Orbit, 2014; 33(6): 399–405 ! Informa Healthcare USA, Inc. ISSN: 0167-6830 print / 1744-5108 online DOI: 10.3109/01676830.2014.949785
ORIGINAL ARTICLE
Floppy Eyelid Syndrome: The Coventry Experience Aaron M. Yeung, Imran Ashfaq, Yajati K. Ghosh, Ioannis Kyprianou, and Harpreet Singh Ahluwalia
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University Hospital Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom
ABSTRACT Purpose: Floppy eyelid syndrome is a condition that is difficult to identify and diagnose and with no clear guidelines on its management. We propose a method of reliably grading this syndrome and have proposed a management algorithm based on the grading. Materials and Methods: Retrospective data collection of patients diagnosed with Floppy eyelid syndrome and treated under the care of a single oculoplastic surgeon over a 9 year period. Results: First, 102 patients were included and were classified into 3 groups. Grade 1 (F1) 7.5%, Grade 2 (F2) 36.5% and Grade 3 (F3) 56%. Only 12% of our cohort required surgery, and 92% of these patients demonstrated improvement in their symptoms. Discussion: Clinical grading of Floppy eyelid syndrome patients will help determine patient’s management plan. In our experience, operating on both upper and lower eyelids at the same time where indicated helps to maintain the normal anatomical relationship and improve epiphora. Keywords: Floppy eyelid, grading, management
INTRODUCTION
Noctural eversion over a period of time may cause mechanical insult to underlying structures including the conjunctiva that subsequently causes keratinization.1 Increased laxity of lids may cause a reduced interface between the eyelids and the surface of the epibulbar region. This in turn, disturbs the ocular surface interface leading to poor tear distribution and ultimately leading to the irritating symptoms patients complain of ref.7 A genetic predisposition with abnormalities in collagen or elastin may influence both FES and Obstructive Sleep Apnoea (OSA).8,9 Increased lid ischaemia secondary to local pressure in association with repurfusion injury during OSA may cause chronic inflammation. This may lead to water retention and damage eyelid skin leading to worsening of eyelid condition.10 Inflammation in FES could potentially cause generalised atrophy, but histological
Floppy eyelid syndrome (FES) is a condition that was initially described in males who were in the middle ages of their lives. These patients exhibited a high Body Mass Index (BMI), had evidence of papillary conjunctivitis and the unique and unusual appearance of floppy eyelids. Culbertson and Ostler1 were the first to report this condition but in more recent times, it has been associated with previously unknown variables including presenting in the female gender,2 affecting patients in other age groups3–5 and even affecting patients that have a normal weight.6 The pathogenesis of FES is still currently unclear, however, there have been numerous hypotheses that may explain this condition that is gradually becoming more recognised and more frequently diagnosed.
Received 11 September 2013; Revised 17 March 2014; Accepted 27 July 2014; Published online 25 September 2014 Correspondence: Aaron Yeung, Specialty Registrar in Ophthalmology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, United Kingdom. Tel: + 44 247 696 4000 Ext 26506. E-mail: [email protected]
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400 A. M. Yeung et al. studies did not detect any sign of chronic inflammation.9 Patients typically present with a chronic papillary conjunctivitis, and demonstrate an upper eyelid that may evert with little effort. In addition, the tarsus can be soft and fold upon itself. There have been other associations reported that are thought to be related to FES including local effects on the cornea and the systemic effects of obstructive sleep apnoea. In a study by Culbertson and Tseng, 71% of patients had cornea abnormalities related to FES and punctate epithelial keratitis was most common feature. It was noted to be diffuse in nature and was only found in the eye with FES.6 They also reported that 10% of the same cohort had keratoconus6 but the underlying associations are not clear. It has been commonly reported that eye rubbing is a predisposing factor in keratoconus.11,12 We feel that similarly eye rubbing in FES might predispose susceptible patients to developing keratoconus. There have been numerous reports that associate OSA and FES.13–15 They have a common factor in that a high proportion of patients have a high BMI index. A high proportion of patients with FES are reported to be affected by OSA,15,16 but interestingly the reverse is not true.16 Treatment options typically fall between conservative treatment or surgery.
Conservative Lid taping, lubrication at night, eye shields, losing weight, topical steroids, lid hygiene and punctal plugs have been recommended in the past.1,7 Failing this, numerous surgical options have been suggested,
recruited over a 9-year period between 2003–2012 and the study adhered to the principles of the Declaration of Helsinki. Data including weight, height, smoking status and visual acuity were recorded from the standard FES proforma in case notes. Patients were asked to describe their symptoms, all of which were recorded included itching, epiphora, irritation, grittiness, reduction in visual acuity, soreness of eyelids, foreign body sensation and discharge. The onset of patients symptoms were classified as acute, subacute and chronic and any diurnal variations were also noted. Acute symptoms were those less than 4 weeks, subacute were less than 3 months and chronic were more than 3 months. Past medical and ocular history were taken as well as a sleep history, which included sleeping posture, whether the patient snored and any history of sleep apnoea. All patients had their Epworth scores evaluated. A complete ophthalmic examination was performed. In particular the eyelids were examined and were graded as mild, moderate or severe in floppiness using a simple clinical grading system. Papillary conjunctivitis, blepharitis, entropian, ectropian, trichiasis, lid ptosis, lash ptosis and cornea pathology were also noted. Patients were classified into 3 groups described as mild (F1), moderate (F2) or severe (F3). Depending on their grading, patients were treated on our proposed management algorithm. We graded our patients with FES based on the amount of exposed tarsal conjunctiva (TC) observed on maximal traction on the upper lid. Grade 1 (F1) between 1/3 to ½ of the TC visible (Figure 1A). Grade 2 (F2) more than ½ of TC visible (Figure 1B). Grade 3 (F3) spontaneous upper lid eversion on minimal lid retraction or on forced lid closure (Figure 1C).
