Study design and population
In this retrospective comparative study, we reviewed the medical records of 13 vitrectomized eyes of 11 patients (mean age, 55.0±10.0 years; male to female ratio, 6:5) and 17 nonvitrectomized eyes of 17 patients (mean age, 62.0±9.0 years; male to female ratio 8:9) with severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy who received IVR injections and were followed for at least 24 months between April 2013 and December 2017 at Atakoy Dunyagoz Hospital.
Exclusion criteria included: alterations that could prevent improvement in BCVA (the presence of apparent retinal pigment epithelium (RPE) atrophy or proliferative diabetic fibrovascular membranes at or near the macula, the presence of diabetic or glaucomatous optic atrophy, etc.), active intraocular inflammation or infection in one or both eyes, uncontrolled or neovascular glaucoma, prior treatment with intravitreal or periocular pharmacologic injections in the studied eye within a 3-month period before the IVR injections, panretinal laser photocoagulation within 6 months or macular focal/grid laser photocoagulation in the studied eye within a 3-month period before the beginning of the study, previous major surgeries like vitrectomy, cataract extraction, or steroid injections within the previous 3 months or during the course of the study, persistence of tractional retinal detachment, vitreomacular traction, epiretinal membrane, and vitreous hemorrhage and systemic diseases that contraindicated IVR injection (history of thromboembolic events including myocardial infarction or cerebral vascular events, uncontrolled hypertension, known coagulation abnormalities or current use of anticoagulative medication other than aspirin).
This study was approved by the Institutional Ethics Committee of Bahcesehir University (Mar/20th/2019; 2019-06/01) and conducted in accordance with the latest version of the Declaration of Helsinki. According to the Regulation on Clinical Studies of Drugs and Biological Products in Turkey (no: 29474), updated on September 13, 2015, retrospective studies are not subject to the requirement of informed consent of patients. The Institutional Ethics Committee of Bahcesehir University, which operates in accordance with this regulation, waived the requirement of informed consent for this study. All patients with vitrectomized eyes were informed about the risks and benefits of vitrectomy before surgery, and a written consent was obtained after a thorough explanation of the procedure. The potential risks and benefits of IVR injections were also discussed extensively with all the patients. All patients gave written informed consent for IVR injections.
All patients underwent a comprehensive clinical assessment and ophthalmologic examination including measurement of BCVA and indirect and contact lens slit lamp fundoscopic examination. The BCVA was measured with a standard Snellen chart and converted to the logarithm of the minimum angle of resolution (logMAR) units. Spectral domain or swept source optical coherence tomography (OCT) (Topcon 3D OCT-2000, Tokyo, Japan) was used to examine the central macular thickness (CMT) and total macular volume (TMV) of all eyes before surgery at baseline, and at months 6, 12, 18, and 24 of the follow-up. In OCT retinal thickness measurement (the distance between the inner surface of RPE and the inner surface of the neurosensory retina), a 3D model of the retina was computed and retinal volumes (RVs) assessed for each of the nine subfields using the inner, intermediate, and outer rings (with diameters of 1 mm, 2.22 mm, and 3.45 mm, respectively) as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS).  CMT was defined as the average thickness of the macula in the central 1 mm ETDRS grid. TMV was calculated by summation of all the volumes obtained in the ETDRS subfields.
The number of intravitreal injections, the duration between the diagnosis of DME and IVR injections, and hemoglobin A1c (HbA1c) levels at baseline were also assessed.
Vitrectomy was performed at least 12 months prior to the start of IVR treatment. The indications for pars plana vitrectomy (PPV) were intravitreal hemorrhage, tractional retinal detachment, vitreomacular traction, and epiretinal membrane. The internal limiting membrane (ILM) was peeled in patients operated on for epiretinal membrane. Before the appearance of DME, the macula was flat in all vitrectomized patients after surgery.
Intravitreal ranibizumab treatment
The indications for anti-VEGF treatment for eyes with DME were CMT of more than 300 μm determined by spectral-domain OCT and/or decimal BCVA less than 0.7. The intravitreal dose of ranibizumab was 0.5 mg/0.05 ml. The nonvitrectomized group of patients initially received three consecutive monthly loading doses of ranibizumab followed by pro re nata (PRN) administration until either an improvement of the central macular edema was confirmed by OCT or the visual acuity was stable. Patients with vitrectomized eyes were treated with PRN regimen from the beginning with monthly follow-ups. A reduction of >10 μm in CMT was defined as an anatomical improvement considering interexamination measurement bias. Retreatment criteria included persistence of submacular fluid, intraretinal cysts, or CMT of more than 300 μm.
Cases without evidence of reduced macular thickness on OCT after IVR injection and a lack of improvement of BCVA were also observed without treatment.
The study data were summarized using descriptive statistics including the mean, standard deviation, minimum, and maximum for continuous variables, and frequency and percent for categorical variables. The Shapiro-Wilk test was used to test the normality of continuous variables. The Mann-Whitney U test was used to compare independent groups. A paired samples t test and the Wilcoxon signed-rank test were used to compare the mean differences between pre- and post-injection values of all parameters. Frequencies were compared between groups using the Chi-square test. In order to test the significance of the correlations between BCVA, CMT, and TMV, the Pearson correlation test was used.
The Statistical Package for the Social Sciences software (SPSS 20.0; IBM Corporation, Armonk, NY, USA) was used for statistical analysis and Excel 2007 was used for all computations involving descriptive statistics. A p value less than 0.05 was assumed to indicate statistical significance.