SpringerLink
Log in

Nomogram-based prediction of clinically significant macular edema in diabetes mellitus patients

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Aims

The aim of the study was to construct and validate a risk nomogram for clinically significant macular edema (CSME) prediction in diabetes mellitus (DM) patients using systemic variables.

Methods

In this retrospective study, DM inpatients who underwent routine diabetic retinopathy screening were recruited and divided into training and validation sets according to their admission date. Ninety-three demographic and systemic variables were collected. The least absolute shrinkage and selection operator was used to select the predictive variables from the training set. The selected variables were used to construct the CSME prediction nomogram. Internal and external validations were performed. The C-index, calibration curve and decision curve analysis (DCA) were reported.

Results

A total of 349 patients were divided into the training set (240, 68.77%) and the validation set (109, 31.23%). The presence of diabetic peripheral neuropathy (DPN) symptoms, uric acid, use of insulin only or not for treatment, insulin dosage, urinary protein grade and disease duration were chosen for the nomogram. The C-index of the prediction nomogram was 0.896, 0.878 and 0.837 in the training set, internal validation and external validation, respectively. The calibration curves of the nomogram showed good agreement between the predicted and actual outcomes. DCA demonstrated that the nomogram was clinically useful.

Conclusions

A nomogram with good performance for predicting CSME using systemic variables was developed. It suggested that DPN symptoms and renal function may be crucial risk factors for CSME. Moreover, this nomogram may be a convenient tool for non-ophthalmic specialists to rapidly recognize CSME in patients and to transfer them to ophthalmologists for early diagnosis and treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Thailand)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Cho NH, Shaw JE, Karuranga S et al (2018) IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281

    Article  CAS  PubMed  Google Scholar 

  2. Tan GS, Cheung N, Simó R et al (2017) Diabetic macular oedema. Lancet Diabetes Endocrinol 5(2):143–155

    Article  CAS  PubMed  Google Scholar 

  3. Flaxel CJ, Adelman RA, Bailey ST et al (2020) Diabetic retinopathy preferred practice pattern®. Ophthalmology 127(1):P66-p145

    Article  PubMed  Google Scholar 

  4. Vié AL, Kodjikian L, Agard E et al (2019) Evaluation of obstructive sleep apnea syndrome as a risk factor for diabetic macular edema in patients with type II diabetes. Retina 39(2):274–280

    Article  PubMed  Google Scholar 

  5. Merante D, Menchini F, Truitt KE et al (2010) Diabetic macular edema: correlations with available diabetes therapies–evidence across a qualitative review of published literature from MEDLINE and EMBASE. Drug Saf 33(8):643–652

    Article  CAS  PubMed  Google Scholar 

  6. Das R, Kerr R, Chakravarthy U et al (2015) Dyslipidemia and diabetic macular edema: a systematic review and meta-analysis. Ophthalmology 122(9):1820–1827

    Article  PubMed  Google Scholar 

  7. Kamoi K, Takeda K, Hashimoto K et al (2013) Identifying risk factors for clinically significant diabetic macula edema in patients with type 2 diabetes mellitus. Curr Diabetes Rev 9(3):209–217

    Article  PubMed  Google Scholar 

  8. Liu E, Craig JE, Burdon K (2017) Diabetic macular oedema: clinical risk factors and emerging genetic influences. Clin Exp Optom 100(6):569–576

    Article  PubMed  Google Scholar 

  9. Milluzzo A, Maugeri A, Barchitta M et al (2021) Epigenetic mechanisms in type 2 diabetes retinopathy: a systematic review. Int J Mol Sci 22(19):10502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Balachandran VP, Gonen M, Smith JJ et al (2015) Nomograms in oncology: more than meets the eye. Lancet Oncol 16(4):e173–e180

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shi R, Niu Z, Wu B et al (2020) Nomogram for the risk of diabetic nephropathy or diabetic retinopathy among patients with type 2 diabetes mellitus based on questionnaire and biochemical indicators: a cross-sectional study. Diabetes Metab Syndr Obes 13:1215–1229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jiang S, Fang J, Yu T et al (2020) Novel model predicts diabetic nephropathy in type 2 diabetes. Am J Nephrol 51(2):130–138

    Article  PubMed  Google Scholar 

  13. Li M, Yuan T, Li S et al (2021) Nomogram analysis of the influencing factors of diabetic foot in patients with diabetes mellitus. Hormones (Athens) 20(2):333–338

