Journal of Pediatric Surgery 50 (2015) 1393–1397
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Management of periorbital microcystic lymphatic malformation with blepharoptosis: Surgical treatment combined with intralesional bleomycin injection☆,☆☆ Xi Yang, YunBo Jin, XiaoXi Lin ⁎, Hui Chen, Gang Ma, XiaoJie Hu, YaJing Qiu, WenXin Yu, Lei Chang, TianYou Wang Department of Plastic Surgery, Shanghai 9th People's Hospital, Shanghai Jiaotong University, School of Medicine
a r t i c l e
i n f o
Article history: Received 17 September 2014 Received in revised form 14 December 2014 Accepted 15 December 2014 Key words: Microcystic lymphatic malformation Periorbital Blepharoptosis Surgery Bleomycin Visual obstruction
a b s t r a c t Objectives: Periorbital microcystic lymphatic malformations (LM) can cause severe symptoms, such as blepharoptosis, amblyopia, chemosis, strabismus, diminished vision, and blindness. The purpose of this study was to evaluate the clinical outcome in periorbital microcystic LM patients with blepharoptosis who underwent surgical treatment combined with intralesional bleomycin injection. Patients and methods: A retrospective study including nine patients diagnosed as periorbital microcystic LM with blepharoptosis was conducted. All of the patients underwent surgical treatment and bleomycin injection from January 2010 to January 2014. The lesion was resected through the lower eyebrow and/or a coronal incision at the first stage, and levator resection was performed at the second stage. Any persistent lesion or its recurrence was managed by intralesional bleomycin injection. Results: Blepharoptosis and visual obstruction were corrected in all patients. Mean follow-up was 24.6 months. Six patients had recurrence during the follow-up, and two patients who had partial eyelid closure after the second stage surgery recovered in three months. Amblyopia, astigmatism, and strabismus were not improved after treatment. All of the patients had excellent aesthetic improvement and corrected blepharoptosis. Conclusions: Resection through a lower eyebrow and coronal incision and levator resection performed in two stages can quickly correct the visual impairment caused by periorbital microcystic lymphatic malformation with blepharoptosis. Intralesional bleomycin injection is a promising adjunctive therapy for residual or recurrent lesions after surgery. © 2015 Elsevier Inc. All rights reserved.
Lymphatic malformation (LM) is a congenital slow-flow vascular anomaly resulting from the abnormal development of the lymphatic system that most commonly involves the head and neck. The incidence is one out of 2000–4000 live births [1]. LMs can be divided, according to the size of the malformed channels, into macrocystic, microcystic or combined (macrocystic/microcystic). Macrocystic lesions are defined as cysts large enough (commonly 2 cm) to be treated by sclerotherapy [2]. Sclerotherapy is now the mainstay of treatment for macrocystic LM but is less effective for microcystic lesion [3]. ☆ Disclosures: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. No commercial associations or financial disclosures to declare. The paper was not presented at a meeting and has not been accepted for presentation at a future meeting. ☆☆ Authors' role/participation: Xi Yang, literature research, clinical studies, statistical analysis, and manuscript editing; YunBo Jin, clinical studies, statistical analysis, and manuscript editing; XiaoXi Lin, guarantor of integrity of entire study; Hui Chen, clinical studies; Gang Ma, statistical analysis; XiaoJie Hu, clinical studies; YaJing Qiu, literature research; WenXin Yu, clinical studies; Lei Chang, clinical studies; TianYou Wang, literature research. ⁎ Corresponding author at: Shanghai 9th People's Hospital, Shanghai Jiaotong University, School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011, China. Tel.: +86 13701997136. E-mail address: [email protected] (X. Lin). http://dx.doi.org/10.1016/j.jpedsurg.2014.12.011 0022-3468/© 2015 Elsevier Inc. All rights reserved.
Resection still remains the first treatment of choice for managing microcystic LM, although bleomycin sclerotherapy seems to be very promising [4]. Periorbital LM is rare and usually presents in certain anatomic locations and patterns. It typically involves the upper eyelid and periocular tissues, and often extends into the adjacent frontotemporal region [5]. These extensive lesions can lead to swelling, intraorbital hemorrhage, ocular proptosis, blepharoptosis, amblyopia, chemosis, strabismus, cellulitis, and ultimately diminished vision and blindness [6]. Greene et al. reported 42 patients with periorbital LM, of whom 52% had blepharoptosis, 40% had diminished vision, and 7% became blind in the affected eye [7]. The most important period during visual acuity development is from birth to 40 weeks [8]. Newborns with large fronto-orbital LMs often develop blepharoptosis, which occludes the visual axis and can result in seriously diminished vision. For those patients, early stage management is necessary to aesthetically improve disfigurement and prevent visual maldevelopment. The aim of this study was to evaluate the clinical outcome of surgical treatment combined with intralesional bleomycin injection in periorbital microcystic LM patients with blepharoptosis.
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Fig. 1. A 4-year-old female patient with a large microcystic LM involving the frontotemple and the upper eyelid. The microcystic lesion was resected during the first stage of the operation (a). The size of extra skin was determined by measuring with a steel ruler and by comparing with the unaffected side. The position of hairline and eyebrow, extra skin for resection, and surgical incisions were marked with methylene blue symmetrically to the other side (b). In the frontotemporal area, the tissue between the periosteum and the skin was resected, including the frontalis muscle. An under-eyebrow incision was used to remove microcystic tissue in the upper eyelid, including the periorbital fat (c). After the lesion was resected, tiny drains in the prelevator space and frontal space were needed (d).
