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| Author, year | Type of study | Study groups | Technology | Parameters | Results |
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| Kwon, 2016 [143] | Descriptive | 18,665 donors (34,234 corneas) | Specular microscopy (Konan Cell Chek EB-10; Konan Medical, Hyogo, Japan) | (i) Sex, age, race, surgery, disease (hypertension, diabetes, glaucoma, depression, dementia, Parkinson, hyperthyroidism and hypothyroidism) and habits (smokers/nonsmokers)
(ii) All independent variables were divided into 2 groups:
(1) ECD>2000 cels/mm2
(2) ECD<2000 cels/mm2 | (i) ECD decreased with age.
(ii) The average ECD of African American donors was higher than those of white or Hispanic donors.
(iii) A history of diabetes and ocular surgery were associated with a lower ECD.
(iv) Age, history of cataract surgery and diabetes were found to be the greatest risk factors for inadequate donor quality with respect to ECD. |
| Schwarz, 2016 [144] | Case-control | 22 donors (27 corneas):
(i) Nondiabetes (9 corneas, 8 donors)
(ii) Diabetes without evidence of advanced disease (8 corneas, 7 donors)
(iii) Diabetes with evidence of advanced disease (10 corneas, 7 donors). | (i) Specular microscopy (technology not specified)
(ii) The adhesion strength of endothelium-descemet membrane complex to the posterior stroma was measured by an own method developed by the investigators (see article). | (i) ECD, hexagonality, and CV.
(ii) Variables obtained from mechanical peel testing were:
(1) Endothelium-descemet membrane complex elastic peel tension (TE)
(2) Elastic stiffness (SE)
(3) Average delamination tension (TD), and maximum tension (TMAX) | (i) The three groups did not differ in ECD, hexagonality, and CV.
(ii) Diabetes with evidence of advanced disease had values for TE, TD, and TMAX greater than nondiabetes and diabetes without evidence of advanced disease corneas. |
| Liaboe, 2017 [145] | Retrospective case-controls | 2112 donors (4185 corneas) divided in 4 groups:
(i) Nondiabetes(2636 corneas)
(ii) NID-diabetes (847 corneas)
(iii) ID-diabetes without medical complications due to diabetes (471 corneas)
(iv) I-diabetes with medical complications due to diabetes (231 corneas). | Noncontact specular microscopy (KeratoAnalyzer EKA-10; Konan Medical USA, Irvine, CA) | Donor age, death to preservation time, ECD, hexagonality, and CV. | (i) I-diabetes with medical complications due to diabetes corneas showed a significant reduction in mean ECD compared with nondiabetic and NI-diabetes.
(ii) There were no significant differences in endothelial cell hexagonality or coefficient of variation among the 4 groups. |
| Aldrich, 2017 [146] | Case-control | 159 donors (229 corneas) all of them with ECD> 2000 cells/mm2. Divided in 4 groups:
(i) Nondiabetes
(ii) NID-diabetes
(iii) ID-diabetes without medical complications due to diabetes
(iv) ID-diabetes with medical complications due to diabetes | (i) Noncontact specular microscopy (KeratoAnalyzer EKA-10; Konan Medical USA, Irvine, CA, USA)
(ii) Transmission electron microscopes (EM 906E; Carl Zeiss Microscopy, Oberkochen, Germany) | (i) ECD, hexagonality, and CV.
(ii) Qualitative and quantitative ultrastructural changes in corneal endothelial cells quantified with transmission electron microscope:
(iii) Number of mitochondria per µm2, surface area per mitochondria in µm2, and total mitochondrial surface area per 20 µm2 field of view. | (i) ID-diabetes with medical complications due to diabetes displayed the lowest spare respiratory values compared to all other groups.
(ii) The remaining mitochondrial respiration and glycolysis metrics did not differ significantly among groups.
(iii) Compared to nondiabetes, the endothelium from ID-diabetes with medical complications due to diabetes had alterations in mitochondrial morphology, pronounced Golgi bodies associated with abundant vesicles, accumulation of lysosomal bodies/autophagosomes, and focal production of abnormal long-spacing collagen. |
| Chen, 2017 [147] | Case-control | (i) 20,026 nondiabetes donor eyes
(ii) 13,617 diabetes donor eyes | Specular microscope (Konan EB-10; Konan, Hyogo, Japan). | ECD | Amongst phakic donors, diabetic ECD was lower in the middle aged subgroups, between 21 and 40 years and between 41 and 60 years. There was no difference in ECD for phakic corneas from the subset aged 61 years or older. |
| Chocron, 2018 [148] | Retrospective case-control | 17056 donors:
(i) Diabetes (4766 patients):
(ii) Metformin consumers
(iii) Nonmetformin consumers
(iv) Controls (12290 patients) | Specular microscopy (Konan Cell Check EB-10; Konan, Hyogo, Japan) | Age, sex, race, medical history, medication list at the time of death, and ECD. | (i) ECD was lower in patients with diabetes.
(ii) ECD was not associated with metformin use in patients with diabetes.
(iii) Metformin use was significantly associated with lower ECD among patients with glaucoma. |
| Skeie, 2018 [149] | Case-control | 19 donors:
(i) 4 nondiabetes
(ii) 10 nonadvanced diabetes (without or with history of home insulin use)
(iii) 5 advanced diabetes with medical complications due to diabetes (history of home insulin use and end-organ damage specifically noted in the medical history) | Multidimensional protein identification technology mass spectrometry | Corneal endothelial cell layer and descemet membrane proteome characterization | (i) Decrease in relative protein abundance in insulin-dependent samples (nonadvanced diabetes insulin-dependent and advanced diabetes) compared to non-insulin-dependent samples (nondiabetes and nonadvanced diabetes without insulin use).
(ii) Comparing the nonadvanced diabetes insulin-dependent and advanced diabetes groups, mitochondria protein levels appear to increase as the disease progresses. |
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