    Article  Google Scholar 

  14. Association AD (2015) Classification and diagnosis of diabetes. Diabetes Care 38(Suppl):S8-s16

    Article  Google Scholar 

  15. Li DY, Yin WJ, Yi YH et al (2019) Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population. Kidney Int 95(3):636–646

    Article  PubMed  Google Scholar 

  16. Solomon SD, Chew E, Duh EJ et al (2017) Diabetic retinopathy: a position statement by the American diabetes association. Diabetes Care 40(3):412–418

    Article  PubMed  PubMed Central  Google Scholar 

  17. Dai P, Chang W, **n Z et al (2021) Retrospective study on the influencing factors and prediction of hospitalization expenses for chronic renal failure in china based on random forest and lasso regression. Front Public Health 9:678276

    Article  PubMed  PubMed Central  Google Scholar 

  18. Xepapadaki E, Nikdima I, Sagiadinou EC et al (2021) HDL and type 2 diabetes: the chicken or the egg? Diabetologia 64(9):1917–1926

    Article  CAS  PubMed  Google Scholar 

  19. Zander E, Herfurth S, Bohl B et al (2000) Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors. Br J Ophthalmol 84(8):871–876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Varma R, Bressler NM, Doan QV et al (2014) Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol 132(11):1334–1340

    Article  PubMed  PubMed Central  Google Scholar 

  21. Acan D, Calan M, Er D et al (2018) The prevalence and systemic risk factors of diabetic macular edema: a cross-sectional study from Turkey. BMC Ophthalmol 18(1):91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Mo R, Shi R, Hu Y et al (2020) Nomogram-based prediction of the risk of diabetic retinopathy: a retrospective study. J Diabetes Res 2020:7261047

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Chen X, **e Q, Zhang X et al (2021) Nomogram prediction model for diabetic retinopathy development in type 2 diabetes mellitus patients: a retrospective cohort study. J Diabetes Res 2021:3825155

    PubMed  PubMed Central  Google Scholar 

  24. Bek T (2020) Systemic risk factors contribute differently to the development of proliferative diabetic retinopathy and clinically significant macular oedema. Diabetologia 63(11):2462–2470

    Article  CAS  PubMed  Google Scholar 

  25. Pradhana D, Priya MNS, Surya J et al (2021) Optical coherence tomography-based prevalence of diabetic macular edema and its associated risk factors in urban south India: a population-based study. Ophthalmic Epidemiol. https://doi.org/10.1080/09286586.2021.1907846

    Article  PubMed  Google Scholar 

  26. Moran EP, Wang Z, Chen J et al (2016) Neurovascular cross talk in diabetic retinopathy: pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol 311(3):H738-749

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zhang B, Chou Y, Zhao X et al (2021) Early detection of microvascular impairments with optical coherence tomography angiography in diabetic patients without clinical retinopathy: a meta-analysis. Am J Ophthalmol 222:226–237

    Article  PubMed  Google Scholar 

  28. Salvi L, Plateroti P, Balducci S et al (2016) Abnormalities of retinal ganglion cell complex at optical coherence tomography in patients with type 2 diabetes: a sign of diabetic polyneuropathy, not retinopathy. J Diabetes Compli 30(3):469–476

    Article  Google Scholar 

  29. Liu ZY, Ma XJ, Liao DY et al (2019) Association of urinary albumin excretion with central foveal thickness and intravitreal conbercept treatment frequency in patients with diabetic macular edema. Int J Ophthalmol 12(10):1598–1604

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yamamoto M, Fujihara K, Ishizawa M et al (2019) Overt proteinuria, moderately reduced egfr and their combination are predictive of severe diabetic retinopathy or diabetic macular edema in diabetes. Invest Ophthalmol Vis Sci 60(7):2685–2689

    Article  CAS  PubMed  Google Scholar 

  31. Lai IP, Huang WL, Yang CM et al (2020) Renal biomarkers for treatment effect of ranibizumab for diabetic macular edema. J Diabetes Res 2020:7239570

    PubMed  PubMed Central  Google Scholar 

  32. Daruich A, Matet A, Moulin A et al (2018) Mechanisms of macular edema: beyond the surface. Prog Retin Eye Res 63:20–68