1. Patients and methods 1.1. Patients Approval for this retrospective clinical study was obtained from the institutional review board of our hospital, and informed written consent was obtained from the parents of all patients. This study included 9 patients, diagnosed with periorbital microcystic LM and blepharoptosis, who were subjected to surgical treatment and intralesional bleomycin
injection between January 2010 and January 2014. Patients with incomplete data and patients with previous history of treatment were excluded. The diagnosis of periorbital microcystic LM was based on clinical presentation and radiologic findings and was confirmed by histopathologic examination after surgery in all patients. Patients were evaluated for sex, age at diagnosis, the symptoms/ complications, and the extent of periorbital involvement. Symptoms that were documented included blepharoptosis, proptosis, amblyopia, restricted extraocular motion, chemosis, astigmatism, strabismus, and
Fig. 2. The remaining lesion of the upper eyelid was resected and the levator resection was performed during the second stage of the operation. The remaining lesion was resected through an under-eyebrow incision (a). The extra length of the levator palpebrae superioris aponeurosis was resected through a tarsal crease incision and the free levator aponeurosis was then reattached to the tarsal plate (b).
X. Yang et al. / Journal of Pediatric Surgery 50 (2015) 1393–1397
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Table 1 Patients' demographics and clinical outcome. Patient no
Age at surgery (years)
Sex
Symptoms before treatment
Extent of periorbital involvement
Clinical outcome
Follow-up (months)
Symptoms after treatment
Complications
1
2
F
Frontotemple and upper eyelid
Excellent
18
Astigmatism, amblyopia
Recurrence
2
4
F
Frontotemple and upper eyelid
Excellent
19
Amblyopia
Recurrence
3
6
M
Frontotemple and upper eyelid
Excellent
24
Amblyopia
Recurrence
4
4
F
Frontotemple and upper eyelid
Excellent
20
Amblyopia, strabismus
Recurrence
5
1
F
Frontotemple and upper eyelid
Excellent
16
6
F
Frontal area and upper eyelid
Excellent
40
Astigmatism, strabismus, chemosis, amblyopia Amblyopia, strabismus
Recurrence, incomplete eyelid closure
6
7
4
F
33
None
Recurrence
2
M
Excellent
30
None
None
9
2
M
Frontotemple and upper eyelid Frontal area and upper eyelid Frontotemple and upper eyelid
Excellent
8
Blepharoptosis, complete visual blockage, astigmatism, amblyopia Blepharoptosis, complete visual blockage, amblyopia Blepharoptosis, complete visual blockage, amblyopia Blepharoptosis, complete visual blockage, amblyopia, strabismus Blepharoptosis, complete visual blockage, astigmatism, strabismus, chemosis, amblyopia Blepharoptosis, complete visual blockage, amblyopia, strabismus Blepharoptosis, partial visual blockage Blepharoptosis, partial visual blockage Blepharoptosis, partial visual blockage
Excellent
21
None
None
decreased vision. Nine patients (3 male, 6 female), whose ages ranged from 1 to 6 years (average = 3.4 years), all had periorbital microcystic LM with blepharoptosis. Six of these patients had complete visual blockage while the other 3 patients had partial visual blockage. Amblyopia occurred in 6 patients, astigmatism was detected in 2 patients, strabismus was diagnosed in 3 patients, and chemosis was observed in 1 patient. The frontotemple and upper eyelid regions were involved in 7 patients. The lesions of the other 2 patients involved the frontal area and the upper eyelid. After the surgical procedures and bleomycin injection, the duration of the follow-up, the symptoms and the complications were recorded. All of the patients were subjected to magnetic resonance image (MRI) scanning to characterize the extent and size of the lesion before and after surgery and bleomycin injection. The clinical outcome was evaluated by assessing the reduction of the lesion and pretreatment and posttreatment photographs. A reduction rate greater than 90% was considered as excellent, from 75% to 90% as good, from 50% to 75% as fair, and from 0% to 50% as poor. 1.2. Surgical techniques The surgical procedure was performed in two stages by three plastic surgeons. In the first stage, nine patients with periorbital microcystic LM were scheduled to undergo lesion resection through coronal and under-eyebrow incision under general anesthesia. In the second stage, the operation of levator resection was performed three to six months after initial surgery. The goal was to remove as much of the lesion as necessary to provide a symmetrical contour and to correct the blepharoptosis and visual obstruction. 1.2.1. First stage The first stage of the operation was performed to resect as much of the microcystic lesion as possible. MRI scanning before the surgery was very important to ascertain the extent and size of the lesion. Usually, the microcystic LM tended to extend extensively from subcutaneous to deep muscle tissue. At first, the amount of the extra skin which needed to be removed was determined by measuring it with a steel ruler and by comparing it with the unaffected side. The position of the hairline and the eyebrow, extra skin for resection, and surgical incisions
Incomplete eyelid closure
