| 甲状腺相关性眼病(TAO)是常见的眼眶疾病之一，占眼眶病发病率的18.1%～47.1%。TAO是一种特殊的眼眶炎症，发病原因和确切发病机制不十分清楚。TAO临床表现为畏光流泪、视功能下降、眼球突出、眼睑红肿、结膜充血水肿、眼睑位置异常、眼球运动受限、复视等，诊断已比较成熟，但治疗方法和效果有待于研究。目前认为，TAO有效治疗措施包括药物治疗、放射治疗和手术治疗。糖皮质激素可抑制炎症反应和免疫反应，减少眶成纤维细胞生成和释放糖胺聚糖(GAGs)，广泛应用于活动期患者的治疗。但全身应用糖皮质激素所带来的全身副作用发生率高达90%，为提高治疗效果、减少副作用发生，有学者提出局部应用糖皮质激素治疗中度TAO。局部治疗早期研究缺乏理想的治疗药物，用药剂量、用药方法、治疗适应症不统一，治疗效果不肯定。本研究采用眶内注射糖皮质激素治疗中度活动型TAO，以寻求一种治疗中度活动型TAO安全、有效的方法，并初步探讨指导临床治疗的TAO分类。
材料与方法
1. 病例选择：临床确诊TAO患者32例(46眼)纳入本组治疗观察。32例患者，复视者16例。接受注射46眼均具有不同程度的睑裂增宽、眼睑退缩、上睑迟落等眼睑征和眼睑红肿、结膜充血、结膜水肿等炎症表现； 视力下降者17眼；眼球突出≥17mm者21眼；眼球运动受限者30眼；角膜病变者8眼；临床活动性评分4～10分，平均(7.67±1.49)分；眼病指数1～9分，平均(4.28±0.28)分。
2. 注射药物及注射方法：药物包括曲安奈得40mg、地塞米松5mg和利多卡因0.5ml。每次注射药物总容量2.0～3.0ml。注射时根据患者临床表现及眼眶冠状CT显示，将药物直接注射到病变部位。一般2～3周重复注射，直至稳定。
3. 随访观察项目：患者每次就诊用标准对数远视力表检查视力，Hertel眼突计测量眼球突出度，记录眼部炎症情况，直尺测量眼睑征，裂隙灯显微镜检查角膜，Hess屏检查显示眼球运动、复视情况。记录患者糖皮质激素全身副作用以及局部注射并发症。
结果
1. 注射次数：每眼注射次数1～10次，平均3.1次。每例患者注射次数1～19次，平均4.6次。
2. 治疗效果：⑴视力：17眼视力下降，治疗后视力≥1.0者6眼，视力提高2行者6眼，有效率70.6%。⑵眼球突出度：21眼眼球突出度≥17mm，治疗后＜17mm者10眼，减少≥2mm者2眼，眼球回退率57.1%。但5只严重眼球突出患眼，治疗后无明显改善。⑶眼部软组织炎症表现：46眼治疗前均有不同程度刺激症状，治疗后消失或明显减轻者37眼，有效率80.4%；44眼眼睑肿胀，治疗后消失者20眼，由中度变为轻度者23眼，有效率97.7%； 42眼泪腺区肿胀，治疗后消失者18眼，由中度变为轻度者22眼，有效率95.2%； 43眼结膜充血，治疗后消失者40眼，有效率93.0%； 22眼结膜水肿，治疗后消失者21眼，有效率95.5%； 39眼泪阜肿胀，治疗后消失者37眼，有效率94.9%。⑷眼睑征：42眼睑裂宽度≥9mm，治疗后＜9mm者20眼，减少≥2mm者14眼，有效率90.0%； 40眼上睑退缩，治疗后消失者22眼，减少≥2mm者15眼，有效率92.5%； 29眼上睑迟落，治疗后均消失，有效率100%； 8眼下睑退缩，治疗后消失者2眼，减少量≥2mm者2眼，有效率50.0%。⑸眼球运动及复视：30眼眼球运动受限，治疗后眼球运动者6眼，减轻≥1级者21眼，有效率90.0%； 16例复视患者，治疗后无复视者8眼，降低≥1级者5眼，有效率81.3%。⑹角膜病变：治疗前8眼角膜上皮点状或片状浸润，7眼注射治疗期间痊愈，有效率87.5%。⑺眼病临床活动性评分及眼病指数：治疗后所有患眼眼病活动性评分均≤3分；眼病指数减少(2.91±0.20)分。⑻根据总体治疗效果评价标准，显效28眼，有效11眼，无效7眼，无加重患眼，总体有效率84.8%。
3. 副作用和并发症：3例4眼出现眼压升高，无视力及视野变化，停止治疗后眼压恢复至正常范围；4例女性患者体重增加，治疗结束体重下降；血糖升高1例，停药恢复； 3例出现睡眠障碍，停药均恢复；患者球后出血并黑朦1眼次，积极治疗后，该眼视力恢复到注射前水平。
结论
1. 眶内局部注射曲安奈得对TAO患眼眼部软组织炎症、眼睑位置异常效果非常显著，对视功能、眼球突出度、眼球运动受限、复视、角膜病变等效果显著；对严重眼球突出TAO患眼治疗效果有限。
2. 眶内局部注射曲安奈得有效减少TAO眼病指数，减轻严重程度；降低TAO临床活动性分数，稳定病情。
3. 眶内局部注射糖皮质激素治疗TAO，是一种安全的治疗方法。
4. 该方法治疗中度活动型TAO安全、有效，并可能作为治疗严重TAO的辅助治疗措施。
5. 严重程度结合临床活动性的TAO分类方法有助于指导临床治疗。
Thyroid-associated ophthalmopathy(TAO) is one of the common orbital diseases, accounting for about 18.1%～47.1% . TAO is a kind of special orbititis, but the precise etiology and pathogenesis remains a point of debate. The predominant clinical signs of TAO include photophobia, weeping, loss of visual acuity, proptosis, soft tissue swelling, chemosis, abnormal lid position, diplopia, and motility disturbances. It is easy to be diagnosed but difficult to be treated for TAO. The effective treatment of TAO includes medicine, ocular radiation and surgery. Corticosteroids can inhibit immune reaction and inflammatory reaction, reducing the proliferation of retrobulbar fibroblasts and the release of glycosaminoglycan, and is suitable for the treatment of active TAO. Since the side-effect incidence of corticosteroids used systemically is up to 90%, it was suggested to use corticosteroids topically. Triamcinolone acetonide, a kind of derivative of triamcinolone, has better efficacy that can last for 2-3 weeks when used topically. In this investigation we used triamcinolone acetonide to treat activate TAO by the way of intraorbital injection to search a safe and effective method for mild active TAO.
