Amniotic membrane for covering high myopic macular hole associated with retinal detachment following failed primary surgery

INTRODUCTION

Myopia is a global public health problem. The population of myopia in China ranking first in the world is nearly 600 million, of which about 300 million are teenagers

. However, the further challenge of myopia is the increased risk of secondary diseases, including cataract,glaucoma, retinal detachment (RD), macular hole (MH), and macular degeneration. These secondary fundus lesions may lead to an irreversible loss of vision

.

随着我国城镇化、农业现代化加快发展，土地流转速度加快，农业适度规模化经营大量涌现，同时，我国人口老龄化，农村青壮劳动力外出打工兼业化日渐突出，普通农户在农业生产过程中过去自身能解决好的许多事情，现在一家一户办不了、办不好、办起来不合算的事越来越多。种好地是国家粮食安全的基础，快乐幸福的生产是农民的内在生活需要，这一切都使得农户对农业生产型服务的需求变得越来越旺，要求也越来越高。2017年，原农业部、国家发改委、财政部印发《关于加快发展农业生产性服务业的指导意见》，鼓励发展农业生产性服务业，有力支撑现代农业发展。

However, the above techniques still have some drawbacks.The techniques related to ILM require excellent surgical ability of operator and need long time to learn these techniques

.In addition, for those patients in this study who already had the ILM peeling but failed to achieve MH healing and retinal reattaching, there is no surplus ILM in their macular region.Therefore, the above techniques are useless for these patients.The techniques such as MH edge massage and autologous blood covering only assist MH healing, but have no essential improvement in the overall clinical effect.

中小河流洪涝风险评估及研究——以哈尔滨地区为例…………………………… 崔 巍，陈文学，白音包力皋等(4.15)

Patients with PMMH always have the characteristics of long ocular axis, complicated with retinal choroid atrophy,posterior scleral staphyloma, tight adhesion of vitreous body and abnormal peripheral retina, so that the difficulty of operation is much higher than that of ordinary MH operation,which poses a challenge to the doctors of fundus disease

.The standard treatment of PMMH was pars plana vitrectomy(PPV) with internal limiting membrane (ILM) peeling and endotamponade

. And the healing rate of PMMH in reports from different countries and regions is between 60% and 70%

.

The SPSS 23.0 software was used for statistical analysis. The measurement data were expressed by mean±standard deviation. The independent sample

-test was used for comparison between groups, and matching sample

-test was used for comparison among groups, and the difference was statistically significant with

＜0.05. The Chisquare and the exact probability method were used to compare the counting data between two groups.

SUBJECTS AND METHODS

This is a prospective non-control case study.The case data were obtained from Wanjiang Eye Hospital of Mianyang. All subjects signed informed consent. And the study was approved by the Medical Ethics Committee of Wanjiang Eye Hospital of Mianyang and in accordance with the ethical requirements of clinicl trials and the Declaration of Helsinki.

The primary disease of all cases was PMMH associated with RD and the axial length was more than 29 mm. The first surgery of PPV with ILM peeling and silicone oil (SO) tamponade was performed in our hospital or other hospitals. The MH was not healed or accompanied by RD more than half a year.

Based on the previous researches, our team proposed a new technique named AM covering. The difference between this new technique and AM plug is that the AM only covers on the surface of MH and will not damage the RPE below the MH. And MH still heals according to its own anatomical structure. And there is no harmful effect on the outer structure of retina, which maximally protects the visual function of patients theoretically. During the operation, the subretinal fluid was removed through MH, and there is no need to add extra iatrogenic retinal hole as internal drainage, so as to reduce iatrogenic injury. The operation is easy and can be performed with only one hand, and there is no need of the ceiling light and fourth incision. As shown in Figure 2B and 2D, the AM was located on the surface of macular area, the macular structure was clear, and the MH was completely healed. The Figure 3A showed the macular structure of a patient with PMMH associated with RD who underwent the surgery of PPV with ILM peeling and SO tamponade. As shown in the Figure 3A, the edge of MH was attached but the central tissue lost after the previous surgery. The Figure 3B showed the macular structure of this patient after second surgery of AM covering. The central lost tissue of foveal reached complete healing. In this study, the removal of SO, reattached of RD and healing of MH were all achieved in these 17 patients who underwent failed primary surgery. This result showed that the technique of AM covering can achieve the same therapeutic effect as AM plug.

All patients underwent comprehensive ophthalmologic examination before surgery,including visual acuity (VA), intraocular pressure (IOP), slit lamp microscopy examination, fundus examination, optical coherence tomography (OCT; Heidelberg Spectralis OCT)examination of macular area, fundus photography. The bestcorrected visual acuity (BCVA) was converted to logMAR VA.