were marked with methylene blue symmetrically to match the other side. A coronal incision and a crescent-shaped incision at the lower border of the eyebrow were needed to resect a large hemispherical frontotemporal and periorbital LM. When the frontotemporal area affected was minimal, an under-eyebrow incision was adequate for surgical excision of the lesion. In the frontotemporal area, the tissue between the periosteum and the skin was resected completely, including the frontalis muscle. It was difficult to excise the LM from the normal tissue, as it lay within and superficial to the frontalis muscle. When resection extended to the periorbita and upper eyelid, a lower eyebrow incision was used to remove microcystic tissue in the upper eyelid, including the periorbital fat. After incision through the orbicularis oculi muscle, the dissection proceeded inferiorly to the anterior surface of the tarsal plate and superiorly to the supraorbital rim. Extra skin was then resected to elevate the upper eyelid to a near normal level. Tiny drains in the prelevator space and frontal space were needed to prevent postoperative seroma (Fig. 1). 1.2.2. Second stage Three to six months after the first stage, the second stage operation procedures were performed, including the resection of the remaining upper eyelid lesion and the levator resection. Complete excision is usually not possible in microcystic LMs. Often there remains residual diffuse microcystic disease in the upper eyelid that can be addressed during the second stage through an incision at the tarsal crease and/or through the former under-eyebrow incision. The orbicularis muscle is preserved, but often the levator apparatus is weakened and stretched, and thus must be dissected and advanced to the tarsal plate. The extra length of the levator palpebrae superioris was resected taking into account measurements made before and during surgery. The free levator aponeurosis was then reattached to the tarsal plate (Fig. 2). 1.3. Bleomycin injection Six months after the two-stage surgery, any remaining or recurrent lesions were treated by bleomycin (Nippon Kayaku Co. Ltd, Tokyo, Japan) injections under general anesthesia. The dose of bleomycin used was based on the estimated size of the lesion. The maximum dose was 1 mg per kilogram per session, and the maximum dose was
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Fig. 3. A 4-year-old female patient with a large microcystic LM involving the frontotemple and the upper eyelid. Before the surgery, she had blepharoptosis, complete visual blockage, strabismus, and amblyopia (a, b). Three months after the first stage operation, blepharoptosis improved significantly (c, d). Twenty months after the second stage procedures and following one session of bleomycin injection, significant aesthetic improvement in her disfiguration and correction of her visual obstruction were achieved (e, f).
15 mg per session. After accessing the lesion with a 21-gauge needle, bleomycin was injected evenly into the lesion, both intravascularly and interstitially. Repeat procedures were performed 8 weeks apart.
2. Results The patients' demographics and clinical outcomes are summarized in Table 1. Blepharoptosis and visual block impairment were corrected in all of the patients. Mean follow-up time was 24.6 months. Amblyopia,
Fig. 4. A 6-year-old male patient with a large microcystic LM involving the frontotemple and the upper eyelid. Before the surgery, he had blepharoptosis, complete visual blockage, strabismus, and amblyopia (a, b). Six months after first stage operation, blepharoptosis markedly improved; there was however remaining lesion in the frontotemporal area (c, d). Fifteen months after the second stage operation and following two sessions of bleomycin injection, the remaining lesion in the frontotemporal area disappeared; significant aesthetic improvement in his disfiguration and correction of his visual obstruction were achieved (e, f).
astigmatism and strabismus showed no improvement after treatment. Six patients had recurrence during the follow-up period, and two patients who had partial eyelid closure after the second stage surgery recovered in three months. Bleomycin pulmonary toxicity was not observed in any patient. All of the patients had excellent clinical outcomes with notable aesthetic improvement of their disfigurement and correction of blepharoptosis (Figs. 3 and 4).
X. Yang et al. / Journal of Pediatric Surgery 50 (2015) 1393–1397
3. Discussions LMs are classified by the size of the malformed channels into macrocystic, microcystic, or combined [9]. The term microcystic was reserved for lesions or parts of lesions containing cysts that are too small to be accessed by a hypodermic needle [10]. The response of this type of soft tissue lesion, without recognizable cysts, to sclerotherapy is less favorable [11]. Thus, whereas sclerotherapy has become the usual primary treatment for persistent macrocystic disease, surgery is still the most common therapy for microcystic LMs and symptomatic LMs. Periorbital lymphatic malformation usually presents with swelling, blepharoptosis, ocular proptosis, strabismus, chemosis, astigmatism, infection, or hemorrhage [12,13]. Blepharoptosis that occludes the visual axis requires prompt resection to prevent amblyopia. Previous normative studies of visual acuity development proved that the largest improvement of visual acuity occurred between birth and 6 months of age in infants [14] and development continues in children until at least 6 years of age [15,16]. Taylor deduced the critical period for deprivation amblyopia by studying children with amblyopia which follows uncomplicated unilateral cataract and the subsequent aphakic blur. He found that correction before 4 months of age produced less visual loss, and when the vision was deprived between 6 and 30 months of age finger counting was the best visual acuity achieved [17]. In our study, 6 of the 9 patients had complete visual blockage and amblyopia before surgery. They showed no improvement in the amblyopia after more than 16 months of follow-up. The time of the surgery for microcystic LM patients with complete visual blockage still needs further studies to pursue a higher level of evidence. Most of our patients underwent surgical treatment in two stages. The goal of first stage procedures was to achieve nearly complete resection of the microcystic lesion in all patients. During the second stage levator resection was performed in all patients. The reasons why blepharoptosis occurs in the periorbital LM patients could be both mechanical and biological. For instance, the large hemispherical mass can cause severe compression, which makes it difficult for the levator palpebrae superioris to lift the upper eyelid. So, after the