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Early retinal neurovascular impairment in patients with diabetes without clinically detectable retinopathy
  1. Yunkao Zeng1,2,
  2. Dan Cao1,
  3. Honghua Yu1,
  4. Dawei Yang1,2,
  5. Xuenan Zhuang1,2,
  6. Yunyan Hu1,
  7. Juan Li1,
  8. Jing Yang1,
  9. Qiaowei Wu1,3,
  10. Baoyi Liu1,3,
  11. Liang Zhang1
  1. 1 Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
  2. 2 Shantou University Medical College, Shantou, China
  3. 3 Southern Medical University, Guangzhou, China
  1. Correspondence to Dr Liang Zhang, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 106, China; zhangliang5413{at}


Aims To investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy.

Methods Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls were recruited. The 16 and 32 Tds flicker electroretinography (ERG) was performed using a mydriasis-free, full-field flicker ERG recording device (RETeval). The vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), FD300 and ganglion cell complex (GCC) thickness in the macula were quantified using optical coherence tomography angiography (OCTA). The retinal nerve fibre layer (RNFL) thickness and the radial peripapillary capillary (RPC) density in the peripapillary area were also measured with OCTA.

Results Parafoveal and perifoveal VD in both SCP and DCP decreased in NDR group in comparison to control group (all p<0.01). However, macular GCC thickness was comparable between the two groups (p=0.661). Peripapillary RNFL thickness and RPC density were significantly lower in NDR group (p<0.001 and p=0.009, respectively). With regard to ERG parameters, delayed implicit time and decreased amplitude were found in NDR group in comparison to the control group (all p<0.01). In the multiple linear regression analyses, delayed implicit time for 16 and 32 Tds stimuli was significantly correlated with increased HbA1c (β=0.350, p<0.001; β=0.328, p<0.001, respectively) and decreased VD of SCP in the parafoveal region (β=−0.266, p=0.013; β=−0.253, p=0.005, respectively). However, delayed implicit time for 16 and 32 Tds stimuli was not correlated with the thickness of GCC (β=−0.008, p=0.818) in multiple linear regression analyses.

Conclusion Functional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions. Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients. Poor control of blood glucose was associated with delayed implicit time of flicker ERG in preclinical diabetic retinopathy.

  • electrophysiology
  • imaging
  • macula
  • retina
  • diagnostic tests/investigation

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  • YZ and DC contributed equally.

  • Contributors LZ, YZ and DC: conception and design. YZ, HY, JL, JY, DY, XZ, QW and BL: data collection, analysis and/or interpretation. YZ and DC: drafting the article. LZ and YZ: final approval of the version to be published.

    All authors revised the article critically for important intellectual content.

    All authors read and approved the final manuscript.

  • Funding This study was funded by National Natural Science Foundation of China (Grant Number 81870663) and Guangzhou Science and Technology Program (Grant Number 201607010343).

  • Disclaimer The sponsors or funding organizations had no role in the design or conduct of this research.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained

  • Ethics approval Research Ethics Committee of the Guangdong General Hospital (No 2016232A).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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