Predictors of proliferative diabetic retinopathy among patients with type 2 diabetes mellitus in Malaysia as detected by fundus photography

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Original Article

Predictors of proliferative diabetic retinopathy among patients

with type 2 diabetes mellitus in Malaysia as detected by fundus

photography

Masliza H. Mohd Ali, MMed

a

, Nani Draman, MMed

b,*

,

Wan M.I.W. Mohamed, MMed

a

, Azhany Yaakub, MMed

c

and

Zunaina Embong, MMed

c

aDepartment of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia bDepartment of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia cDepartment of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

Received 29 December 2015; revised 3 March 2016; accepted 4 March 2016; Available online 22 April 2016

ﺍﻟ ﻤ ﻠ ﺨ ﺺ ﺃ ﻫ ﺪﺍ ﻑ ﺍﻟ ﺒ ﺤ ﺚ : ﻣ ﺮ ﺽ ﺍﻟ ﻌﻴ ﻦ ﺍﻟ ﻨﺎ ﺗ ﺞ ﻋ ﻦ ﺩﺍ ﺀ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﻫ ﻮ ﺍﻟ ﺴ ﺒ ﺐ ﺍ ﻷ ﻛﺜ ﺮ ﺷ ﻴ ﻮ ﻋ ﺎ ﻟﻔ ﻘﺪ ﺍ ﻥ ﺍﻟ ﺒ ﺼ ﺮ ﻟﺪ ﻯ ﺍﻟ ﺒﺎ ﻟﻐ ﻴ ﻦ ﻭ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒ ﻜﻴ ﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟ ﺘ ﻜﺎ ﺛ ﺮ ﻱ ﻫ ﻮ ﺍﻟ ﺴ ﺒ ﺐ ﺍﻟ ﺮ ﺋﻴ ﺲ ﻟﻠ ﻌ ﻤ ﻰ . ﺗ ﻬ ﺪ ﻑ ﻫ ﺬﻩ ﺍﻟ ﺪ ﺭ ﺍ ﺳ ﺔ ﻟﺘ ﺤ ﺪﻳ ﺪ ﺍﻟ ﻌ ﻮﺍ ﻣ ﻞ ﺍﻟ ﻤ ﻬ ﻴﺌ ﺔ ﻻ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒ ﻜﻴ ﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟ ﺘ ﻜﺎ ﺛ ﺮ ﻱ ﺍﻟ ﺘ ﻲ ﺗﻢ ﺗ ﺤ ﺪﻳ ﺪ ﻫ ﺎ ﺑ ﻮ ﺍ ﺳ ﻄ ﺔ ﺗ ﺼ ﻮ ﻳ ﺮ ﻗﺎ ﻉ ﺍﻟ ﻌﻴ ﻦ ﺑﻴ ﻦ ﻣ ﺮ ﺿ ﻰ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟ ﻨ ﻮ ﻉ ٢ ﻓ ﻲ ﻋ ﻴﺎ ﺩﺓ ﺍﻟ ﺴ ﻜ ﺮ ﺑﺎ ﻟﻤ ﺴ ﺘ ﺸ ﻔ ﻰ ﺍﻟ ﺠ ﺎﻣ ﻌ ﻲ ﺑ ﺠ ﺎﻣ ﻌ ﺔ ﺳ ﻴﻨ ﺰ ﻣﺎ ﻟﻴ ﺰ ﻳﺎ . ﻃ ﺮ ﻕ ﺍﻟ ﺒ ﺤ ﺚ : ﻓ ﻲ ﻫ ﺬﻩ ﺍﻟ ﺪ ﺭ ﺍ ﺳ ﺔ ﺍ ﻻ ﺳ ﺘﻌ ﺎﺩ ﻳﺔ , ﺭ ﻭ ﺟ ﻌ ﺖ ﺻ ﻮ ﺭ ﻗﺎ ﻉ ﺍﻟ ﻌﻴ ﻦ ﻟﻤ ﺮ ﺿ ﻰ ﺩﺍ ﺀ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﻨ ﻮ ﻉ ٢ ﺍﻟ ﺬﻳ ﻦ ﺧ ﻀ ﻌ ﻮﺍ ﻟﻔ ﺤ ﺺ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺑﺎ ﺳ ﺘ ﺨ ﺪﺍ ﻡ ﻛﺎ ﻣﻴ ﺮ ﺍ ﻗﺎ ﻉ ﺍﻟ ﻌﻴ ﻦ ﻏ ﻴ ﺮ ﺍﻟ ﻤ ﻮ ﺳ ﻌ ﺔ ﻟﻠ ﺤ ﺪﻗ ﺔ ﻓ ﻲ ﺍﻟ ﻔﺘ ﺮ ﺓ ﻣ ﻦ ﻳﻨ ﺎﻳ ﺮ ٢٠٠٨ ﻡ ﺇﻟ ﻰ ﺩﻳ ﺴ ﻤﺒ ﺮ ٢٠١٢ ﻡ . ﻭ ﺻ ﻨﻔ ﺖ ﺻ ﻮ ﺭ ﻗﺎ ﻉ ﺍﻟ ﻌﻴ ﻦ ﺇﻟ ﻰ ﻣ ﺠ ﻤ ﻮ ﻋ ﺘﻴ ﻦ : ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﺘ ﻜﺎ ﺛ ﺮ ﻱ ، ﻭ ﻋ ﺪ ﻡ ﻭ ﺟ ﻮ ﺩ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ . ﺗﻢ ﺍﻟ ﺤ ﺼ ﻮ ﻝ ﻋ ﻠ ﻰ ﺍﻟﺒ ﻴﺎ ﻧﺎ ﺕ ﺍ ﻻ ﺟ ﺘﻤ ﺎ ﻋ ﻴﺔ ﻭﺍ ﻟﺪ ﻳﻤ ﻮ ﻏ ﺮ ﺍﻓ ﻴﺔ , ﻭﺍ ﻟﻤ ﻠ ﻒ ﺍﻟ ﺸ ﺨ ﺼ ﻲ ﺍﻟ ﺴ ﺮ ﻳ ﺮ ﻱ ﻭﺍ ﻷ ﻳ ﻀ ﻲ ﻣ ﻦ ﺍﻟ ﺴ ﺠ ﻼ ﺕ ﺍﻟ ﻄ ﺒﻴ ﺔ . ﻛ ﻤﺎ ﺗﻢ ﺍ ﺳ ﺘ ﺨ ﺪﺍ ﻡ ﺍ ﻻ ﻧ ﺤ ﺪﺍ ﺭ ﺍﻟﻠ ﻮ ﺟ ﺴ ﺘ ﻲ ﻟﺘ ﺤ ﺪﻳ ﺪ ﺍﻟ ﻌ ﻮﺍ ﻣ ﻞ ﺍﻟ ﻤ ﺮ ﺗﺒ ﻄ ﺔ ﻻ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﺘ ﻜﺎ ﺛ ﺮ ﻱ . ﺍﻟ ﻨﺘ ﺎﺋ ﺞ : ﺗﻢ ﺍ ﺧ ﺘﻴ ﺎ ﺭ ١٢٠ ﻣ ﺮ ﻳ ﻀ ﺎ ، ﻣﻨ ﻬ ﻢ ٣٠ ﻣ ﺮ ﻳ ﻀ ﺎ ﻓ ﻲ ﻣ ﺠ ﻤ ﻮ ﻋ ﺔ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﺘ ﻜﺎ ﺛ ﺮ ﻱ ﻭ ٩٠ ﻣ ﺮ ﻳ ﻀ ﺎ ﻓ ﻲ ﻣ ﺠ ﻤ ﻮ ﻋ ﺔ ﻋ ﺪ ﻡ ﻭ ﺟ ﻮ ﺩ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ . ﻛﺎ ﻥ ﻣﺘ ﻮ ﺳ ﻂ ﺍﻟ ﻌ ﻤ ﺮ ﻟﻤ ﺮ ﺿ ﻰ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﺘ ﻜﺎ ﺛ ﺮ ﻱ ٥٢ ﻋ ﺎﻣ ﺎ ﻭ ٥٨ ﻋ ﺎﻣ ﺎ ﻓ ﻲ ﻣ ﺠ ﻤ ﻮ ﻋ ﺔ ﻋ ﺪ ﻡ ﻭ ﺟ ﻮ ﺩ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ . ﻭ ﻛﺎ ﻥ ﺍ ﺭ ﺗﻔ ﺎ ﻉ ﺿ ﻐ ﻂ ﺍﻟ ﺪ ﻡ ﻭﺍ ﺭ ﺗﻔ ﺎ ﻉ ﺍﻟ ﺪ ﻫ ﻮ ﻥ ﺍ ﻷ ﻛﺜ ﺮ ﺷ ﻴ ﻮ ﻋ ﺎ ﻟ ﻸ ﻣ ﺮ ﺍ ﺽ ﺍﻟ ﻤ ﺼ ﺎ ﺣ ﺒﺔ ﻓ ﻲ ﻫ ﺬﻩ ﺍﻟ ﺪ ﺭ ﺍ ﺳ ﺔ . ﻣ ﺴ ﺘ ﻮ ﻯ ﺍﻟ ﻬﻴ ﻤ ﻮ ﻏ ﻠﻮ ﺑﻴ ﻦ ﺍﻟ ﻐﻠ ﻴﻜ ﻮ ﺯ ﻳ ﻼ ﺗ ﻲ < ٦.٥ ٪ ﻭ ﻣ ﺴ ﺘ ﻮ ﻯ ﺍﻟﺒ ﺮ ﻭ ﺗﻴ ﻦ ﺍﻟ ﺸ ﺤ ﻤ ﻲ ﺧ ﻔﻴ ﺾ ﺍﻟ ﻜﺜ ﺎﻓ ﺔ < ٢.٦ ﻣ ﻤ ﻮ ﻝ ⁄ ﻝ ﻛﺎ ﻧﺎ ﺃ ﻋ ﻠ ﻰ ﻓ ﻲ ﻣ ﺠ ﻤ ﻮ ﻋ ﺔ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﺘ ﻜﺎ ﺛ ﺮ ﻱ . ﺍﻟ ﻌ ﻤ ﺮ ) ﻗﻴ ﻤ ﺔ ﺏ ¼ ٠.٠٣٢ ( ﻣ ﺪﺓ ﺩﺍ ﺀ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ) ﻗﻴ ﻤ ﺔ ﺏ ¼ ٠.٠٢٢ ( ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﻜﻠ ﻴﺔ ) ﻗﻴ ﻤ ﺔ ﺏ ¼ ٠.٠٠٢ ( ﻭﺍ ﻻ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﻌ ﺼ ﺒ ﻲ ﺍﻟ ﻄ ﺮ ﻓ ﻲ ) ﻗﻴ ﻤ ﺔ ﺏ ¼ ٠.٠٠١ ( ﻛﺎ ﻥ ﻟﻪ ﺍ ﺭ ﺗﺒ ﺎ ﻁ ﻛﺒ ﻴ ﺮ ﻣ ﻊ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒﻜ ﻴﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟﺘ ﻜﺎ ﺛ ﺮ ﻱ . ﺍ ﻻ ﺳ ﺘﻨ ﺘﺎ ﺟ ﺎ ﺕ : ﺍﻟ ﺘﻨ ﺒ ﺆ ﺍ ﺕ ﺍﻟ ﻜﺒ ﻴ ﺮ ﺓ ﻻ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒ ﻜﻴ ﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟ ﺘ ﻜﺎ ﺛ ﺮ ﻱ ﺑﻴ ﻦ ﻣ ﺮ ﺿ ﻰ ﺍﻟ ﺴ ﻜ ﺮ ﺍﻟ ﻨ ﻮ ﻉ ٢ ، ﻛ ﻤﺎ ﺗﻢ ﻛ ﺸ ﻔ ﻬﺎ ﺑﺘ ﺼ ﻮ ﻳ ﺮ ﻗﺎ ﻉ ﺍﻟ ﻌﻴ ﻦ ﻫ ﻲ ﺍﻟ ﻌ ﻤ ﺮ , ﻭ ﻣ ﺪﺓ ﺍ ﻹ ﺻ ﺎﺑ ﺔ ﺑﺪ ﺍﺀ ﺍﻟ ﺴ ﻜ ﺮ ﻱ , ﻭ ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﻜﻠ ﻴﺔ , ﻭ ﺍ ﻻ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﻌ ﺼ ﺒ ﻲ ﺍﻟ ﻄ ﺮ ﻓ ﻲ . ﺍﻟ ﻜﻠ ﻤ ﺎ ﺕ ﺍﻟ ﻤ ﻔﺘ ﺎ ﺣ ﻴ ﺔ : ﺍ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﺸ ﺒ ﻜﻴ ﺔ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ﺍﻟ ﺘ ﻜﺎ ﺛ ﺮ ﻱ ؛ ﺍ ﻻ ﻋ ﺘ ﻼ ﻝ ﺍﻟ ﻌ ﺼ ﺒ ﻲ ﺍﻟ ﻄ ﺮ ﻓ ﻲ ﺍﻟ ﺴ ﻜ ﺮ ﻱ ؛ ﺍ ﺭ ﺗﻔ ﺎ ﻉ ﺿ ﻐ ﻂ ﺍﻟ ﺪ ﻡ ؛ ﻣ ﺮ ﺍ ﺟ ﻌ ﺔ ﺻ ﻮ ﺭ ﺓ ﻗﺎ ﻉ ﺍﻟ ﻌ ﻴ ﻦ ؛ ﺗ ﺼ ﻮ ﻳ ﺮ ﻗﺎ ﻉ ﺍﻟ ﻌﻴ ﻦ Abstract