compression ceases, the ability to open the eye should improve significantly. Additionally, the length of the levator palpebrae superioris involved in microcystic LM is longer than normal, and will not improve after the mass is removed. In our study, blepharoptosis improved a lot after the mechanical compression was relieved three to six months after the first operation, and the extra length of the levator palpebrae superioris could be measured more precisely. This could explain why the levator resection performed during the first operation was not as accurate compared with the levator resections performed during the second stage. As with any microcystic LM, complete resection is usually not possible because of the diffuse distribution of the abnormal lymphatic channels. In our group of 9 patients, 6 of them experienced mild disease recurrence after surgery. However, repeat resection is not worthwhile for these patients. Bleomycin has been reported to have significantly effects on LM. Qin et al. reported 200 patients treated by intratumorous injection of bleomycin-A5, and was effective in 97%, while the curative rate was 86.5% [18]. Recently, Chaudry et al. described 31 patients with microcystic LM treated with intralesional bleomycin injection, 38% of whom had lesion size reduction (N90%) [4]. Intralesional bleomycin injection was also effective in treating the remaining or recurrent lesions after surgery in our patients. One of the main complications of intralesional bleomycin injection is bleomycininduced pneumonitis. Muir et al. reported 95 patients with hemangiomas and congenital vascular malformations treated by bleomycin, and the maximal single session dose was 1 mg/kg, not exceeding
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15 mg. No pulmonary fibrosis was documented [19]. Intralesional bleomycin injection appears to be safe and effective in microcystic LM, but it takes more sessions and much longer time than surgery especially when the lesions are large. Periorbital microcystic LM with blepharoptosis that occludes the visual axis needs prompt intervention. Resection should be performed at first because it is the quickest way to resolve the visual obstruction and prevent visual impairment. As the visual obstruction was corrected by surgery, even though sclerotherapy takes much longer, bleomycin injection was an effective adjunctive treatment for residual or recurrent lesions. 4. Limitations The main limitation of our study is the small number of patients, this was partly owing to the fact that only periorbital microcystic LMs with blepharoptosis were included. In addition, a longer follow-up period would be optimal for patients with amblyopia. 5. Conclusions Resection through a lower-eyebrow and coronal incision and levator resection performed in two stages can quickly correct the visual impairment caused by periorbital microcystic lymphatic malformation with blepharoptosis. Intralesional bleomycin injection is a promising adjunctive method of treatment for residual or recurrent lesions noted after surgery. References [1] Perkins JA, Manning SC, Tempero RM, et al. Lymphatic malformations: current cellular and clinical investigations. Otolaryngol Head Neck Surg 2010;142(6): 789–94. [2] Greene AK, Perlyn CA, Alomari AI. Management of lymphatic malformations. Clin Plast Surg 2011;38(1):75–82. [3] Alomari AI, Karian VE, Lord DJ, et al. Percutaneous sclerotherapy for lymphatic malformations: a retrospective analysis of patient-evaluated improvement [J]. J Vasc Interv Radiol 2006;17(10):1639–48. [4] Chaudry G, Guevara CJ, Rialon KL, et al. Safety and efficacy of bleomycin sclerotherapy for microcystic lymphatic malformation. Cardiovasc Intervent Radiol 2014;1–6. [5] Bisdorff A, Mulliken JB, Carrico J, et al. Intracranial vascular anomalies in patients with periorbital lymphatic and lymphaticovenous malformations. Am J Neuroradiol 2007;28(2):335–41. [6] Wiegand S, Eivazi B, Bloch LM, et al. Lymphatic malformations of the orbit. Clin Exp Otorhinolaryngol 2013;6(1):30–5. [7] Greene AK, Burrows PE, Smith L, et al. Periorbital lymphatic malformation: clinical course and management in 42 patients. Plast Reconstr Surg 2005;115(1):22–30. [8] Catford GV, Oliver A. Development of visual acuity. Arch Dis Child 1973;48(1):47. [9] Burrows PE. Endovascular treatment of slow-flow vascular malformations. Tech Vasc intervent Radiol 2013;16(1):12–21. [10] Chaudry G, Burrows PE, Padua HM, et al. Sclerotherapy of abdominal lymphatic malformations with doxycycline. J Vasc Interv Radiol 2011;22(10):1431–5. [11] Churchill P, Otal D, Pemberton J, et al. Sclerotherapy for lymphatic malformations in children: a scoping review. J Pediatr Surg 2011;46(5):912–22. [12] Wilson ME, Parker PL, Chavis RM. Conservative management of childhood orbital lymphangioma. Ophthalmology 1989;96(4):484–9. [13] Tunç M, Sadri E, Char DH. Orbital lymphangioma: an analysis of 26 patients. Br J Ophthalmol 1999;83(1):76–80. [14] Salomao SR, Ventura DF. Large sample population age norms for visual acuities obtained with Vistech-Teller Acuity Cards. Invest Ophthalmol Vis Sci 1995;36(3): 657–70. [15] Mayer DL, Dobson V. Visual acuity development in infants and young children, as assessed by operant preferential looking. Vision Res 1982;22(9):1141–51. [16] Neu B, Sireteanu R. Monocular acuity in preschool children: assessment with the Teller and Keeler acuity cards in comparison to the C-test. Strabismus 1997;5(4): 185–202. [17] Taylor D. Critical period for deprivation amblyopia in children. Trans Ophthalmol Soc U K 1978;99(3):432–9. [18] Qin ZP, Xin ZF, Ren L, et al. Long-term results of intratumorous bleomycin-A5 injection for head and neck lymphangioma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86(2):139–44. [19] Muir T, Kirsten M, Fourie P, et al. Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int 2004; 19:766–73.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Management of periorbital microcystic lymphatic malformation with blepharoptosis: Surgical treatment combined with intralesional bleomycin injection☆,☆☆ Xi Yang, YunBo Jin, XiaoXi Lin ⁎, Hui Chen, Gang Ma, XiaoJie Hu, YaJing Qiu, WenXin Yu, Lei Chang, TianYou Wang Department of Plastic Surgery, Shanghai 9th People's Hospital, Shanghai Jiaotong University, School of Medicine
