Characteristics of macular microvasculature before and after idiopathic macular hole surgery

INTRODUCTION

An idiopathic macular hole (MH), caused by tangential traction, can be successfully closed by pars plana vitrectomy with gas-fluid exchange. The anatomic and functional outcomes were further improved by the advent of peeling of the internal limiting membrane (ILM). However,the postoperative visual acuity (VA) is sometimes poor despite successful anatomic closure. Long-term restoration of the microstructure and function of the fovea has been evaluated following surgery for idiopathic MH. Previous studies in eyes with MH have focused mainly on disruption of the outer retina, including the external limiting membrane (ELM), the ellipsoid zone (EZ), and the photoreceptors with respect to the visual prognosis.

Recently, researchers demonstrated an association of disorganization of the retinal inner layers (DRIL) with VA in various retinal diseases. The presence of vitreous cortex,proliferative glial tissue, and retinal hydration has been suggested as factors in the formation of macular holes in histologic studiesand possibly contribute to DRIL. DRIL indicates specific anatomic damage to the structures in the retinal layers that transmit visual data and also a poor inner retinal circulation.

對于公路工程施工所使用的機(jī)械設(shè)備，應(yīng)該確保機(jī)械設(shè)備不是老舊設(shè)備，若經(jīng)常出現(xiàn)故障將直接影響施工進(jìn)度，應(yīng)該在項目資金可支配的情況下，優(yōu)先考慮購買或者租賃技術(shù)先進(jìn)的機(jī)械設(shè)備，確保項目的施工效果和施工進(jìn)度能夠滿足預(yù)期的要求。

With the development of imaging technology, optical coherence tomography angiography (OCTA) provides highresolution, depth-resolved images for evaluation of the retinal capillary plexuses in eyes with MH in a noninvasive and dye-free manner. In our previous work, we used a commercially available OCTA device with custom-built imaging software and concluded that disorders in the inner retinal vessels corresponded to disruption of the outer retinal layers and VA in the setting of dysfunctional vasculature.The recovery of the retinal microvasculature in patients with a surgically closed MH remains to be elucidated. Meanwhile,limited information is available regarding quantitative evaluation of the preoperative status of the retinal microvasculature in eyes with MH. Accurate OCTA measurements should correct for ocular magnification and require information on axial length.Until now, no study has accurately quantified the changes that occur in the vasculature of the macula in eyes with MH after surgical treatment or the relationship between preoperative vascular parameters and the postoperative VA.The aims of this retrospective study were to characterize macular microvasculature in the superficial and deep retinal layers following surgery in patients with idiopathic MH using OCTA and to investigate the association of preoperative microvascular parameters in the inner retina with postoperative best-corrected visual acuity (BCVA) and healing.

SUBJECTS AND METHODS

This study was approved by the Ethics Committee at Wenzhou Medical University and complied with the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients.

Independent-test and Mann-Whitneytest were used to compare continuous variables between the groups. Repeated-measures analysis of variance was used to evaluate differences in the chronologic data. Post multiple comparisons were evaluated using the Bonferroni test. The Pearson correlation test was used to determine the associations between preoperative vascular parameters and postoperative BCVA. The associations between preoperative vascular parameters and postoperative healing stage were evaluated using the Spearman correlation test. All data are expressed as the means±standard deviations and analyzed with SPSS version 22.0 software (IBM Corp., Armonk, NY, USA).logMAR values of 2.0 and 3.0 were assigned for counting fingers and hand motion vision, respectively.<0.05 indicated statistical significance.