All subjects were treated with SO removal combined with biological amniotic membrane (bAM;Ruiji Co., Ltd., Jiangxi Province, China) covering on MH and C

F

tamponade. The specific methods were as follows: 1)All patients underwent the SO removal firstly with a 3-port,25-gauge surgical incision. 2) Phacoemulsification combined with intraocular lens (IOL) implantation was performed simultaneously in the case with cataracts. 3) The vitreous cavity was injected with triamcinolone acetonide (TA) to observe whether there was residual vitreous cortex, and if so,the residual vitreous cortex should be thoroughly removed.4) After staining ILM by indocyanine green, we observed whether there was any residual ILM around MH and whether the peeling range of ILM was sufficient in the previous operation. And the peeling range of ILM would be extended if necessary. After the first two steps completed, the liquid under the retina was removed by fluid-air exchange. A 2×3 mm

peeling range AM was pre-soaked in balanced saline use ILM tweezers, then passed the transplant through a 25-gauge valved trocar into the vitreous cavity and laid flat on the surface of MH. And adjusted the position of the transplant to the middle of the MH, make sure the edge of transplant was exceeded the MH (Figure 1). The flute needle was used to remove residual liquid around the transplant so that it was tightly attached retina and no longer moved. Last, 13% C

F

was injected into vitreous cavity and the incision was sutured. After the surgery, the patients need to rest in face down or lateral position for 2 to 3wk, with anti-inflammatory and symptomatic treatment. All patients were reexamined OCT and scanning laser ophthalmosocopy (SLO) in 2wk, 1, 3, 6, and 12mo after surgery.

（1）建立资产管理绩效考核制度。逐步建立资产考核制度，并与科室绩效挂钩。运用信息化手段，执行定期盘点与不定期巡查相结合的管理办法，奖优罚劣。

The low success rate of first surgery necessarily requires a second operation. It is one of the problems that need to be solved urgently for operators that how to improve the success rate in more complex secondary surgery. To solve this problem,Capoross

invented a technique named human amniotic membrane (hAM) tamponade to treat recurrent MH and had achieved perfect effect in clinical application. However, this technique still has disadvantages of complicated operation and iatrogenic injury. Inspired by this study, we improved this technique. The improved technique of covering AM for rescuing failed primary surgery of PMMH had gained good effect.

RESULTS

A total of 17 eyes of 17 subjects met the inclusion criteria, and all subjects completed the treatment and one year follow-up without missing. The subjects included 6 males and 11 females with an average age of 49.18±5.42 (ranged 39 to 58)y. The mean preoperative BCVA was 1.66±0.22 (logMAR), and the mean ocular axial length was 30.28±1.04 (ranged 29.10 to 32.41)mm. Fourteen eyes had posterior sclera staphyloma, 12 eyes were combined with high IOP secondary to SO emulsification,3 eyes combined with IOL eye, 14 eyes combined with cataracts. The basic clinical features before surgery are shown in Table 1.

SO was removed successfully from all eyes, MH healed,and RD reattached. The recovery conditions of typical cases are shown in Figures 2 and 3. After surgery, one patient(5.89%, 1/17) was found AM translocation half a month,then performed a second operation to adjust AM and C

F

tamponade. The VA improved in 15 eyes (82.35%, 15/17),no change in 2 eyes (11.76%, 2/17). The mean VA was raised from 1.66±0.22 before surgery to 1.08±0.27 (

=9.83,

0.01).Comparison of the indicators of the patients before and after surgery are shown in Table 2. No serious complications occurred in all cases. The postoperative data in Tables 1, 2 and Figures 2, 3 were all 12mo after surgery.

DISCUSSION

The PMMH and its related complication (MH associated with RD) seriously affect the visual function of patients. If the treatment is not timely, the risk of secondary blindness and eye atrophy is extremely high. The treatment of PMMH mainly depends on surgery. Although there are many surgical techniques in clinical treatment, the curative effect is unsatisfactory or the surgery is difficult to be popularized due to technical difficulties.

Based on the low success rate of routine surgery, the scholars from all over the world have made a lot of improvements and innovations in surgical techniques. The technique mainly focused on the treatment method of ILM and the healing of MH, including autologous transplantation of ILM

, inverted ILM flap

, MH edge massage

, autologous blood covering

, lens capsule transplantation

, autologoustransplantation of retinal free flap

, the hAM plug

,

.These innovative techniques have made some achievements in improving the healing rate of MH.

