Inner limiting membrane peeling prevents secondary epiretinal membrane after vitrectomy for proliferative diabetic retinopathy

INTRODUCTION

Secondary epiretinal membrane (ERM) is not a rare complication after vitrectomy. About 8.97% to 47.7%patients occurred secondary ERM after vitrectomy without internal limiting membrane (ILM) peeling for rhegmatogenous retinal detachment (RRD)

. The location of retinal breaks at the equator is a significant risk factor [odds ratio (OR),3.9; 95% confidence interval (CI), 1.3-11.2]

. It might cause visual impairment or metamorphopsia

, thus requiring further membrane peeling surgery. A series of clinical studies found ILM peeling prevent the development of secondary ERM for RRD, although better best-corrected visual acuity (BCVA)among ILM peeling patients was not found

. There were also some studies found ILM peeling can be as a prophylactic treatment to prevent macular pucker formation in patients who underwent retinectomy

.

2.2.2.1 危害癥狀。葉片先出現水漬狀青灰色斑點，沿葉脈向兩端擴展，形成邊緣暗褐色、中央淡褐色或青灰色的大斑。后期病斑常縱裂，嚴重時融合，葉片變黃枯死(圖2)。

However, in practice, there are no uniform criteria for the surgical removal of the secondary ERM after vitrectomy for PDR. We encountered rapid and apparent development of secondary ERM in some cases with a mild postoperative reaction. We investigated the original ILM peeling for the prevention of secondary ERM and postoperative visual acuity(VA) and risk factors for secondary ERM development.

治療結果：試驗組28例，一次治愈2例，6-12月后二次治愈13例，6-12月后行第三次131-I治療者13例；第一次治愈（以下均含甲低）2例，第二次治愈13例，第三次治愈（含甲低）13例，1年后甲低11例。對照組29例，一次治愈（含甲低）25例，二次治愈（含甲低）4例，1年后甲低26例。血管雜音：試驗組與對照組血管雜音消失治愈后基本相同，甲低發生率對照組高于實驗組，有統計學意義。結果見表1。

農業經濟管理是指在市場環境和社會經濟條件的實際情況下，根據國家相關的經濟政策方針而對農村經濟施行的一種管理活動。具體到不同的地區，農業經濟管理就要充分考慮到各地不同的市場環境和經濟條件，并要在國家相關經濟政策方針的框架內實現對農業經濟發展的指導，制定相關的發展目標。而其中核心的部分就是將規劃、決定、調控及組織協調的過程實施于生產資料再生產過程中的生產、分配、交換、消費等環節，或與農業、金融、銷售、物流等資源進行跨行業整合，打通現代農業發展的產業鏈條，實現對農村經濟發展的法制化、規范化、科學化，以促進農村經濟發展水平、社會穩定和人們整體生活水平的提高。

SUBJECTS AND METHODS

ERMs were assessed by two experienced ophthalmologists(Wen H and Lin Z) using the OCT (Heidelberg Spectralis OCT, Heidelberg, Germany) photographs. In the OCT scan,postoperative ERM was defined as hyper-reflective line internal to the ILM. If there were inconsistencies on the ERMs, the photographs were sent to the 3

senior vitreoretinal surgeon with equal or more experience for consultation (Wu RH). To reduce subjective bias, the blind method was applied during assessment.

Although the occurrence of secondary ERM after diabetic vitrectomy is common, its mechanism remains unclear. Several factors are likely contributed to the high incidence of ERMs.First, residual native vitreous collagen and ILM in the macular area may act as a scaffold for cellular proliferation. Second,VH, postoperative inflammation, and the damaged retinal surface may provide an ideal environment for the growth of secondary ERMs. ILM peeling may therefore decrease the incidence of secondary ERM because it removes the scaffold that proliferates astrocytes, myofibroblasts, and retinal pigment epithelium cells

. Our results confirm that ILM peeling could effectively reduce the formation of secondary ERM. This result is consistent with previous studies that ILM peeling significantly reduced postoperative ERM after PPV for PDR

. In the current study, we observed that the overall incidence of secondary ERM was 26.9%. Furthermore, from the Cox proportional curve, we observed that the incidence of secondary ERM was lower in ILM peeling group that in ILM non-peeling group at any follow-up point. The incidence of ERM was 37.0% in ILM non-peeling group and 14.0% in ILM peeling group. Several previous studies have reported similar incidences of secondary ERM in ILM non-peeling groups, ranging from 20% to 52.8%, depending on the case mix and the methods of detection

. In fact, more factors associated with ERM formation were presented in ILM peeling group. In ILM peeling group, the patients had a higher rate of preoperative ERM, fibrovascular membrane, retinal attachment, PRP, and air tamponade. PDR eyes with more severe preoperative vitreoretinal changes may be more prone to secondary ERM

. Under diabetic conditions, a local proinflammatory and proangiogenic environment in eyes provides a strong stimulation for tissue proliferation, which is associated with the frequent incidence of ERM

. As well as head-down tilt after gas injection in the postoperative period,a higher number of cells on the macular surface would also result in an increased risk of ERM. In the current study, when considering the comprehensive risk factors, ILM peeling was the only independent risk factor for postoperative secondary ERM, which strongly emphasized the importance of ILM peeling during vitrectomy for patients with PDR.

