Impact of Diabetes Mellitus on Retinal Microvasculature in Patients Without Clinical Retinopathy Using Optical Coherence Tomography Angiography
Conditions: Diabetic Retinopathy, DR
Sponsor: Sohag University

 
Sohag University    
Faculty of Medicine 
Department of Ophthalmology                   
 
Impact of Diabetes Mellitus on Retinal Microvasculature 
in Patients without Clinical Retinopathy Using Optical 
Coherence Tomography Angiography 
Study Protocol Submitted for Partial Fulfillment  
of Master Degree in ophthalmology 
Presented by 
Mohamed Abdou Saeed 
M.B.B.CH 
Resident of Ophthalmology    
  Sohag University Hospital. 
Supervised by 
Engy Mohamed Mostafa 
Professor of Ophthalmology  
Faculty of Medicine, Sohag University 
Amr Mounir Mohamed 
Assistant Professor of Ophthalmology 
Faculty of Medicine, Sohag University. 
Alaa Abdelsadek Ahmed 
Lecturer of Ophthalmology 
Faculty of Medicine, Sohag University. 
 
Sohag University  
2024 
 

    
 
Introduction  
Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) 
and is the leading cause of preventable blindness in working aged people [1].  
Fluorescein angiography (FA) is the gold standard investigation for evaluation of Diabetic 
Retinopathy, yet it is time-consuming and requires invasive intravenous dye administration that 
may cause various reactions such as vomiting and urticaria [2].  
The advent of Optical Coherence Tomography Angiography (OCTA) overcame these 
disadvantages and added value of imaging rapid and high-resolution images of the retinal 
microvasculature without intravenous dye administration [3, 4].  
OCTA identifies features of preclinical retinopathy that are not detectable by clinical examination 
and evaluates early ischemic changes as enlarged foveal avascular zones (FAZ) [5-8] , reduced 
vessel density [8, 9] that are reported to present without clinical retinopathy and also 
microaneurysm formation which is the most common early clinically visible manifestation of DR 
[10]. 
Duration of diabetes has been reported to be a strong predictor for the progression of DR as 
persistent elevated blood glucose level gradually leads to weakening of the walls of small retinal 
blood vessels leading to tiny bulges and even leakage [11, 12]. 
Aim of the work 
To assess the impact of duration of DM on OCTA parameters in diabetic patients without 
clinical Diabetic retinopathy. 
 
 
 
 

    
 
 
Patients and Methods 
Study design: Observational, Cross-sectional study.  
Study setting: Sohag University Hospital, department of Ophthalmology.  
Study population: patients will be recruited from diabetics who will present for retinopathy 
screening examination at outpatient clinic of Sohag University Hospital.  
Sample size determination: every group would include from 60 to 80 eyes calculated by 
Yamane’s formula: n = N/ (1+N (e) 2, where n = the sample size, N = the population of the 
study and e = the margin error in the calculation. 
The study will be conducted after acquiring the approval of the Medical Research Ethics 
Committee in the Faculty of Medicine, Sohag University considering that all study participants 
will be carefully cognized with  the nature, presentation and  potential consequences of the 
disease, investigation options and importance of regular follow up and tight control by an 
informed consent. 
Inclusion criteria: 
1) Age : Above 40 years old 
2) Type of DM: Type 2. 
3) Fundus examination: no macular edema or other signs of clinical retinopathy.  
Exclusion criteria:  
1) Age : below 40 years old 
2) Ocular history : any history of significant ocular injury or disease that could affect the retinal 
microvasculature such as retinal vascular occlusion, glaucoma, or vitreo-macular disease, as 
such conditions have also been noted to show sub-clinical OCTA changes [13, 14]. 
3) Fundus examination: macular edema or any other signs of clinical retinopathy. 
 

    
 
 
Procedure: patients recruited for the study will be subjected to the following: 
 Personal history: including name, age, sex, occupation and residency. 
 Medical history: including duration of DM, type of DM, use of DM medications, most 
recent hemoglobin A1C and presence of comorbid diseases. 
 Ocular examination: including extra-ocular examination, anterior segment examination, 
visual acuity assessment, IOP measurement and posterior segment examination. 
Signs of diabetic retinopathy to be detected include; Micro-aneurysm, Dot and Blot hemorrhages, 
Flame-shaped splinter hemorrhages, Retinal edema and hard exudates, Cotton-wool spots, venous 
loops and venous and Intra-retinal microvascular abnormalities (IRMA). 
Patients who meet the inclusion criteria will be divided into three groups depending on the 
duration of diabetes: 0–5 years (short), 6–10 years (medium), and more than 10 years (long). 
Fourth control group of patients who meet the criteria and don’t have DM will be included. 
OCTA images will be obtained for the patients by a comprehensive wide-field OCT device 
(Optovue RTVue XR 100 Avanti, Germany) with 6 × 6 mm field of view centered at the fovea.  
One eye will be selected for inclusion from each patient. If both eyes from an individual patient 
are similar the right eye will be included in the study. The effect of eye motion-related artifacts 
is minimized using VTRAC eye tracking software [19].  
Images to be included in the study will be required to have a signal strength greater than 7, 
minimal motion artifacts, decentralization from the foveal center of less than 20 µm, and minimal 
evidence of obscuration by media opacities [20].  
Image analysis will be automatically performed by the AngioVue Comprehensive software, 
which will provide automated segmentation and calculation of retinal microvascular metrics such 
as FAZ-related and SVD. The analysis will include the inner retina between the inner limiting 
membrane and an anterior offset from the retinal pigment epithelium of 110 µm. The superficial 
capillary plexus (SCP) as the superficial 70% of the inner retina, and the deep capillary plexus 
(DCP) is the remaining 30% [21].  

    
 
OCTA parameters derived from the SCP and DCP will be classified into two categories:  
(1) FAZ related metrics: FAZ area, FAZ perimeter and FAZ flow density (FD) 
(2) Vessel density-related metrics: superficial vessel density (SVD) and deep vessel density 
(DVD) in the 6 mm patch (6 mm diameter around the foveal center), 1 mm patch (1 mm diameter 
around the foveal center), and inner ring (1 mm patch excluding the FAZ) [9, 20].  
 
Statistical Analysis  
Statistical analysis will be performed using SPSS software 23 (SPSS, Inc., Chicago, IL, USA). 
The Shapiro–Wilk test will be used. Comparisons between groups will be made using the 
Kruskal–Wallis H test or one-way ANOVA test. Differences between two groups will be 
estimated with a Mann– Whitney U test or t-test. Multivariate linear regression models will be 
used to analyze potential associations between each OCTA parameter and systemic risk factors. 
All p values will be based on two-tailed testing and considered to be statistically significant if p 
< 0.05. A Bonferroni correction will be applied when appropriate. 
 
 
 
 
 
 
 
 

    
 
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