| Objective:Thyroid associated ophthalmopathy（TAO）is the most common orbital disease in adults and the most common manifestation of extraglandular organ involvement in Graves’disease.This study focuses on intensity modulated radiotherapy combined with periorbital injection of glucocorticoid in the treatment of TAO,in order to analyze the clinical efficacy,influencing factors and safety of the combination therapy,and to quantitatively analyze the clinical efficacy of the combination therapy from the point of view of imaging.The difference between the combined therapy and the single periorbital injection of glucocorticoid was compared and analyzed.Materials and Methods:Chapter 1:TAO patients who were treated in the ophthalmology clinic of West China Hospital of Sichuan University from December 2011 to June 2020 and received intensity modulated radiotherapy combined with periorbital injection of glucocorticoid were included.They were assessed as moderate and severe active stage,NOSPECS grade 4 or above,clinical activity score（CAS）3 or above or imaging showed extraocular muscle involvement,significantly thickened or multiple muscles moderately and severely thickened and strengthened.Those who received combined therapy were included in the combined treatment group,and those who received single periorbital injection were included in the single injection group.The treatment of the combined treatment group included one intensity modulated radiotherapy and three periorbital injections.The treatment scheme of the single injection group was three times of periorbital injection.The injection site of triamcinolone acetonide injection（1ml:40mg）for periorbital injection is related to the clinical manifestation:if only the superior rectus muscle is involved,40mg is injected in the superior orbital quadrant,if the upper eyelid is normal and only the inferior rectus muscle is involved,40mg is injected in the extraorbital inferior quadrant.If all four rectus muscles are involved,20mg is injected in the superior orbital quadrant and the outer inferior quadrant respectively.The interval of injection was 1 month.Intensity modulated radiotherapy was performed before and after the second periorbital injection with a total dose of 20Gy and was divided into 10 doses within 2 weeks.The baseline data and symptoms and signs of the patients were collected,including eye pain,diplopia,tears,foreign body sensation,eyelid,conjunctiva,eye movement,cornea,lens,fundus and other eye signs.The results of specialist examination and evaluation were collected,including visual acuity,intraocular pressure,exophthalmos,upper eyelid retraction,CAS score,NOSPECS grade and so on.Combined symptoms and signs,TAO score system and curative effect evaluation method were established,and the clinical efficacy,influencing factors and safety of the combined treatment were comprehensively analyzed.The difference of clinical efficacy between the combined treatment group and the single injection group was compared and analyzed.Chapter 2:Patients with moderate-to-severe active TAO who were treated in the ophthalmology clinic of West China Hospital of Sichuan University from December 2011 to June 2020 and received intensity modulated radiotherapy combined with periorbital glucocorticoid injection were included in the same criteria as the first part.Meanwhile,orbital enhanced MRI examination was performed before and after treatment,and the image was clear and complete.Collect the baseline data and clinical data of patients,as in the first chapter.The imaging parameters were measured,including the cross-sectional area of extraocular muscle in coronal section of enhanced T1WI fat suppression sequence,the ratio of signal intensity of extraocular muscle to ipsilateral temporal muscle,exophthalmos and thickness of medial orbital fat of T1WI sequence.To explore the relationship between TAO imaging characteristic parameters and clinical manifestations,to compare and analyze changes of imaging parameters and their correlation with CAS scores before and after treatment,to compare and analyze imaging differences between those with CAS 3 or above（group1）and those with CAS less than 3（group 2）.Results:Chapter 1:A total of 376 patients（752 eyes）were included.The average age was 49.26±11.18 years old.There were significant differences in visual acuity,intraocular pressure,exophthalmos,upper eyelid retraction and CAS score before and after treatment（P<0.001）.The improvement rates of soft tissue involvement such as eyelid swelling,conjunctival congestion,conjunctival edema and eyelid insufficiency were 75.0%,79.0%,81.9%and 88.9%respectively.The improvement rates of diplopia,limited eye movement and corneal involvement were 87.8%,47.1%and 96.9%,respectively.After combined treatment,the visual acuity,intraocular pressure,exophthalmos and CAS score were significantly improved in patients with poor efficacy of intravenous hormone therapy and compressive optic neuropathy（P<0.05）.The TAO scores decreased gradually at the first visit,during the course of radiotherapy,1 month after radiotherapy,3 months after radiotherapy and 6 months after radiotherapy,and the difference was statistically significant（P<0.001）.After treatment,the proportion of obvious improvement,moderate improvement,mild improvement and no improvement was 59.8%,36.2%,2.1%and 1.9%respectively,and the overall improvement rate was 98.1%.The curative effect of hypothyroidism in patients with hyperthyroidism treated with iodine 131 was significantly weaker than