Objectives: Diabetic eye disease is the most common cause of visual loss in adults, and proliferative diabetic retinopathy (PDR) is the main cause of blindness. This study aimed to determine the predisposing factors for PDR that were identified by fundus photography among patients with type 2 diabetes mellitus (DM) at the Diabetic Clinic at Hospital Universiti Sains Malaysia.

Methods: In this retrospective study, fundus photo re-view was performed on patients with type 2 DM who had undergone diabetic retinopathy screening using a non-mydriatic fundus camera from January 2008 until December 2012. Fundus photos were classified into 2 groups, PDR and no apparent diabetic retinopathy (no DR). Socio-demographic data and clinical and metabolic profiles were obtained from the medical records. Logistic regression was used to determine the factors associated with PDR.

*Corresponding address: Department of Family Medicine,

School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.

E-mail:drnani@usm.my(N. Draman)

Peer review under responsibility of Taibah University.

Production and hosting by Elsevier

Taibah University

Journal of Taibah University Medical Sciences

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1658-3612Ó2016 The Authors.

Production and hosting by Elsevier Ltd on behalf of Taibah University. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/).http://dx.doi.org/10.1016/j.jtumed.2016.03.002

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Results: A total of 120 patients were selected, with 30 patients in the PDR group and 90 patients in the no DR group. The mean age of patients with PDR was 52 (7.94) years and was 58 (12.31) years in the no DR group. Hypertension and hyperlipidaemia were the most com-mon comorbidities identified in this study. The HbA1c level>6.5% and LDL level>2.6 mmol/L were higher in the PDR group. Age (p ¼ 0.032), duration of DM (p ¼ 0.022), nephropathy (p ¼ 0.002) and peripheral neuropathy (p¼0.001) were significantly associated with PDR.

Conclusion: The significant predictors of PDR among patients with type 2 DM as detected by fundus photog-raphy were age, duration of DM, nephropathy and pe-ripheral neuropathy.

Keywords: Diabetic peripheral neuropathy; Fundus photo review; Fundus photography; Hypertension; Proliferative diabetic retinopathy

Ó2016 The Authors.

