Combined central retinal artery and vein occlusion associated with primary antiphospholipid syndrome treated by injection of dexamethasone intravitreal implant and anticoagulant therapy: a case report

以降低茶園小貫小綠葉蟬蟲(chóng)口基數(shù)為目的。一是加強(qiáng)茶園管理，及時(shí)清除雜草，及時(shí)分批勤采，可隨采摘的嫩芽葉帶走大量的卵及低齡若蟲(chóng)[2]；二是12月下旬用石硫合劑晶體150～200倍液封園，可有效降低蟲(chóng)口基數(shù)。

We present a case of combined central retinal artery and vein occlusion associated with primary antiphospholipid syndrome (APS) treated by injection of dexamethasone intravitreal implant (Ozurdex

) and anticoagulant therapy.Written informed consent was obtained by the patient to allow publication of this case. The study was conducted in accordance with the tenets of the Declaration of Helsinki.

APS is an autoimmune thrombophilic state characterized by multi-organ arterial and/or venous thrombosis and/or pregnancy morbidity, associated with circulating antiphospholipid antibodies (aPL) including lupus anticoagulant, anticardiolipin(aCL), and anti-β2-glycoprotein antibody

. Primary APS occurs in patients without any underlying disorders, whereas secondary APS is accompanied by autoimmune diseases, most commonly systemic lupus erythematosus (SLE)

.

The most common ocular involvement in APS includes retinal artery or vein occlusion, arterial ischemic optic neuropathy,and retinal vasculitis

. Presentation of a combination of central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO) in primary APS is extremely rare, which could not be diagnosed until the ocular symptom occurred.

The young patient was hospitalized and immediately referred to a hematologist, under whose guidance, oral anticoagulants of 150 mg aspirin was given per day. Intravitreal injection of dexamethasone intravitreal implant was given on the second day of admission. In the following 4wk, her BCVA of the right eye recovered from 6/60 to 6/6, the flame-shaped retinal hemorrhages as well as retinal edema regressed gradually to a normal appearance (Figure 1C, 1D), the average macular sensitivity of the right eye improved from 10.3 to 15.2 dB(Figure 3B), and macular perfusion greatly improved in both capillary layers except for few ischemic areas above the macula (Figure 2B). Intravitreal dexamethasone was safe and well tolerated since there were no significant complications such as intraocular pressure hypertension and cataract during the follow-up. After being discharged from hospital, she was closely followed up for more than 1y, and prothrombin time was regularly monitored during her visits. The retina regained a normal appearance and no further thrombotic event occurred after 2mo of intravitreal injection. During the 1-year followup, repeated serologic studies showed that serum anti-β2-glycoprotein antibody had returned to normal.

Ophthalmic examination revealed that her best corrected visual acuity (BCVA) was 6/60 in the right eye and 6/6 in the left eye. A relative afferent pupillary defect was seen in the right eye. Slit-lamp examination in both eyes was normal. The right fundus showed engorged and tortuous retinal veins, diffuse flame-shaped retinal hemorrhages, hard exudates, cottonwool-spots, a pale and edematous retina and a swollen disc(Figure 1A), whereas the left fundus appeared normal (Figure 1B). Mild macular edema and significantly reduced macular perfusion in the right eye was revealed by optical coherence tomography angiography (OCTA; Figure 2A). Macular sensitivity of the right eye, measured by microperimetry,was remarkably reduced when compared to the left eye(Figure 3A). Ischemic areas in OCTA, especially the deep capillary layer, correlated with lower macular sensitivity on microperimetry.

Multiple clinical and laboratory investigations were performed to determine the underlying causative disease. She was investigated for cardiovascular diseases, hyperlipidemia,diabetes, hypertension, infections, and autoimmune disorders.The echocardiogram revealed clinically insignificant mild tricuspid regurgitation. Duplex carotid ultrasonography appeared normal on both sides. Laboratory investigations included complete blood count, erythrocyte sedimentation rate, serum lipids, antineutrophillic cytoplasmic antibodies,homosysteine, rheumatoid factors, aPL, and functional assays for protein C and protein S to detect the hypercoagulable state. All the investigations were relatively normal except that the level of anti-β2-glycoprotein antibody was 31.46 RU/mL(normal ＜20 RU/mL). Although not included in the diagnostic criteria

, the value of anti-β2-glycoprotein antibody has a high specificity for APS

. Therefore, the diagnosis of primary APS was conjectured based on positive serum anti-β2-glycoprotein antibody and clinical manifestation of retinal thrombosis.

[3]韓光,常穎,張連波,等.手術(shù)安全核查表實(shí)施的干預(yù)模式及效果分析[J].中國(guó)醫(yī)藥指南,2012,8(3):1-2.

