Reduced choroidal peripapillary capillaries in thyroidassociated ophthalmopathy with early stage of dysthyroid optic neuropathy

INTRODUCTION

Thyroid-associated ophthalmopathy (TAO), also known as Graves’ ophthalmopathy, is an autoimmune disorder which has characteristic ocular manifestations,such as proptosis, eyelid retraction, eyelid lag and restrictive extraocular myopathy

. Among a series of TAO associated clinical findings, dysthyroid optic neuropathy (DON) is the most severe vision-threatening condition. The pathogenesis of DON is complicated, which is not fully understood by far.The most widely accepted theory is that DON is caused by the combined effects of mechanical, vascular and inflammatory process. Mostly, DON is secondary to a compartment syndrome in orbital apex, which is caused by enlargement of extraocular muscles and orbital fat resulting from orbital fibroblast deposition of hyaluronic acid

.

Our study demonstrated that a significant reduction of choroidal RPC observed in DON patients rather than normal and TAO without DON by using OCTA. RPC is a superficial capillary layer which comprise a unique vascular plexus. There have been reports demonstrating that RPC is necessary to metabolic demands of retinal ganglion cell (RGC) axons

.As the RGC axons are vulnerable to decease of blood flow, the structural changes to RPC network could lead to pathogenesis of RGC axonal loss

. There is evidence also showing an correlation between RPC loss and RNFL changes in chronic glaucoma

. The change of peripapillary microvasculature could not be efficiently detected by OCT

, which indicates that OCTA could be the most effective and easiest way to detect changes in retinal and/or choroidal microvasculature.Our data indicated a significant correlation between RPC reduction and VF defect. However, the decrease of choroidal RPC density could not be reversed 6mo after relieving optic nerve compression by either corticosteroid treatment or optic nerve decompression surgery though vision acuity significantly improved. However, longer term follow-up is required to further understand if the reduction of choroidal RPC could be recovered or permanently affected. Therefore, it is suggesting that choroidal RPC density could be clinically useful for early diagnose of DON.

There are around 4% to 8% TAO patients having DON

,of which the irreversible vision loss is largely caused by delayed diagnosis due to lack of efficient detecting method at early stage of TAO. It has been reported that the axonal changes of optic nerve are detected in patients with DON

.The compression caused by enlarged extraocular muscles and orbital fat may stretch the optic nerve and reduce the blood flow supply of retina. A report demonstrated that blood flow volume of superior ophthalmic vein decreased in DON eyes

.These findings suggest that the changes of optic nerve and hemodynamic state of the eye might be valuable for early diagnosis of DON.

There is no specific diagnosis guideline for DON due to various of clinical manifestations and limited detecting methods. Most clinicians diagnose DON by a combination of radiological findings and clinical manifestations. However, some patients may not present external signs, such as proptosis, because in some cases, DON only caused by congestion at the orbital apex

. The decline of visual acuity also sometimes lag behind other clinical presentations of DON, therefore, a number of tests should be run to evaluate the function of optic nerve for diagnosis of DON, including papillary exam, automated visual field (VF) and contrast sensitivity

.

圖畫書講讀，應(yīng)該建立在對(duì)圖畫書藝術(shù)的理解和把握的基礎(chǔ)上。兒童對(duì)圖畫書的喜愛(ài)，與圖畫書的內(nèi)容、形式、表達(dá)，與其圖畫文字的共同講述故事，與其獨(dú)有的藝術(shù)設(shè)計(jì)和效果，都有著密不可分的關(guān)系。圖畫書因此建立起不同于其他讀物的欣賞方式，兒童更有自己進(jìn)入圖畫書藝術(shù)世界的方法和途徑，有符合他們心理和趣味的審美體驗(yàn)。教師進(jìn)行圖畫書的講讀活動(dòng)，應(yīng)盡可能在認(rèn)識(shí)圖畫書藝術(shù)構(gòu)成和特點(diǎn)的基礎(chǔ)上進(jìn)行，幫助兒童積累或調(diào)動(dòng)他們自己的閱讀經(jīng)驗(yàn)，盡可能充分地、全方位地欣賞圖畫書作品，獲得愉悅并提升審美能力。

