title: Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark): study design and baseline characteristics.
abstract: OBJECTIVE
  Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the 'Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers'(LANDMark) study.
  
  
  METHODS
  The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry.
  
  
  RESULTS
  76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold was significantly higher (i.e., sensitivity was lower) in T1W (1.0±1.1mbars) than T1WO (0.7±0.7mbars) and controls (0.6±0.4mbars) (p<0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0±6.4mm/mm(2)) compared to T1WO (19.1±5.8mm/mm(2)) and controls (23.2±6.3mm/mm(2)) (p<0.001). Corneal nerve fibre length was lower in T1WO compared to controls.
  
  
  CONCLUSIONS
  The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pritchard
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Katie
authors.initials: K
authors.lastname: Edwards
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Cirous
authors.initials: C
authors.lastname: Dehghani
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Hassan
authors.initials: H
authors.lastname: Fadavi
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Jeziorska
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Ioannis N
authors.initials: IN
authors.lastname: Petropoulos
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Georgios
authors.initials: G
authors.lastname: Ponirakis
authors.affiliation: Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Russell
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Geoff P
authors.initials: GP
authors.lastname: Sampson
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Ayda M
authors.initials: AM
authors.lastname: Shahidi
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vagenas
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, UK.
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia. Electronic address: n.efron@qut.edu.au.
authors.forename: Nathan
authors.initials: N
authors.lastname: Efron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003315:Cornea / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D003316:Corneal Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D011446:Prospective Studies; D012677:Sensation / Q000502:physiology*; D055815:Young Adult
keywords: Corneal confocal microscopy; Diabetic neuropathy; LANDMark study; Longitudinal trial; Non-contact corneal aesthesiometry