Surgery Full thickness wedge excision,9,17,18 lateral tarsal strip (LTS)3,19 and lateral canthal plication20 have been recognised as surgical options for the treatment of FES with varying results. At present there is no specific grading for floppiness of the lid. In addition, there are no clear treatment guideline pathways in the management of FES. The objective of our study was to describe our management algorithm in the management of FES based on our experience of FES.
RESULTS We identified 102 patients, 34 females and 68 males, mean age 51.7 yr (range 20–77 yr). The patients were mostly Caucasian (86%) and 14% were of Indian ethnicity, the latter disproportionately higher for the local population. Patients with increasing severity of FES were older and had a higher BMI. There was a mean follow-up of 30 months.
Presenting Symptoms MATERIALS AND METHODS We retrospectively collected the data of 102 patients with FES that were treated under the care of a single consultant oculoplastic surgeon (HA). Patients were
All patients had been referred by general practitioners or other ophthalmologists for non-resolving conjunctivitis or epiphora. Specifically 70% of our patients mainly presented with epiphora, followed by Orbit
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dysfunction in an attempt to reduce the bacterial lipolytic enzymes in meibomian gland secretions. Lash Ptosis In our series 59% of our patients displayed signs of lash ptosis. Mild lash ptosis in an asymptomatic patient requires no active treatment. In patients where the patient has no ptosis, but limitation of superior field by lash ptosis, lash curlers can be tried. Lid shortening procedures generally correct lash ptosis as well as tightening the lids. Anterior lamellar repositioning is reserved for patients with corneal touch and severe lash ptosis.
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Ocular Comorbidity Two cases had keratoconous 2%, one patient had previous central retinal vein occlusion (CRVO) (1%), one patient had thyroid eye disease (1%) and one had optic neuropathy (1%), and 10% of patients had primary open angle glaucoma (POAG). Corneal and Conjunctival Involvement
FIGURE 1. Grading of Floppy Eyelid. A: Grade 1 (F1); B: Grade 2 (F2); C: Grade 3 (F3).
irritation (44%), grittiness, itching, soreness, foreign body sensation and ocular discomfort/irritation.
Ocular Findings and Their Management
Most of the patients in our cohort had punctate epithelial keratopathy as the main corneal manifestation. This may be as a result of nocturnal exposure or secondary to topical medication toxicity. We suggest use of preservative free topical drops to preserve corneal integrity wherever possible. 72% had papillary conjunctivitis. We grade papillary conjunctivitis as mild, moderate and severe dependent on the number of papillae. The majority of patients in this study had moderate papillary conjunctivitis (65%). The severity of papillary conjunctival changes determines the use of regular topical lubricants and reserves topical steroids for treatment of more severe cases. Atopic conjunctivitis was diagnosed in 10% of cases in our series. These patients had history of atopy with giant papillary conjunctival changes. All were prescribed topical antihistamines and mast cell inhibitors with a good response.
Floppiness of Lids In all, 56% of our patients had grade F2 and 36.5% had grade F3.
Surgery
Posterior Blepharitis and Tear Dysfunction More than three quarters of cases in our series had posterior blepharitis and associated qualitative tear dysfunction. Patients were given strict instructions with demonstration of twice-daily lid hygiene with dedicated lid wipes and also given a patient information leaflet. Patients were commenced on topical lubricants in all cases with lubricant ointment at bedtime. Oral doxycycline 100 mg once daily was reserved for more severe cases of meibomian gland
Only 12% of our patients required lid shortening procedures for treatment of their symptoms in the 9-year follow-up. The median age of these patients undergoing surgery was 67 years (range 25–74 yr). The most common indication for embarking on surgery was severity of the condition and lack of or only partial response to conservative regimes. All patients underwent a shortening of their upper and lower lid. A lateral tarsal strip was used to shorten all lower lids, while we initially performed wedge excisions (middle and lateral 1/3) and since
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402 A. M. Yeung et al. 2007 modified upper lid tarsal strips for upper lid shortening. In our series all patients where upper lid surgery was planned had significant coexisting lower lid laxity. Currently upper lid modified tarsal strip is our procedure of choice for upper lid shortening. We feel that both upper and lower lids should be shortened simultaneously rather than the upper lid in isolation to avoid altering the normal relationship between the upper and lower lids. Lower lid tightening is particularly helpful where epiphora is a significant complaint and the lid is lax. Of F3 grades, 26% (9/35) of patients underwent surgery and 5% of F2 grades (3/58) had surgery. At a median follow up period of 16 months all patients had good lid position and 92% demonstrated improved symptomatology. The main symptoms that showed improvement was foreign body sensation, soreness and epiphora.
