Purpose
To analyze the effect of intensified topical steroid therapy after Descemet membrane endothelial keratoplasty combined with cataract surgery (triple-DMEK) on the incidence of postoperative cystoid macular edema (CME).
Design
Single-center comparative clinical study with historical controls.
Methods
Setting : Department of Ophthalmology, University of Cologne, Germany, tertiary hospital, performing 500 corneal transplant surgeries per year. Patients : Total of 131 patients (150 eyes) undergoing triple-DMEK surgery. Inclusion Criterion : Triple-DMEK surgery. Exclusion Criteria : Prior retinal surgery, history of prior CME. Interventions : Prednisolone acetate eye drops 1% 5 times daily for the first week after surgery. After an internal change of therapy regimen: Prednisolone acetate eye drops 1% hourly for the first postoperative week. We compared 75 consecutive eyes before with 75 consecutive eyes after the change of therapy regimen. Patients received macular spectral-domain optical coherence tomography (SD OCT) preoperatively, as well as 6 weeks and 3 and 6 months post surgery. Main Outcome Measure : Development of CME detected by macular SD OCT during 6 months postoperatively.
Results
Both groups were comparable regarding baseline age, sex, central corneal thickness, rebubbling rate, and visual acuity. With topical steroid therapy 5 times per day during the first postoperative week, we observed 9 cases of subsequent CME (12%). With hourly topical steroid therapy none of the patients developed CME subsequently ( P = .003). Apart from the topical steroids during the first week, medical treatment was identical in both groups.
Conclusions
Early intensified postoperative topical steroid therapy constitutes an effective prophylactic treatment to reduce incidence of CME after triple-DMEK surgery.
Cystoid macular edema (CME) is a frequent postoperative complication of posterior lamellar keratoplasty with or without cataract surgery (triple-Descemet stripping automated endothelial keratoplasty [DSAEK]/Descemet membrane endothelial keratoplasty [DMEK]). A recent prospective study with regular spectral-domain optical coherence tomography (SD OCT) controls reported an incidence of CME after DMEK and triple-DMEK of 12%–13%. CME here was defined as newly developed accumulation of intra- or subretinal fluid within the central retinal subfield of the SD OCT. Most frequently CME occurs within the first 6 months after surgery. Low-grade sterile inflammation is discussed to be the cause of CME. Elevated protein levels in the anterior chamber of CME patients after cataract surgery also indicate an inflammatory cause. Although CME usually resolves after initiation of intensive topical anti-inflammatory therapy and long-term prognosis for best-corrected visual acuity (BCVA) seems to be favorable, the initially decreased visual acuity burdens the patient and in some cases even intravitreal injection of steroids becomes necessary. Intravitreal injections constitute a risk for long-term elevated eye-pressure, as well as infection. Given this information, we changed our internal therapy regimen during the first week from topical steroid therapy applied 5 times a day to an hourly regimen. We hypothesized that the increased release of proinflammatory cytokines during triple-DMEK surgery may explain the high rate of postoperative CME and speculated that by increased early postoperative anti-inflammatory therapy the rate of CME could be reduced. We therefore compared the rate of CME, defined as described above, in 75 consecutive eyes prior to the change of therapy regimen with 75 consecutive eyes after the change of therapy regimen.
Methods
This single-center comparative clinical study with historical controls was conducted at the Department of Ophthalmology, University of Cologne, Germany, a tertiary hospital specialized for corneal surgery, performing more than 500 corneal transplant surgeries per year. The protocol followed the tenets of the Helsinki protocol. All patients were prospectively included in the Cologne DMEK Databank: Long Term Safety and Outcome, and were followed up in highly standardized fashion. The ethics committee of the University of Cologne, Germany approved data collection and analysis within the Cologne DMEK Databank (file number 14-373). All patients gave informed consent for storage and analysis of their data before surgery. Inclusion criterion was the need for triple-DMEK surgery. Exclusion criteria were prior retinal surgery and history of prior CME because of uncontrollable risk for CME. Since a single surgeon (C.C.) conducted all surgeries according to a standardized technique, surgeon effects are excluded. Out of more than 1000 DMEK surgeries performed so far, prior to first inclusions within this study, the surgeon had already performed over 200 triple-DMEK surgeries. Surgeries were performed between December 3, 2012 and January 9, 2015.
We performed surgery as previously described. In short, we obtained a standardized 8 mm graft under balanced salt solution (Alcon, Freiburg, Germany) in a stepwise manner with the donor cornea fixed to a Hanna punch block (Moria, Doylestown, Pennsylvania, USA). The spontaneously formed roll of endothelium–Descemet membrane was transferred into culture medium for immediate transplantation. All preparation steps were performed directly before transplantation surgery. Before grafting Descemet membrane into the recipient, we performed the cataract surgery according to the following specifications. After clear cornea tunnel incision and capsulorrhexis, the lens was extracted using the phaco-chop technique. After polishing of the posterior lens capsule, a preloaded 1-piece acrylic lens was implanted into the capsular bag under viscoelastic substance cover. All lenses could be implanted into the capsular bag. The corneal tunnels were hydrated after irrigation and aspiration and complete removal of viscoelastics and did not require suturing in any case. In the host cornea the central 9 mm of the Descemet membrane was peeled under air filling of the complete anterior chamber. The donor graft was stained with trypan blue solution (VisionBlue; Dutch Ophthalmic Research Corp, Rotterdam, Netherlands) and injected into the fluid-filled anterior chamber with a conventional lens injector cartridge endothelial side outward. The graft was rotated 90 degrees by blunt strikes to the corneal surface, unfolded by a sterile air-bubble injection on top of the graft, and then pressed against the corneal stroma by complete filling of the anterior chamber with sterile air. If necessary, Descemet folds were removed by a LASIK roller (BD Visitec, Abingdon, UK). The anterior chamber was filled with air for up to 90% of anterior chamber volume. Patients had to maintain a postoperative supine position for 24 hours. The air dissolved spontaneously during approximately 5 days postoperatively. Only in case of angle closure mechanism with pronounced intraocular pressure (IOP) elevation (>40 mm Hg) due to insufficient iridectomy was the air partly removed via a paracentesis. This was necessary in 5 cases.
