Increased Levator Muscle Function by Supramaximal Resection in Patients with Blepharophimosis-Ptosis–Epicanthus Inversus Syndrome

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CLINICAL SCIENCES Increased Levator Muscle Function by Supramaximal Resection in Patients With Blepharophimosis-Ptosis–Epicanthus Inversus Syndrome

Christian E. Decock, MD; Akash D. Shah, MD; Christophe Delaey, MD, PhD; Ramses Forsyth, MD, PhD; Wouter Bauters, MD; Philippe Kestelyn, MD, PhD; Elfride De Baere, MD, PhD; Ilse Claerhout, MD, PhD

Objective: To study the efficacy and clinical and ana- (SD) 1.9 (0.9) mm preoperatively to 7.4 (1.1) mm post- tomical results of supramaximal levator resection in pa- operatively (P value Ͻ.001). This improvement could be tients with blepharophimosis-ptosis–epicanthus inver- attributed to the presence of a very long and thin ten- sus syndrome (BPES) with severe congenital ptosis with don, as well as a striated muscle belly. This elongated apo- poor levator function (LF). neurosis inhibits the levator muscle from having suffi- cient impact on the vertical eyelid excursion. Methods: Eleven patients with molecularly proven BPES underwent supramaximal levator resection. Palpebral fis- Conclusions: We demonstrated that supramaximal le- sure height and LF were measured preoperatively and vator resection performed in patients with BPES not only postoperatively. results in good cosmetic appearance in terms of ptosis reduction in the majority of cases but also in a signifi- Results: All patients showed an excellent reduction in cant increase of the levator palpebrae superioris func- ptosis with a single intervention resulting in a clear vi- tion. An anatomical substrate was found to explain these sual axis. Palpebral fissure height improved from mean findings. To our knowledge, this is the first study to pro- (SD) 3.3 (0.7) mm preoperatively to 7.1 (0.9) mm post- vide evidence of a marked increase in LF in BPES due to operatively (P value Ͻ.001). Four patients underwent ad- resection of the elongated tendon with reinsertion of the ditional surgery because of cosmetic issues with eyelid muscle belly. height asymmetry. All patients showed a marked, con- sistent, and lasting improvement in LF, going from mean Arch Ophthalmol. 2011;129(8):1018-1022

HE BLEPHAROPHIMOSIS- To compensate for the ptosis, affected ptosis–epicanthus inversus individuals use the frontalis muscle, wrin- syndrome (BPES) is a com- kling the forehead to draw the eyebrows plex eyelid malformation upward, which results in a characteristic characterized by 4 major facial appearance. Moreover, in a com- characteristics that are present at birth: pensatory mechanism, they tilt their head T 3 blepharophimosis, ptosis, epicanthus in- backward into a chin-up position. versus, and telecanthus.1 The inheritance Surgical correction of the complex eye- of this syndrome is autosomal dominant. lid malformation, and in particular the se- Ptosis is a drooping of the upper eye- vere ptosis, is recommended not only for lid causing narrowing of the vertical pal- cosmetic reasons but also because of func- pebral fissure. Most patients with molecu- tional implications, since severe ptosis can larly proven BPES have a severe congenital cause amblyopia, strabismus, and refrac- Author Affiliations: tive errors.4 Departments of Ophthalmology In general, patients presenting with se- (Drs Decock, Delaey, Kesteyln, Video available online at vere congenital ptosis with poor levator and Claerhout), Pathology www.archophthalmol.com muscle function are treated with a fronta- (Dr Forsyth), and Radiology lis suspension using fascia lata (so-called Ͻ (Dr Bauters) and Center for ptosis with poor levator function (LF) ( 4 Crawford frontalis suspension).5-7 Some Medical Genetics (Dr De Baere), mm of vertical eyelid excursion). In indi- people, however, advocate the use of su- Ghent University Hospital, viduals with BPES, ptosis has been thought pramaximal levator resection in these Ghent, Belgium; and 8-10 Department of Orbit and to be secondary to dysplasia of the leva- cases. Excellent functional and aes- Oculoplasty, Bombay City Eye tor palpebrae superioris (LPS) muscle but thetic results have been demonstrated using Hospital, Mumbai, India very little is known about its actual ana- both techniques.11 Ptosis is significantly re- (Dr Shah). tomical substrate.2,3 duced in most patients; however, none of

