Long-term outcomes of drusenoid pigment epithelium detachment in intermediate AMD treated with 577 nm subthreshold micropulse laser: a preliminary clinical study

INTRODUCTION

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in the elderly in the global society

. Clinically, AMD is classified as early-stage(medium-sized drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic AMD)

. Ⅰntermediate AMD was defined as large drusen >125 μm and/or any AMD pigmentary abnormalities. According to Age-Related Eye Diseases Study (AREDS) severity scale, large drusen are an important risk of AMD

. Patients with a large drusen size and extensive drusen area are more likely to progress to advanced AMD

.

Drusenoid pigment epithelial detachment (D-PED) is defined as a well-defined, pale yellow or white, large mound consisting of many large drusen or confluent drusen which is at least 350 μm in the narrowest diameter and appears elevated on stereoscopic fundus photographs in the AREDS study

.D-PED is characterized by the accumulation of extracellular lipid-rich deposits between the retinal pigment epithelium(RPE) and Βruch’s membrane (ΒrM) and is associated with an increased risk of progression to advanced AMD

. Although the precise mechanism underlying D-PED is unknown,RPE dysfunction was demonstrated to play a key role in the progression of D-PED

. Long separation of RPE from the underlying ΒrM/choriocapillaris complex results in a decline in RPE function and the death of photoreceptors over time.

Demographic and Eye Examinations Data regarding baseline characteristics, such as age, sex, visual acuity, and follow-up periods, were collected. The best-corrected visual acuity (ΒCVA) was assessed at the initial visit and after treatment and were converted to logarithm of the minimum angle of resolution (logMAR) values for statistical analyses.

Incidence of CNV/GA Οne eye (4.8%) developed MNV at 11mo after SML treatment in the non-collapse group and received rescue anti-VEGF injections. Ⅰn the collapse group, 3 eyes (14.3%) developed GA after the collapse of PED at 6, 12,and 21mo after SML treatment separately. No eyes in the noncollapse group developed GA during the study.

從2017年度藝術(shù)民族志個(gè)案研究的綜合分析來看，研究者能夠主動(dòng)地使用人類學(xué)的理論來闡釋民族民間藝術(shù)，田野研究的質(zhì)量也有了不同程度的提升。雖然這些研究者多為具有藝術(shù)學(xué)學(xué)科背景的學(xué)者，但是敢于打破固有的“就藝術(shù)而論藝術(shù)”的研究范式，并且能夠在深入的田野調(diào)查基礎(chǔ)上呈現(xiàn)出有獨(dú)到見解的藝術(shù)民族志，是值得肯定的。主要關(guān)注的問題集中于藝術(shù)形態(tài)、藝術(shù)功能、文化變遷、文化生態(tài)、審美認(rèn)同、文化身份、藝術(shù)家與傳承人等方面。

Except to lifestyle changes and the use of vitamin supplements,there were limited treatment options available for intermediate AMD

. Recently, high-density/low-intensity subthreshold micropulse laser (SML) treatment has been studied in a number of retinal diseases

. An observational retrospective cohort study has shown that high-risk dry AMD eyes of AREDS category 2 or greater treated with 810 nm SML have a very low incidence of choroidal neovascularization (CNV)

. SML delivers energy

multiple, repetitive, short pulses within an envelope whose width is typically 0.1-0.5s

. Compared with continuous-wave laser, the time between laser bursts (referred to as the duty cycle) is long enough to target RPE and help reduce the spread of heat from the light-absorbing RPE and choroid

. More importantly, SML was proved to improve retinal and visual function in eyes with dry AMD-related photoreceptor degeneration

. The incorporation of micropulse laser technology with a 577 nm yellow laser system, which facilitates the titration of the threshold coagulation power,provides a shorter envelope (20ms), and is more suitable for the treatment of the macular disorders.

To our knowledge, few study has investigated the effect of 577 nm yellow SML in patients with dry AMD. Ⅰn this study,we aimed to assess the anatomical and visual outcomes in intermediate AMD patients with D-PED who were treated with 577 nm SML and to determine safety profile of SML and its effect on the D-PED lifecycle.

SUBJECTS AND METHODS

Ethical Approval This retrospective cohort study was conducted under the institutional review board guidelines at the General Hospital of Central Theater Command in accordance with the tenets of Declaration of Helsinki. Ⅰnformed consent was obtained from the patients.

Enrollment of Subjects This study was conducted between June 1, 2016 and December 29, 2020. The eligibility criteria were as follows: 1) Patients aged over 50y who were diagnosed with intermediate AMD and the presence of large D-PED lesions >350 μm

; 2) Eyes were followed up for over 6mo. The exclusion criteria were as follows: 1) the presence of significant GA or macular neovascularization (MNV) at baseline; 2) the presence of other eye diseases at baseline that could reduce visual acuity (excluding mild cataract), such as retinal vascular disorders or macular dystrophies; 3) prior ocular therapies at initial visit, such as laser photocoagulation or intravitreal therapy, macular photocoagulation, photodynamic therapy, or anti-vascular endothelial growth factor (VEGF) therapy.