a r t i c l e
i n f o
Article history: Received 17 September 2014 Received in revised form 14 December 2014 Accepted 15 December 2014 Key words: Microcystic lymphatic malformation Periorbital Blepharoptosis Surgery Bleomycin Visual obstruction
a b s t r a c t Objectives: Periorbital microcystic lymphatic malformations (LM) can cause severe symptoms, such as blepharoptosis, amblyopia, chemosis, strabismus, diminished vision, and blindness. The purpose of this study was to evaluate the clinical outcome in periorbital microcystic LM patients with blepharoptosis who underwent surgical treatment combined with intralesional bleomycin injection. Patients and methods: A retrospective study including nine patients diagnosed as periorbital microcystic LM with blepharoptosis was conducted. All of the patients underwent surgical treatment and bleomycin injection from January 2010 to January 2014. The lesion was resected through the lower eyebrow and/or a coronal incision at the first stage, and levator resection was performed at the second stage. Any persistent lesion or its recurrence was managed by intralesional bleomycin injection. Results: Blepharoptosis and visual obstruction were corrected in all patients. Mean follow-up was 24.6 months. Six patients had recurrence during the follow-up, and two patients who had partial eyelid closure after the second stage surgery recovered in three months. Amblyopia, astigmatism, and strabismus were not improved after treatment. All of the patients had excellent aesthetic improvement and corrected blepharoptosis. Conclusions: Resection through a lower eyebrow and coronal incision and levator resection performed in two stages can quickly correct the visual impairment caused by periorbital microcystic lymphatic malformation with blepharoptosis. Intralesional bleomycin injection is a promising adjunctive therapy for residual or recurrent lesions after surgery. © 2015 Elsevier Inc. All rights reserved.
Lymphatic malformation (LM) is a congenital slow-flow vascular anomaly resulting from the abnormal development of the lymphatic system that most commonly involves the head and neck. The incidence is one out of 2000–4000 live births [1]. LMs can be divided, according to the size of the malformed channels, into macrocystic, microcystic or combined (macrocystic/microcystic). Macrocystic lesions are defined as cysts large enough (commonly 2 cm) to be treated by sclerotherapy [2]. Sclerotherapy is now the mainstay of treatment for macrocystic LM but is less effective for microcystic lesion [3]. ☆ Disclosures: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. No commercial associations or financial disclosures to declare. The paper was not presented at a meeting and has not been accepted for presentation at a future meeting. ☆☆ Authors' role/participation: Xi Yang, literature research, clinical studies, statistical analysis, and manuscript editing; YunBo Jin, clinical studies, statistical analysis, and manuscript editing; XiaoXi Lin, guarantor of integrity of entire study; Hui Chen, clinical studies; Gang Ma, statistical analysis; XiaoJie Hu, clinical studies; YaJing Qiu, literature research; WenXin Yu, clinical studies; Lei Chang, clinical studies; TianYou Wang, literature research. ⁎ Corresponding author at: Shanghai 9th People's Hospital, Shanghai Jiaotong University, School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011, China. Tel.: +86 13701997136. E-mail address: [email protected] (X. Lin). http://dx.doi.org/10.1016/j.jpedsurg.2014.12.011 0022-3468/© 2015 Elsevier Inc. All rights reserved.
Resection still remains the first treatment of choice for managing microcystic LM, although bleomycin sclerotherapy seems to be very promising [4]. Periorbital LM is rare and usually presents in certain anatomic locations and patterns. It typically involves the upper eyelid and periocular tissues, and often extends into the adjacent frontotemporal region [5]. These extensive lesions can lead to swelling, intraorbital hemorrhage, ocular proptosis, blepharoptosis, amblyopia, chemosis, strabismus, cellulitis, and ultimately diminished vision and blindness [6]. Greene et al. reported 42 patients with periorbital LM, of whom 52% had blepharoptosis, 40% had diminished vision, and 7% became blind in the affected eye [7]. The most important period during visual acuity development is from birth to 40 weeks [8]. Newborns with large fronto-orbital LMs often develop blepharoptosis, which occludes the visual axis and can result in seriously diminished vision. For those patients, early stage management is necessary to aesthetically improve disfigurement and prevent visual maldevelopment. The aim of this study was to evaluate the clinical outcome of surgical treatment combined with intralesional bleomycin injection in periorbital microcystic LM patients with blepharoptosis.
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Fig. 1. A 4-year-old female patient with a large microcystic LM involving the frontotemple and the upper eyelid. The microcystic lesion was resected during the first stage of the operation (a). The size of extra skin was determined by measuring with a steel ruler and by comparing with the unaffected side. The position of hairline and eyebrow, extra skin for resection, and surgical incisions were marked with methylene blue symmetrically to the other side (b). In the frontotemporal area, the tissue between the periosteum and the skin was resected, including the frontalis muscle. An under-eyebrow incision was used to remove microcystic tissue in the upper eyelid, including the periorbital fat (c). After the lesion was resected, tiny drains in the prelevator space and frontal space were needed (d).