Materials and Methods
1. Case choices：32 cases (46eyes) of active TAO were brought into the investigation. 16 of 32 patients suffered with diplopia. All the eyes presented with eye-lid signs and inflammatory findings, and 17 eyes with the decrease of visual acuity, 21 eyes with proptosis, 30 eyes with motility disturbances, 8 eyes with corneal involvement. The mean clinical activity score and eye-disease index of 46 eyes were 7.67±1.49 and 4.28±0.28 respectively.
2. Drugs and injection methods：According to the clinic signs and coronary orbit CT scans, we injected drugs including 40mg triamcinolone acetonide, 5mg dexamethasone, 20000u gentamicin, 0.5ml lidocaine into involved tissue. Commonly the next injection was done after 2-3 weeks and 3 times made one period till stabilization.
3. Parameters observed：Naked and corrected vision was tested by standarded logarithm vision chart, degree of proptosis was tested by Hertel exophthalmometer, signs of ocular inflammatory were noted, corneal was examined by slit-lamp microscope, oculomotor and diplopia was checked by Hess screen every time when patients on outpatient. All the side-effects of corticosteroids and complications of intraorbital injection were also enregistered.
Results
1. Times of injection：The mean times of injection on one eye was 3.1 and on one patient was 4.6.
2. Effect：⑴ Visual acuity：Visual acuity increased up to 1.0 or over it in 6 eyes, increased more than 2 lines in 6 eyes, and the effective rate was 70.6%. ⑵Proptosis: Proptosis reduced to 17mm or below in 10 eyes, reduced more than 2mm in 2 eyes, and the effective rate was 57.1%. But there was no distinct improvement in 5 eyes with severe proptosis. ⑶Signs of inflammatory in soft tissue：Activate signs disappeared or distinctly alleviated in 37eyes and the effective rate was 80.4%. Lid swelling disappeared in 20 eyes, alleviated from moderate to mild in 23 eyes and the effective rate was 97.7%. Swelling in lacrimal district disappeared in 18 eyes, alleviated from moderate to mild in 22 eyes and the effective rate was 95.2%. Conjunctival congestion disappeared in 40 eyes and the effective rate was 93.0%. Chemosis disappeared in 21 eyes and the effective rate was 95.5%. Swelling in lacrimal caruncle disappeared in 37 eyes and the effective rate was 94.9%. ⑷Eyelid signs：Palpebral fissure reduced to 9mm or below in 20 eyes, reduced more than 2mm in 14 eyes and the effective rate was 90.0%. Upper eyelid retraction disappeared in 22 eyes, reduced more than 2mm in 15 eyes and the effective rate was 92.5%. All the upper eyelid lag in 29 eyes disappeared. Lower eyelid retraction disappeared in 2 eyes, alleviated more than 2mm in 2 eyes and the effective rate was 50%. ⑸Motility disturbances and diplopia ：Motility disturbances recovered in 6 eyes, alleviated no less than one degree in 21 eyes and the effective rate was 90.0%. Diplopia disappeared in 8 eyes, alleviated more than one degree in 5 eyes and the effective rate was 81.3%. ⑹Corneal involvment：Corneal recovered in 7 eyes and the effective rate was 87.5%. ⑺Activation scores and eye-disease index：All clinical activity scores were 3 or below and the mean eye-disease index reduced 2.91±0.20 after therapy. ⑻According to the criterion of effect, the general effective rate was 84.8%.
3. Side-effects and complications：Ophthalmotonic increase occurred in 4 eyes. Weight gain occurred in 4 female cases. Glycemia occurred in one case. Sleep-disorder occurred in 3 cases；occurred in one case. Retrobulbar hemorrhage and amourosis occurred once in one eye and the vision recovered after treatment.
Conclusions
1. The patients suffered with TAO had gotten distinctly improvement in visual acuity, proptosis, inflammatory of soft tissue, eye-lid signs, motility disturbances and corneal involvement by the way of intraorbital injection of triamcinolone acetonide, but the efficacy for severe proptosis is limit.
2. Intraorbital injection of triamcinolone acetonide can effectively reduce eye-disease index and clinical activity score of TAO.
3. There is no severe side-effect of corticosteroids and topical complication of intraorbital injection and the method is safe and ecnomic.
4. Intraorbital injection of triamcinolone acetonide is a safe and effective method treating moderate TAO in the period of activation and perhaps can be used as an auxiliary method treating severe TAO.
5. The classification based on the degree of severity and CAS of TAO is helpful for the treatment on TAO.
Key words: thyroid-associated ophthalmopathy(TAO); intraorbital injection; classification; corticosteroids
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