Purpose
To investigate effects of enoxaparin on postoperative inflammation in patients with moderate nonproliferative diabetic retinopathy (NPDR) and nuclear cataract.
Design
Prospective masked controlled trial.
Methods
setting : Institutional practice. study population : The study included 51 eyes of 51 diabetes mellitus (DM) patients with moderate NPDR and grade 2-3 nuclear cataracts. Group 1 included randomly selected patients who received enoxaparin in balanced salt solution (BSS) during cataract surgery, while standard BSS was used in Group 2. observation procedure : Patients were followed up 1 day, 1 week, and 1 and 2 months after the surgery. main outcome measures : Anterior chamber cell and flare.
Results
Postoperatively, 20 patients from Group 1 and 4 patients in Group 2 had less than a mean of 10 cells at day 1 ( P = .012). At the first week, 20 patients from Group 1 and 10 patients from Group 2 had less than a mean of 10 cells ( P = .004). When compared for flare, 20 patients from Group 1 and 8 patients from Group 2 had a flare between 0 and +1 at postoperative day 1 ( P < .001). By the end of postoperative first week, 24 patients from Group 1and 18 patients from Group 2 had a flare between 0 and +1 ( P = .012). There was no difference between groups in terms of postoperative inflammation at the first and second months after the surgery.
Conclusion
The results of the study suggest that enoxaparin added into the infusion fluid may reduce postoperative inflammation in patients with DM, and this result supports the anti-inflammatory effect of enoxaparin.
Cataract is one of the major causes of vision loss in diabetic patients. Although surgery is the gold standard for treatment of cataracts, complications, such as worsening of retinopathy and macular edema that may lead to low visual acuity, may occur in diabetic patients. Therefore, the success rate of cataract surgeries in diabetic patients is lower than that in nondiabetic patients. For this reason, the prevention and treatment of complications associated with cataract surgery have been studied extensively in the literature.
Nowadays, the more commonly used, less invasive phacoemulsification surgery has greatly decreased postoperative complications compared to intracapsular cataract surgery. It has been suggested that the inflammation that occurs secondary to surgery-related blood-aqueous barrier (BAB) damage triggers the development of retinopathy and is a risk factor for the progression of retinopathy. Edema in iris capillaries increases fragility by reducing the vessel wall resistance; it has been reported that, in diabetic patients, surgery-related trauma damages the BAB and increases postoperative inflammation and flare. The severity of BAB damage in cataract surgery has been investigated in both extracapsular cataract extraction and phacoemulsification, and inflammation has been reported to continue up to 3 months. The prevalence of BAB damage was found to be higher in phacoemulsification surgery in diabetic patients than in normal patients.
Heparin, in addition to its anticoagulant effect, also has anti-inflammatory and antiproliferative properties. Therefore, the use of heparin-coated intraocular lenses and techniques such as adding heparin into irrigation fluid during cataract surgery have been used extensively. Although heparin-induced adverse effects were not reported in these studies, there is always a risk of bleeding. Enoxaparin, a low-molecular-weight heparin, has been developed to avoid possible side effects of heparin. Enoxaparin has been used to reduce bleeding during vascular surgery and to prevent deep vein thrombosis in hip or knee replacement surgeries. In addition, it was used to evaluate the effects of inflammation in eye surgery. Rumelt and associates reported that enoxaparin reduced postoperative inflammation and surgery-related complications in pediatric cataract surgeries.
Cataract surgery in diabetic patients is challenging because of postoperative inflammation. In this study, we investigated the effects of low-molecular-weight heparin in infusion fluid during cataract surgery on postoperative inflammation in patients with moderate nonproliferative diabetic retinopathy and nuclear cataract.
Methods
This prospective, randomized, double-masked study was conducted between August 20, 2010 and September 28, 2012. The study was approved by the ethics committee of the medical faculty of the Mustafa Kemal University. All patients signed informed consent forms. This study was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) under the following number: ACTRN12613000775718.
A Consort flow diagram and the Consort statement as they pertain to this study are included as a Supplemental Figure (Supplemental Material available at AJO.com ). The study included 57 eyes from 57 non-insulin-dependent diabetes mellitus (DM) patients that had moderate nonproliferative diabetic retinopathy (NPDR) according to the Early Treatment Diabetic Retinopathy Study (ETDRS) and had grade 2-3 nuclear cataracts based on the classification of Lens Opacity Classification System III (LOCS III). Group 1 included randomly selected patients who received 40 mg/500 cc enoxaparin (Clexane 4000; Aventis Pharma, Surrey, England, United Kingdom) in balanced salt solution (BSS) during cataract surgery, whereas standard BSS was used during surgeries of patients in Group 2.
