Exposure keratopathy (EK) is a general term for diseases in which the cornea is exposed to the external environment for a prolonged period due to incomplete eyelid closure or impaired blinking, resulting in tear film disruption and corneal epithelial damage. It is also called lagophthalmic keratitis.
The core pathology of this disease is lagophthalmos. Lagophthalmos refers to a condition in which blinking or eyelid closure is incomplete, leaving the eyeball exposed. When this condition persists, the cornea and conjunctiva become dry, starting with punctate epithelial damage and progressing to vascular invasion, keratinization, and even corneal infiltration and ulceration.
The underlying diseases are diverse. Typical examples include facial nerve palsy (Bell’s palsy, post-cerebrovascular accident, post-acoustic neuroma surgery, etc.), myasthenia gravis, thyroid eye disease, trauma, orbital tumors, and overcorrection after levator resection. It can occur in neurological, metabolic, or post-surgical conditions—essentially the consequence of any situation where eyelid closure fails.
Normal ocular surface homeostasis is maintained by lubrication and nutrient supply from the tear film (lipid layer, aqueous layer, mucin layer), redistribution of tears by blinking, and complete eyelid closure during sleep7). If any part of this system fails, the tight junctions of the corneal epithelium are damaged, allowing easy entry of microorganisms and foreign bodies, and the corneal epithelial barrier breaks down.
A systematic review and meta-analysis (23 studies, 3,519 patients) of ICU patients reported a pooled prevalence of EK of 34.0% and a pooled incidence of 23.0% 1). Although it is a complication often overlooked in critical care, it is a condition frequently encountered even in non-ophthalmology departments. While it is often reversible if recognized early and protective interventions are initiated, prolonged corneal epithelial defects can lead to bacterial infection, significantly worsening visual prognosis. Therefore, management of this disease focuses more on “pre-onset risk assessment and prevention” than on “treatment after onset.”
Notably, in cases with trigeminal nerve palsy, patients may not complain of pain even with severe epithelial defects due to reduced corneal sensation. In patients after neurosurgery with combined facial nerve palsy and trigeminal nerve dysfunction, the cornea may deteriorate rapidly with few subjective symptoms, making objective slit-lamp examination essential.
When caused by nocturnal lagophthalmos, symptoms worsen in the morning and gradually improve during the day, showing a characteristic diurnal variation.
The initial finding is superficial punctate keratitis (SPK) in the inferior cornea. It is detected as punctate epithelial defects localized to the lower one-third of the cornea on fluorescein staining. Corneal epithelial damage due to incomplete eyelid closure is compartmentalized inferiorly, with almost no epithelial damage above a certain level. Conversely, when compartmentalized corneal epithelial damage limited to the lower part is observed, incomplete eyelid closure or nocturnal lagophthalmos should be strongly suspected.
As it progresses, the following findings are observed.
External findings include assessment of incomplete blinking, degree of lagophthalmos itself, proptosis, and eyelid deformity or malposition. The presence or absence of Bell’s phenomenon (upward rotation of the eye during eyelid closure) is important for prognosis. In cases where Bell’s phenomenon is preserved, corneal damage often remains mild even with severe incomplete eyelid closure.
In lagophthalmos due to facial nerve palsy, findings of general facial muscle paralysis such as ipsilateral eyebrow drooping, lower eyelid ectropion (scleral show), disappearance of the nasolabial fold, and drooping of the mouth corner are present. In supranuclear cases, contralateral hemiplegia is associated; in pontine lesions (Foville syndrome, Millard-Gubler syndrome), abducens nerve palsy and contralateral pyramidal tract symptoms are combined.
Mild nocturnal lagophthalmos is difficult for the patient to confirm. If there is unexplained inferior punctate superficial keratopathy, it is useful to have family members record the eyelid closure status at night with a smartphone or similar device. Observation not only in the sitting position but also in the supine position is important. If punctate corneal epithelial damage localized to the inferior area persists, the presence of nocturnal lagophthalmos should be strongly suspected.
The causes of EK include all conditions that prevent eyelid closure. Lagophthalmos is broadly classified into the following four types by cause.
Paralytic Lagophthalmos
Caused by facial nerve (cranial nerve VII) palsy: Bell’s palsy (reactivation of herpes simplex virus) is the most common. It can also occur due to cerebrovascular disease, after acoustic neuroma surgery, or trauma. Weakened contraction of the orbicularis oculi muscle leads to lower eyelid ptosis/ectropion, eyebrow drooping, and drooping of the mouth corner. Supranuclear cases are associated with contralateral hemiplegia.