Production and hosting by Elsevier Ltd on behalf of Taibah University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Diabetic retinopathy can be present at the time of diagnosis of type 2 diabetes mellitus (T2DM) due to the insidious onset of the disease, as documented in the United Kingdom Prospective Diabetes Study (UKPDS), in which 39% of men and 35% of women had retinopathy at the time of diagnosis.1 Diabetic retinopathy is a microvascular complication that results from prolonged uncontrolled diabetes mellitus (DM).2 Diabetic retinopathy can be graded into categories of no apparent diabetic retinopathy (no DR), non-proliferative diabetic reti-nopathy (NPDR), proliferative diabetic retireti-nopathy (PDR) and advance diabetic eye disease (ADED).3PDR and ADED are major causes of blindness among patients with DM and are associated with an increased risk of cardiovascular disease, diabetic nephropathy and mortality.4

The occurrence of PDR is due to progressive retinal ischemia leading to vision loss, traction retinal detachment and vitreous haemorrhage.5 Early detection of vision loss and blindness resulting from diabetic retinopathy is important as it is reversible.3 Therefore, an annual eye examination is recommended for patients with DM. Despite this recommendation, according to the National Health Malaysian Survey (NHMS) III 2006 findings, only 45% of patients with DM had undergone an eye examination at least once after their diagnosis of diabetes.6

The prevalence of diabetic retinopathy in Malaysia has been reported to range from 44.1%7to 48.6%.8Other studies have shown that the prevalence of diabetic retinopathy in Malaysia is 12.3% for Type 1 DM and 22.3% for Type 2 DM.9 Most published Malaysian data are primarily hospital-based.9e11 Nevertheless, the prevalence of PDR varies from 2.0% for patients who had diabetes for less

than 5 years to 15.5% for patients who had diabetes for 15 years or more.4In Malaysia, the 2007 Diabetic Eye Registry reported a prevalence of PDR of 7.1%.12 Meanwhile, a recent study conducted in a primary care setting on Borneo Island in 2011 reported a prevalence of PDR of 3.2%.13

Many risk factors for PDR have been identified, such as elevated glycosylated haemoglobin A1c (HbA1c), elevated diastolic and systolic blood pressure, increased duration of diabetes, the severity of retinopathy at baseline, increased waist-to-hip ratio and the onset of type 1 DM before pu-berty.14 PDR is unavoidable and develops irrespective of pharmacological treatment of DM and hypertension. Most published Malaysian data primarily focus on diabetic retinopathy as a whole rather than considering its different stages. In this study, we focused on patients with PDR who were identified during diabetic retinopathy screening using a non-mydriatic fundus camera with the aim of determining the associating factors among PDR patients. These data will provide useful local information regarding PDR and create awareness about the severity of PDR among patients with type 2 DM.

Materials and Methods

This was a retrospective record review of fundus photos from patients with type 2 DM at the Diabetic Clinic, Hos-pital Universiti Sains Malaysia (HUSM) from January 2008 until December 2012. All patients with diabetes who were referred to the Diabetic Clinic were screened for diabetic retinopathy using a non-mydriatic fundus camera. Patients who were more than 18 years old with type 2 DM and who were diagnosed with PDR on the fundus photograph were selected. Patients with Type 1 DM, NPDR, ADED, glau-coma, cataract, retinal vaso-occlusive disease, or poor fundus view or had images due to opaque media and retinal disease were excluded.

The definition for PDR was based on the International Clinical Diabetic Retinopathy and Diabetic Macular Oedema Disease Severity Scale,3which consist of one of the following:

i) Neo-vascularisation

ii) Vitreous/preretinal haemorrhage

For the study group (PDR group), either unilateral or bilateral PDR features on fundus photography were included in the study, while, for the control group, only a bilateral normal fundus was considered for simple random sampling.

The screening process for the study group was based on cases that were diagnosed one year before or after the first fundus photography result. This is because many of the diag-nostic tests were not routinely performed in the study centre.

Diabetic nephropathy was diagnosed based on the pres-ence of proteinuria determined by a positive dipstick on 2 separate occasions, 1 year before or after the first fundus photography. The urinary albumin creatinine (UACR) ratio test is not routinely performed in the study centre.

Diabetic neuropathy is recognized by the American Dia-betes Association (ADA) as the presence of symptoms and/ or signs of peripheral nerve dysfunction in people with dia-betes after the exclusion of other causes.15In this study, any documentation regarding numbness and/or abnormal

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sensation over the hands and feet (stoking and glove distribution) within 1 year before or after the first fundus photography was considered to be diabetic neuropathy. Screening for diabetic neuropathy using a microfilament was not routinely performed in the study centre.

There was no systematic grading of diabetic foot ulcers documented in the medical record. Consequently, any documentation of a diabetic foot ulcer within 1 year before or after the first fundus photography was considered to be evidence of a diabetic foot.

Stroke was considered if a stroke had occurred within 1 year before or after the first fundus photography. Any documentation of cardiac events, such as acute coronary syndrome, arrhythmia, heart failure or significant ECG changes, that occurred during follow-up within 1 year before or after the first fundus photography was considered to be evidence of coronary artery disease.