The AngioVue version 2017.1.0.155 software was used. The macular region was imaged using a central 3×3 mmarea. Low-quality OCTA images with a scan quality <5/10, severe artifacts attributable to poor fixation, or failure of automatic layer segmentation were excluded. The area and perimeter of the foveal avascular zone (FAZ) were determined by the software embedded in the instrument. The vessel density (VD) was calculated as the percentage of pixels with a flow signal greater than the threshold value and automatically measured using custom-built imaging software implemented in MATLAB (Mathworks,Natick, MA, USA). The mean brightness of the FAZ was taken as the threshold for the retinal vessels. Parafoveal and perifoveal VDs were calculated in the regions of the radius between 0.5 and 0.875 mm and between 0.875 and 1.25 mm,respectively, from the foveal center (Figure 1A, 1B). To reduce the effects of decentration of the FAZ and the artifacts at the edge of the scan, a circular area with a diameter of 2.5 mm was used instead of the entire 3×3-mmarea.

這樣支撐背后的壓力和心酸，我也有過切身體會。他坦言，也有撐不住的時候。2014到2015年間，因為太過忙碌，他一度感覺到崩潰?！坝卸螘r間我喝什么酒都沒味道，喝什么酒都不開心，再好的酒也覺得提不起來興奮點，身邊的人能明顯感受到。那段時間該做的工作還是在做，該進(jìn)行的課也還在講。很多東西比較得心應(yīng)手了，不會做得太差，但當(dāng)時狀態(tài)是不好的。明顯感覺到自己學(xué)習(xí)狀態(tài)不夠好，精神不夠集中，喝酒也有點食肉不知其味那種感覺?！毙液?，他都撐過來了。不對！可以說，你發(fā)現(xiàn)所有厲害的牛人，在贏得掌聲之后，永遠(yuǎn)都還覺得自己不夠努力。他們把這歸結(jié)為不夠上進(jìn)，其實是謙遜使然。

layer, and outer plexiform layer could not be identified. Two independent observers interpreted the OCTA and OCT images.The observers reached a consensus in all cases.To eliminate the effect of magnification, the images obtained by OCTA and OCT were corrected by Bennett’s formula using the axial length. The relationship between the OCT image measurements and the actual scan diameter was expressed by the formula t=p×q×s, where t is the actual axial length, p is the magnification factor determined by the camera of the OCT imaging system, q is the magnification factor in relation to the eye, and s is the original measurement obtained from the OCT image. The correction factor q was determined using q=0.01306×(AL–1.82).

Preoperative minimum diameter of the MH was measured in the OCT images. The postoperative healing stage,,restoration of the photoreceptor layer, was graded from 1 to 3. Grade 1 was assigned when the EZ and ELM were disrupted, grade 2 when the EZ was disrupted but the ELM was restored, and grade 3 when both the ELM and EZ were restored. DRIL was defined as the horizontal extent within the central 2000 μm for which any boundaries between the ganglion cell-inner plexiform layer complex, inner nuclear

英國人洛克曾說過“在缺乏教養(yǎng)的人身上，勇敢就會成為粗暴，學(xué)識就會成為迂腐，機(jī)制就會成為逗趣，質(zhì)樸就會成為粗魯，溫厚就會成為諂媚?！比暨@種現(xiàn)象發(fā)生在承載著實現(xiàn)中華民族偉大復(fù)興夢希望的大學(xué)生身上，恐怕是所有人都不想看到的。而事實卻是部分大學(xué)生責(zé)任感與使命感缺乏、浮躁與迷惘俱在、審美價值觀扭曲，這是不容否認(rèn)的現(xiàn)象。因此，面對當(dāng)前的大學(xué)生審美價值觀現(xiàn)狀，作為審美教育的影視藝術(shù)教育理應(yīng)成為改變這一現(xiàn)狀的中堅力量，積極引導(dǎo)大學(xué)生樹立正確的審美價值觀。與其他的價值觀教育途徑相比，影視藝術(shù)教育會通過左右大學(xué)生的審美價值觀進(jìn)而在潛移默化中影響大學(xué)生整個價值觀念體系的形成。

All procedures were performed by a single surgeon. Standard 3-port pars plana vitrectomy was performed using 23-gauge instruments. Cataract surgery was performed on all 20 phakic eyes. A 31-year-old patient underwent cataract surgery for congenital cataract. A concentration of 0.025% indocyanine green (ICG) was injected into the vitreous cavity and washed out no later than 3 seconds by 23-gauge cutter. Then the ILM was peeled by carefully grasping with forceps without retinal damage to about 4-disc diameters centered on the macula. All patients performed fluid‐air exchange with air, and the sclerotomies were sutured.Patients were instructed to remain in a prone position for 3-5d postoperatively.F: Female; M: Male; OS: Left eye; OD: Right eye; BCVA: Best-corrected visual acuity.