that in patients with normal thyroid function.The curative effect was better when the course of disease was less than 6 months,the thyroid function was normal,the smokers never smoked,and the CAS score 3 or above.There was no significant difference in age,sex,course of ophthalmopathy,history of thyroid dysfunction,smoking history,CAS score and NOSPECS grade between the two groups.The changes of visual acuity,intraocular pressure,exophthalmos,upper eyelid retraction and CAS score in the combined treatment group were higher than those in the single injection group before and after treatment.The improvement rates of soft tissue involvement such as eyelid swelling,conjunctival congestion,conjunctival edema and eyelid insufficiency in the combined treatment group were higher than those in the single injection group.The overall improvement rate of diplopia,limited eye movement and corneal involvement in the combined treatment group was higher than that in the single injection group.The proportion of obvious improvement and moderate improvement in the combined treatment group was higher than that in the single injection group.The overall improvement rate in the combined treatment group was 98.1%,mainly significant improvement,and the overall improvement rate in the single injection group was 82.7%,mainly moderate improvement.The incidence of complications in the single injection group was higher than that in the combined treatment group.Chapter 2:A total of 155 patients（310 eyes）were included with an average age of 49.13±11.38 years.The average cross-sectional area of extraocular muscle in patients with TAO was inferior rectus,medial rectus,superior rectus and lateral rectus,respectively,and the thickest inferior rectus was about 50.3%.The average signal strength ratio of extraocular muscle from large to small is inferior rectus,medial rectus,superior rectus,lateral rectus,and the strongest signal of inferior rectus is about 55.1%.The largest cross-sectional area or signal intensity ratio of extraocular muscle was positively correlated with visual acuity（log MAR）,intraocular pressure,exophthalmos and CAS score（P<0.05）.There were significant differences in cross-sectional area/the ratio of signal intensity of the four extraocular muscles,the sum of cross-sectional area/the ratio of signal strength of extraocular muscles,and the largest cross-sectional area/ratio of signal strength of extraocular muscles before and after treatment（P<0.001）.There were significant differences in exophthalmos and medial fat thickness before and after treatment（P<0.001）.The changes of cross-sectional area/the ratio of signal intensity of extraocular muscle and the largest cross-sectional area/ratio of signal intensity of extraocular muscle before and after treatment were positively correlated with the change of CAS score.Exophthalmos values,cross-sectional area/the ratio of signal intensity of four extraocular muscles,the sum of cross-sectional area/signal strength ratio of extraocular muscle and the largest cross-sectional area/ratio of signal strength of extraocular muscle in group 1 were higher than those in group 2（P<0.05）.Before and after treatment,the changes of the sum of cross-sectional area/signal intensity ratio of extraocular muscle and the largest ratio of cross-sectional area/signal intensity ratio of extraocular muscle in group 1 were larger than those in group 2.Conclusion:Intensity modulated radiotherapy combined with periorbital injection of glucocorticoid can greatly improve the efficacy of patients with moderate and severe active TAO,especially in patients who has received intravenous hormone pulse therapy or in patients with compressive optic neuropathy.Intensity modulated radiotherapy combined with periorbital injection of glucocorticoid is more effective and safe with fewer complications than periorbital injection of glucocorticoid alone.When conditions permit,this combination therapy can be used as the first choice for patients with moderate and severe active TAO,especially in elderly patients with glucocorticoid treatment taboos.The patients with short course of disease,normal thyroid function,never smoking and CAS score 3 or above had the best curative effect.The curative effect of hypothyroidism in patients with hyperthyroidism after I131treatment was even worse.Enhancing the signal intensity of MRI can reflect the degree of inflammation and is helpful to evaluate the therapeutic effect.From the perspective of imaging,intensity modulated radiotherapy combined with periorbital injection of triamcinolone acetonide has a strong anti-inflammatory effect on patients with moderate and severe active TAO.In order to comprehensively evaluate the disease activity and severity of TAO patients,clinicians not only need to use CAS score,but also need to refer to the parameters such as cross-sectional area and enhanced signal of extraocular muscles in imaging materials.To sum up,this study explored the clinical efficacy,influencing factors and safety of intensity modulated radiotherapy combined with periorbital corticosteroid injection,which provided a new treatment choice for patients with moderate and severe active TAO and a certain reference value for the evaluation system of TAO efficacy.The treatment model of intensity modulated radiotherapy with periorbital glucocorticoid injection still needs further well-designed,large,multicenter,randomized controlled trials to confirm its clinical effectiveness. |
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