Floppy eyelid syndrome (FES) is a disease first reported in 1981 by Culbertson and Ostler in 11 middle-aged obese men 1). It is characterized by a thin, rubbery tarsal plate of the upper eyelid that easily everts with upward traction, accompanied by chronic papillary conjunctivitis 1).
FES is defined as a combination of eyelid hyperlaxity and reactive papillary conjunctivitis 2). Eyelid hyperlaxity results from remodeling of the connective tissue inherent to the tarsal plate, and its pathophysiology differs from age-related dermatochalasis, ptosis, and blepharochalasis 2).
Similar concepts related to FES are summarized below2).
| Term | Definition |
|---|---|
| FES (typical) | Associated with obesity/OSA, papillary conjunctivitis, common in middle-aged men |
| Lax eyelid syndrome (LES) | Eyelid laxity + conjunctival reaction regardless of age, sex, or BMI |
| Lax eyelid condition | Eyelid laxity without conjunctival findings |
FES is a typical subset strongly associated with obesity and obstructive sleep apnea (OSA), accompanied by papillary conjunctivitis. Lax eyelid syndrome (LES) is a broader concept that includes eyelid laxity and conjunctival reactive changes regardless of age, sex, or BMI. Clinically, the two often overlap, and no consensus has been established.
Main complaints include foreign body sensation, tearing, dryness, mucous discharge, redness, photophobia, eyelid swelling, and decreased vision2,3). Symptoms are most severe upon waking, reflecting mechanical irritation of the cornea and conjunctiva caused by the lax eyelid flipping during sleep against a pillow1,2). The affected side tends to match the preferred sleeping side1).
This is because the relaxed upper eyelid turns over due to contact with a pillow or other object during sleep, causing direct mechanical stimulation of the cornea and conjunctiva. The fact that the preferred sleeping side matches the affected side is due to this mechanism.
The main findings on slit-lamp examination are shown in the table below.
| Finding | Characteristics |
|---|---|
| Papillary conjunctivitis | Commonly occurs in the upper tarsal conjunctiva; a defining finding of FES |
| Punctate keratopathy | Most common corneal finding; diffuse |
| Corneal scarring and neovascularization | Seen in severe cases |
| Lash ptosis | Finding associated with decreased elastin |
| MGD (Meibomian gland dysfunction) | Decreased lipid production and ductal dilation |
Papillary conjunctivitis of the upper tarsal conjunctiva is the most characteristic finding in FES1). Regarding the cornea, various complications such as superficial punctate keratitis, corneal scarring, and keratoconus have been reported2,11).
Increased tear evaporation rate, delayed tear clearance, elevated tear MMP-9, and decreased lipid content are observed2). Blepharitis and MGD are also frequently associated8,9).
The prevalence in adults is reported to be 3.8–15.8%2). The median delay in diagnosis is 17 months from the initial visit4), and many cases remain undiagnosed and progress as chronic ocular surface inflammation.
The mean age of onset is 45–55 years, but cases have also been reported in children1,2). Initially described only in males, 25–37% of cases are female2). A population-based study of 4,737 individuals aged 45–69 years reported a prevalence of 6.7% in males and 14.6% in females, with a higher frequency in women12).
Reports both supporting and refuting a positive correlation with BMI (obesity) exist2,4), and the association with smoking is negative4).
OSA is the systemic disease most strongly associated with FES.
A prospective study by Chambe et al. (127 patients) confirmed a high rate of OSA in FES patients5), and Muniesa et al. reported an independent association between FES and OSA6).
Keratoconus is the most well-known ocular complication. Since the first report in 1982, Culbertson & Tseng reported that corneal complications including keratoconus are seen in FES 11). The preferred side of keratoconus is the same as the patient’s preferred sleeping side 11), and it has been shown that abnormal increase of oxytalan fibers is common to both diseases 10). Elevated MMP-9 in tears is also observed in both FES and keratoconus 8).
Regarding the association with glaucoma, FES patients have a higher prevalence of glaucoma even after BMI adjustment 2), and FES may serve as a screening tool for glaucoma in the OSA population 2).
Other reported complications include spontaneous globe luxation 2) and blepharochalasis 2).
Obstructive sleep apnea (OSA)
Most important related disease. Up to 100% of FES patients have OSA 7).
Screening: All FES patients should undergo Epworth Sleepiness Scale assessment and OSA questionnaire. For those with a score >10 or symptoms, consider PSG (overnight polysomnography) 2).
Obesity-related systemic diseases
Associations with hypertension, ischemic heart disease, and diabetes have been reported 3,4).
Others: Cases of gastroesophageal reflux disease, asthma, chronic renal failure, hypercholesterolemia, and schizophrenia have also been described 4).
Hereditary connective tissue disorders
An association with Ehlers-Danlos syndrome (COL5A1/COL5A2 mutations) has been reported 2).
Others: FES has also been reported in pachydermoperiostosis and cutis laxa 2).