許多專家學(xué)者都認(rèn)為從定性到定量綜合集成方法是系統(tǒng)學(xué)討論班最大的成果，這是中國人智慧和原始創(chuàng)新。我們認(rèn)為還有一個重大的成果，就是系統(tǒng)學(xué)討論班培養(yǎng)了一批研究復(fù)雜系統(tǒng)工程的人才，這批人在各個領(lǐng)域及各類復(fù)雜系統(tǒng)工程研究和實踐中發(fā)揮了重要作用，繼承和發(fā)展并廣泛實踐了錢學(xué)森系統(tǒng)思想、理論、方法等。

The medical records of patients who had undergone successful MH closure by vitrectomy and ILM peeling in the Fundus Department at the Eye Hospital, Wenzhou Medical University, from June 2018 to May 2020 were reviewed. Each patient underwent a complete ophthalmic examination, including slit-lamp examination, intraocular pressure measurement, fundoscopy, preoperative axial length measurement, OCT (Spectralis; Heidelberg Engineering,Heidelberg, Germany), and OCTA (AngioVue; Optovue,Inc., Fremont, CA, USA). The slit-lamp, fundoscopy, OCT,and OCTA examinations were performed before surgery and 2wk, 1, and 3mo after surgery. The inclusion criterion was a Gass stage 2-3 idiopathic full-thickness MH confirmed on OCT. Eyes with macular disease, such as age-related macular degeneration, epimacular membrane, myopic choroidal neovascularization, a spherical equivalent refractive error>±6.0 diopters, significant cataract (LOCS scale higher than N2, C1, P2)or macular edema after surgery, glaucoma,other marked complications, or a history of intraocular surgery were excluded. Chronic macular holes (defined by visual symptoms of greater than 1y), heavy smokers, or patients with systemic disease, such as diabetes, hypertension were also excluded. The patients were divided into groups according to whether or not their 3-month postoperative BCVA was <20/32 or ≥20/32.

RESULTS

Fortythree eyes of 43 patients with an MH underwent vitrectomy with ILM peeling between June 2018 and May 2020. Twentythree eyes were excluded (8 for high myopia, 4 for severe cataract that prevented acquisition of high-quality OCTA images, 4 for age-related macular degeneration, 2 for diabetic retinopathy, 2 for myopic choroidal neovascularization, 2 for OCTA images of poor quality, and 1 loss in postoperative follow-up), leaving 20 eyes of 20 patients for inclusion (Table 1).

The patients mean age was 59.1±10.1y. Fourteen patients were female (70%) and 6 (30%) were male. The mean preoperative axial length was 23.9±1.1 (range 21.77-25.52) mm. Before surgery, the mean minimum diameter of the hole was 462.9±208.3 (range 206-871) μm.

The logMAR BCVA improved from 0.98±0.59 (range 0.22-2.00,Snellen equivalent 20/200) preoperatively to 0.93±0.64 (range 0.30-3.00, Snellen 20/160) at 2wk, 0.47±0.25 (range 0.15-1.00, Snellen 20/63) at 1mo, and 0.30±0.25 (range 0-1.00,Snellen 20/40) at 3mo postoperatively. Ten patients (50%) had evidence of different degrees of DRⅠL on OCT images during the post-surgery recovery of MHs (Figure 1C, 1D).