Cicatricial Lagophthalmos
Caused by scar contracture after trauma or surgery: Occurs after blepharoplasty (reported incidence of 47%), facial burns, and chemical burns. The scar opposes the contraction of the orbicularis oculi muscle.
Mechanical Lagophthalmos
Incomplete eyelid closure due to proptosis: Typical in thyroid eye disease (Graves’ disease). Also occurs with orbital tumors, craniosynostosis, and high myopia. Exposure worsens when combined with upper eyelid retraction.
Physiological Lagophthalmos
Incomplete eyelid closure without organic abnormality: Includes incomplete closure during nighttime sleep. Reported in up to 23% of the general population and is a major cause of morning eye pain.
The motor nucleus of the facial nerve is located in the pons, and different neurological syndromes arise depending on the site of the lesion. Although orbicularis oculi dysfunction is common, associated findings help localize the lesion.
In critically ill ICU patients, the risk of EK is more than ten times higher than in general outpatient settings. A systematic review identified the following factors as significant risks1).
| Risk Factor | Odds Ratio |
|---|---|
| Lagophthalmos | 9.62 |
| Conjunctival edema | 3.89 |
| Blink rate ≤5/min | 12.07 |
Mechanical ventilation (OR 25.85), sedation (OR 11.36), low GCS score, and high APACHE II score are also significant risk factors 1). Sedatives and neuromuscular blocking agents impair both the blink reflex and Bell’s phenomenon 7). Increased venous pressure from positive pressure ventilation causes secondary conjunctival edema, worsening lagophthalmos. High-flow oxygen therapy directly dries the corneal surface, and combined with air conditioning drafts and low humidity, accelerates tear evaporation.
Diagnosis of EK is based on history and clinical findings. Special tests are not required, but systematic evaluation of eyelid closure, corneal sensation, and tear film is important.
History taking: Obtain detailed information on surgical history (blepharoplasty, neurosurgery, levator resection), comorbidities (thyroid disease, diabetes, facial nerve palsy, myasthenia gravis, Parkinson’s disease), medications (sedatives, muscle relaxants), trauma history, and sleep environment. Morning eye pain strongly suggests nocturnal lagophthalmos.
Eyelid closure assessment: It is most important to check for involuntary incomplete blinking during the examination. Observe not only in the sitting position but also in the supine position. Record the width (mm) of the residual palpebral fissure when instructed to close the eyes, both with gentle and forced closure. Since nocturnal lagophthalmos cannot be detected in the clinic, having family members record it with a mobile device is useful.
Slit-lamp examination and staining pattern evaluation: Evaluate punctate keratopathy in the lower cornea with fluorescein staining 5). Rose bengal and lissamine green are also useful for detecting epithelial damage. A compartmental staining pattern limited to the lower third of the cornea strongly suggests lagophthalmos, and the absence of staining in the upper cornea is diagnostically valuable.
Six items to observe: In daily practice, systematically check the following: presence of filamentary keratitis, meibomian gland status, degree of eyelid closure and opening, tear volume (BUT, tear meniscus), corneal sensation, and eye movements (especially resting position). Missing these may lead to overlooking the cause.
Corneal sensation test: Evaluate with a Cochet-Bonnet aesthesiometer before instilling topical anesthetics. A value less than 40 mm indicates reduced sensation. This is essential for differentiating from neurotrophic keratopathy (due to trigeminal nerve disorder). In lagophthalmos with preserved sensation, pain is perceived, so clinical symptoms and findings are consistent; in cases with reduced sensation, the condition progresses asymptomatically, requiring stricter objective evaluation and intervention.
Tear film tests: Measure Schirmer test and tear break-up time (BUT). The presence of dry eye affects treatment strategy.
Bell’s phenomenon assessment: Evaluate the presence of upward eye rotation during eyelid closure. If Bell’s phenomenon is preserved, even severe incomplete closure may reduce exposure of the lower cornea.
Imaging for underlying disease: In paralytic or mechanical lagophthalmos, perform intracranial and orbital imaging (head MRI, orbital CT). Be careful not to miss acoustic neuroma, cerebrovascular disease, or compressive optic neuropathy (CON) due to thyroid eye disease.
It is evaluated by the width (mm) of the residual palpebral fissure when the patient is instructed to close the eyes. There are grades ranging from mild (1 mm or less) to severe (several mm or more). It is important to confirm in both sitting and supine positions. Lagophthalmos during sleep cannot be detected by examination while awake, so observation or photography by family members is useful. If fluorescein staining reveals localized epithelial damage in the lower part, it strongly suggests incomplete eyelid closure.