Systemic Associations Obesity and OSA 55% of our patients were obese (BMI 430), Mean BMI 33.4 ± 6.3 (range 23–49). These patients were advised to lose weight and referred to the dietician at the hospital or via their general practitioner (GP). Previous evidence suggests that losing weight improves symptoms especially in patients with OSA. Interestingly, we did not find any correlation between BMI and the severity of FES. 86% of our patients showed a positive correlation of sleep posture with the worst-affected side including bilateral cases with face on pillow position. Then, 92% of patients agreed they snored which was confirmed by their partners, and 47% of patients gave history of symptoms suggestive of a sleep disorder of which only 16%, however, were referred for formal sleep studies as the rest failed to meet the referral criteria for referral to the sleep clinic. We assess all patients for symptoms indicative of obstructive sleep apnoea such as snoring, apnoea attacks and daytime somnolence using the Epworth sleepiness scoring scale 410 before referring to the sleep centre for formal sleep studies. In our sleep clinic the respiratory physicians use a domiciliary monitoring system to confirm OSA then auto-titrate CPAP before actually prescribing a set therapeutic level. Patients are encouraged to sleep on their backs or the less affected side. 22% (8/36) of grade 3, 10% (6/59) of grade 2 and 14% (1/7) of grade 1 were referred for formal sleep apnoea studies. Hypertension Hypertension may result from obesity and is also a common association with OSA and FES. Almost 50% of our patients were hypertensive on treatment. We
suggest a blood pressure check on all new patients and advise referral to a physician or cardiologist if systolic BP 4160 mmHg or Diastolic BP 4100 mmHg. Then, 21% were regular heavy smokers (420 cigarettes/day). We grade our patients on their combined severity of symptoms and signs. Our treatment regime is based on symptomatic relief and prevention of long-term sequelae.
DISCUSSION Ezra et al.21 recently reported their experience on the long term outcomes of patients with FES. They demonstrated that medial and lateral canthal plication and upper lid LTS compared more favourably than full thickness wedge excision21 as they demonstrated a greater long term survival outcome. In our experience, full thickness wedge excisions or modified lateral tarsal strips were performed on the upper lid and lateral tarsal strips were performed on the lower lid. In contrast to Ezra21 we found significant lower lid laxity to be present in all our patients with severe disease requiring upper lid tightening. Perhaps this could be due to our practice of reserving surgery for patients predominantly with severe disease or due to a difference in population base and racial distribution. We currently only use the modified lateral tarsal strip for all upper lid shortening as it seems to cause less postoperative morbidity like oedema and bruising. Any medial canthal tendon laxity is also addressed at the same time. Surgical lid shortening and tightening procedures include wedge excision; lateral tarsal strip and reinforcement of the tarsus with auricular conchal tarsus are often reported to be the gold standard for the long term treatment of FES with immediate relief of symptoms. Unfortunately recurrences do occur months or years later after lid tightening procedures. Surgical shortening has been shown to improve conjunctival inflammation and papillary conjunctivitis with objective evaluation by impression cytology especially for moderate-to-severe disease. Tightening of the upper lid also tends to improve relative blepharoptosis as well as lash ptosis. In our series only 12% underwent surgery. Although most reports claim a characteristic feature of FES is the resistance to topical treatment we have good short to medium term results using preservative free medication to treat the ocular surface disease combined with the treatment of the systemic disease. An important realization for the successful treatment of FES is to explore all options logically and to treat the patient and not the eye. Recurrence of symptoms Orbit
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Floppy Eyelid Syndrome even after surgery is possible as the patient continues an established sleep habit. Ezra and co-workers reported on the associations of FES. They compared patients with FES to age, sex and BMI matched controls22 and documented that there was a strong association between FES and OSA, keratoconus and lash ptosis. In our cohort only 47% of patients gave history of symptoms suggestive of a sleep disorder of which only 16 % however were referred for formal sleep studies as the rest failed to meet the referral criteria for referral to the sleep clinic. In our series 59% of our patients displayed signs of lash ptosis. Up-regulation of elastolytic enzymes such as matrix metalloproteinases 7 and 9 are thought to be stimulated by repeated mechanical stress (eg. eye rubbing and sleeping habits) can cause eyelash misdirection commonly reported.23 In our series lash ptosis predominantly seemed to be a feature of moderate or severe (F2,F3) disease. Clinically we felt that perhaps what is described as lash ptosis might be a sequelae of mild posterior lamellar shortening secondary to chronic inflammation and resultant cicatrization. It raises the question whether this could be a mild upper lid entropion. Interestingly we noted one case of CRVO in a patient who was also diagnosed with OSA. There have been a few reports on the association of retinal vein occlusion with OSA.24,25 Nocturnal hypoxaemia, hypercapnia and intrathoracic pressure changes occur in OSA. Retinal vein occlusion is postulated to be due to reduced velocity of blood flow circulation secondary to hypoxemia and elevated nocturnal intracranial pressure. In addition, the ocular perfusion pressure tends to decrease nocturnally. The reduction in ocular perfusion pressure may be a risk factor for both the single optic neuropathy case and the reported 10% of patients that presented with POAG.26 In our study we noted that only 2% of patients presented with keratoconus. This may be due to the fact that we only looked for obvious clinical signs of keratoconus on slit lamp examination and did not perform routine cornea topography, and therefore may be under diagnosing keratoconus in our cohort. One hypothesis of keratoconus occurring in FES is that the eye rubbing by patients with FES predisposes susceptible patients in developing keratoconus.11,12 In our group, both patients that presented with keratoconus only had F2 grade floppiness. An interesting observation was that F3 grades did not appear to provoke clinically detectable keratoconus. Perhaps F1 grades only irritated the inferior cornea while in F3 grades, the superior cornea and F2 the central cornea are affected. One might cautiously hypothesize that perhaps F2 grades are most likely to predispose to !