1. Patients and methods 1.1. Patients Approval for this retrospective clinical study was obtained from the institutional review board of our hospital, and informed written consent was obtained from the parents of all patients. This study included 9 patients, diagnosed with periorbital microcystic LM and blepharoptosis, who were subjected to surgical treatment and intralesional bleomycin
injection between January 2010 and January 2014. Patients with incomplete data and patients with previous history of treatment were excluded. The diagnosis of periorbital microcystic LM was based on clinical presentation and radiologic findings and was confirmed by histopathologic examination after surgery in all patients. Patients were evaluated for sex, age at diagnosis, the symptoms/ complications, and the extent of periorbital involvement. Symptoms that were documented included blepharoptosis, proptosis, amblyopia, restricted extraocular motion, chemosis, astigmatism, strabismus, and
Fig. 2. The remaining lesion of the upper eyelid was resected and the levator resection was performed during the second stage of the operation. The remaining lesion was resected through an under-eyebrow incision (a). The extra length of the levator palpebrae superioris aponeurosis was resected through a tarsal crease incision and the free levator aponeurosis was then reattached to the tarsal plate (b).
X. Yang et al. / Journal of Pediatric Surgery 50 (2015) 1393–1397
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Table 1 Patients' demographics and clinical outcome. Patient no
Age at surgery (years)
Sex
Symptoms before treatment
Extent of periorbital involvement
Clinical outcome
Follow-up (months)
Symptoms after treatment
Complications
1
2
F
Frontotemple and upper eyelid
Excellent
18
Astigmatism, amblyopia
Recurrence
2
4
F
Frontotemple and upper eyelid
Excellent
19
Amblyopia
Recurrence
3
6
M
Frontotemple and upper eyelid
Excellent
24
Amblyopia
Recurrence
4
4
F
Frontotemple and upper eyelid
Excellent
20
Amblyopia, strabismus
Recurrence
5
1
F
Frontotemple and upper eyelid
Excellent
16
6
F
Frontal area and upper eyelid
Excellent
40
Astigmatism, strabismus, chemosis, amblyopia Amblyopia, strabismus
Recurrence, incomplete eyelid closure
6
7
4
F
33
None
Recurrence
2
M
Excellent
30
None
None
9
2
M
Frontotemple and upper eyelid Frontal area and upper eyelid Frontotemple and upper eyelid
Excellent
8
Blepharoptosis, complete visual blockage, astigmatism, amblyopia Blepharoptosis, complete visual blockage, amblyopia Blepharoptosis, complete visual blockage, amblyopia Blepharoptosis, complete visual blockage, amblyopia, strabismus Blepharoptosis, complete visual blockage, astigmatism, strabismus, chemosis, amblyopia Blepharoptosis, complete visual blockage, amblyopia, strabismus Blepharoptosis, partial visual blockage Blepharoptosis, partial visual blockage Blepharoptosis, partial visual blockage
Excellent
21
None
None
decreased vision. Nine patients (3 male, 6 female), whose ages ranged from 1 to 6 years (average = 3.4 years), all had periorbital microcystic LM with blepharoptosis. Six of these patients had complete visual blockage while the other 3 patients had partial visual blockage. Amblyopia occurred in 6 patients, astigmatism was detected in 2 patients, strabismus was diagnosed in 3 patients, and chemosis was observed in 1 patient. The frontotemple and upper eyelid regions were involved in 7 patients. The lesions of the other 2 patients involved the frontal area and the upper eyelid. After the surgical procedures and bleomycin injection, the duration of the follow-up, the symptoms and the complications were recorded. All of the patients were subjected to magnetic resonance image (MRI) scanning to characterize the extent and size of the lesion before and after surgery and bleomycin injection. The clinical outcome was evaluated by assessing the reduction of the lesion and pretreatment and posttreatment photographs. A reduction rate greater than 90% was considered as excellent, from 75% to 90% as good, from 50% to 75% as fair, and from 0% to 50% as poor. 1.2. Surgical techniques The surgical procedure was performed in two stages by three plastic surgeons. In the first stage, nine patients with periorbital microcystic LM were scheduled to undergo lesion resection through coronal and under-eyebrow incision under general anesthesia. In the second stage, the operation of levator resection was performed three to six months after initial surgery. The goal was to remove as much of the lesion as necessary to provide a symmetrical contour and to correct the blepharoptosis and visual obstruction. 1.2.1. First stage The first stage of the operation was performed to resect as much of the microcystic lesion as possible. MRI scanning before the surgery was very important to ascertain the extent and size of the lesion. Usually, the microcystic LM tended to extend extensively from subcutaneous to deep muscle tissue. At first, the amount of the extra skin which needed to be removed was determined by measuring it with a steel ruler and by comparing it with the unaffected side. The position of the hairline and the eyebrow, extra skin for resection, and surgical incisions
Incomplete eyelid closure