Optical coherence tomography angiography (OCTA) is a noninvasive imaging facility which could be applied to measure the thickness of retinal nerve fiber layer (RNFL), macular and many other parameters of the eye. OCTA is a high-speed optical coherence tomography (OCT) that could characterize a map of blood flow and vessel network of different layer and area of the retina and choroid, which is achieved by comparing the captured signals between sequential scans taken at same crosssection. OCTA assists clinicians to non-invasively visualize and assess retinal and choroidal perfusion, while at the same time the assessment is trustworthy due to its reliable reproducibility,sensitivity and specificity

. With the emergence of OCTA,it is possible to study the correlation between microvascular perfusion changes and the development of DON.

Here we demonstrated that OCTA could detect early defects in density of radial peripapillary capillaries (RPC) around optic disc in DON, which was also significantly correlated with defect of VF and vision. The findings suggested that OCTA could be used to early diagnose DON in clinics.

SUBJECTS AND METHODS

Ethical Approval This was a retrospective cross-sectional study conducted at the Department of Ophthalmology in Shanghai General Hospital, China, from January 2019 to December 2020. The study protocol and ethics were approved by the Ethics Committee of Shanghai General Hospital (ref 2020KY206). The study was conducted complied with the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants.

李閨女又呸了一口：李六如，真是越來(lái)越不知道羞恥了。原先拆遷時(shí)，你想當(dāng)個(gè)先進(jìn)也就算了。如今，又勾結(jié)佟金鑫占了那點(diǎn)口糧田。你說(shuō)，老少爺們今后怎么活？

Significant Reduction of Radial Peripapillary Capillaries in Dysthroid Optic Neuropathy Next, we further divided the patients of TAO into two subgroups, DON and non-DON,according to the criteria described in method section. DON had a significant reduction in both VF and the percentage of choroidal RPC, including whole and peripapillary, compared to both normal and TAO without DON (Figure 1). The percentage of whole choroidal RPC significantly reduced from 50.33%±0.3173% in normal to 49.16%±0.5463% in TAO without DON and further to 48.24%±0.4978% in DON(

=0.0041). The percentage of peripapillary choroidal RPC was also significant reduced from 53.24%±0.3914% in normal to 52.27%±0.5562% in TAO without DON, and further reduced to 51.50%±0.5399% in DON (

=0.03; Table 3). In agreement to the findings, the representative OCTA images also illustrated that the choroidal capillaries around optic disc were thinner in DON patients than that in normal and TAO without DON (Figure 2). There was no significant difference between DON, TAO without DON and normal controls in most tested parameters (Table 3). The above data suggested that change of choroidal RPC could be a specific sign in DON,and there was a possibility that the reduction of choroidal RPC in DON correlates with VF defect.

Patients diagnosed with TAO were based on Barley criteria

.Inclusion criteria for TAO participant were: 1) At least 18 years of age; 2) No history of radioactive iodine therapy or thyroidectomy. TAO participants were further divided into two groups, DON and non-DON. The diagnosis of DON was based on clinical findings

: 1) Decreased visual acuity compared to previous medical records; 2) Apparent VF defect mean deviation (MD) ＜-10 dB in Humphrey test; 3) Relative afferent pupillary defect; 4) Evidence of apical crowding in computed tomography or magnetic resonance imaging.

RTVue-XR Avanti system has been designed to minimize scanning time based on the SSADA algorithm. The system can also measure the variation of OCT signals among consecutive scans, therefore the motion of blood flow could be captured. In order to quantify and analyze the nerve fiber layer and macular circulation,

retinal angiogram images were processed and vessel density was calculated using the Avanti trend analysis software.

Exclusion criteria for all participants were: 1) Any retinal pathology and optic neuropathy, such as uveitis and diabetic retinopathy; 2) Any complication inducing VF loss, such as glaucoma or ocular tumor; 3) Any history of ocular trauma or intraocular surgery; 4) Vulnerable individuals or those who cannot conduct any test required in this study.

Humphrey Visual Field Test Humphrey Visual Field Analyzer II 750 (Carl Zeiss Meditec) was used to test VF for all participants, the data was calculated by Humphrey Swedish Interactive Threshold Algorithm (SITA) 30-2 test.The included results should meet the criteria that fixation loss was less than 20%, and both false-negative errors and falsepositive errors were less than 15%. All tests were performed without any inappropriate operation, such as eyelid artefacts,inattention, and fatigue effects. Any defects of VF caused by other diseases was excluded as described before.