Since up to 100% of FES patients have been reported to have OSA, screening is recommended for all patients. Perform a history of snoring, daytime sleepiness, and nocturnal awakenings, and assess the Epworth Sleepiness Scale (ESS score). If the score is >10 or symptoms are suspicious, consider overnight polysomnography (PSG).
Tarsal plate changes are the core pathology of this disease. A decrease in elastin quantity (first reported by Netland et al. 1994) 9), an increase in oxytalan and elaunin fibers, and a decrease in total elastin content are observed 8,9,10). MMP-7 and MMP-9 are increased in the conjunctival epithelium, tarsal stroma, and vessel walls, and are detected even in areas without inflammation 8). Regarding collagen changes, they were initially considered normal, but Ezra et al. reported enhanced immunostaining of type I and type III collagen 10).
In the meibomian glands, decreased lipid production, ductal dilation, obstruction, and granuloma formation are seen 8,9). Fibroblasts derived from FES have high intrinsic contractility and an elevated threshold to external stress 2).
Conjunctiva shows neutrophil infiltration, goblet cell loss, keratinization, and mucin leakage 1,8).
Cornea shows decreased corneal hysteresis (CH), and reduced elastic deformability increases the risk of keratoconus and glaucoma 2).
Mechanical hypothesis (Culbertson & Ostler 1981): Physical irritation from eyelid eversion during sleep leads to inflammation and tarsal remodeling 1). Similar to tendons and ligaments, mechanical loading enhances turnover of ECM proteins and MMPs 2).
Ischemia-reperfusion hypothesis (Culbertson & Tseng 1994): Local ischemia in the lateral or prone position, along with MMP-2 elevation and oxidative stress during reperfusion, degrades connective tissue 11). In OSA, intermittent systemic hypoxia increases MMP-9 and leptin, promoting elastic fiber degradation 2,8).
Leptin hypothesis: Hyperleptinemia dose-dependently enhances MMP-9 expression and is involved in the pathology of both FES and OSA 2).
Genetic predisposition: The association of FES with Ehlers-Danlos syndrome (type V collagen abnormality) suggests a genetic background 2).
Inflammatory hypothesis: The coexistence of MGD, autoimmune diseases, and rosacea suggests involvement of inflammatory pathways, but inflammatory cell infiltration in the tarsal stroma is sparse 10).
FES is a clinical diagnosis; there are no specific laboratory markers 2). The eyelid eversion test is the most important diagnostic maneuver. The upper eyelid is pulled upward and laterally, the patient is asked to look downward, and easy eversion along with papillary conjunctivitis clinically diagnoses FES 2).
All patients undergo slit-lamp examination, intraocular pressure measurement, visual acuity testing, fluorescein staining, and tear film tests (BUT, Schirmer, InflammaDry) 2). If keratoconus is suspected, retinoscopy and corneal topography are performed 2).
Horizontal Eyelid Distraction Distance
Upper eyelid >5mm, lower eyelid >6mm is considered laxity 2).
Fox et al. grading: <6mm=Grade0 / 6-8mm=Grade1 / 9-11mm=Grade2 / 12-15mm=Grade3 / >15mm=Grade4 2).
Vertical Eyelid Lift Distance
A difference between resting position and maximum lift of 15–25mm strongly suggests FES (McNab) 7).
Sredkova reported a cutoff of >11mm 2).
In anterior eyelid distraction comparison, symptomatic eyes averaged 17.09mm versus 11.72mm in asymptomatic eyes, a significant difference 2).
| Classification (Source) | Grade 0 | Grade 1 | Grade 2 | Grade 3 |
|---|---|---|---|---|
| Chambe et al.5) | Normal | Asymptomatic upper eyelid laxity | Papillary conjunctivitis + laxity | Grade 2 + eversion on horizontal traction |
| Upper eyelid elevation method2) | Conjunctiva not exposed | Less than 1/3 of conjunctiva exposed (mild) | 1/3 to 1/2 exposed (moderate) | More than 1/2 exposed (severe) |
FES is a clinical diagnosis without specific markers. The basic steps are the upper eyelid eversion test and confirmation of papillary conjunctivitis, with a horizontal traction distance >5 mm indicating laxity. Slit-lamp examination, fluorescein staining, and tear film tests are performed in all cases. Additionally, the Epworth Sleepiness Scale is used to assess OSA, and if the score is >10, PSG is considered.
Diseases that are clinically easily confused with FES are shown in the table below.
| Disease | Difference from FES |
|---|---|
| Dermatochalasis | Laxity of the skin; the tarsal plate itself is normal. No laxity on eyelid eversion test. |
| Ptosis | Primarily decreased MRD1 due to levator aponeurosis disorder. Tarsal plate flexibility is preserved. |
| Blepharochalasis | Onset in youth. History of recurrent eyelid edema, leading to secondary laxity. |
| Superior limbic keratoconjunctivitis (SLK) | Fluorescein staining positive in the superior limbus. No eyelid laxity. |
| Allergic conjunctivitis | Papillary changes present. Differentiate with detailed history (seasonal/allergen) and eversion test. |
Dermatochalasis is laxity of the skin with a normal tarsal plate, so it can be easily differentiated by the eyelid eversion test. Ptosis primarily involves decreased MRD1 and levator aponeurosis abnormality, which is pathophysiologically different from the papillary conjunctivitis and tarsal laxity of FES.