We estimated a sample size of 30 patients in the PDR group based on a power of 80%, an

a

of 0.05 and a reduction rate of 10%.16 Using random sampling, a ratio of 3:1 was used for the recruitment of the control group (Type 2 DM with no DR or normal fundus) for a total of 90 patients. Study procedure

The list of patients who received fundus photography from January 2008 until December 2012 was obtained from the fundus camera book record at the Diabetic Clinic, HUSM. Fundus photographs were divided into 3 groups: no DR, PDR and other findings. Information on patient socio-demographics, diabetic complications (neuropathy, ne-phropathy, stroke, and cardiovascular disease), glycaemic control (HbA1c), and cardiovascular risk factors (body mass index, blood pressure, lipids, and smoking history) were collected from the patients’ medical records and cross-checked with the database of the HUSM laboratories. Statistical analysis

Statistical analyses were performed using the Statistical Program for Social Sciences (SPSS version 22.0). For the descriptive analysis, numerical variables are described as the mean and standard deviation. Categorical data are presented as the frequency and percentage. Simple logistic regression analysis was used to assess the significance of variables in predicting the outcomes. Significant variables with apvalue of <0.25 were then assessed via multivariable analysis by using multiple logistic regression.

The study protocol was approved in 2013 by the Research and Ethics Committee, School of Medical Sciences, Uni-versiti Sains Malaysia. This study was conducted in accor-dance with the principles set forth by the 18th World Medical Assembly (Helsinky, 1964) and all subsequent amendments. The patients’ personal identification and clinical data were kept confidential, and data were reported as collective information.

Result

A total of 4341 fundus photos of patients were reviewed. There were 33 patients with PDR, 2952 patients with no DR

or a normal fundus, and 1356 patients with other findings. One-hundred-twenty patients were suitable for the study, of which 90 had with no DR and 33 had PDR. However, medical reports were missing for 3 patients with PDR, leaving 30 patients in the final PDR group.

The mean (SD) age of patients with no DR and PDR was 57 years (12.3) and 52 years, respectively (7.9). There were more females in the PDR group (53.3%) compared with the no DR group (45.6%). The majority of patients were Malay (n¼98), while the non-Malay ethnic group was in the mi-nority (n¼22). The majority of the no DR patients were non-smokers (84.4%) and had type 2 DM for less than 10 years (68.9%). A total of 60.0% of patients in the PDR group had type 2 DM for more than 10 years. Hypertension (76.7% in no DR and 73.3% in PDR) and hyperlipidaemia (85.6% in no DR and 80.0% in PDR) were the most com-mon comorbidities. Systolic blood pressure (SBP) and

Table 1: Socio-demographic data of type 2 DM patients with no DR and PDR group. Variables No DR (n¼90) PDR (n¼30) n (%) n (%) Age (years) 57 (12.3)a 52 (7.9)a Gender Male 49 (54.4) 14 (46.7) Female 41 (45.6) 16 (53.3) Race Non Malay 17 (18.9) 5 (16.7) Malay 73 (81.1) 25 (83.3) Smoking Nonsmoker 76 (84.4) 20 (66.7) Smoker 14 (15.6) 10 (33.3) Duration 10 years 62 (68.9) 12 (40.0) >10 years 28 (31.1) 18 (60.0) Hypertension Yes 69 (76.7) 22 (73.3) No 21 (23.3) 8 (26.7) Hyperlipidaemia Yes 77 (85.6) 24 (80.0) No 13 (14.4) 6 (20.0) Medication OHA 70 (77.8) 13 (36.7) OHAþinsulin 14 (15.5) 11 (43.3) Insulin 6 (6.7) 6 (20.0) BMI (kg/m2) <23 12 (25.0) 4 (25.0) 23 78 (75.0) 26 (75.0) SBP (mmHg) 130 (17.2)a 143.9 (26.5)a DBP (mmHg) 77 (8.8)a 83.0 (10.2)a HbA1c (%) 8.6 (2.49)a 10.0 (1.95)a TC (mmol/L) 4.9 (1.26)a 5.9 (2.02)a LDL (mmol/L) 2.6 (1.01)a 3.1 (1.17)a TG (mmol) 1.7 (0.91)a 2.2 (1.73)a HDL (mmol/L) 1.2 (0.30)a 1.4 (0.26)a

Abbreviation: HbA1c¼Glycosylated hemoglobin; BMI¼Body

mass index; FBS¼Fasting blood sugar; TC¼Total cholesterol;

TG¼Triglyceride; LDL¼Low density lipoprotein; HDL ¼

High density lipoprotein, SBP ¼ systolic blood pressure,

DBP ¼ diastolic blood pressure, OHA ¼ oral hypoglycemic

agent.

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diastolic blood pressure (DBP) were higher in the PDR group than in the no DR group. Poor diabetic control (HbA1c level>6.5%) and high LDL levels (>2.6 mmol/L) were more common in the PDR group. However, the body mass index (BMI) for both groups was similar (Table 1).

With reference to diabetic complications, the majority of patients in the PDR group had nephropathy (56.7%) and peripheral neuropathy (76.9%) compared with those in the no DR group (7.8% and 24.4%, respectively) (Table 2). Age (p ¼ 0.032), duration of DM (p ¼ 0.022), nephropathy (p ¼ 0.002) and peripheral neuropathy (p ¼ 0.001) were significantly associated with PDR (Table 3).