統(tǒng)計分析結(jié)果表明(表3)：不同施肥處理間新竹株數(shù)、胸徑以及產(chǎn)量均無明顯差異；不同密度條件下，新竹株數(shù)與產(chǎn)量同樣沒有產(chǎn)生明顯差異，而對于平均胸徑，則低密度林分明顯高于高密度林分(P=0.041<0.05)。

關(guān)于企業(yè)社會責(zé)任的研究有多種研究視角，但是多數(shù)研究關(guān)注于顧客和社會。事實上，企業(yè)員工在企業(yè)社會責(zé)任的履行和完善過程中是一個不可忽略的對象。企業(yè)社會責(zé)任強(qiáng)調(diào)企業(yè)自覺承擔(dān)員工的責(zé)任，保證企業(yè)內(nèi)部雇員的利益，強(qiáng)調(diào)企業(yè)內(nèi)部的和諧，促進(jìn)勞動關(guān)系的改善。民營企業(yè)員工對于企業(yè)社會責(zé)任的認(rèn)知和態(tài)度，對于企業(yè)社會責(zé)任的實施和提升，有很重要的影響力。但是，從中國當(dāng)前現(xiàn)狀來看，民營企業(yè)對員工履行社會責(zé)任并沒有成熟的社會責(zé)任體系可供參考，對民營企業(yè)履行對員工的社會責(zé)任的研究勢在必行。

There were significant changes in all vascular parameters after MH surgery (Table 3). The changes in parafoveal and perifoveal VD in both layers are shown in Figures 2 and 3.Before vitrectomy, the mean parafoveal and perifoveal VD values were 47.4%±2.7% and 47.2%±0.03%, respectively, in the superficial layer and 49.2%±0.05% and 47.7%±0.04%,respectively, in the deep layer. A significant reduction in VD was observed 2wk after surgery. Furthermore, there was evidence of recovery of the macular microvasculature in the superficial plexus at 1 and 3mo postoperatively. In the deep plexus, there was no difference between the preoperative VD and the VD at 1mo postoperatively in either region. The mean perifoveal VD at 3mo postoperatively was even greater than that before surgery.

The mean preoperative area and perimeter of the FAZ were 0.43 mmand 2.8 mm, respectively (Figure 2A, 2D). Significant reductions in the mean values for the FAZ parameters were observed during the follow-up period (Table 3 and Figure 2).

There was a correlation between decreased preoperative parafoveal and perifoveal VD in the deep layer and worse 3-month VA(Pearson’s=-0.667 and -0.619, respectively; Table 4, Figure 4A, 4C). A larger FAZ perimeter (Spearman’s=-0.524) and decreased perifoveal VD preoperatively in the deep layer(Pearson’s=0.486) was associated with lower healing stage of photoreceptor layers (Figure 4B, 4D). There was no correlation between FAZ, superficial vasculature parameters and VA at 3mo after surgery. No correlation was found between preoperative superficial VDs and postoperative healing stage.

DISCUSSION

Several studies have investigated the preoperative configuration of MH using OCT and searched for predictors of the visual outcome after surgery. To the best of our knowledge,postoperative visual recovery has not been evaluated as a predictive parameter by OCTA in eyes with MH. We demonstrated that the preoperative macular microvasculature was denser in eyes with MH that had better VA after surgery,especially in the deep capillaries. Moreover, correlation analysis revealed that a decrease from the preoperative deep capillary VD was strongly correlated with worse postoperative VA. We speculate that this could be attributed to several possible mechanisms. Tornambeproposed the“hydration theory”, whereby during formation of an MH, after the posterior hyaloid has created a retinal defect, vitreous fluid first passes through the inner retina and disrupts homeostasis.Liquid vitreous fluid then accumulates, the MH appears to enlarge, and the inner retinal tissue become swollen, especially in the outer plexiform layer. DRⅠL was recently identified to be a sign of poor inner retinal circulation, indicating disruption of the pathways that transmit visual information from the photoreceptors to the ganglion cells and seemed to be a correlated predictive biomarker for VA in various diseases. We observed a similar phenomenon in a previous study. Given their special watershed-like position, the deep capillaries may be more prone to ischemia and contribute to disruption of the photoreceptor layer and then visual function. The suggested pathophysiologic changes within the inner retinal vasculature,which are supported by histopathologic and imaging studies,collectively may have accounted for the decreased deep blood flow seen in our study.