The principle of treatment is to treat the underlying disease, and in the meantime, corneal protection is performed stepwise. Options range from pharmacotherapy to surgical intervention, selected according to severity and prognosis.
Taping is a non-invasive, though not covered by insurance, conservative method effective for mild to moderate lagophthalmos. The direction of traction is critically important, and the following two methods are used according to the purpose.
The key point is to “pull the lower eyelid outward/upward or inward/upward so that the eyelid margin contacts the ocular surface tightly.” A force to close the palpebral fissure horizontally is necessary; simple vertical taping is ineffective because the force is not transmitted at the fissure. Recently, tape-splint tarsorrhaphy (TST) has been reported as a non-invasive alternative, but recurrence due to poor compliance is common 2).
Moisture goggles maintain a moist environment around the eyes and suppress tear evaporation. They are useful in air-conditioned environments and during sleep. They also provide physical protection from wind and dust when going out.
In ICU patients, eye care is often overlooked, and routine intervention protocols are necessary. The Simple Eye Band (SEB) is a non-adhesive, non-invasive device made of cotton gauze, with Velcro fixation that allows easy removal for eye drops and examinations. Case reports have shown healing of epithelial defects within 3 to 6 days 5). In sedated patients, a combination of artificial tears every few hours, eye ointment before sleep, and secure eyelid closure (tape or SEB) is used.
Tarsorrhaphy: Suturing the upper and lower tarsal plates to physically reduce the exposed corneal area 7). Using a silicone band for dissection and 5-0 Dacron sutures, the upper and lower tarsal plates are sewn together. If the ends of the sutures are tied in a bow knot and made visible on the face, removal is easy when necessary. It can be temporary (absorbable sutures) or permanent (suturing after eyelid margin incision). Reliable eyelid closure is achieved, but long-term placement carries a risk of skin infection. It is an established procedure for conditions with ocular surface disorders such as neurotrophic keratopathy, lagophthalmos, and Stevens–Johnson syndrome.
Botulinum toxin injection: Injection of botulinum toxin near the levator palpebrae superioris muscle induces temporary chemical ptosis lasting about 3 months. It is used to protect against persistent corneal epithelial defects.
Upper eyelid weight implantation (gold plate method): A metal weight is placed under the skin of the upper eyelid to assist passive eyelid closure by gravity. It is widely used for paralytic lagophthalmos due to facial nerve palsy. Traditionally, gold weights have been used, but recent reports suggest that platinum chains are denser, thinner, have a lower extrusion rate, and offer better cosmesis 7).
Lateral tarsal strip procedure: For lower eyelid laxity and ectropion, the lateral canthal tendon is shortened and re-fixed to restore contact between the cornea and the lower eyelid margin. It is a standard procedure for paralytic and involutional ectropion and also contributes to tear film maintenance.
Levator palpebrae superioris lengthening or disinsertion: Performed for lagophthalmos due to upper eyelid retraction. Indications include cases of thyroid eye disease and overcorrection after ptosis surgery. The upper eyelid is lowered to allow closure.
Kuhnt-Szymanowski procedure and medial canthoplasty: May be chosen by plastic surgeons for mild cases.
Temporalis muscle transfer: Dynamic reconstruction with muscle transfer for severe facial nerve palsy. Aims for long-term restoration of eyelid closure function.
Upper eyelid lipofilling (autologous fat injection): As a novel technique for unilateral facial paralysis, autologous fat injection into the upper eyelid has been reported to provide weight and assist eyelid closure. Compared to weight insertion, the risk of migration is lower and cosmetic outcomes are superior7).
Scleral contact lenses: For chronic lagophthalmos resistant to conventional treatment, the cornea is covered and protected by a tear reservoir7). In patients who have lost the eyelids due to severe chemical burns, scleral lens wear has been reported to achieve visual acuity of 20/20 and resolution of epithelial erosion4). They are also useful for protecting corneal grafts after transplantation in chronic lagophthalmos, and cases have achieved corrected visual acuity of 1.0 with mini-scleral lenses3). PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem) is a representative device.
Approximately one in three critically ill ICU patients develops exposure keratopathy. Under sedation or mechanical ventilation, the blink reflex is suppressed, so regular eye evaluation and moisturizing care are necessary. We recommend asking the attending physician or nurse about the frequency of moisturizing care with artificial tears or eye ointment, and how often eyelid closure status is checked.