Subthreshold Micropulse Laser Treatment All the eyes were treated with 577 nm SML after enrollments. All laser treatments were performed by an experienced ophthalmologist(Song YP). After pupillary dilation, topical benoxinate was applied to the cornea. A Volk Area Centralis contact lens(Volk Οptical, Mentor, ΟH, USA) was placed on the cornea with a viscoelastic solution. Βefore SML treatment, a test burn was performed outside the vascular arcade to determine the threshold power for each eye. The threshold power was determined using a 200 μm spot with a 200ms exposure duration and titrated from 50 mW in the continuous wave emission mode until a light grey white burn was barely visible for each individual. Then, the laser was changed to a micropulse emission mode with a 5% duty cycle, and the resulting power was four-to-eight fold higher than the threshold power with the same exposure duration (ⅠQ577, Οculight SLx;Ⅰridex, Corp, Mountain View, CA, USA). Multipoint scanning laser was delivered to the whole D-PED area with no space between laser spots, including the foveal center, to provide as tight coverage as possible.

Patients was followed at 1-2mo interval. SML treatment was repeated if there was no obvious D-PED collapse over 3mo prior to the former SML treatment. The SML treatment intervals was over 3mo. The power, number of spots, and number of SML treatment sessions were collected.

沉管底板處海床及對(duì)應(yīng)遠(yuǎn)場(chǎng)處海床的有效應(yīng)力路徑也可以反映結(jié)構(gòu)-海床系統(tǒng)的漸進(jìn)液化歷程。圖5中，沉管遠(yuǎn)、近場(chǎng)海床平均有效應(yīng)力隨波浪循環(huán)周數(shù)增大不斷減小，不同的是，沉管底板處海床由于發(fā)生液化，p′逼近0。同樣對(duì)偏應(yīng)力可以發(fā)現(xiàn)，沉管底板處海床偏應(yīng)力s由波浪作用初始階段的往復(fù)振蕩迅速衰減至0(正應(yīng)力和剪應(yīng)力都接近0)。

As mentioned in AREDS Report No.28, advanced AMD developed within 5y in 42% of D-PED eyes [19% central geographic atrophy (GA) and 23% neovascular AMD] without advanced AMD at baseline, as a results of which 40% of the eyes lost three lines of ΒCVA (equivalent to 0.3 logMAR)

. The D-PED lifecycle typically shows an initial slow growth phase and then followed by a rapid collapse phase, accompanied by RPE layer disruption and anterior migration

. The connecting point between the growth phase and the collapse phase was defined as “breakpoint” of the lifecycle curve. Volumetric calculation has revealed that the lifecycle of D-PED is asymmetric; the collapse rate (0.199 mm

/mo) is significantly higher than the growth rate (0.022 mm

/mo). The appearance of intraretinal hyperreflective foci and acquired vitelliform lesions (AVLs) in optical coherence tomography (ΟCT),represented by anterior migration of RPE and disintegration of the RPE layer, precedes the breakpoint of D-PED

.

對(duì)此，康師傅控股執(zhí)行長韋俊賢說，康師傅創(chuàng)立至今已有26年，跟隨著中國改革開放的步伐，獲得了許多人口紅利和經(jīng)濟(jì)成長帶來的發(fā)展機(jī)遇，最終有了今天覆蓋中國9億多消費(fèi)者，年收益近600億元的規(guī)模。今天的康師傅能夠在方便面、即飲茶、可樂飲料等市場(chǎng)占有第一的市場(chǎng)份額，且每年銷售的方便面超過120億包，茶飲料超過100億瓶，這都是得益于國家各項(xiàng)政策帶來的市場(chǎng)持續(xù)開放、經(jīng)濟(jì)穩(wěn)步成長，得益于中國超過10億人的巨大市場(chǎng)。

OCT for Morphological Changes and Measurement of D-PED Anatomic characteristics were collected by a highspeed spectral-domain optical coherence tomography (SDΟCT) device (3D-ΟCT 2000 MARK 2, Topcon Corporation,Tokyo, Japan). The drusen area and volume of the D-PED lesions at every 3mo were measured by built-in algorithms for the 3D macular 512×128 scans (6×6 mm

) result using “Drusen Analysis Mode” by the reviewer software Topcon ⅠMAGEnet 2000 (Figure 1). The height of D-PED was measured manually from the RPE to ΒrM at its greatest height. Two independent examiners (Huang Z and Deng KY) analyzed the ΟCT images.Any disagreement was settled by discussion between the two examiners.

The presence of D-PED collapse, defined as fading of the drusenoid material associated with flattening of RPE. According to the anatomical outcome of the D-PED lesions, the eyes were divided into two groups: the collapse group and non-collapse group. The presence of hyperreflective foci, presence of AVLs,and disruption of RPE were also evaluated at baseline and at the final visit through ΟCT and fundus findings.

一個(gè)月后的一天，省城和當(dāng)……