Discussion

In this study, age, duration of diabetes, nephropathy and peripheral neuropathy were significantly associated with PDR. The mean age of patients with PDR was 52 years old, which is younger than that reported by M.C. Boelter et al., who reported that the average age of patients with PDR was 60.3(9.9) years.16In the latter study, age was not associated with PDR, although blood pressure and glucose levels were poorly controlled, with a mean HbA1c of 10%. Patients with high HbA1c are prone to a worsening of retinopathy compared with patients with low HbA1c levels.5 PDR in our study developed much earlier compared with that studied by Boelter et al. The relatively young age of patients with PDR in our study has a significant socioeconomic impact because this age is considered to be working age. Therefore, for this age group, issues such as proper treatment, compliance, diet control and follow-up present major obstacles. These difficulties result in prolonged hyper-glycaemia and an increased severity of diabetic eye disease. Consequently, the incidence of blindness among patients with diabetes is more common in this age group.17

Our study also revealed that a duration of DM of more than 10 years is significantly associated with PDR. This finding is consistent with the results from a local study con-ducted in Sarawak in which the presence and severity of dia-betic retinopathy correlated with the length of time the patient

had been diagnosed with DM.18 Persistent hyperglycaemia leads to an increase in protein kinase activity and the formation of glycation end products (AGEs). Elevated protein kinase activity, in turn, leads to an increase in the permeability of retinal vessels, alteration of retinal blood flow, basement membrane thickening and increased levels of vascular endothelial growth factor leading to ocular neovascularization.19,20 Furthermore, increased formation of AGEs causes the formation of micro-aneurysms and loss of capillary endothelium.21All of these factors contribute to the progression of diabetic retinopathy from NPDR and PDR. The prevalence of PDR varies from 1.2% to 67% in individuals with DM less than 10 years and those with DM for 35 or more years, respectively.22

Nephropathy is significantly associated with PDR. Pa-tients who develop severe diabetic retinopathy are prone to develop diabetic nephropathy.18 Based on Diabetic Nephropathy Malaysian CPG, the diagnosis of diabetic nephropathy is made by the presence of proteinuria, defined as UACR >30 mg/g. However, in this study, because UACR is not routinely performed, the presence of proteinuria was based on the positive results of dipsticks on 2 separate occasions. In a study involving non-insulin dependent patients with DM, Salvage et al. also found that increased urine albumin excretion was associated with an increased prevalence of diabetic retinopathy. Furthermore, urine albumin excretion was an indicator of renal disease and generalized vascular damage.23

In this study, approximately 76.9% of patients with PDR had peripheral neuropathy, consistent with the observation by Dyck PJ et al. that severe retinopathy is associated with neuropathy.24Therefore, patients with PDR should undergo a complete neurologic examination to exclude diabetic peripheral neuropathy. Boulton AJ et al. reported that 15% of people with diabetes who develop foot ulcers develop peripheral neuropathy (nerve damage) and/or ischaemia (lack of blood supply).25 Neuropathy leads to a loss of sensation and muscular control and can cause a variety of other abnormalities and symptoms, such as pain. Despite the association between peripheral neuropathy and PDR, we did not demonstrate an association between diabetic foot and PDR. This is because a foot examination during follow up was not routinely performed, leading to under-reporting. In addition, the number of patients is too small to be able to arrive at a valid conclusion. For these reasons, the relationship between diabetic foot and PDR cannot be properly evaluated.

We reviewed 4341 fundus photos of patients with type 2 DM. Thirty-three patients were noted to have PDR as a result of this routine yearly screening. This finding reflects the poor metabolic control among patients with type 2 DM during follow up at Hospital USM. Therefore, data from this study can serve as a reference point for promoting better diabetic care in the future. Additional research should also be conducted to identify the underlying factors contributing to type 2 DM.

Conclusion

Age, duration of diabetes >10 years, nephropathy and peripheral neuropathy are significantly associated with PDR. Table 2: Distribution of diabetic complications in no DR and

PDR group. Variables No DR (n¼90) PDR (n¼30) n (%) n (%) Nephropathy Yes 7 (7.80) 17 (56.7) No 83 (92.2) 13 (43.3) Peripheral neuropathy Yes 22 (24.4) 23 (76.9) No 68 (75.6) 7 (23.3) Diabetic foot Yes 0 (0.0) 5 (16.7) No 90 (100.0) 25 (83.3)

Coronary artery disease

Yes 8 (8.9) 1 (3.3)

No 82 (91.1) 29 (96.7)

Stroke

Yes 3 (3.3) 0 (0)

(5)

The use of a non-mydriatic fundus camera as a screening tool for diabetic retinopathy in patients with DM offers a good detection rate. Reviewing the fundus photo to determine the stage of PDR is useful in identifying poor metabolic control in patients with diabetes.

Limitation

In this study, there are several limitations. This is a retrospective study that relied on medical records. Therefore, the main problem was the difficulties encountered in tracing medical records because many of them were not available due to logistic problems. In addition, there was also the problem of missing data combined with difficulties in obtaining com-plete data, such as the duration of diabetes, smoking status, and the prevalence of peripheral neuropathy.

Unequal ethnic distribution is the other limitation of this study. This study was performed in HUSM, a tertiary centre in which the majority of the population is Malay. Thus, the prevalence of PDR in this study may not be representative of

that in the larger community and should not be applied to other ethnic groups.

This study is also subject to referral bias as the number of patients with PDR and a normal fundus was identified a priori.

Recommendation

We would like to recommend a prospective cohort study be conducted with a larger sample size that includes additional variables, such as compliance, physical activity, and dietary profile. A determination of the levels of in-flammatory markers, such as C-reactive protein, and mo-lecular factors, such as vascular endothelial growth factor (VEGF), may also provide a better overview of the disease entity.

Conflict of interest

The authors have no conflict of interest. Table 3: Associated factors for no DR and PDR group.

