PMID- 28296936
OWN - NLM
STAT- MEDLINE
DCOM- 20170912
LR  - 20190208
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 3
DP  - 2017
TI  - Spatial analysis improves the detection of early corneal nerve fiber loss in 
      patients with recently diagnosed type 2 diabetes.
PG  - e0173832
LID - 10.1371/journal.pone.0173832 [doi]
LID - e0173832
AB  - Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) 
      length and density (CNFL, CNFD) in patients with diabetes, but the spatial 
      pattern of CNF loss has not been studied. We aimed to determine whether spatial 
      analysis of the distribution of corneal nerve branching points (CNBPs) may 
      contribute to improving the detection of early CNF loss. We hypothesized that 
      early CNF decline follows a clustered rather than random distribution pattern of 
      CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing 
      (QST) were performed in a cross-sectional study including 86 patients recently 
      diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, 
      CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern 
      analysis (SPPA) including 10 indices and functional statistics. Compared to 
      controls, patients with diabetes showed lower CNBP density and higher nearest 
      neighbor distances, and all SPPA parameters indicated increased clustering of 
      CNBPs (all P<0.05). SPPA parameters were abnormally increased >97.5th percentile 
      of controls in up to 23.5% of patients. When combining an individual SPPA 
      parameter with CNFL, >/=1 of 2 indices were >99th or <1st percentile of controls in 
      28.6% of patients compared to 2.1% of controls, while for the conventional 
      CNFL/CNFD/CNBD combination the corresponding rates were 16.3% vs 2.1%. SPPA 
      parameters correlated with CNFL and several NCS and QST indices in the controls 
      (all P<0.001), whereas in patients with diabetes these correlations were markedly 
      weaker or lost. In conclusion, SPPA reveals increased clustering of early CNF 
      loss and substantially improves its detection when combined with a conventional 
      CCM measure in patients with recently diagnosed type 2 diabetes.
FAU - Ziegler, Dan
AU  - Ziegler D
AUID- ORCID: 0000-0001-8956-3552
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
AD  - Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine 
      University, Dusseldorf, Germany.
AD  - German Center for Diabetes Research (DZD), Munchen-Neuherberg, Germany.
FAU - Winter, Karsten
AU  - Winter K
AD  - Institute of Anatomy, University of Leipzig, Leipzig, Germany.
FAU - Strom, Alexander
AU  - Strom A
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
AD  - German Center for Diabetes Research (DZD), Munchen-Neuherberg, Germany.
FAU - Zhivov, Andrey
AU  - Zhivov A
AD  - Department of Ophthalmology, University of Rostock, Rostock, Germany.
FAU - Allgeier, Stephan
AU  - Allgeier S
AD  - Institute for Applied Computer Science, Karlsruhe Institute of Technology, 
      Karlsruhe, Germany.
FAU - Papanas, Nikolaos
AU  - Papanas N
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
FAU - Ziegler, Iris
AU  - Ziegler I
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
FAU - Bruggemann, Jutta
AU  - Bruggemann J
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
FAU - Ringel, Bernd
AU  - Ringel B
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
FAU - Peschel, Sabine
AU  - Peschel S
AD  - Department of Ophthalmology, University of Rostock, Rostock, Germany.
FAU - Kohler, Bernd
AU  - Kohler B
AD  - Institute for Applied Computer Science, Karlsruhe Institute of Technology, 
      Karlsruhe, Germany.
FAU - Stachs, Oliver
AU  - Stachs O
AD  - Department of Ophthalmology, University of Rostock, Rostock, Germany.
FAU - Guthoff, Rudolf F
AU  - Guthoff RF
AD  - Department of Ophthalmology, University of Rostock, Rostock, Germany.
FAU - Roden, Michael
AU  - Roden M
AD  - Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine 
      University, Leibniz Center for Diabetes Research, Dusseldorf, Germany.
AD  - Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine 
      University, Dusseldorf, Germany.
AD  - German Center for Diabetes Research (DZD), Munchen-Neuherberg, Germany.
CN  - German Diabetes Study (GDS) Group
LA  - eng
PT  - Journal Article
DEP - 20170315
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cornea/*physiopathology
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nerve Fibers/*physiology
PMC - PMC5352008
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/03/16 06:00
MHDA- 2017/09/13 06:00
PMCR- 2017/03/15
CRDT- 2017/03/16 06:00
PHST- 2016/11/23 00:00 [received]
PHST- 2017/02/27 00:00 [accepted]
PHST- 2017/03/16 06:00 [entrez]
PHST- 2017/03/16 06:00 [pubmed]
PHST- 2017/09/13 06:00 [medline]
PHST- 2017/03/15 00:00 [pmc-release]
AID - PONE-D-16-46504 [pii]
AID - 10.1371/journal.pone.0173832 [doi]
PST - epublish
SO  - PLoS One. 2017 Mar 15;12(3):e0173832. doi: 10.1371/journal.pone.0173832. 
      eCollection 2017.