This study was approved by the institutional review boards of Tokyo Women’s Medical University and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from each patient. Pars plana vitrectomy was performed because it has been reported that macular edema and visual acuity can be improved by this procedure in CRVO patients
. We retrospectively studied 10 eyes of 10 patients with macular edema with CRVO who were treated with PPV. Ten patients (mean age: 71.6 ± 7.2 years; 7 women and 3 men) were included in this uncontrolled study conducted at the Department of Ophthalmology of Tokyo Women’s Medical University between May 2009 and July 2011. Patients were diagnosed as having hypertension if the systolic blood pressure was ≥140 mm Hg and diastolic blood pressure was >90 mm Hg, or if the systolic pressure was ≥140 mm Hg at one examination and the diastolic pressure was ≥90 mm Hg on a different day, or if the patient was already taking antihypertensive medication. A diagnosis of hyperlipidemia was based on a total cholesterol≥240 mg/dL, triglycerides≥160 mg/dL, low-density lipoprotein cholesterol≥130 mg/dL, or use of cholesterol-lowering medication.
The indications for treatment of macular edema with PPV were: (1) cystoid macular edema, (2) a foveal thickness greater than 300 μm, and (3) best-corrected visual acuity worse than 20/50. The exclusion criteria were (1) previous ocular surgery, (2) diabetes mellitus with diabetic retinopathy, (3) previous macular laser photocoagulation, (4) previous intravitreal injection of anti-VEGF agents or triamcinolone acetonide, (5) a history of ocular inflammation, (6) marked retinal hemorrhage (including macular bleeding involving the intrafoveal or subfoveal spaces), (7) coexisting ocular disease (i.e., epiretinal membrane or glaucoma), and (8) retreatment during the 6-month follow-up period.
All patients had undergone a comprehensive ophthalmologic examination, including best-corrected visual acuity measurement, intraocular pressure determination, indirect ophthalmoscopy, and slit-lamp biomicroscopy with a contact lens before and at 3, and 6 months after treatment. In addition, retinal sensitivity was investigated by microperimetry, and retinal thickness and retinal volume were measured by OCT.
Ten patients received pars plana vitrectomy under local anaesthesia. When PPV was done, all epiretinal materials, the residual cortex, and the posterior hyaloid were removed from the retinal surface around the macula as completely as possible with the assistance of triamcinolone acetonide (the minimum necessary volume was injected and then was removed as thoroughly as possible at the end of surgery, because it can influence cystoid macular edema). Internal limiting membrane (ILM) peeling was not done because peeling-related retinal injury can have a variable effect on retinal sensitivity, which could have caused bias in this study. Intraoperative scatter laser photocoagulation to the ischemic region of the retina was not done. During surgery, iatrogenic peripheral retinal tears did not occur in any of the patients. Concurrent phacoemulsification with intraocular lens insertion into the bag was performed. All of the patients who had cataract surgery were classified into Emery-Little grades I or II according to the new World Health Organization Simplified Cataract Grading System. All patients were followed up for at least 6 months postoperatively. Neovascular glaucoma and iris neovasculariation were not detected in any of the patients after follow up for six months, so trabeculectomy or tube shunt surgery was not performed up to that time.
As baseline screening, patients underwent ophthalmoscopy and biomicroscopic examination using a slit-lamp with a fundus contact lens. They also underwent standard fundus color photography and fluorescein angiography, which was performed with a Topcon TRC-50EX fundus camera, an image-net system (Tokyo Optical Co. Ltd., Japan), and a preset lens with a slit-lamp.