通過(guò)本次研究可以看出,兇險(xiǎn)性前置胎盤患者相對(duì)于普通前置胎盤患者來(lái)說(shuō),面臨的威脅更大,可能導(dǎo)致的不良妊娠結(jié)局與不良新生兒結(jié)局的概率更高。另外,在一般資料對(duì)比中我們可以看出,高齡產(chǎn)婦、孕次和產(chǎn)次較高的產(chǎn)婦其發(fā)生兇險(xiǎn)型前置胎盤的可能性更大,因此,臨床上對(duì)于此類前置胎盤產(chǎn)婦要給予特別關(guān)注。

OCTA Image Acquisition and Processing The RTVue-XR Avanti could be used to visualize vascular structures of distinct layers of the retina and choroid. The scan was non-invasive and achieved by low-coherence interferometry. RTVue-XR Avanti used an 840 nm light source as the scan beam wavelength with an A-scan rate of 70 000 A-scan per second. Motion artefacts were minimized by dual orthogonal volumetric imaging of the retina. Each studied eye received four volumetric raster scans,which were composed of two horizontal priority (X-fast)and two vertical priority (Y-fast) scans. The scans provided consecutively information outside a 6×6 mm

field size of observed structures and assessed the details of retina in distinct layers.

Inclusion criteria for normal subjects were: 1) at least 18 years of age; 2) normal clinical appearance of the optic disc; 3) no RNFL loss; 4) no VF defect.

Measurement of Radial Peripapillary Capillaries, Macular Ganglion Cell Complex and Peripapillary RNFL The thickness of peripapillary RNFL and macular GCC were obtained using RNFL 4.5 scanning mode and analyzed by the GCC scan algorithm installed in the RTVue-XR Avanti. The RNFL thickness was measured around the optic disc with a circle of 4.5 mm diameter using RNFL mode, while the GCC scan was examined around the fovea with a square area of 6×6 mm

.GCC scan covers multiple layers of the retina, including the RNFL, the ganglion cell layer and the inner plexiform layer.The calculation of the scanned segmentations of the RNFL and GCC was analyzed by the SSADA algorithm. Furthermore,the SSADA algorithm can also measure and analyze separated areas of the retina including average, superior and inferior hemi-retinal RNFL and GCC.

Statistical Analysis All the data were calculated as mean and standard deviations and compared between groups. For the comparison between two groups, Student’s

test was used to compare the average values of all the measurements. Gender frequency comparison was analyzed by the Chi-square test.The correlation analysis was performed by univariate analysis with Pearson correlation test and multivariate analysis with ANOVA testing to determine the correlation between RPC and other parameters, such as visual acuity and MD and pattern standard deviation (PSD) of VF. Statistical significance was considered as

＜0.05. One-way ANOVA test with Tukey correction was applied for multiple comparison among groups with resultant significance level set at

＜0.01.

RESULTS

Demographic Data and Clinical Features Table 1 summarizes the clinical characteristics of each group. According to the inclusive and exclusive criteria, 34 eyes were included in normal group, while 64 eyes were included in TAO group.TAO was further divided into two groups, DON and TAO without DON, with 39 eyes in DON and 25 eyes in non-DON respectively. There was no statistically significant difference in DON, TAO without DON and normal controls, regarding to age and gender. The visual acuity of DON was significantlylower than the other two groups, though the CAS showed no difference between non-DON and DON.

據(jù)世界衛(wèi)生組織首份《全球糖尿病報(bào)告》顯示，全球糖尿病患者人數(shù)從1980年的1.08億增加到2014年的4.22億。目前我國(guó)確診的糖尿病患者已經(jīng)超過(guò)1億，居世界首位。據(jù)統(tǒng)計(jì)，糖尿病在我國(guó)的發(fā)病率已經(jīng)超過(guò)11.2%，處于糖尿病前期的人數(shù)占總?cè)丝诘?0.1%，我國(guó)約70%的糖尿病患者不知道自己已經(jīng)患上糖尿病。……