Patients who underwent laser photocoagulation in the previous 3 months and patients with small pupils, posterior synechiae, and history of uveitis were excluded from the study. One hour before surgery, 1% cyclopentolate (Sikloplejin; Abdi İbrahim, Istanbul, Turkey) and 2.5% phenylephrine (Mydfrin; Alcon Pharmaceuticals, Fort Worth, Texas, USA) were applied 3 times every 15 minutes to achieve cycloplegia. Topical anesthesia with proparacaine hydrochloride (5% Alcaine; Alcon-Couvreur, Puurs, Belgium) was used. All patients were operated by the same surgeon. After the 2.75 mm clear corneal incision, continuous curvilinear capsulorrhexis was performed. The lens was removed by phacoemulsification, followed by removal of the cortex using the bimanual irrigation aspiration system. A single-piece foldable acrylic intraocular lens (IOL) was implanted into the capsular bag. Subconjunctival steroid treatment was not applied after the surgery. Patients were treated with 0.1% dexamethasone (Maxidex; Alcon-Couvreur) and 0.3% ciprofloxacin (Ciloxan; Alcon-Couvreur) for 1 month: 8 times a day for the first week, 6 times a day during the second week, 4 times a day during the third week, and 2 times a day during the fourth week. The same ophthalmologist evaluated cell flare, fibrin formation, and synechiae by using slit-lamp biomicroscopy 1 day, 1 week, 1 month, and 2 months after the surgery. Inflammation was evaluated by counting cells in the anterior chamber and the flare degree (between 0 and +4) was evaluated based on the previously described oblique intense beam technique at high magnification (×1.6). During each visit, the average number of cells in the anterior chamber was calculated by counting the cells 3 times. The ophthalmologist doing these assessments was masked to patients’ treatment group.
Statistical analyses were performed using SPSS for Windows (SPSS 16.0; SPSS Inc, Chicago, Illinois, USA). Mann-Whitney U test and the χ 2 test were used to investigate differences in terms of sex and age. Fisher exact test, χ 2 test, and Mann-Whitney U test were used to compare postoperative inflammation between groups. P < .05 was considered to be statistically significant.
Results
Fifty-seven patients were recruited for the research. In 1 patient from Group 1, posterior capsule rupture occurred and this patient was excluded from the study. In total, 5 patients did not come to follow-up visits. Consequently, statistical analysis was carried out on the remaining 51 patients (51 eyes). The mean age of the patients was 61.4 ± 5.9 (range, 52-75) years. Twenty-six patients (51%) were female and 25 (49%) were male. Twelve patients from the treatment group and 4 patients in the control group had less than a mean of 10 cells at postoperative day 1 ( P = .012) ( Table ). At postoperative week 1, 20 patients from the treatment group and 10 patients from the control group had less than a mean of 10 cells ( P = .004) ( Table ). In addition, when groups were compared for flare, at postoperative day 1, 20 patients from the treatment group and 8 patients from the control group had a flare between 0 and +1 ( P < .001) ( Table ). By the end of postoperative week 1, 24 patients from the treatment group and 18 patients from the control group had a flare between 0 and +1 ( P = .012) ( Table ). When the flare degree and the cell number were compared 1 month and 2 months after the surgery, there was no difference between the treatment group and the control group. In 1 patient in the treatment group, the phaco tip caught the iris during the surgery. In this patient, minimal postoperative hyphema was observed, which was resolved completely within 2 days. After surgery, no inflammation-related complications such as synechiae and precipitates on the IOL surface were observed in the treatment group patients. Postoperative fibrin formation occurred in 1 patient in the control group. This patient underwent subconjunctival triamcinolone treatment and fibrin formation was resolved after 1 week. In 1 patient from the enoxaparin group, the posterior capsule was torn during surgery and the surgery was continued with BSS without enoxaparin. This patient was not included in the statistical analysis. There were no significant differences in terms of sex and age between the groups.
| Group 1 (25 Eyes) | Group 2 (26 Eyes) | Statistical Difference | Statistical Test | |
|---|---|---|---|---|
| Sex (male/female) | 13/12 | 13/13 | .886 | χ 2 |
| Mean age ± SD (min-max) | 61.5 ± 6.7 (52-75) | 61.3 ± 5, 1 (54-72) | .962 | Mann-Whitney U |
| Anterior chamber cell | ||||
| Post-op 1st day | ||||
| <10 | 12 | 4 | .012 | χ 2 |
| >10 | 13 | 22 | ||
| Post-op 7th day | ||||
| <10 | 20 | 10 | .004 | χ 2 |
| >10 | 5 | 16 | ||
| Post-op 1st month | ||||
| <10 | 25 | 24 | .490 | Fisher exact test |
| >10 | 0 | 2 | ||
| Post-op 2nd month | ||||
| None | 25 | 26 | >.999 | Mann-Whitney U |
| Anterior chamber flare | ||||
| Post-op 1st day | ||||
| 0 to +1 | 20 | 8 | <.001 | χ 2 |
| +2 to +3 | 5 | 18 | ||
| Post-op 7th day | ||||
| 0 to +1 | 24 | 18 | 0,012 | χ 2 |
| +2 to +3 | 1 | 8 | ||
| Post-op 1st month | ||||
| 0 | 24 | 20 | 0.099 | Fisher exact test |
| +1 | 1 | 6 | ||
| Post-op 2nd month | ||||
| None | 25 | 26 | >0.999 | Mann Whitney U |
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