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keratoconus, as the thinnest central portion of the cornea is most vulnerable in this group of patient.
Take Home Messages In our experience if surgical intervention is required, operating on both the upper and lower lids at the same time is recommended if significant lower lid laxity is present. This will help to maintain the normal anatomical relationship between the upper and lower lids especially when epiphora is a dominant symptom. Lash ptosis is a characteristic that has been reported to be associated with FES.22,27 This has been an accepted feature, but we are still uncertain of the pathogenesis of lash ptosis in FES. An upregulation of matrix metalloproteinases due to mechanical stress of eyelid rubbing has been postulated to lead to eyelash misdirection.28 In our experience, we found that the lash ptosis was associated with posterior migration of meibomian gland orifices and clinical cicatricial changes in the tarsal conjunctiva. We felt that it was not dissimilar to a mild upper lid entropion due to posterior lamellar cicatrization. Based on our experience of FES, we have clinically graded patients according to the severity of their floppy eyelids and severity of symptoms. We propose a management algorithm based on our experience (Figure 2). We propose that a multidisciplinary approach to the management of FES is possible through our treatment algorithm. Our experience with 102 consecutive cases of FES seems to suggest early diagnosis and institution of topical treatments appear to help manage the vast majority of patients conservatively alleviating the need for early surgery. This data is particularly useful as there is no current agreed consensus for best practice in literature on the management of FES as an entity. We feel that our clinical grading of severity, the treatment algorithm and success with non-surgical conservative treatment helps to reassure ophthalmologists to persevere with this regime, reserving surgery for the more severe cases. It is important that when we examine patients with suspected FES that we should also screen for POAG, optic neuropathy and retinal vein occlusions and treat any systemic vascular perfusion problems where necessary and may refer them to our physician colleagues if in doubt.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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FIGURE 2. Management pathway based on grading of Floppy Eyelid Syndrome.
REFERENCES 1. Culbertson WW, Ostler HB. The floppy eyelid syndrome. Am J Ophthalmol 1981;92(4):568–575. 2. Paciuc M, Mier ME. A woman with the floppy eyelid syndrome. Am J Ophthalmol 1982;93(2):255–256. 3. Eiferman RA, Gossman MD, O’Neill K, Douglas CH. Floppy eyelid syndrome in a child. Am J Ophthalmol 1990; 109(3):356–357. 4. Gross RH, Mannis MJ. Floppy eyelid syndrome in a child with chronic unilateral conjunctivitis. Am J Ophthalmol 1997;124(1):109–110. 5. Nuruddin M. Management of floppy eyelid associated with Down’s Syndrome: A case report. Orbit 2012; 31(5):370–372.
6. Culbertson WW, Tseng SC. Corneal disorders in floppy eyelid syndrome. Cornea 1994;13(1):33–42. 7. Parunovic A. Floppy eyelid syndrome. Br J Ophthalmol 1983;67(4):264–266. 8. Leibovitch I, Selva D. Floppy eyelid syndrome: clinical features and the association with obstructive sleep apnea. Sleep Med 2006;7(2):117–122. 9. Netland PA, Sugrue SP, Albert DM, Shore JW. Histopathologic features of the floppy eyelid syndrome. Involvement of tarsal elastin. Ophthalmology 1994; 101(1):174–181. 10. Liu DT, Di Pascuale MA, Sawai J, et al. Tear film dynamics in floppy eyelid syndrome. Invest Ophthalmol Vis Sci 2005; 46(4):1188–1194. 11. Krachmer JH. Eye rubbing can cause keratoconus. Cornea 2004;23(6):539–540. Orbit
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Floppy Eyelid Syndrome 12. Sugar J, Macsai MS. What causes keratoconus? Cornea 2012;31(6):716–719 13. Kadyan A, Asghar J, Dowson L, Sandramouli S. Ocular findings in sleep apnoea patients using continuous positive airway pressure. Eye (Lond) 2010; 24(5):843–850. 14. McNab AA. Reversal of floppy eyelid syndrome with treatment of obstructive sleep apnoea. Clin Experiment Ophthalmol 2000;28(2):125–126. 15. McNab AA. The eye and sleep. Clin Experiment Ophthalmol 2005;33(2):117–125. 16. Karger RA, White WA, Park WC, et al. Prevalence of floppy eyelid syndrome in obstructive sleep apnea-hypopnea syndrome. Ophthalmology 2006; 113(9):1669–1674. 17. Dutton JJ. Surgical management of floppy eyelid syndrome. Am J Ophthalmol 1985;99(5):557–560. 18. Moore MB, Harrington J, McCulley JP. Floppy eyelid syndrome. Management including surgery. Ophthalmology 1986;93(2):184–188. 19. Viana GA, Sant’Anna AE, Righetti F, Osaki M. Floppy eyelid syndrome. Plast Reconstr Surg 2008; 121(5):333e–334e. 20. Karesh JW, Nirankari VS, Hameroff SB. Eyelid imbrication. An unrecognized cause of chronic ocular irritation. Ophthalmology 1993;100(6):883–889.