Conservative therapy is the first-line treatment for FES and is performed using a combination of the following methods1,2).
When FES is complicated by OSA, CPAP (continuous positive airway pressure therapy) is also effective for FES symptoms 2,15). Case reports have documented complete remission of ocular symptoms and findings after 4 days to 4 years of CPAP use 2).
In a prospective study by Acar et al. (2014), 18 months of CPAP in patients with moderate to severe OSA resulted in statistically significant improvements in FES grade, OSDI, BUT, Schirmer values, and corneal fluorescein staining 15). However, dry eye symptoms may temporarily worsen at the start of CPAP, so patients should be informed 15).
McNab reported that a combination of CPAP and uvulopalatopharyngoplasty improved papillary conjunctivitis and eyelid laxity in FES 7). Eye irritation due to air leakage around the mask occurs in 21% (14/67 cases) of CPAP users, so checking mask fit is important 2).
The effects of other OSA treatments (mandibular advancement device, bariatric surgery, upper airway stimulation, uvulopalatal surgery) on FES have not yet been established 2).
Surgery is indicated for cases that do not respond to conservative treatment and CPAP therapy 2).
This procedure involves creating a tarsal strip from the posterior lamella after lateral canthotomy and suturing it to the periosteum (± periosteal flap) of the lateral orbital rim 2). Burkat & Lemke (2005) performed LTS on 70 non-OSA FES patients (all 4 eyelids) and reported symptom improvement in 91% and long-term fixation stability in 97.5% 13). The scar is hidden in the lateral canthal crease, providing good cosmesis 2).
This procedure involves placing a vertical incision in the lateral third of the eyelid, performing a pentagonal full-thickness excision, and then closing in layers 2). Improvement in goblet cell count and cell morphology by impression cytology was confirmed in 91% (20/22 cases) 2), and secondary improvement in ptosis (mean MRD increase of 1.3 mm) has also been reported 2). However, there is a risk of vertical scarring, and modifications are needed for defects larger than 3 mm 2).
In a long-term follow-up of 101 cases by Ezra et al. (2010), the overall mean recurrence rate for surgery was 44% 14). LTS and medial/lateral canthal plication had significantly better long-term survival rates compared to FTWE 14), and FTWE is currently not recommended due to high recurrence rates (25.6–60.6%) 14).
| Procedure | Advantages | Disadvantages | Notes |
|---|---|---|---|
| LTS | Cosmetic scar, 97.5% long-term fixation stability 13) | Limited to lateral canthal surgery | Periosteal flap facilitates suturing |
| FTWE | Goblet cell improvement, secondary ptosis improvement | High recurrence rate, vertical scar | Not recommended by Ezra et al. 14) |
| Medial/lateral canthal plication | Long-term outcomes comparable to LTS14) | Risk of lacrimal canaliculus injury | Can be combined with LTS |
| Medial wedge excision | Effective in cases with predominant medial laxity | Cosmetic scar somewhat poor | No recurrence reported at 18 months |
Other reported techniques include tarsal reinforcement using autologous auricular cartilage graft and modified FTWE (wingtip flap method, Periman & Sires method)2).
The lateral tarsal strip (LTS) procedure has the highest long-term stability, with 91% symptom improvement and 97.5% long-term fixation stability reported. Full-thickness wedge excision (FTWE) has a high recurrence rate of 25.6–60.6%, and based on long-term outcome data from Ezra et al., it is currently not recommended. LTS should be considered as the first choice when conservative therapy or CPAP therapy is ineffective.
Some cases improve with conservative therapy, but tarsal laxity itself is an irreversible change, leading to a chronic course2). Postoperative recurrence rates are reported as 25.6–60.6% depending on the procedure (highest for FTWE), and long-term follow-up is necessary14).
OSA treatment (especially long-term CPAP) can improve FES findings, but note that there may be temporary worsening in the early phase of CPAP initiation15). Regular screening for keratoconus and glaucoma is important2), and in untreated OSA cases, systemic management considering increased cardiovascular risk is required2).
The main checkpoints during follow-up are shown below.
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Hashemi H, Rastad H, Emamian MH, Fotouhi A. Floppy eyelid syndrome and its determinants in Iranian adults: a population-based study. Eye Contact Lens. 2017;43(6):406-410. doi:10.1097/ICL.0000000000000297. PMID: 27415581.
Burkat CN, Lemke BN. Acquired lax eyelid syndrome: an unrecognized cause of the chronically irritated eye. Ophthalmic Plast Reconstr Surg. 2005;21(1):52-58. doi:10.1097/01.IOP.0000150257.12345.4C. PMID: 15677948.
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