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 the patients with simple severe congenital ptosis with poor polyglactin 910 sutures placed on the anterior plane of the tar- LF have shown an increase in LF after their surgery. sus, approximately 2 mm from its superior border. Finally, the The objective of this study was to investigate the ef- skin was closed with single polyglactin 910 absorbable syn- ficacy as well as the clinical and anatomical results of su- thetic 6-0 sutures (Vicryl Rapide; Johnson & Johnson, New pramaximal levator resection in patients with BPES. The Brunswick, New Jersey). outcome of this procedure was studied in a unique co- STATISTICAL ANALYSIS hort of 11 consecutive patients with molecularly proven BPES with severe congenital ptosis and poor LF. Statistical analysis was performed using the t test. A P value of less than .05 was considered statistically significant. METHODS RESULTS PATIENTS A total of 22 eyelids from 11 patients underwent ptosis Eleven consenting consecutive patients with molecularly proven repair using supramaximal levator resection. Preopera- BPES were included in this study conducted at a tertiary ocu- tive and postoperative figures are summarized in the loplastic referral center. In general, the presence of the 4 ma- Table jor criteria (blepharophimosis, ptosis, epicanthus inversus, and . All patients had an LF of less than 4 mm. mostly telecanthus) was initially used to accept a clinical di- High-resolution MRI scan performed preoperatively agnosis of BPES. The fifth anatomical hallmark, namely the lower in 8 patients clearly revealed the presence of the LPS as eyelid malpositioning (data not shown), was also present in all a thin, well-distinct structure running from the tarsal plate cases. Mutation screening of the FOXL2 gene (sequencing and into the LPS/superior rectus complex. From there on, it deletion screening of the coding region) was performed to con- could no longer be identified running apically because firm the diagnosis of BPES in all individuals.12 The age of the of loss of signal intensity. patients at the time of ptosis surgery varied between 4 and 13 Supramaximal levator resection resulted in lifting up the years, partially depending on the moment it became possible upper eyelid from a mean (SD) preoperative vertical PF to correctly measure LF. The 13-year-old patient had never had height of 3.3 (0.7) mm to 7.1 (0.9) mm (P value Ͻ.001). surgery proposed prior to consultation with us. Surgical pro- cedures were performed between 2006 and 2009. This study The PF height ranged between 2 and 5 mm preoperatively was conducted following the tenets of Helsinki with formal eth- and between 6 and 9 mm postoperatively. All patients had ics committee approval. a free visual axis following a single procedure, eliminating the risk for amblyopia. In 7 of 11 patients, a satisfactory METHODS level of symmetry in PF height was obtained. Of the re- maining 4 patients, 3 had more than 1.5-mm asymmetry Ocular parameters measured during the preoperative and post- in PF width and underwent an additional unilateral fron- operative evaluation visits included vertical palpebral fissure talis suspension. The fourth patient underwent a bilateral (PF) height and LF (lid excursion from downgaze to upgaze frontalis suspension for cosmetic reasons. Although the PF while immobilizing the frontalis muscle). Prior to ptosis sur- height increased from 2 to 3 mm to 6 mm, the parents pre- gery, 8 patients underwent a high-resolution magnetic reso- ferred additional lifting of the upper eyelid. nance imaging (MRI) scan and the resected part of the LPS was Most striking was that a marked improvement in LF subjected to histopathological analysis. was noted in all our patients following supramaximal levator resection. This is demonstrated in the Figure. The SURGICAL PROCEDURE LF increased from a mean (SD) value of 1.9 (0.9) mm preoperatively to 7.4 (1.1) mm postoperatively (P value All patients underwent a staged surgical repair of the complex Ͻ eyelid anomalies by the same oculoplastic surgeon (C.D.C.). .001). The mean (SD) improvement in LF was 5.4 (1.5) The first step consisted of a modified technique to treat the tele- mm, ranging from 2 up to 8 mm improvement. A video canthus, epicanthus inversus, and the malpositioning of the taken 6 weeks postoperatively (video, http://www lower eyelid (data not shown). This first step was then fol- .archophthalmol.com) clearly illustrates this increased LF. lowed by a supramaximal levator muscle resection at least 3 Results remained stable during a follow-up period of months later. at least 1 year. No postoperative complications were noted General anesthesia was used in all patients. Both eyes were and the well-known lagophthalmos following ptosis re- operated on during the same session. A skin approach at 6 mm pair in severe congenital ptosis was severely reduced, al- above the gray line was used. A skin orbicularis muscle flap most absent, in all our operated-on patients. was dissected free from the orbital septum. The septum was Histopathological analysis of the resected levator tis- incised 2 mm above its insertion on the levator aponeurosis. The preaponeurotic fat was pulled away with a Desmarres spoon, sue showed well-formed striated muscle fibers on the most resulting in a clear view on the anterior plane of the levator apical part (data not shown). This striated muscle com- muscle. The posterior plane was then dissected free from the ponent was connected to the tarsal plate by a very long, upper border of the tarsus and from the underlying conjunc- thin, disorganized collagenous structure suggestive of le- tiva. The medial and lateral levator horns were cut at a 45° angle vator aponeurosis. to avoid the superior oblique tendon and the lacrimal gland and ductules, respectively. This also allowed us to free the levator COMMENT muscle even further and permitted a maximal or supramaximal levator resection (defined as 30 mm or more measured during surgery). This was followed by reinsertion of the LPS rem- In simple severe congenital ptosis with poor LF, some nant on the tarsus with 2 double-armed absorbable 5-0 people advocate frontalis suspension with autogenous fas-