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21. Ezra DG, Beaconsfield M, Sira M, et al. Long-term outcomes of surgical approaches to the treatment of floppy eyelid syndrome. Ophthalmology 2010; 117(4):839–846. 22. Ezra DG, Beaconsfield M, Sira M, et al. The associations of floppy eyelid syndrome: a case control study. Ophthalmology 2010;117(4):831–838. 23. Schlotzer-Schrehardt U, Stojkovic M, HofmannRummelt C, et al. The pathogenesis of floppy eyelid syndrome: involvement of matrix metalloproteinases in elastic fiber degradation. Ophthalmology 2005; 112(4):694–704. 24. Glacet-Bernard A, Leroux les Jardins G, Lasry S, et al. Obstructive sleep apnea among patients with retinal vein occlusion. Arch Ophthalmol 2010;128(12):1533–1538. 25. Leroux les Jardins G, Glacet-Bernard A, Lasry S, et al. [Retinal vein occlusion and obstructive sleep apnea syndrome]. J Fr Ophthalmol 2009;32(6):420–424. 26. Faridi O, Park SC, Liebmann JM, Ritch R. Glaucoma and obstructive sleep apnoea syndrome. Clin Exper Ophthalmol 2012;40(4):408–419. 27. McNab AA. Floppy eyelid syndrome and obstructive sleep apnea. Ophthal Plast Reconstr Surg 1997;13(2):98–114. 28. Miyamoto C, Espirito Santo LC, Roisman L, et al. Floppy eyelid syndrome: review. Arq Bras Oftalmol 2011; 74(1):64–66.
ORIGINAL ARTICLE
Floppy Eyelid Syndrome: The Coventry Experience Aaron M. Yeung, Imran Ashfaq, Yajati K. Ghosh, Ioannis Kyprianou, and Harpreet Singh Ahluwalia
Orbit Downloaded from informahealthcare.com by University of Connecticut on 02/04/15 For personal use only.
University Hospital Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom
ABSTRACT Purpose: Floppy eyelid syndrome is a condition that is difficult to identify and diagnose and with no clear guidelines on its management. We propose a method of reliably grading this syndrome and have proposed a management algorithm based on the grading. Materials and Methods: Retrospective data collection of patients diagnosed with Floppy eyelid syndrome and treated under the care of a single oculoplastic surgeon over a 9 year period. Results: First, 102 patients were included and were classified into 3 groups. Grade 1 (F1) 7.5%, Grade 2 (F2) 36.5% and Grade 3 (F3) 56%. Only 12% of our cohort required surgery, and 92% of these patients demonstrated improvement in their symptoms. Discussion: Clinical grading of Floppy eyelid syndrome patients will help determine patient’s management plan. In our experience, operating on both upper and lower eyelids at the same time where indicated helps to maintain the normal anatomical relationship and improve epiphora. Keywords: Floppy eyelid, grading, management
INTRODUCTION
Noctural eversion over a period of time may cause mechanical insult to underlying structures including the conjunctiva that subsequently causes keratinization.1 Increased laxity of lids may cause a reduced interface between the eyelids and the surface of the epibulbar region. This in turn, disturbs the ocular surface interface leading to poor tear distribution and ultimately leading to the irritating symptoms patients complain of ref.7 A genetic predisposition with abnormalities in collagen or elastin may influence both FES and Obstructive Sleep Apnoea (OSA).8,9 Increased lid ischaemia secondary to local pressure in association with repurfusion injury during OSA may cause chronic inflammation. This may lead to water retention and damage eyelid skin leading to worsening of eyelid condition.10 Inflammation in FES could potentially cause generalised atrophy, but histological
Floppy eyelid syndrome (FES) is a condition that was initially described in males who were in the middle ages of their lives. These patients exhibited a high Body Mass Index (BMI), had evidence of papillary conjunctivitis and the unique and unusual appearance of floppy eyelids. Culbertson and Ostler1 were the first to report this condition but in more recent times, it has been associated with previously unknown variables including presenting in the female gender,2 affecting patients in other age groups3–5 and even affecting patients that have a normal weight.6 The pathogenesis of FES is still currently unclear, however, there have been numerous hypotheses that may explain this condition that is gradually becoming more recognised and more frequently diagnosed.