On the day before surgery (approximately 16 hours preoperatively) all 150 patients received a yttrium-aluminum-garnet laser iridotomy at 6 o’clock in miosis (1 drop pilocarpine 2%), which was enlarged intraoperatively by a 20 gauge cutter. In our clinical experience, this procedure results in less pronounced iris bleeding than iridectomy with the 20 gauge cutter alone. Preoperatively, as well as at every follow-up visit, Snellen BCVA (given as logMAR in the following), macular SD OCT (Spectralis HRA+OCT; Heidelberg Engineering GmbH, Dossenheim, Germany), slit-lamp OCT (Heidelberg Engineering GmbH), and Scheimpflug corneal topography as well as thickness analysis (PentaCam; Oculus, Wetzlar, Germany) were performed. Macular SD OCT was performed with the following specifications: scan area 20 × 15 degrees (5.8 × 4.4 mm), 37 B-scans, distance between B-scans 121 μm, 29 images averaged per scan. Follow-up visits were performed at 6 weeks, 3 months, and 6 months postoperatively. We performed additional visits in any case of questionable postoperative result according to the patients’ ophthalmologist. In 2 cases we contacted the patients’ ophthalmologist, who performed the follow-up visits, including SD OCT.
Prior to April 1, 2014 all patients were treated with topical steroids (prednisolone acetate 1%) 5 times daily for the first postoperative month. Steroids were then tapered 1 drop per month (the last drop to be carried on for at least 1 year). Based on published results and on our own clinical experience, we changed our routine therapy regimen to hourly topical steroids for the first postoperative week, starting from April 1, 2014. These were applied until 11 o’clock in the evening. One week later topical steroids were reduced to 5 times daily for the rest of the first month and thereafter again tapered 1 drop per month (the last drop to be carried on for at least 1 year, ie, the old scheme used before). All other surgical and medical treatments were unchanged. We analyzed the last 75 eyes of patients before and the first consecutive 75 eyes of patients after the change of therapy regimen for the development of CME within the first 6 months post surgery. Macular edema was defined as newly developed accumulation of intra- or subretinal fluid within the central retinal subfield of the SD OCT.
Statistical analysis was performed using commercially available software (GraphPad Prism; GraphPad, La Jolla, California, USA). Significance levels were calculated with Fisher exact test to compare frequencies of CME and possible confounding factors, as well as Mann-Whitney test to compare age, BCVA, and central corneal thickness. Significance levels of P < .05 were deemed significant. The confidence intervals were calculated with a computer program written in the free statistical software “R” ( http://CRAN.R-project.org ), using the formulas given in Altman and associates to provide the calculations. The program was validated using the calculation examples given by Altman and associates.
Results
Baseline Characteristics
We analyzed 150 eyes of 131 patients. The last 75 consecutive eyes of patients before the change of therapy regimen (Group 1) were compared to the first 75 consecutive eyes of patients after the change of therapy regimen (Group 2). Both groups were comparable regarding possible confounding factors influencing macular integrity ( Table ). Corneal disorders leading to triple-DMEK procedure were Fuchs endothelial dystrophy in 147 cases and keratopathy due to pseudoexfoliation in 3 cases (none of these 3 cases developed CME). We saw inactive choroidal neovascularization without CME development during the observation period in 1 patient.
| Group 1 (N = 75) (Topical Steroids 5×/d) | Group 2 (N = 75) (Topical Steroids Hourly) | P Value | |
|---|---|---|---|
| Male, n (%) | 38 (51%) | 48 (64%) | .137 |
| Female, n (%) | 37 (49%) | 27 (36%) | |
| Age, mean ± SD (range) | 70 ± 8 years (51–89) | 68 ± 10 years (24–85) | .376 |
| BCVA, mean ± SD [range] | 0.51 ± 0.22 logMAR (20/60 Snellen) [range 1.30–0.22] | 0.51 ± 0.38 logMAR (20/60 Snellen) (range 2.00–0.22) | .157 |
| Central corneal thickness, mean ± SD (range) | 631 ± 82 μm (513–1038 μm) | 642 ± 87 μm (515–987 μm) | .666 |
| Diabetes mellitus, n | Total: 7 With CME: 1 | Total: 4 With CME: 0 | .533 |
| Open-angle glaucoma, n | Total: 2 With CME: 0 With prostaglandin therapy: 2 | Total: 6 With CME: 0 With prostaglandin therapy: 0 | .276 |
| Dry AMD, n | Total: 1 With CME: 1 | Total: 3 With CME: 0 | .620 |
| Macular pucker,n | Total: 3 With CME: 0 | Total: 5 With CME | .719 |
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