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table. Summary of Preoperative and Postoperative Details in Patients With BPES Operated on for Severe Ptosis Using Supramaximal Levator Resection

Levator Function, mm PF Width, mm Age at Ptosis Increase in Levator Case Surgery, y Eye Preop Postop Preop Postop Function, mm Additional Surgery 1 6 Right 1726 6 Bilateral frontalis suspension Left 3736 4 2 4 Right 2746 5 Unilateral frontalis suspension Left 1948 8 3 5 Right 2948 7 Left 1748 6 4 6 Right 2927 7 Left 3928 6 5 5 Right 2 6 NR 6 4 Left 3 6 NR 6 3 6 13 Right 2837 6 Left 3738 4 7 7 Right 2848 6 Left 2847 6 8 4 Right 2 8 NR 7 6 Left 3 5 NR 6 2 9 4 Right 0737 7 Left 0-1 8 3 7 8 10 5 Right 3859 5 Unilateral frontalis suspension Left 2636 4 11 7 Right 1739 6 Unilateral frontalis suspension Left 0736 7

Abbreviations: BPES, blepharophimosis-ptosis–epicanthus inversus syndrome; NR, not recorded; PF, palpebral fissure; Postop, postoperatively; Preop, preoperatively.

cia lata (Crawford frontalis suspension), whereas oth- gave these eyelids an almost physiological behavior (as ers favor supramaximal resection. Both these interven- illustrated in the video taken 6 weeks postoperatively). tions will increase PF height and reduce ptosis; however, This is a very unusual finding that, to the best of our neither will result in a recovery of LF. knowledge, has never been reported in simple severe Almost all patients with molecularly proven BPES de- congenital ptosis. scribed have a severe ptosis and a very poor to almost Tronina et al14 previously described a novel, com- absent LF. The decreased LF in patients with BPES was plex, 1-stage surgical treatment of 51 patients with BPES, formerly believed to be due to dysplasia of the posterior including shortening of the medial canthal tendon, re- LPS.2,3 section of the tarsus and levator muscle, and skin plasty. In this study, we set out to examine the efficacy as They also noted a similar marked increase in LF follow- well as the clinical and anatomical results of (supra) ing surgery (average increase in LF of 5.6 mm). maximal levator resection for the treatment of ptosis in Improvement in LF after ptosis correction in simple 11 patients with molecularly proven BPES. Following severe congenital ptosis is never seen. In 1955, Berke and this procedure, all our patients had an excellent reduc- Wadsworth showed in their hallmark article15 on the his- tion in ptosis with a free visual axis, reducing the risk topathological findings in simple severe congenital pto- for amblyopia. Seven patients obtained a satisfactory sis that the severe ptosis is due to absence of levator stri- cosmetic result with a single intervention, whereas 4 ated muscle fibers replaced by a fatty degeneration. others needed additional frontalis suspension for cos- Consequently, shortening of this (nonmuscular) struc- metic reasons only (PF width asymmetry or insufficient ture can never increase LF. reduction of ptosis from a cosmetic point of view). The The marked and unexpected improvement in levator rate of reintervention is not that much different from muscle function seen after supramaximal LPS resection that found by Taylor et al13 using the Crawford frontalis in patients with BPES prompted us to search for the ana- suspension technique for ptosis repair. In the latter tomical substrate of this finding. We investigated 8 pa- study, reintervention was required in 2 of 13 patients, tients with high-resolution 3-T MRI with supercoil and also for cosmetic purposes. we also performed a detailed anatomical and histopatho- The most striking finding in our study, however, was logical examination of the resected LPS. the marked improvement in LF obtained in all oper- These MRI findings offer an explanation for the sur- ated-on eyelids. Mean (SD) LF was 1.9 (0.9) mm preop- gical findings reported herein. A thorough workup re- eratively and increased to 7.4 (1.1) mm postoperatively. vealed the presence of well-formed striated muscle in the The mean (SD) value of muscle function improvement most apical part of the levator muscle. In comparison with following surgery was 5.4 (1.5) mm. Improvement in a normally functioning eyelid, however, this muscle belly LF, almost absent lagophthalmos, and fair blinking was located at 20 to 25 mm instead of 10 mm from the

