Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark): study design and baseline characteristics

Diabetes Res Clin Pract. 2014 May;104(2):248-56. doi: 10.1016/j.diabres.2014.02.011. Epub 2014 Feb 20.


Aims: 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.

Keywords: Corneal confocal microscopy; Diabetic neuropathy; LANDMark study; Longitudinal trial; Non-contact corneal aesthesiometry.

Publication types

  • Controlled Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cornea / innervation
  • Cornea / pathology*
  • Cornea / physiopathology
  • Corneal Diseases / etiology
  • Corneal Diseases / pathology
  • Corneal Diseases / physiopathology*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / pathology*
  • Diabetic Neuropathies / physiopathology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Nerve Fibers / pathology*
  • Prospective Studies
  • Sensation / physiology*
  • Young Adult