Received 11 September 2013; Revised 17 March 2014; Accepted 27 July 2014; Published online 25 September 2014 Correspondence: Aaron Yeung, Specialty Registrar in Ophthalmology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, United Kingdom. Tel: + 44 247 696 4000 Ext 26506. E-mail: [email protected]
399
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400 A. M. Yeung et al. studies did not detect any sign of chronic inflammation.9 Patients typically present with a chronic papillary conjunctivitis, and demonstrate an upper eyelid that may evert with little effort. In addition, the tarsus can be soft and fold upon itself. There have been other associations reported that are thought to be related to FES including local effects on the cornea and the systemic effects of obstructive sleep apnoea. In a study by Culbertson and Tseng, 71% of patients had cornea abnormalities related to FES and punctate epithelial keratitis was most common feature. It was noted to be diffuse in nature and was only found in the eye with FES.6 They also reported that 10% of the same cohort had keratoconus6 but the underlying associations are not clear. It has been commonly reported that eye rubbing is a predisposing factor in keratoconus.11,12 We feel that similarly eye rubbing in FES might predispose susceptible patients to developing keratoconus. There have been numerous reports that associate OSA and FES.13–15 They have a common factor in that a high proportion of patients have a high BMI index. A high proportion of patients with FES are reported to be affected by OSA,15,16 but interestingly the reverse is not true.16 Treatment options typically fall between conservative treatment or surgery.
Conservative Lid taping, lubrication at night, eye shields, losing weight, topical steroids, lid hygiene and punctal plugs have been recommended in the past.1,7 Failing this, numerous surgical options have been suggested,
recruited over a 9-year period between 2003–2012 and the study adhered to the principles of the Declaration of Helsinki. Data including weight, height, smoking status and visual acuity were recorded from the standard FES proforma in case notes. Patients were asked to describe their symptoms, all of which were recorded included itching, epiphora, irritation, grittiness, reduction in visual acuity, soreness of eyelids, foreign body sensation and discharge. The onset of patients symptoms were classified as acute, subacute and chronic and any diurnal variations were also noted. Acute symptoms were those less than 4 weeks, subacute were less than 3 months and chronic were more than 3 months. Past medical and ocular history were taken as well as a sleep history, which included sleeping posture, whether the patient snored and any history of sleep apnoea. All patients had their Epworth scores evaluated. A complete ophthalmic examination was performed. In particular the eyelids were examined and were graded as mild, moderate or severe in floppiness using a simple clinical grading system. Papillary conjunctivitis, blepharitis, entropian, ectropian, trichiasis, lid ptosis, lash ptosis and cornea pathology were also noted. Patients were classified into 3 groups described as mild (F1), moderate (F2) or severe (F3). Depending on their grading, patients were treated on our proposed management algorithm. We graded our patients with FES based on the amount of exposed tarsal conjunctiva (TC) observed on maximal traction on the upper lid. Grade 1 (F1) between 1/3 to ½ of the TC visible (Figure 1A). Grade 2 (F2) more than ½ of TC visible (Figure 1B). Grade 3 (F3) spontaneous upper lid eversion on minimal lid retraction or on forced lid closure (Figure 1C).
Surgery Full thickness wedge excision,9,17,18 lateral tarsal strip (LTS)3,19 and lateral canthal plication20 have been recognised as surgical options for the treatment of FES with varying results. At present there is no specific grading for floppiness of the lid. In addition, there are no clear treatment guideline pathways in the management of FES. The objective of our study was to describe our management algorithm in the management of FES based on our experience of FES.
RESULTS We identified 102 patients, 34 females and 68 males, mean age 51.7 yr (range 20–77 yr). The patients were mostly Caucasian (86%) and 14% were of Indian ethnicity, the latter disproportionately higher for the local population. Patients with increasing severity of FES were older and had a higher BMI. There was a mean follow-up of 30 months.
Presenting Symptoms MATERIALS AND METHODS We retrospectively collected the data of 102 patients with FES that were treated under the care of a single consultant oculoplastic surgeon (HA). Patients were
All patients had been referred by general practitioners or other ophthalmologists for non-resolving conjunctivitis or epiphora. Specifically 70% of our patients mainly presented with epiphora, followed by Orbit
Floppy Eyelid Syndrome
401
dysfunction in an attempt to reduce the bacterial lipolytic enzymes in meibomian gland secretions. Lash Ptosis In our series 59% of our patients displayed signs of lash ptosis. Mild lash ptosis in an asymptomatic patient requires no active treatment. In patients where the patient has no ptosis, but limitation of superior field by lash ptosis, lash curlers can be tried. Lid shortening procedures generally correct lash ptosis as well as tightening the lids. Anterior lamellar repositioning is reserved for patients with corneal touch and severe lash ptosis.
Orbit Downloaded from informahealthcare.com by University of Connecticut on 02/04/15 For personal use only.
Ocular Comorbidity Two cases had keratoconous 2%, one patient had previous central retinal vein occlusion (CRVO) (1%), one patient had thyroid eye disease (1%) and one had optic neuropathy (1%), and 10% of patients had primary open angle glaucoma (POAG). Corneal and Conjunctival Involvement
FIGURE 1. Grading of Floppy Eyelid. A: Grade 1 (F1); B: Grade 2 (F2); C: Grade 3 (F3).
irritation (44%), grittiness, itching, soreness, foreign body sensation and ocular discomfort/irritation.