參紅通絡(luò)顆粒以“痰瘀伏邪”為理論核心，由人參、紅景天、丹參等中藥組成，具有益氣活血、化痰通絡(luò)作用。吳成哲等通過(guò)對(duì)CD34陽(yáng)性新生微血管數(shù)（MVC）、微血管的密度（MVD）的觀察，發(fā)現(xiàn)該顆粒對(duì)MVC、MVD具有明顯的增強(qiáng)作用，同時(shí)促進(jìn)VEGF mRNA因子、血小板衍生生長(zhǎng)因子（PDGF）mRNA因子的表達(dá)，促進(jìn)心肌梗死區(qū)微血管的新生。

A 12-year-old female visited our hospital because of a sudden loss of vision in her right eye for 2wk. One day before the initial onset, a similar symptom lasting an hour occurred in the same eye, but spontaneously recovered. She denied any history of connective tissue disease or other systemic illness, nor did she have a history of drug abuse. Family history was also unremarkable.

In summary, we present a case of combined CRAO and CRVO in a patient with primary APS. Prompt diagnosis and treatment of ocular symptoms associated with this disease is detrimental.Despite anticoagulation therapy, the patient was treated by injection of dexamethasone intravitreal implant (Ozurdex

),illustrating the effectiveness of anti-inflammatory agents.This case emphasized the importance of systemic evaluation,in patients with combined CRAO and CRVO without conventional risk factors, especially in atypical young patients.

Her rapid recovery suggests that prompt diagnosis and treatment of ocular symptoms associated with this disease is essential for recovery of retinal function and morphology. The pathogenesis of primary APS is complex and multi-factorial.One recent study suggested that retinal vein occlusion could behave as an organ-specific manifestation of APS

. Traditional medications that have been implemented for the treatment of primary APS include anticoagulant therapy. More recently,anti-vascular endothelial growth factor (VEGF) therapies have been introduced as an acceptable alternative to alleviate ocular symptoms

. Since various factors are involved in its pathogenesis, among which inflammation plays an important role, we believe that Ozurdex, an approved dexamethasone intravitreal implant, might be more effective in alleviating macular edema and improving visual acuity based on its anti-inflammatory mechanism, which is key in initiating procoagulant activity

.

除了這些學(xué)術(shù)有專攻的研究機(jī)構(gòu)外，目前對(duì)新漢學(xué)進(jìn)行再研究的成果主要來(lái)自于中國(guó)人民大學(xué)、南京大學(xué)、武漢大學(xué)、北京大學(xué)等高校。相對(duì)來(lái)說(shuō)，這些研究得到所在機(jī)構(gòu)支持的力度較??；其研究特點(diǎn)是學(xué)者們利用自己個(gè)人的學(xué)術(shù)資源或者學(xué)術(shù)專長(zhǎng)，通過(guò)長(zhǎng)期的知識(shí)積累以及對(duì)海外中國(guó)研究的持續(xù)關(guān)注，形成了帶有較強(qiáng)個(gè)體研究特征的一系列研究成果。

Supported by National Natural Science Foundation of China (No.82174445); Natural Science Foundation of Beijing of China (No.7192235).

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1 Sammaritano LR. Antiphospholipid syndrome.

2020;34(1):101463.

2 Kokosi M, Lams B, Agarwal S. Systemic lupus erythematosus and antiphospholipid antibody syndrome.

2019;40(3):519-529.

3 Suvajac G, Stojanovich L, Milenkovich S. Ocular manifestations in antiphospholipid syndrome.

2007;6(6):409-414.

4 Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW,Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA,Khamashta MA. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.

1999;42(7):1309-1311.

5 Audrain MAP. Value of autoantibodies to beta2-glycoprotein 1 in the diagnosis of antiphospholipid syndrome.

2002;41(5):550-553.

6 Hernández JL, Sanlés I, Pérez-Montes R, Martínez-Taboada VM,Olmos JM, Salm?n Z, Sierra I, Escalante E, Napal JJ. Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion.

2020;190:63-68.

7 Jabrane M, Ez-Zahraoui MR, Hajji I, Fadili W, Moutaouakil A,Laouad I. Central retinal vein occlusion in a patient on hemodialysis secondary to antiphospholipid syndrome: case report.

2017;13(4):245-247.

8 Mathis T, Cerquaglia A, Weber M, Guillarme-Sallit R, Malclès A,Voirin N, Servant M, Sudhalkar A, Bilgic A, Denis P, Sève P, Bodaghi B, Kodjikian L. Uveitis treated with dexamethasone implant.

2021;41(3):620-629.