Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis

Abstract

Citation: Lagali NS, Allgeier S, Guimarães P, et al. Reduced corneal nerve fiber density in type 2 diabetes by wide-area mosaic analysis. Invest Ophthalmol Vis Sci. 2017;58:6318-6327. DOI:10.1167/iovs.17-22257 PURPOSE. To determine if corneal subbasal nerve plexus (SBP) parameters derived from widearea depth-corrected mosaic images are associated with type 2 diabetes. METHODS.One hundred sixty-three mosaics were produced from eyes of 82 subjects by laserscanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ‡ 10 years).RESULTS. In mosaics with a mean size of 6 mm 2 in subjects aged 69.1 6 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 6 4.2 vs. 15.0 6 3.2 mm/ mm 2 , P ¼ 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both shortduration (14.0 6 4.0 mm/mm 2 , 3.2 6 3.9 years since diagnosis) and long-duration diabetes (12.7 6 4.2 mm/mm 2 , 15.4 6 4.2 years since diagnosis; ANOVA P ¼ 0.023). Lower mCNFL was associated with presence of diabetes (P ¼ 0.032) and increased hemoglobin A1c (HbA1c) levels (P ¼ 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes.CONCLUSIONS. Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.

Longitudinal Changes in Corneal Cell and Nerve Fiber Morphology in Young Patients with Type 1 Diabetes with and without Diabetic Retinopathy: A 2-Year Follow-up Study

“…29 The diagnostic ability of IVCCM may be further enhanced by assessing the inferior whorl or using wide-area mosaics, which take into account both proximal and distal corneal nerve morphology. 30,31 Multiple pathogenetic mechanisms, including advanced glycation, increased flux through the sorbitol pathway, and oxidative stress, have been implicated in the development of diabetic neuropathy. 32 Experimental studies using a combination of menhaden oil, a-lipoic acid, and enalapril have been shown to ameliorate oxidative and inflammatory stress and improve distal corneal nerve morphology.…”

Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9

“…For the purpose of this study in 2014, previous participants were invited as part of a 10 year follow-up. Details of the subject recruitment including inclusion and exclusion criteria and study flowchart are given elsewhere 30 . Subjects did not have active corneal disease or inflammation, and were not taking any topical ocular medications at the time of examination.…”

“…Those with diagnosed diabetes were further sub-grouped into short duration (diagnosis <10 years prior to ophthalmic examination, 11 individuals) and long duration (≥10 years since diagnosis, 28 individuals). Subgroupings were based on the oral glucose tolerance test (OGTT) and the clinical diagnosis of type 2 diabetes mellitus, with details given elsewhere 30 . The study subjects were all residents in the same county, located in the northern part of Sweden.…”

“…Given the strong association of inflammation and inflammatory cytokine markers with the development of type 2 diabetes and the further association of the eye with complications of diabetes such as retinopathy and DPN, we sought to investigate a possible relationship of corneal inflammatory dendritic cell subpopulations, distinguished by phenotype, with the development and progression of type 2 diabetes. Because of the possible confounding influence of local variations in the corneal DC subpopulations, we employed wide-area mosaicking of the corneal sub-basal plexus in three dimensions 29 , 30 to depict and analyse cells within a large region of the central cornea. We further sought to investigate possible circulating inflammatory biomarkers associated with the corneal dendritic cells.…”

Wide-field corneal subbasal nerve plexus mosaics in age-controlled healthy and type 2 diabetes populations

“…A full description of the cohort of subjects with inclusion and exclusion criteria has been given elsewhere 33 . Subjects were examined based on an initial cohort of 129 age- and sex-matched subjects aged 60±1 years at initial inclusion in 2004 (ref.…”