Variable SLR MLR Pvalue

Crude ORa(95%CI)b Pvalue Adjust ORa(95%CI)b Wald stat

Age (years) 0.96 (0.92, 0.99) 0.022 0.92 (0.86,0.94) 0.08 0.032 SBP (mmHg) 1.03 (1.01, 1.05) 0.003 DBP (mmHg) 1.07 (1.01, 1.13) 0.011 TC (mmol/L) 1.54 (1.15, 2.06) 0.004 LDL (mmol/L) 1.42 (0.98, 2.07) 0.070 Gender Male 1.00 Female 1.37 (0.60, 3.13) 0.461 Race Non-Malay 1.00 Malay 1.164 (0.39, 3.48) 0.785 Smoking Non-Smoker 1.00 Smoker 2.71 (1.05, 7.01) 0.039 Duration of DM <10 year 1.00 >10 year 3.32 (1.41, 7.82) 0.006 5.21 (1.26, 21.48) 1.65 0.022 Hypertension No 1.00 Yes 0.837 (0.33, 2.15) 0.712 Hyperlipidaemia No 1.00 Yes 0.68 (0.232, 1.97) 0.472 Nephropathy No 1.00 Yes 15.80 (5.39, 44.60) <0.001 10.23 (10.23, 45.72) 2.33 0.002 Peripheral neuropathy No 1.001 Yes 0.16 (3.84, 26.87) <0.001 14.23 (3.05, 66.42) 2.66 0.001

Coronary artery disease

No 1.00

Yes 0.353 (0.42, 2.95) 0.337

Interaction and multicollinearity was checked. Model assumption were checked by Hosmer Lemeshow Test (p¼0.120), Classification table

(93.8%). Backward and forward logistic regression variable selection method was applied.

Abbreviation: BMI¼Body mass index; TC¼Total cholesterol; TG¼Triglyceride; LDL¼Low density lipoprotein; HDL¼High density

lipoprotein.

aOdds ratio.

(6)

Authors’ contributions

All of the authors have contributed significantly to this article, including designing the study, collecting data, ana-lysing and interpreting the data, and preparing and approving the final draft of the article.

Ethical approval

The study protocol was approved in 2013 by the Research and Ethics Committee, School of Medical Sciences, Uni-versiti Sains Malaysia.

Acknowledgements

The authors are grateful to all of the participants, health clinic staff and others who contributed to the successful completion of this study. We would also like to express our appreciation to the Biostatistics Department for their guidance.

References

1.Kohner EM, Aldington SJ, Stratton IM, Manley SE, Holman RR, Matthews DR, Turner RC. United Kingdom Prospective Diabetes Study, 30: diabetic retinopathy at diag-nosis of noneinsulin-dependent diabetes mellitus and associated risk factors.Arch Ophthalmol 1998; 116(3): 297e303.

2.Ramachandran A, Snehalatha C, Viswanathan V. Burden of type 2 diabetes and its complications-the Indian scenario.Curr Science-Bangalore 2002; 83(12): 1471e1476.

3.Malaysia MoH. Clinical practise guideline on screening of dia-betic retinopathy; 2011.

4.Klein R, Klein BE, Moss SE. Epidemiology of proliferative diabetic retinopathy.Diabetes Care 1992; 15(12): 1875e1891. 5.Klein R, Klein BE, Moss SE, Cruickshanks KJ. Relationship of

hyperglycemia to the long-term incidence and progression of diabetic retinopathy.Arch Intern Med 1994; 154(19): 2169e2178. 6.Letchuman G, Wan Nazaimoon W, Wan Mohamad W, Chandran LR, Tee GH, Jamaiyah H, Isa MR, Zanariah H, Fatanah I, Ahmad FY. Prevalence of diabetes in the Malaysian national health morbidity survey III 2006.Med J Malays 2010; 65(3): 180e186.

7.Hoe TG. Prevalence of diabetic retinopathy in the University Hospital diabetic population.Med J Malays 1983; 38(1). 8.Shriwas S, Rahman IA, Reddy S, Mohammad M,

Mohammad W, Mazlan M. Risk factors for retinopathy in diabetes mellitus in Kelantan, Malaysia.Med J Malays 1996; 51(4): 447e452.

9.Goh P. Status of diabetic retinopathy among diabetics regis-tered to the diabetic eye registry, national eye database, 2007. Med J Malays 2008; 63: 24e28.

10. Nazaimoon WW, Letchuman R, Noraini N, Ropilah AR, Zainal M, Ismail IS, Wan Mohamad WB, Faridah I, Singaraveloo M, Sheriff IH, Khalid BA. Systolic hypertension and duration of diabetes mellitus are important determinants of retinopathy and microalbuminuria in young diabetics.Diabetes Res Clin Pract 1999; 46(3): 213e221.

11. Tajunisah I, Nabilah H, Reddy S. Prevalence and risk factors for diabetic retinopathyea study of 217 patients from University of Malaya Medical Centre.Med J Malays 2006; 61(4): 451e456.

12. Mafauzy M, Hussein Z, Chan S. The status of diabetes control in Malaysia: results of DiabCare 2008. Med J Malays 2011; 66(3): 175e181.

13. Mallika P, Lee P, Cheah W, Wong J, Syed Alwi SAR, Norhayati H, Tan AK. Risk factors for diabetic retinopathy in diabetics screened using fundus photography at a primary health care setting in East Malaysia.Malays Fam Physician Off J Acad Fam Physicians Malays 2011; 6(2e3): 60.