The pathophysiology of exposure keratopathy is a process in which impairment of eyelid closure, disruption of the tear film, and corneal epithelial damage progress in a chain.
Normal eyelid movement is controlled by three muscles and three neural systems.
The nucleus of the facial nerve that innervates the orbicularis oculi muscle is located in the pons. Therefore, brainstem lesions at the pontine level (Foville syndrome, Millard-Gubler syndrome) may combine lagophthalmos with abducens nerve palsy and pyramidal tract symptoms. Peripherally, the facial nerve takes a long, tortuous course, making it susceptible to paralysis from viral infection (Bell’s palsy), trauma, tumor, or surgery (acoustic neuroma resection).
The tear film consists of three layers from the outside: the lipid layer (from meibomian glands), the aqueous layer (from main and accessory lacrimal glands), and the mucin layer (from conjunctival goblet cells and epithelial cells). The lipid layer prevents tear evaporation, the aqueous layer provides nutrition, oxygen supply, and antibacterial defense, and the mucin layer maintains tear adhesion to the corneal epithelium.
Normal tear distribution requires the blink reflex, appropriate blink rate, and complete eyelid closure during sleep and blinking 7). Incomplete eyelid closure fundamentally disrupts this system.
When the tear film is locally disrupted due to corneal exposure, the following cascade occurs:
Damage is concentrated in the lower cornea because the lower cornea is most exposed when the eye is open, and in cases where Bell’s phenomenon is not preserved, the lower cornea remains exposed even during attempted eyelid closure.
When facial nerve palsy is combined with trigeminal nerve disorder, patients do not complain of pain due to reduced sensation, and the condition becomes more severe. After neurosurgical procedures such as acoustic neuroma surgery or trigeminal nerve microvascular decompression, both the facial and trigeminal nerves may be affected, leading to a combination of exposure due to incomplete eyelid closure and delayed wound healing due to reduced corneal sensation. In such cases, the condition becomes refractory, also involving the pathophysiology of neurotrophic keratopathy.
In ICU patients, multiple mechanisms act simultaneously 1). Sedatives and neuromuscular blocking agents relax the orbicularis oculi muscle, causing lagophthalmos. At the same time, the blink reflex and Bell’s phenomenon are also impaired. Positive pressure ventilation impedes venous return and leads to conjunctival edema. High-flow oxygen therapy directly dries the corneal surface. The overlap of these factors explains the high prevalence of EK in ICU patients 1). Additionally, due to reduced alertness, subjective symptoms are lost, so abnormalities can only be detected objectively.
A high prevalence of EK (34%) in ICU patients has been confirmed by a large-scale meta-analysis 1), highlighting the importance of developing eye care protocols. Risk factors such as mechanical ventilation (OR 25.85) and sedation (OR 11.36) have been identified 1), and standardizing preventive interventions for high-risk patients is a future challenge. Internationally, efforts are underway to incorporate the timing of ophthalmological evaluation and the frequency of artificial tear administration into nursing guidelines.
Non-invasive eye protection devices such as the Simple Eye Band (SEB) have been reported 5). Compared to conventional taping or surgical tarsorrhaphy, they have the advantage of no skin damage from adhesives and allow easy repeated eye drops and examinations. New-generation nighttime lid seals like SleepTite/SleepRite are also being introduced clinically.
As a novel surgical technique replacing conventional gold plate insertion, autologous fat injection into the upper eyelid to assist eyelid closure has been reported 7). Studies in patients with unilateral facial palsy have shown immediate improvement in corneal discomfort and good cosmetic and functional outcomes, with the advantage of avoiding the risks of migration and extrusion specific to weight insertion.
Scleral contact lenses are gaining attention as a treatment that can achieve both corneal protection and visual improvement in chronic lagophthalmos refractory to conventional therapy 3)4). Including the PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem) device, expansion of indications and accumulation of long-term outcomes are ongoing 7).
For thyroid eye disease, the leading cause of mechanical lagophthalmos, the anti-IGF-1R antibody teprotumumab has been approved in Europe and the United States. It has been reported to improve proptosis, diplopia, and visual function, as well as reduce tear deficiency and ocular surface damage 7). Since controlling the underlying disease reduces lagophthalmos itself, this treatment is also noteworthy from the perspective of preventing exposure keratopathy. In cases with marked eyelid retraction or lid lag, a stepwise combination of orbital decompression, eyelid lengthening, and lateral tarsorrhaphy is considered to reduce the area of corneal exposure.