There were significant differences in preoperative VA, perimeter of the FAZ, and parafoveal and perifoveal VD in the deep plexus between the group with a 3-month BCVA<20/32 and the group with the 3-month BCVA≥20/32 (Table 2). Ⅰn the group with the 3‐month BCVA<20/32, the preoperative VA was significantly worse,and the perimeter of the FAZ was larger. In the deep capillary layer, the VDs in both regions was smaller. The minimum diameter of the hole and the area of the FAZ were larger, albeit not significantly so. No significant differences were found in patient age, preoperative stage, axial length, or VD in either region of the superficial layer.

We quantitively demonstrated recovery of the macular vasculature with magnification correction before and after surgical intervention in eyes with MH. Scupolareported significant improvement in retinal function at 3mo after closure of an MH that was confirmed to be maintained at 6 and 12mo by focal electroretinography. Therefore, we compared the microvascular networks in eyes with MH before, 2wk,1, and 3mo postoperatively. Significant reductions in FAZ parameters were observed 2wk postoperatively, suggesting a movement of foveal tissue toward the central fovea and a centripetal movement when the MH is closed. However, the 2‐week postoperative VDs decreased significantly, and the VA improved only slightly, indicating prompt structural recovery but delayed functional repair. Kimand Demirelreported that the postoperative VD in eyes with a closed MH,particularly in the deep plexus, was lower than that in either fellow eyes or healthy eyes. In the present study, most VD values recovered only to the preoperative status, indicating a lack of functional vascular integrity after surgery. The disrupted microvasculature may impede the dynamic healing process and provide another explanation for the unsatisfactory visual gain after surgery despite successful anatomic closure of the MH.

Correlational analysis revealed a moderate correlation of a decreased deep perifoveal VD and an increased FAZ perimeter with poor healing. The ischemia in inner retinal vasculature is considered to contribute to the disorganization of the outer retina and to lead to poor restoration of the microstructure of the fovea.

This study has several limitations. The first is its retrospective design and relatively small sample size. The second relates to the fact that eyes with MH tend to have poorer stable fixation before surgical closure, leading to exclusion of OCTA images with poor quality upon visual inspection.In conclusion, OCTA analysis before and after surgery in eyes with MH demonstrated the preoperative macular microvasculature and suggests that the status of the deep plexus could predict the postoperative visual outcome.Quantification of the retinal vasculature postoperatively would provide an explanation for the limited visual recovery after surgical closure of MH.

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手寫苗文文字樣本經(jīng)過掃描儀進(jìn)入計算機(jī)后，因紙張的厚度、光潔度和取樣設(shè)備質(zhì)量的不穩(wěn)定都會造成錄入后的數(shù)字圖像文字畸變，形成粘連、筆畫中斷和圖像噪點等干擾，所以在進(jìn)行文字識別之前，務(wù)必要對帶有噪聲的文字圖像進(jìn)行處理。圖像預(yù)處理方法有許多經(jīng)驗成果〔9-10〕，其大體步驟包括文字圖像大小歸一化、灰度化、二值化、規(guī)范化等等。

Supported by the National Natural Science Foundation of China (No.81900910; No.81700884); Natural Science Foundation of Zhejiang Province (No.LQ19H120003;No.LGF21H120005); Key Project Jointly Constructed by Zhejiang Pronvince and Ministry (No.WKJ-ZJ-2037); Basic Scientific Research Project of Wenzhou (No.Y20210194).

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