进而，本文对控制变量进行了平滑性检验，即要求除了受教育年限外，其他控制变量在断点两边应该是连续的。根据非参数局部线性回归方法，表6描述了控制变量的连续性检验结果。根据最后一列Lwald估计量结果可以发现，这些控制变量满足平滑性假定。

Secondary fundus lesions caused by pathological myopia (high myopia) is the second major cause of low vision and blindness after cataract in China

. Pathological myopia macular hole(PMMH) and its related complications are difficult points in current clinical treatment.

The lens capsule transplantation, autologous transplantation of retinal free flap, and other innovative techniques can be applied in patients with recurrent and refractory MH in our study. In particularly, autologous transplantation of retinal free flap requires cutting a piece of retinal tissue in the peripheral retina. This operation itself may cause a new harm to retina,and is prone to occur complications such as choroidal and retinal hemorrhage. The two kinds of surgical techniques also require extremely high skill of the operator and are not suitable for wide application.

In recent two years, the technique of amniotic membrane(AM) plug has been paid more and more attention and favor because of its low cost and high healing rate of MH. The so-called AM plug is a kind of technique which transplant the AM, as embolus, under the MH and between the retinal neuroepithelium and pigment epithelium to plug hole, and promote MH healing. In fact, AM as an adjunctive therapy is nothing new, which has been applied in various clinical specialties, and play a good role in promoting the treatments of many diseases

. For example, the AM is used to assist the treatment of otitis media with tympanic membrane perforation in otolaryngology

, and used to assist ocular surface reconstruction and prevent symblepharon in operation of severe ocular surface diseases in the specialty of ophthalmic keratopathy

, and so on. But the application of AM in the treatment of MH is an innovation. The representative researches were from the team of Caporossi

. These researches verified good curative effect of AM plug in treatment of patients with PMMH and MH associated with RD

.

However, the technique of AM plug still needs to be discussed and improved in clinical application. The disadvantages of using AM plug invented by Caporossi

can be summarized as follows: the AM is filled between the retinal nerve epithelium and retinal pigment epithelium (RPE) during operation, which may touch or damage the RPE under the MH and damage visual function. Because the AM was plugged in the retinal interlayer, the structure of macular area is disordered after the MH healing, and the influence to macular function cannot be ignored. And bimanualness is required during the operation, so that an extra surgical incision will be added when the ceiling lamp is used. Furthermore, after MH filled by AM,subretinal fluid needs to be removed from a drainage hole artificially cut from the posterior retina. These two operating steps increase the harm to retina. Compared with autologous transplantation of retinal free flap, AM plug has significantly reduced iatrogenic injuries and improved clinical efficacy.But based on the above analysis, this technique has space for further upgrading and improvement.

The material used in this study was bAM rather than fresh hAM mentioned in the research

. The advantage of bAM is that this material is easy to obtain and can be used directly,while fresh hAM requires temporary processing of grafts,and there is a potential transmission risk of infectious disease.Although the main disadvantage of bAM is that it provides less somatomedin than fresh hAM during HM healing, bAM has played a good therapeutic effect in promoting MH healing in our research.

The ocular axial length was less than 29 mm.The cases had undergone the surgery of macular buckling or posterior scleral reinforcement. The cases could not, or had no value for second surgery because of systemic disease, ocular inflammation, or already blindness.

我又打量了一下屋里的摆设，心里更慌了，因为这显然不是在我家里。我不在自家床上睡觉又会在哪里呢，我努力回忆了几次，可脑子里始终是一截黏糊糊的空白。

第二，要完善对于不负责任的社会中介机构的惩治力度，轻则处以不同程度的罚款，情节严重的要吊销其营业执照，剥夺其审计资格。只有加大惩戒力度，才能让这些中介机构在合理合法的范围内进行独立审计，从而对会计信息的披露起到外部的补充作用。

筛选15名未参与专家评估和仪器测试的消费者，对参加测试的57名消费者的面部图片随机进行水光感评价，评分区间为1～10分，1分代表完全没有水光感，10分代表水光感非常明显。

In summary, the technique of AM covering uses the materials which are easy to obtain, and has potential advantages such as no damage and short learning curve. The design of this technique avoids the defects of previous surgical techniques, improves the success rate of surgery for MH and MH associated with RD, and protects the visual function of patient to the maximum extent. This technique is especially suitable for the patients who have unhealed MH after multiple operations and have no ILM in macular area. Limited to the small number of cases in this study, more randomized controlled studies with a longer follow-up period are needed to corroborate our results.

Supported by Medical Research Project of Sichuan Province (No.S20018).

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