were marked with methylene blue symmetrically to match the other side. A coronal incision and a crescent-shaped incision at the lower border of the eyebrow were needed to resect a large hemispherical frontotemporal and periorbital LM. When the frontotemporal area affected was minimal, an under-eyebrow incision was adequate for surgical excision of the lesion. In the frontotemporal area, the tissue between the periosteum and the skin was resected completely, including the frontalis muscle. It was difficult to excise the LM from the normal tissue, as it lay within and superficial to the frontalis muscle. When resection extended to the periorbita and upper eyelid, a lower eyebrow incision was used to remove microcystic tissue in the upper eyelid, including the periorbital fat. After incision through the orbicularis oculi muscle, the dissection proceeded inferiorly to the anterior surface of the tarsal plate and superiorly to the supraorbital rim. Extra skin was then resected to elevate the upper eyelid to a near normal level. Tiny drains in the prelevator space and frontal space were needed to prevent postoperative seroma (Fig. 1). 1.2.2. Second stage Three to six months after the first stage, the second stage operation procedures were performed, including the resection of the remaining upper eyelid lesion and the levator resection. Complete excision is usually not possible in microcystic LMs. Often there remains residual diffuse microcystic disease in the upper eyelid that can be addressed during the second stage through an incision at the tarsal crease and/or through the former under-eyebrow incision. The orbicularis muscle is preserved, but often the levator apparatus is weakened and stretched, and thus must be dissected and advanced to the tarsal plate. The extra length of the levator palpebrae superioris was resected taking into account measurements made before and during surgery. The free levator aponeurosis was then reattached to the tarsal plate (Fig. 2). 1.3. Bleomycin injection Six months after the two-stage surgery, any remaining or recurrent lesions were treated by bleomycin (Nippon Kayaku Co. Ltd, Tokyo, Japan) injections under general anesthesia. The dose of bleomycin used was based on the estimated size of the lesion. The maximum dose was 1 mg per kilogram per session, and the maximum dose was
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Fig. 3. A 4-year-old female patient with a large microcystic LM involving the frontotemple and the upper eyelid. Before the surgery, she had blepharoptosis, complete visual blockage, strabismus, and amblyopia (a, b). Three months after the first stage operation, blepharoptosis improved significantly (c, d). Twenty months after the second stage procedures and following one session of bleomycin injection, significant aesthetic improvement in her disfiguration and correction of her visual obstruction were achieved (e, f).
15 mg per session. After accessing the lesion with a 21-gauge needle, bleomycin was injected evenly into the lesion, both intravascularly and interstitially. Repeat procedures were performed 8 weeks apart.
2. Results The patients' demographics and clinical outcomes are summarized in Table 1. Blepharoptosis and visual block impairment were corrected in all of the patients. Mean follow-up time was 24.6 months. Amblyopia,
Fig. 4. A 6-year-old male patient with a large microcystic LM involving the frontotemple and the upper eyelid. Before the surgery, he had blepharoptosis, complete visual blockage, strabismus, and amblyopia (a, b). Six months after first stage operation, blepharoptosis markedly improved; there was however remaining lesion in the frontotemporal area (c, d). Fifteen months after the second stage operation and following two sessions of bleomycin injection, the remaining lesion in the frontotemporal area disappeared; significant aesthetic improvement in his disfiguration and correction of his visual obstruction were achieved (e, f).
astigmatism and strabismus showed no improvement after treatment. Six patients had recurrence during the follow-up period, and two patients who had partial eyelid closure after the second stage surgery recovered in three months. Bleomycin pulmonary toxicity was not observed in any patient. All of the patients had excellent clinical outcomes with notable aesthetic improvement of their disfigurement and correction of blepharoptosis (Figs. 3 and 4).
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3. Discussions LMs are classified by the size of the malformed channels into macrocystic, microcystic, or combined [9]. The term microcystic was reserved for lesions or parts of lesions containing cysts that are too small to be accessed by a hypodermic needle [10]. The response of this type of soft tissue lesion, without recognizable cysts, to sclerotherapy is less favorable [11]. Thus, whereas sclerotherapy has become the usual primary treatment for persistent macrocystic disease, surgery is still the most common therapy for microcystic LMs and symptomatic LMs. Periorbital lymphatic malformation usually presents with swelling, blepharoptosis, ocular proptosis, strabismus, chemosis, astigmatism, infection, or hemorrhage [12,13]. Blepharoptosis that occludes the visual axis requires prompt resection to prevent amblyopia. Previous normative studies of visual acuity development proved that the largest improvement of visual acuity occurred between birth and 6 months of age in infants [14] and development continues in children until at least 6 years of age [15,16]. Taylor deduced the critical period for deprivation amblyopia by studying children with amblyopia which follows uncomplicated unilateral cataract and the subsequent aphakic blur. He found that correction before 4 months of age produced less visual loss, and when the vision was deprived between 6 and 30 months of age finger counting was the best visual acuity achieved [17]. In our study, 6 of the 9 patients had complete visual blockage and amblyopia before surgery. They showed no improvement in the amblyopia after more than 16 months of follow-up. The time of the surgery for microcystic LM patients with complete visual blockage still needs further studies to pursue a higher level of evidence. Most of our patients underwent surgical treatment in two stages. The goal of first stage procedures was to achieve nearly complete resection of the microcystic lesion in all patients. During the second stage levator resection was performed in all patients. The reasons why blepharoptosis occurs in the periorbital LM patients could be both mechanical and biological. For instance, the large hemispherical mass can cause severe compression, which makes it difficult