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C D

E F

G H

Figure. Two patients with blepharophimosis-ptosis–epicanthus inversus syndrome before and after surgery. A and B, Preoperatively. Note the 4 major clinical characteristics: (1) blepharophimosis, (2) ptosis, (3) epicanthus inversus, and (4) telecanthus. C and D, After surgical correction (telecanthus-ptosis) in primary gaze. E-H, Vertical eyelid excursion going from downgaze to upgaze following levator resection showing a good postoperative levator muscle function.

insertion of the tarsal plate, much deeper into the orbit. rectly onto the tarsal plate, it can regain some impact on On histopathological analysis, striated muscle fibers are the eyelid position, resulting in a fair motility. Thus, our found in patients with BPES, unlike the fatty degenera- findings might indicate that the decreased LF in pa- tion typically seen in patients with simple severe con- tients with BPES is not due to dysplasia of the posterior genital ptosis and a similar poor LF. LPS, as was generally accepted, but is probably due to a By performing supramaximal levator resection, the ma- congenital malformation at the level of the anterior apo- jority of tissue resected is in fact the aponeurosis like the neurosis, sparing to a certain extent the levator (stri- anterior part of the muscle. After eliminating this ten- ated) muscle. don (that is too long), and after reinserting the rest of In conclusion, we demonstrated that supramaximal the LPS, the presence of the striated LPS muscle com- levator resection in patients with BPES resulted in marked ponent provokes a marked increase in the LF. improvement of muscle function and was able to obtain Although LF in patients with BPES is increased after good cosmetic appearance in most patients. This novel supramaximal resection, it does not attain normal val- insight into the treatment of the complex eyelid malfor- ues. We hypothesize that this is probably due to a mal- mation in BPES will have an important impact on future development of the muscle. If it were just a matter of surgical management of this condition. It can be antici- deeper localization into the orbit than normal (on a ten- pated that future randomized clinical trials will further don of 20 to 25 mm in comparison with a 10-mm ten- sustain these important findings. don in normal individuals), one would expect a normal LF in combination with the severe ptosis as is classically Submitted for Publication: July 26, 2010; final revision seen in aponeurotic ptosis (long tendon, ptosis, but nor- received December 7, 2010; accepted December 15, 2010. mal LF). Correspondence: Christian E. Decock, MD, Depart- The tendon of the LPS in patients with BPES is too ment of Ophthalmology, Ghent University Hospital, De long and thin, thereby impairing the already subnor- Pintelaan 185, B-9000 Ghent, Belgium (christian.decock mally developed levator muscle even more. Resecting the @ugent.be). elongated aponeurosis brings the levator muscle in a more Financial Disclosure: None reported. anterior and therefore more physiological position. Be- Online-Only Material: The video is available at http: cause the levator muscle is now connected more di- //www.archophthalmol.com.

