evaluate the safety and tolerability of conjunctival rings (CRs), a novel device for drug delivery to the posterior segment of the eye.
  
  
  
  In animal studies, CRs containing 5% dexamethasone sodium phosphate (DSP) or vehicle solution were placed on the right and left eyes of C57BL/6J mice, respectively. Contact lenses (CLs) containing vehicle solution were used as a control. Twenty-four hours after placement of the CRs, corneal fluorescein staining was graded based on the McDonald-Shadduck scoring system, ranging from 0 to 4. In humans, CRs containing vehicle solution were placed on the right eye of healthy volunteers for 9 hours. The corneal curvature, corneal thickness, intraocular pressure, visual acuity, tear production (Schirmer I test), tear film break-up time and fluorescein staining scores of the cornea (scores ranging from 0 to 3) and conjunctiva (scores ranging from 0 to 6) were assessed before and after wearing the CRs. The release characteristics of DSP from CRs were also evaluated.
  
  
  
  In animal experiments, corneal fluorescein staining scores were 1 or less in all the groups, and there was no significant difference between the CR group and the CL group. In the preclinical safety evaluation of CR for humans, ophthalmic examination revealed that CR caused no significant changes in all the parameters investigated including corneal curvature (p = 0.77), corneal thickness (p = 0.96), intraocular pressure (p = 0.59), visual acuity (p = 0.14), Schirmer I test results (p = 0.76), tear film break-up time (p = 0.68), corneal fluorescein staining scores (p = 0.64), and conjunctival fluorescein staining scores (p = 0.52). The DSP release from CRs occurs within a few hours, which is similar to the drug-release property of medicated CL, as reported previously.
  
  
  
  The current data showed the safety and tolerability of CR as a drug delivery device for the treatment of posterior segment diseases.
authors.affiliation: a Laboratory of Ocular Cell Biology and Visual Science , Hokkaido University Graduate School of Medicine , Sapporo , Japan.|b Department of Ophthalmology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: a Laboratory of Ocular Cell Biology and Visual Science , Hokkaido University Graduate School of Medicine , Sapporo , Japan.|b Department of Ophthalmology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohguchi
authors.affiliation: a Laboratory of Ocular Cell Biology and Visual Science , Hokkaido University Graduate School of Medicine , Sapporo , Japan.|b Department of Ophthalmology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.affiliation: a Laboratory of Ocular Cell Biology and Visual Science , Hokkaido University Graduate School of Medicine , Sapporo , Japan.|b Department of Ophthalmology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murata
authors.affiliation: c Research Laboratories, Senju Pharmaceutical Co., Ltd. , Kobe , Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Yasueda
authors.affiliation: d Research Laboratories, SEED Co., Ltd. , Saitama , Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Obata
authors.affiliation: d Research Laboratories, SEED Co., Ltd. , Saitama , Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: d Research Laboratories, SEED Co., Ltd. , Saitama , Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: a Laboratory of Ocular Cell Biology and Visual Science , Hokkaido University Graduate School of Medicine , Sapporo , Japan.|b Department of Ophthalmology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.affiliation: a Laboratory of Ocular Cell Biology and Visual Science , Hokkaido University Graduate School of Medicine , Sapporo , Japan.|b Department of Ophthalmology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery*; D003315:Cornea / Q000000981:diagnostic imaging / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004867:Equipment Design; D005143:Eyelids / Q000000981:diagnostic imaging / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008810:Mice, Inbred C57BL; D057972:Posterior Eye Segment / Q000000981:diagnostic imaging / Q000601:surgery*
chemical_list: D005938:Glucocorticoids
keywords: Conjunctival ring; drug delivery device; hydrogel exoplant