The 23- or 25-gauge PPVs were performed under retrobulbar(50% mixture of 2% lidocaine and 0.75% bupivacaine) or general anesthesia using three different vitrectomy machines(Accurus Surgical System, Alcon Laboratories, Fort Worth,TX; Stellaris PC, Bausch & Lomb, Bridgewater Township,NJ; Constellation Vision System, Alcon Laboratories) by 5 surgeons. The ERM will be peeled off if there was already ERM at the time of first vitreous surgery. But the removal of ILM was depended on the doctor’s judgment. The ILM was stained with indocyanine green (Dandong Yi Chuang Pharmaceutical Co., Ltd, Liaoning Province, China) and then removed by ILM peeling forceps. ILM was peeled in the entire macular area (at least 2 disc diameters around the fovea). A combined surgery (PPV + phacoemulsification or intraocular lens implantation), pan retinal photocoagulation (PRP), and intraocular tamponade with air were performed, if necessary,depending on the surgeons’ experience.

The research protocol complies with the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of Wenzhou Medical Eye Hospital. The informed consent was waived. Patients’ clinical information was obtained from archived electronic medical records.

The VA in decimal fraction was converted into logarithm of the minimum angle of resolution (logMAR)values. A BCVA of ＜0.02 was recorded as a logMAR value of 1.7. The normally distributed parameters were presented as mean±standard deviation, whereas median and quartile range was used for non-normally distributed parameters. The Chisquare or Fisher’s exact test, as appropriate, was performed to compare discrete categorized data. Univariate logistic regressions were used to assess the relationship between postoperative ERM development and risk factors, including age, sex, history of retinal laser treatment, and ILM peeling.Next, multivariate logistic regression was performed for postoperative ERM, adjusted age and sex, and factors with a

value of ＜0.1 in the univariate analysis. The OR, hazard ratio, and 95%CIs were presented. A Cox proportional hazard regression was conducted for postoperative ERMs with adjustment of covariates. Statistical analysis was performed using SAS for Windows (Statistical Analysis System, version 9.1.3, SAS Inc., Cary, NC, USA).

RESULTS

As showed in Figure 2, after adjusting for the factors screened from the univariate model, a Cox proportional hazard regression for the incidence of secondary ERM was performed.which showed only ILM peeling remained significant (hazard ratio, 0.47; 95%CI, 0.23-0.98;

=0.04).

We evaluated perioperative factors to identify their potential effect on the postoperative development of secondary ERM(Table 3). Univariate logistical regression showed that the incidence of secondary ERM significantly increased in cases without ILM peeling, preoperative intravitreal injection of anti-VEGF, preoperative VH, and history of retinal laser treatment.Multivariate analysis revealed that ILM peeling was highly associated with the prevention of secondary ERM development(OR, 0.38; 95%CI, 0.17-0.86,

＜0.05).

The intra- and postoperative details for both groups are presented in Table 2. More patients in ILM peeling group underwent combined surgery with phacoemulsification (89.2%

73.1% ;

=0.006), fibrovascular membrane peeling (57.0%

33.6%;

＜0.001), retinal attachment (22.6%

11.8%;

=0.04), PRP(76.3%

61.3%;

=0.02), and air tamponade (57.0%

33.6%;

＜0.001). The follow-up duration was 9.3±5.4mo in ILM non-peeling group and 8.0±4.1mo in ILM peeling group(

=0.06). During the follow-up period, supplemental PRP treatment was more common in ILM non-peeling group thanin ILM peeling group (12.6%

4.3%;

=0.04). At the final follow-up, in ILM non-peeling group, the median logMAR VA was statistically better than in ILM peeling group (0.40

0.52;

=0.04). The median logMAR VA improvement was 0.90 in ILM non-peeling group and 0.49 in ILM peeling group with significant difference (

=0.03). Compared with patients in ILM peeling group, patients in ILM non-peeling group had higher incidence of secondary ERM (37.0%

14.0%;

＜0.001; Table 2). There was no difference between ILM nonpeeling group [3.63mo (interquartile range, 1.45-5.88mo)]and ILM peeling group [3.39mo (interquartile range, 3.21-4.64mo)] in the timing of secondary ERM development during the follow-up (

=0.80). Figure 1 shows a typical example of ERM development in ILM non-peeling group.

Total 212 eyes of 197 patients (average age, 55.8±11.6y;49.8% men) were enrolled in our study. The overall duration of follow-up was 8.7±4.9mo. There were 93 eyes in ILM peeling group and 119 in ILM non-peeling group. The baseline clinical characteristics of all patients are shown in Table 1.There were no differences in patient age, sex, status of lens,BCVA, and intraocular pressure between the groups. Patients in ILM peeling group had a higher proportion of preoperative ERM (39.8%

16.0%;

＜0.001) and preoperative intravitreal anti-VEGF injection (61.3%

17.6%;

＜0.001), a lower proportion of VH (19.4%

63.9%;

＜0.001) and retinal laser treatment history (3.2%

15.1%;

=0.004) compared with those in ILM non-peeling group.

DISCUSSION

Secondary ERM development causes visual deterioration and macular disorders such as macular cysts or macular thickening after successful surgical treatment of PDRs

. Recently, it has been reported that ILM peeling might decrease the ERM formation and diabetic macular edema

. Although a previous randomized clinical trial that enrolled 207 patients with PDR reported a beneficial role of ILM peeling in patients with PDR for improvement in VA

, ILM peeling was evaluated in patients with PDR undergoing PPV for the primary indication of VH as the primary objective. Most of these patients had VH, making the cohort different from our patient population. This study examined the effectiveness of ILM peeling during vitrectomy for PDR in reducing secondary ERM as well as identifying risk factors.

廣墾旅游集團主營酒店、旅游和出租車三大業務板塊。作為墾區十大產業集團之一的旅游集團，近年來在省農墾集團“走出去”發展經營理念的指導下，大力整合墾區酒店、旅游、出租車資源，目前已將業務領域由廣州輻射到茂名、湛江、汕頭、揭陽等廣東地市以及北京地區。……