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 8. Pak J, Shields M, Putterman AM. Superior tarsectomy augments super- REFERENCES maximum levator resection in correction of severe blepharoptosis with poor levator function. Ophthalmology. 2006;113(7):1201-1208. 1. Oley C, Baraitser M. Blepharophimosis, ptosis, epicanthus inversus syndrome 9. Press UP, Hu¨bner H. Maximal levator resection in the treatment of unilateral con- (BPES syndrome). J Med Genet. 1988;25(1):47-51. genital ptosis with poor levator function. Orbit. 2001;20(2):125-129. 2. Allen CE, Rubin PA. Blepharophimosis-ptosis-epicanthus inversus syndrome 10. Mauriello JA, Wagner RS, Caputo AR, Natale B, Lister M. Treatment of congen- (BPES): clinical manifestation and treatment. Int Ophthalmol Clin. 2008;48 ital ptosis by maximal levator resection. Ophthalmology. 1986;93(4):466-469. (2):15-23. 11. Epstein GA, Putterman AM. Super-maximum levator resection for severe uni- 3. Strømme P, Sandboe F. Blepharophimosis-ptosis-epicanthus inversus syn- lateral congenital blepharoptosis. Ophthalmic Surg. 1984;15(12):971-979. drome (BPES). Acta Ophthalmol Scand. 1996;74(1):45-47. 12. Beysen D, De Jaegere S, Amor D, et al. Identification of 34 novel and 56 known 4. Beckingsale PS, Sullivan TJ, Wong VA, Oley C. Blepharophimosis: a recommen- FOXL2 mutations in patients with Blepharophimosis syndrome. Hum Mutat. 2008; dation for early surgery in patients with severe ptosis. Clin Experiment Ophthalmol. 29(11):E205-E219. 2003;31(2):138-142. 5. Crawford JS. Repair of ptosis using frontalis muscle and fascia lata: a 20-year 13. Taylor A, Strike PW, Tyers AG. Blepharophimosis-ptosis-epicanthus inversus syn- review. Ophthalmic Surg. 1977;8(4):31-40. drome: objective analysis of surgical outcome in patients from a single unit. Clin 6. Morax S, Benia L. Suspension of the eyelid to the frontal muscle in the surgery Experiment Ophthalmol. 2007;35(3):262-269. of ptosis: technic and indications [in French]. J Fr Ophtalmol. 1986;9(6-7): 14. Tronina SA, Bobrova NF, Khrinenko VP. Clinical and anatomical substantiation 461-470. of levator resection in the complex surgical treatment of BPES. Orbit. 2006; 7. Reny A, George JL. Treatment of severe ptosis by suspension of the upper eye- 25(1):5-10. lid using the autogenic frontal muscle and fascia lata: analysis of 34 interven- 15. Berke RN, Wadsworth JA. Histology of levator muscle in congenital and ac- tions [in French]. J Fr Ophtalmol. 1983;6(10):797-807. quired ptosis. AMA Arch Ophthalmol. 1955;53(3):413-428.

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