A masked grader independently assessed ischemic retinal vascular occlusion on the fluorescein angiograms by measuring the ischemic area of the retina with the public domain Scion Image program, as reported previously
[10–12]. On digital photographs of the fundus, the optic disc was outlined with a cursor and then its area was measured, as was also done for the nonperfused area of the retina. Then the nonperfused area was divided by the disc area to calculate the severity of retinal ischemia. If the non-perfused area divided by the disc area gave a value of 10 or more, this was defined as indicating the presence of retinal ischemia (ischemic CRVO group)
Measurement of BCVA
Each patient underwent measurement of best-corrected visual acuity (BCVA) with an SC-2000 System chart (Nidek, Gamagori, Japan). BCVA was measured in decimal units on a Landolt chart by the orthopticists. The chart brightness was set at 80–320 cd/m2, and chart contrast was more than 74%. The results were converted to the logarithm of the minimum angle of resolution scale (log MAR).
Measurement of optical coherence tomography
OCT was performed with an instrument from Zeiss-Humphrey Ophthalmic Systems (Zeiss Stratus OCT3, Carl Zeiss Meditec, Dublin, CA, USA) to measure the foveal thickness. At each visit, all patients underwent Stratus OCT examination in the vertical cross-section with the instrument centered on the fovea and in the fast macular thickness mode. On these views, retinal thickness was defined as the distance between the inner surface of the neurosensory retina and the retinal pigment epithelium. Foveal thickness was calculated as the average retinal thickness within a circle of 500-μm radius centered on the fovea. A retinal thickness map and retinal volume map were obtained by scanning 6×6 mm (20°×20°) areas of the macular region, which was divided into the following nine subfields: 1) fovea, 2) superior inner macula, 3) nasal inner macula, 4) inferior inner macula, 5) temporal inner macula, 6) superior outer macula, 7) nasal outer macula, 8) inferior outer macula, and 9) temporal outer macula
. The diameters of the central, inner, and outer circles were 1, 3, and 6 mm, respectively. In each region, measurement of retinal thickness and volume was automatically performed by computer software. The mean macular thickness at the one subfield (fovea) covering the central 1×1 mm (4°×4°), at five subfields (fovea, superior inner, nasal inner, inferior inner, and temporal inner) covering the central 3×3 mm (10°×10°), and at all nine subfields covering the entire central 6×6 mm (20°×20°) were thus determined.
Functional mapping by microperimetry
Microperimetry with the MP-1 (Nidek, Gamagori, Japan) is performed using an infrared fundus camera with a liquid crystal display controlled by special software. The MP-1 software contains an automatic tracking system for fundus movements; this evaluates every acquired frame for shifts in the x and y directions of the fundus with respect to a reference frame obtained by an infrared camera at the beginning of the examination. Each patient underwent fundus-monitored microperimetry with the MP-1 system (Nidek, Gamagori, Japan). Its software performs automatic tracking of fundus movements and evaluates every frame acquired for fundus shift in the x and y directions relative to a reference frame obtained with an infrared camera at the beginning of the examination. Microperimetry settings were identical for all examinations: Goldmann III stimuli were presented in random order according to a 4-2-1 double staircase strategy. The stimulus intensity ranged from 0 to 20 decibels (dB) (0 dB corresponded to the strongest signal intensity of 127 cd/m2) in 1-dB steps, and the duration of each stimulus was 200 ms. The fixation target was varied in size according to the patient’s visual acuity. Retinal sensitivity maps were obtained by using the macula 20 degrees program of the MP-1. During the examination, background illumination was set at 1.27 cd/m2. Mean retinal sensitivity was calculated from the sensitivity for each of nine subfields on the retinal map generated by OCT. The mean macular sensitivities at the five locations covering the central 4° field, at 29 locations covering the central 10° field (five subfields; fovea, superior inner, nasal inner, inferior inner, and temporal inner), and at the 57 locations covering the entire central 20° field (all nine subfields) were thus determined.
All analyses were performed with SAS System 9.1 software (SAS Institute Inc., Cary, North Carolina, USA). Results are presented as the mean ± SD or as the frequency. One-way repeated measures analysis of variance (ANOVA) was used to evaluate the changes of visual acuity, macular sensitivity, macular thickness, and macular volume. Two-tailed P values of less than 0.05 were considered to indicate statistical significance.