    Article  PubMed  Google Scholar 

  33. Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48

    Article  CAS  PubMed  Google Scholar 

  34. Ciardella AP (2004) Partial resolution of diabetic macular oedema after systemic treatment with furosemide. Br J Ophthalmol 88(9):1224–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Krizova L, Kalousova M, Kubena AA et al (2015) Correlation of vitreous vascular endothelial growth factor and uric acid concentration using optical coherence tomography in diabetic macular edema. J Ophthalmol 2015:478509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Zhu DD, Wang YZ, Zou C et al (2018) The role of uric acid in the pathogenesis of diabetic retinopathy based on notch pathway. Biochem Biophys Res Commun 503(2):921–929

    Article  CAS  PubMed  Google Scholar 

  37. Kuwata H, Okamura S, Hayashino Y et al (2017) Serum uric acid levels are associated with increased risk of newly developed diabetic retinopathy among Japanese male patients with type 2 diabetes: A prospective cohort study (diabetes distress and care registry at Tenri [DDCRT 13]). Diabetes Metab Res Rev 33(7):e2905

    Article  CAS  Google Scholar 

  38. Pilemann-Lyberg S, Hansen TW, Persson F et al (2019) Uric acid is not associated with diabetic nephropathy and other complications in type 1 diabetes. Nephrol Dial Transplant 34(4):659–666

    Article  CAS  PubMed  Google Scholar 

  39. Wang Y, Lin Z, Zhai G et al (2020) Prevalence of and risk factors for diabetic retinopathy and diabetic macular edema in patients with early and late onset diabetes mellitus. Ophthalmic Res. https://doi.org/10.1159/000508335

    Article  PubMed  Google Scholar 

  40. Stratton IM, Adler AI, Neil HA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321(7258):405–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Nathan DM, Genuth S, Lachin J et al (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329(14):977–986

    Article  CAS  PubMed  Google Scholar 

  42. Wang PH, Lau J, Chalmers TC (1994) Metaanalysis of the effects of intensive glycemic control on late complications of type I diabetes mellitus. RETINA 14(3):287–288

    Article  CAS  Google Scholar 

  43. Zhao C, Wang W, Xu D et al (2014) Insulin and risk of diabetic retinopathy in patients with type 2 diabetes mellitus: data from a meta-analysis of seven cohort studies. Diagn Pathol 9:130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Zhang J, Ma J, Zhou N et al (2015) Insulin use and risk of diabetic macular edema in diabetes mellitus: a systemic review and meta-analysis of observational studies. Med Sci Monit 21:929–936

    Article  PubMed  PubMed Central  Google Scholar 

  45. **gi AM, Tankeu AT, Ateba NA et al (2017) Mechanism of worsening diabetic retinopathy with rapid lowering of blood glucose: the synergistic hypothesis. BMC Endocr Disord 17(1):63

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Fei Z, Gao W, Xu X et al (2021) Serum superoxide dismutase activity: a sensitive, convenient, and economical indicator associated with the prevalence of chronic type 2 diabetic complications, especially in men. Free Radic Res 55(3):275–281

    Article  CAS  PubMed  Google Scholar 

  47. Zhao JS, ** HX, Gao JL et al (2018) serum extracellular superoxide dismutase is associated with diabetic retinopathy stage in chinese patients with type 2 diabetes mellitus. Dis Markers 2018:8721379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The research was funded by Science and Technology Projects of Guangzhou, China (3030901006062), and Project of Administration of Traditional Chinese Medicine of Guangdong Province, China (20221077).

Funding

The research was funded by Science and Technology Projects of Guangzhou, China (3030901006062) and Project of Administration of Traditional Chinese Medicine of Guangdong Province, China (20221077).

Author information

Author notes

  1. Zi**g Li and **aowen Deng contributed equally to the manuscript as first authors.

Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 54 South **anlie Road, Guangzhou, 510060, China

    Zi**g Li, Lijun Zhou, Tu Lu & Chen** **

  2. Department of Ophthalmology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510020, China

    Zi**g Li, **aowen Deng & Yuqing Lan

Authors
  1. Zi**g Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. **aowen Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lijun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tu Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuqing Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chen** **
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yuqing Lan or Chen** **.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Informed consent

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques

This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 51 kb)

Supplementary file2 (DOCX 20 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Deng, X., Zhou, L. et al. Nomogram-based prediction of clinically significant macular edema in diabetes mellitus patients. Acta Diabetol 59, 1179–1188 (2022). https://doi.org/10.1007/s00592-022-01901-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-022-01901-3

Keywords

Search

Navigation