14. Porta M, Sjoelie A-K, Chaturvedi N, Stevens L, Rottiers R, Veglio M, Fuller JH. Risk factors for progression to pro-liferative diabetic retinopathy in the EURODIAB Prospec-tive Complications Study. Diabetologia 2001; 44(12): 2203e 2209.

15. Fowler MJ. Microvascular and macrovascular complications of diabetes.Clin Diabetes 2008; 26(2): 77e82.

16. Boelter MC, Gross JL, Canani L, Costa LA, Lisboa HR, Tres GS, Lavinsky J, Azevedo MJ. Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes. Braz J Med Biol Res 2006; 39(8): 1033e1039.

17. Dogru M, Ino-ue M, Nakamura M, Yamamoto M. Modifying factors related to asymmetric diabetic retinopathy.Eye 1998; 12(6): 929e933.

18. Mallika PS, Aziz S, Goh P, Lee PY, Cheah WL, Chong MS, Tan AK. Diabetic retinopathy in native and non-native sar-awakians-findings from the diabetic eye registry.Med J Malays 2012; 67(4): 369.

19. Miller JW, Adamis AP, Aiello LP. Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy.Diabetes Metab Rev 1997; 13(1): 37e50.

20. Xia P, Aiello LP, Ishii H, Jiang ZY, Park DJ, Robinson GS, Takagi H, Newsome WP, Jirousek MR, King GL. Character-ization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms, and endothelial cell growth.J Clin Invest 1996; 98(9): 2018.

21. Wautier J, Guillausseau P. Advanced glycation end products, their receptors and diabetic angiopathy.Diabetes Metab 2001; 27(5; Part 1): 535e544.

22. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years.Arch Ophthalmol 1984; 102(4): 520e526.

23. Savage S, Estacio RO, Jeffers B, Schrier RW. Urinary albumin excretion as a predictor of diabetic retinopathy, neuropathy, and cardiovascular disease in NIDDM. Diabetes Care 1996; 19(11): 1243e1248.

24. Dyck P, Davies J, Wilson D, Service FJ, Melton 3rd LJ, O’Brien PC. Risk factors for severity of diabetic poly-neuropathy: intensive longitudinal assessment of the Rochester Diabetic Neuropathy Study cohort.Diabetes Care 1999; 22(9): 1479e1486.

25. Boulton A. The diabetic foot: from art to science. The 18th Camillo Golgi lecture.Diabetologia 2004; 47(8): 1343e1353.

How to cite this article: Mohd Ali MH, Draman N, Mohamed WMIW, Yaakub A, Embong Z. Predictors of proliferative diabetic retinopathy among patients with type 2 diabetes mellitus in Malaysia as detected

by fundus photography. J Taibah Univ Med Sc

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References

  1. www.sciencedirect.com
  2. (http://creativecommons.org/licenses/by-nc-nd/4.0/
  3. http://dx.doi.org/10.1016/j.jtumed.2016.03.002Journal of Taibah University Medical Sciences (2016) 11(4), 353
  4. KohnerEM,
  5. 1476http://refhub.elsevier.com/S1658-3612(16)30003-8/sref2
  6. Malaysia MoH.Clinical practise guideline on screening of
  7. Klein R, Klein BE, Moss SE. Epidemiology of proliferativediabetic retinopathy.
  8. 2178http://refhub.elsevier.com/S1658-3612(16)30003-8/sref5
  9. 186http://refhub.elsevier.com/S1658-3612(16)30003-8/sref6
  10. Hoe TG. Prevalence of diabetic retinopathy in the UniversityHospital diabetic population.
  11. 452http://refhub.elsevier.com/S1658-3612(16)30003-8/sref8
  12. Goh P. Status of diabetic retinopathy among diabetics regis-tered to the diabetic eye registry, national eye database, 2007.
  13. 221http://refhub.elsevier.com/S1658-3612(16)30003-8/sref10
  14. 456http://refhub.elsevier.com/S1658-3612(16)30003-8/sref11
  15. 181http://refhub.elsevier.com/S1658-3612(16)30003-8/sref12
  16. Mallika P, Lee P, Cheah W, Wong J, Syed Alwi SAR,Norhayati H, Tan AK. Risk factors for diabetic retinopathy in
  17. Porta M, Sjoelie A-K, Chaturvedi N, Stevens L, Rottiers R,Veglio M, Fuller JH. Risk factors for progression to
  18. Fowler MJ. Microvascular and macrovascular complications ofdiabetes.
  19. 1039http://refhub.elsevier.com/S1658-3612(16)30003-8/sref16
  20. 933http://refhub.elsevier.com/S1658-3612(16)30003-8/sref17
  21. 2012; 67(4): 369.
  22. Miller JW, Adamis AP, Aiello LP. Vascular endothelial growthfactor in ocular neovascularization and proliferative diabetic
  23. Xia P, Aiello LP, Ishii H, Jiang ZY, Park DJ, Robinson GS,Takagi H, Newsome WP, Jirousek MR, King GL.
  24. 544.http://refhub.elsevier.com/S1658-3612(16)30003-8/sref21
  25. 526http://refhub.elsevier.com/S1658-3612(16)30003-8/sref22
  26. Savage S, Estacio RO, Jeffers B, Schrier RW. Urinary albuminexcretion as a predictor of diabetic retinopathy, neuropathy,
  27. 1486http://refhub.elsevier.com/S1658-3612(16)30003-8/sref24
  28. Boulton A. The diabetic foot: from art to science. The 18thCamillo Golgi lecture.