Causes and Clinical Impact of Loss to Follow-up in Patients With Proliferative Diabetic Retinopathy
Conditions: Diabetic Retinopathy
Sponsor: Assiut University

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Causes and clinical impact of loss to follow-up in patients with 
proliferative diabetic retinopathy 
 
MATERIALS AND METHODS 
This study was reviewed and approved by the Medical Research and Ethics Committee of 
the Faculty of Medicine at Assiut University (Assiut, Egypt). Written informed consent was 
obtained from all patients after the nature/purpose of the study and risks/benefits of study 
participation were explained. All study conduct adhered to the tenets of the declaration of 
Helsinki. 
Study population 
This prospective cohort study was conducted between May 25, 2013 and June 5, 2018 and 
included treatment-naïve patients who had developed PDR in one eye with a best corrected 
visual acuity (BCVA) ranging from 20/22 to 20/69, as determined by the Snellen 
equivalent. Patients were allocated to receive PRP, IVIs of anti-VEGF, or a combination of 
both procedures. Treatment decisions for each patient was guided by careful consideration 
of relative advantages of each treatment and the anticipated compliance with follow up and 
treatment recommendations. A single retina specialist (M.S.) performed all laser and 
injection procedures at the Retina outpatient clinic in Assiut University Hospital (Assiut, 
Egypt). No new patients were recruited in the last 6 months of the observation period. 
Exclusion criteria were outlined as follows: 1) patients receiving follow-up ophthalmic care 
for their PDR with or without interventions at any other medical care provider during the 
observation period, as declared by the patients at any follow up visit; 2) patients LTFU who 
did not resume follow-up until the end of the observation period; 3) patients needing PPV 

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at first presentation or having additional retinal pathology; and 4) patients receiving their 
treatment procedure during December 2017 or having vitreous hemorrhage that failed to 
clear up by June 2018 but still ineligible candidates for PPV. LTFU was defined as missing 
any follow-up visit for any interval exceeding 6 months provided that patients eventually 
resumed care before the end of the study period (time zero was defined as the date of the 
missed follow-up visit). 
Patient characteristics and clinical assessment 
Patient characteristics, including age and sex, were collected. Each patient received detailed 
complete ophthalmic examinations, including BCVA measurements, which were converted 
to a logarithm of the minimum angle resolution (Log MAR); intraocular pressure (IOP); slit 
lamp biomicroscopy; and indirect ophthalmoscopy, at the initial visit and at each follow-up 
visit. Fundus photography and fluorescein angiography were also performed at enrollment 
and when indicated during the follow-up period. The number of PRP sessions and IVIs of 
anti-VEGF and the need for PPV were also recorded. For LTFU subjects, a convenient 
treatment plan was established when care had resumed. 
Subject questionnaire 
Subjects in the LTFU group were asked to complete an 8 item questionnaire regarding the 
reason(s) for missing their follow-up appointment. The questionnaire items were carefully 
chosen based on pilot discussions with subjects that had been in similar situations before 
conducting the study. Subjects were reminded that their answers would remain confidential 
and would not influence their future medical care. For patients with reading difficulties, the 
questionnaire was vocally administered. The questionnaire asked about the following 
potential causes for LTFU: (1) lack of information provided by medical care providers on 
follow-up need and/or date, (2) lack of concern and/or compliance (self-reported by 

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subject), (3) lack of trust in and/or satisfaction with treatment, (4) lack of treatment 
affordability, (5) difficulty with transportation, (6) other disabling conditions (comorbidity) 
that hindered appointment attendance, (7) lack of a social support system, and (8) 
employment obligations. Because discussing treatment affordability and the potential lack 
of a support system may have upset some subjects, these questions were placed at the end 
of the survey to establish subject trust and to prevent emotional distress from confounding 
responses to the other questions. Subjects rated the impact of each item using a 5-point 
scale: 1 = “not significant at all” and 5 = “strongly significant cause.” Only completed 
surveys were used for analyses. 
Statistical analysis 
Statistical tests were performed using SPSS, version 24 (SPSS, Inc., Chicago, IL, USA). 
Continuous variables are presented as mean ± standard deviation, and the frequency 
distributions of categorical variables were recorded. Age, sex, and type of intervention were 
used as categorical risk factors, and the differences in the rates of these factors for LTFU 
were assessed using chi- square tests. Univariate logistic regression was used to determine 
the odds of LTFU based on age, sex, and the type of intervention used. Factors with a P 
value < 0.1 were then used in a multivariate logistic regression model to determine the 
adjusted odds ratios for each risk factor. A t-test was used to compare the mean log MAR 
BCVA between compliant patients group and LTFU group. Need for PPV was assessed in 
patients who followed-up and those who were LTFU; this information was analyzed in 
relation to risk factors (age, sex and interventions) using a chi-square test. Spearman’s rank 
correlation coefficients were used to assess correlations between the answer scale given for 
each question and the scales given for other questions as well as age and intervention used. 

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Statistical significance was set at P < 0.05. Questionnaire responses were analyzed by mode 
of answers and frequencies.