Ocular Findings and Their Management
Most of the patients in our cohort had punctate epithelial keratopathy as the main corneal manifestation. This may be as a result of nocturnal exposure or secondary to topical medication toxicity. We suggest use of preservative free topical drops to preserve corneal integrity wherever possible. 72% had papillary conjunctivitis. We grade papillary conjunctivitis as mild, moderate and severe dependent on the number of papillae. The majority of patients in this study had moderate papillary conjunctivitis (65%). The severity of papillary conjunctival changes determines the use of regular topical lubricants and reserves topical steroids for treatment of more severe cases. Atopic conjunctivitis was diagnosed in 10% of cases in our series. These patients had history of atopy with giant papillary conjunctival changes. All were prescribed topical antihistamines and mast cell inhibitors with a good response.
Floppiness of Lids In all, 56% of our patients had grade F2 and 36.5% had grade F3.
Surgery
Posterior Blepharitis and Tear Dysfunction More than three quarters of cases in our series had posterior blepharitis and associated qualitative tear dysfunction. Patients were given strict instructions with demonstration of twice-daily lid hygiene with dedicated lid wipes and also given a patient information leaflet. Patients were commenced on topical lubricants in all cases with lubricant ointment at bedtime. Oral doxycycline 100 mg once daily was reserved for more severe cases of meibomian gland
Only 12% of our patients required lid shortening procedures for treatment of their symptoms in the 9-year follow-up. The median age of these patients undergoing surgery was 67 years (range 25–74 yr). The most common indication for embarking on surgery was severity of the condition and lack of or only partial response to conservative regimes. All patients underwent a shortening of their upper and lower lid. A lateral tarsal strip was used to shorten all lower lids, while we initially performed wedge excisions (middle and lateral 1/3) and since
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402 A. M. Yeung et al. 2007 modified upper lid tarsal strips for upper lid shortening. In our series all patients where upper lid surgery was planned had significant coexisting lower lid laxity. Currently upper lid modified tarsal strip is our procedure of choice for upper lid shortening. We feel that both upper and lower lids should be shortened simultaneously rather than the upper lid in isolation to avoid altering the normal relationship between the upper and lower lids. Lower lid tightening is particularly helpful where epiphora is a significant complaint and the lid is lax. Of F3 grades, 26% (9/35) of patients underwent surgery and 5% of F2 grades (3/58) had surgery. At a median follow up period of 16 months all patients had good lid position and 92% demonstrated improved symptomatology. The main symptoms that showed improvement was foreign body sensation, soreness and epiphora.
Systemic Associations Obesity and OSA 55% of our patients were obese (BMI 430), Mean BMI 33.4 ± 6.3 (range 23–49). These patients were advised to lose weight and referred to the dietician at the hospital or via their general practitioner (GP). Previous evidence suggests that losing weight improves symptoms especially in patients with OSA. Interestingly, we did not find any correlation between BMI and the severity of FES. 86% of our patients showed a positive correlation of sleep posture with the worst-affected side including bilateral cases with face on pillow position. Then, 92% of patients agreed they snored which was confirmed by their partners, and 47% of patients gave history of symptoms suggestive of a sleep disorder of which only 16%, however, were referred for formal sleep studies as the rest failed to meet the referral criteria for referral to the sleep clinic. We assess all patients for symptoms indicative of obstructive sleep apnoea such as snoring, apnoea attacks and daytime somnolence using the Epworth sleepiness scoring scale 410 before referring to the sleep centre for formal sleep studies. In our sleep clinic the respiratory physicians use a domiciliary monitoring system to confirm OSA then auto-titrate CPAP before actually prescribing a set therapeutic level. Patients are encouraged to sleep on their backs or the less affected side. 22% (8/36) of grade 3, 10% (6/59) of grade 2 and 14% (1/7) of grade 1 were referred for formal sleep apnoea studies. Hypertension Hypertension may result from obesity and is also a common association with OSA and FES. Almost 50% of our patients were hypertensive on treatment. We
suggest a blood pressure check on all new patients and advise referral to a physician or cardiologist if systolic BP 4160 mmHg or Diastolic BP 4100 mmHg. Then, 21% were regular heavy smokers (420 cigarettes/day). We grade our patients on their combined severity of symptoms and signs. Our treatment regime is based on symptomatic relief and prevention of long-term sequelae.