for the levator palpebrae superioris to lift the upper eyelid. So, after the compression ceases, the ability to open the eye should improve significantly. Additionally, the length of the levator palpebrae superioris involved in microcystic LM is longer than normal, and will not improve after the mass is removed. In our study, blepharoptosis improved a lot after the mechanical compression was relieved three to six months after the first operation, and the extra length of the levator palpebrae superioris could be measured more precisely. This could explain why the levator resection performed during the first operation was not as accurate compared with the levator resections performed during the second stage. As with any microcystic LM, complete resection is usually not possible because of the diffuse distribution of the abnormal lymphatic channels. In our group of 9 patients, 6 of them experienced mild disease recurrence after surgery. However, repeat resection is not worthwhile for these patients. Bleomycin has been reported to have significantly effects on LM. Qin et al. reported 200 patients treated by intratumorous injection of bleomycin-A5, and was effective in 97%, while the curative rate was 86.5% [18]. Recently, Chaudry et al. described 31 patients with microcystic LM treated with intralesional bleomycin injection, 38% of whom had lesion size reduction (N90%) [4]. Intralesional bleomycin injection was also effective in treating the remaining or recurrent lesions after surgery in our patients. One of the main complications of intralesional bleomycin injection is bleomycininduced pneumonitis. Muir et al. reported 95 patients with hemangiomas and congenital vascular malformations treated by bleomycin, and the maximal single session dose was 1 mg/kg, not exceeding
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15 mg. No pulmonary fibrosis was documented [19]. Intralesional bleomycin injection appears to be safe and effective in microcystic LM, but it takes more sessions and much longer time than surgery especially when the lesions are large. Periorbital microcystic LM with blepharoptosis that occludes the visual axis needs prompt intervention. Resection should be performed at first because it is the quickest way to resolve the visual obstruction and prevent visual impairment. As the visual obstruction was corrected by surgery, even though sclerotherapy takes much longer, bleomycin injection was an effective adjunctive treatment for residual or recurrent lesions. 4. Limitations The main limitation of our study is the small number of patients, this was partly owing to the fact that only periorbital microcystic LMs with blepharoptosis were included. In addition, a longer follow-up period would be optimal for patients with amblyopia. 5. Conclusions Resection through a lower-eyebrow and coronal incision and levator resection performed in two stages can quickly correct the visual impairment caused by periorbital microcystic lymphatic malformation with blepharoptosis. Intralesional bleomycin injection is a promising adjunctive method of treatment for residual or recurrent lesions noted after surgery. References [1] Perkins JA, Manning SC, Tempero RM, et al. Lymphatic malformations: current cellular and clinical investigations. Otolaryngol Head Neck Surg 2010;142(6): 789–94. [2] Greene AK, Perlyn CA, Alomari AI. Management of lymphatic malformations. Clin Plast Surg 2011;38(1):75–82. [3] Alomari AI, Karian VE, Lord DJ, et al. Percutaneous sclerotherapy for lymphatic malformations: a retrospective analysis of patient-evaluated improvement [J]. J Vasc Interv Radiol 2006;17(10):1639–48. [4] Chaudry G, Guevara CJ, Rialon KL, et al. Safety and efficacy of bleomycin sclerotherapy for microcystic lymphatic malformation. Cardiovasc Intervent Radiol 2014;1–6. [5] Bisdorff A, Mulliken JB, Carrico J, et al. Intracranial vascular anomalies in patients with periorbital lymphatic and lymphaticovenous malformations. Am J Neuroradiol 2007;28(2):335–41. [6] Wiegand S, Eivazi B, Bloch LM, et al. Lymphatic malformations of the orbit. Clin Exp Otorhinolaryngol 2013;6(1):30–5. [7] Greene AK, Burrows PE, Smith L, et al. Periorbital lymphatic malformation: clinical course and management in 42 patients. Plast Reconstr Surg 2005;115(1):22–30. [8] Catford GV, Oliver A. Development of visual acuity. Arch Dis Child 1973;48(1):47. [9] Burrows PE. Endovascular treatment of slow-flow vascular malformations. Tech Vasc intervent Radiol 2013;16(1):12–21. [10] Chaudry G, Burrows PE, Padua HM, et al. Sclerotherapy of abdominal lymphatic malformations with doxycycline. J Vasc Interv Radiol 2011;22(10):1431–5. [11] Churchill P, Otal D, Pemberton J, et al. Sclerotherapy for lymphatic malformations in children: a scoping review. J Pediatr Surg 2011;46(5):912–22. [12] Wilson ME, Parker PL, Chavis RM. Conservative management of childhood orbital lymphangioma. Ophthalmology 1989;96(4):484–9. [13] Tunç M, Sadri E, Char DH. Orbital lymphangioma: an analysis of 26 patients. Br J Ophthalmol 1999;83(1):76–80. [14] Salomao SR, Ventura DF. Large sample population age norms for visual acuities obtained with Vistech-Teller Acuity Cards. Invest Ophthalmol Vis Sci 1995;36(3): 657–70. [15] Mayer DL, Dobson V. Visual acuity development in infants and young children, as assessed by operant preferential looking. Vision Res 1982;22(9):1141–51. [16] Neu B, Sireteanu R. Monocular acuity in preschool children: assessment with the Teller and Keeler acuity cards in comparison to the C-test. Strabismus 1997;5(4): 185–202. [17] Taylor D. Critical period for deprivation amblyopia in children. Trans Ophthalmol Soc U K 1978;99(3):432–9. [18] Qin ZP, Xin ZF, Ren L, et al. Long-term results of intratumorous bleomycin-A5 injection for head and neck lymphangioma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86(2):139–44. [19] Muir T, Kirsten M, Fourie P, et al. Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int 2004; 19:766–73.