DISCUSSION Ezra et al.21 recently reported their experience on the long term outcomes of patients with FES. They demonstrated that medial and lateral canthal plication and upper lid LTS compared more favourably than full thickness wedge excision21 as they demonstrated a greater long term survival outcome. In our experience, full thickness wedge excisions or modified lateral tarsal strips were performed on the upper lid and lateral tarsal strips were performed on the lower lid. In contrast to Ezra21 we found significant lower lid laxity to be present in all our patients with severe disease requiring upper lid tightening. Perhaps this could be due to our practice of reserving surgery for patients predominantly with severe disease or due to a difference in population base and racial distribution. We currently only use the modified lateral tarsal strip for all upper lid shortening as it seems to cause less postoperative morbidity like oedema and bruising. Any medial canthal tendon laxity is also addressed at the same time. Surgical lid shortening and tightening procedures include wedge excision; lateral tarsal strip and reinforcement of the tarsus with auricular conchal tarsus are often reported to be the gold standard for the long term treatment of FES with immediate relief of symptoms. Unfortunately recurrences do occur months or years later after lid tightening procedures. Surgical shortening has been shown to improve conjunctival inflammation and papillary conjunctivitis with objective evaluation by impression cytology especially for moderate-to-severe disease. Tightening of the upper lid also tends to improve relative blepharoptosis as well as lash ptosis. In our series only 12% underwent surgery. Although most reports claim a characteristic feature of FES is the resistance to topical treatment we have good short to medium term results using preservative free medication to treat the ocular surface disease combined with the treatment of the systemic disease. An important realization for the successful treatment of FES is to explore all options logically and to treat the patient and not the eye. Recurrence of symptoms Orbit
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Floppy Eyelid Syndrome even after surgery is possible as the patient continues an established sleep habit. Ezra and co-workers reported on the associations of FES. They compared patients with FES to age, sex and BMI matched controls22 and documented that there was a strong association between FES and OSA, keratoconus and lash ptosis. In our cohort only 47% of patients gave history of symptoms suggestive of a sleep disorder of which only 16 % however were referred for formal sleep studies as the rest failed to meet the referral criteria for referral to the sleep clinic. In our series 59% of our patients displayed signs of lash ptosis. Up-regulation of elastolytic enzymes such as matrix metalloproteinases 7 and 9 are thought to be stimulated by repeated mechanical stress (eg. eye rubbing and sleeping habits) can cause eyelash misdirection commonly reported.23 In our series lash ptosis predominantly seemed to be a feature of moderate or severe (F2,F3) disease. Clinically we felt that perhaps what is described as lash ptosis might be a sequelae of mild posterior lamellar shortening secondary to chronic inflammation and resultant cicatrization. It raises the question whether this could be a mild upper lid entropion. Interestingly we noted one case of CRVO in a patient who was also diagnosed with OSA. There have been a few reports on the association of retinal vein occlusion with OSA.24,25 Nocturnal hypoxaemia, hypercapnia and intrathoracic pressure changes occur in OSA. Retinal vein occlusion is postulated to be due to reduced velocity of blood flow circulation secondary to hypoxemia and elevated nocturnal intracranial pressure. In addition, the ocular perfusion pressure tends to decrease nocturnally. The reduction in ocular perfusion pressure may be a risk factor for both the single optic neuropathy case and the reported 10% of patients that presented with POAG.26 In our study we noted that only 2% of patients presented with keratoconus. This may be due to the fact that we only looked for obvious clinical signs of keratoconus on slit lamp examination and did not perform routine cornea topography, and therefore may be under diagnosing keratoconus in our cohort. One hypothesis of keratoconus occurring in FES is that the eye rubbing by patients with FES predisposes susceptible patients in developing keratoconus.11,12 In our group, both patients that presented with keratoconus only had F2 grade floppiness. An interesting observation was that F3 grades did not appear to provoke clinically detectable keratoconus. Perhaps F1 grades only irritated the inferior cornea while in F3 grades, the superior cornea and F2 the central cornea are affected. One might cautiously hypothesize that perhaps F2 grades are most likely to predispose to !
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keratoconus, as the thinnest central portion of the cornea is most vulnerable in this group of patient.
Take Home Messages In our experience if surgical intervention is required, operating on both the upper and lower lids at the same time is recommended if significant lower lid laxity is present. This will help to maintain the normal anatomical relationship between the upper and lower lids especially when epiphora is a dominant symptom. Lash ptosis is a characteristic that has been reported to be associated with FES.22,27 This has been an accepted feature, but we are still uncertain of the pathogenesis of lash ptosis in FES. An upregulation of matrix metalloproteinases due to mechanical stress of eyelid rubbing has been postulated to lead to eyelash misdirection.28 In our experience, we found that the lash ptosis was associated with posterior migration of meibomian gland orifices and clinical cicatricial changes in the tarsal conjunctiva. We felt that it was not dissimilar to a mild upper lid entropion due to posterior lamellar cicatrization. Based on our experience of FES, we have clinically graded patients according to the severity of their floppy eyelids and severity of symptoms. We propose a management algorithm based on our experience (Figure 2). We propose that a multidisciplinary approach to the management of FES is possible through our treatment algorithm. Our experience with 102 consecutive cases of FES seems to suggest early diagnosis and institution of topical treatments appear to help manage the vast majority of patients conservatively alleviating the need for early surgery. This data is particularly useful as there is no current agreed consensus for best practice in literature on the management of FES as an entity. We feel that our clinical grading of severity, the treatment algorithm and success with non-surgical conservative treatment helps to reassure ophthalmologists to persevere with this regime, reserving surgery for the more severe cases. It is important that when we examine patients with suspected FES that we should also screen for POAG, optic neuropathy and retinal vein occlusions and treat any systemic vascular perfusion problems where necessary and may refer them to our physician colleagues if in doubt.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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FIGURE 2. Management pathway based on grading of Floppy Eyelid Syndrome.
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