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C-51834

LASIK and dry eye syndrome

This article discusses the presentation and management of dry eye following refractive error treatment with LASIK.

Introduction

The most common type of laser surgery for the correction of refractive error is laser-assisted in situ keratomileusis (LASIK).1,2 Dry eye is a significant and common complication following LASIK. Dry eye is a complex multifactorial disease characterised by ocular discomfort, which can significantly impact upon a patient’s quality of life and level of post-operative satisfaction.3,4 This article will discuss the management of dry eye complications following LASIK.

Ocular anatomy and tear secretion

The tear film is described as a multilayer film that protects, lubricates and provides essential nutrition to the cornea by coating the ocular surface.5 The lacrimal gland, situated in the superior-temporal region of each orbit is the major source of tear fluid and tear proteins.6 The meibomian glands are positioned within the eyelids and secrete a mixture of lipids and proteins providing a barrier to prevent the evaporation of tear fluid from the ocular surface.7–9 The base layer of the tear film is the mucous layer. It supports the overlying tear fluid and helps maintain a moist ocular surface and is secreted by corneal and conjunctival goblet cells.10 The production and secretion of tears from both the lacrimal gland and the meibomian glands is regulated by the nervous system which allows adjustment of secretion dependent upon the daily demands of the ocular surface.11 

The cornea is the most densely innervated tissue in the human body.12,13 Nerve bundles are distributed uniformly around the circumference of the cornea; they enter the stroma radially from all directions and progress anteriorly through Bowman’s membrane to provide a dense plexus of nerves beneath the basal epithelial layer of the cornea.13,14 Potentially damaging stimuli such as thermal, mechanical and chemical factors are detected by corneal polymodal nociceptors and mechanoreceptors.15,16 Innervation of these primary afferent neurons evokes increases in both aqueous and mucin secretion to protect the ocular surface from damage.16

Dry eye syndrome, a disease that is reported to affect over 30% of the population over 50 years of age, can be the result of an altered or inadequate tear film and it is thought to be associated with poor regulation of tear production via these sensory neurons in the tear reflex arc.16,17 Ocular surgery, particularly laser refractive surgery, can negatively affect the ocular surface and tear film dynamics resulting in dry eye syndrome.18,19

LASIK procedure

LASIK requires a two-step surgical process. Firstly, there is the creation of a corneal flap, either by mechanical microkeratome or femtosecond laser. The flap is then lifted to allow access to the corneal stroma. Laser ablation of the corneal stroma beneath the flap alters the curvature and thickness of the stroma resulting in an alteration to the refractive power of the cornea.1,20 

During flap creation, approximately 37% of the main stromal nerve fibre bundles are damaged or severed. This results in only those nerve fibres sited at the intact flap hinge still being able to reach the central cornea.13,21 This denervation of the cornea during refractive surgery is the cause of a decrease in corneal sensitivity following the procedure. As a result it is thought to be the primary cause for reported dry eye symptoms post-operatively (see Figure 1: Dry eye stained with Rose Bengal. Image courtesy of Allon Barsam).21,22

Figure 1

Post-operative dry eye

Post-LASIK corneal sensitivity can be decreased for over six months,23 and the sub-basal nerve fibre density can still be half that of pre-operative levels at 12 months post-operatively.24

The central corneal sub-basal nerve fibre recovery following both LASIK and photorefractive keratectomy (PRK) has been compared over a five-year period. It has been found that recovery is much slower in LASIK than in PRK patients, taking five years and two years to return to pre-operative levels, respectively. This slower recovery may be attributed to a more severe level of denervation following LASIK compared with PRK. However, it should be noted that normal corneal clarity and good vision following laser surgery is not related to sub-basal nerve fibre density.25

Corneal sensitivity and dry eye symptoms following mechanical microkeratome and femtosecond laser microkeratome LASIK have been investigated. The thinner and more planar-shaped corneal flap created by the femtosecond method is thought to reduce damage to the corneal nerves compared with the mechanical microkeratome method. However, corneal sensitivity reduction occurs with both methods of flap creation. Tear break-up time is typically higher in patients that have undergone flap creation with femtosecond laser compared to mechanical microkeratome.26 

While nerve bundles radially enter the corneal stroma around its entire circumference, corneal modelling suggests that long ciliary nerves enter the cornea nasally and temporally. The effect of corneal flap hinge location on corneal sensitivity and dry eye symptoms following LASIK has been investigated using meta-analysis. It is reported that a horizontal hinge location results in less initial sensory disturbance of the cornea which results in fewer dry eye symptoms reported by patients early on. 

Despite this initial difference, at six months post-operatively there was no significant difference between the impact of corneal flap hinge locations on corneal sensitivity or dry eye symptoms.27 There is now clear evidence demonstrating that corneal sensitivity decreases following LASIK and is believed to cause post-operative dry eye symptoms by interrupting the tear reflex arc and, therefore, reducing lacrimal gland secretion.21,28 The high incidence of patients reporting dry eye symptoms following LASIK is thought to be due to a decrease in tear production while the tear film stability remains constant.29 Dry eye symptoms affect 50% of patients one week post-operatively following LASIK. This figure then decreases by 10% at one month following the procedure. At the six-month post-operative stage, between 20-40% of LASIK patients still report dry eye symptoms.30,31

It is not only the nerve fibre bundles that are damaged during LASIK. Goblet cell density has also been found to decrease following the procedure.47 In order to maintain a healthy and wet ocular surface mucin is secreted from goblet cells in the corneal epithelium and the conjunctiva.48 Not only does mucin lubricate the ocular surface during ocular movements, such as blinking, but it is also believed to significantly contribute to tear film stability.49,50 

Research has found that patients with dry eye disease have a significant reduction in goblet cell density when compared with normal, healthy eyes.51 It is believed that an unstable tear film can be attributed to alterations in goblet cell secretion.49 

During LASIK a suction ring is applied to the peripheral conjunctiva, which provides a vacuum on the anterior surface of the eye. It enables a smooth and steady environment for which to create the flap.52 The loss of goblet cell density following LASIK is attributed to this procedure.47,52,53

A significant decrease in goblet cell density following LASIK has been found and that it can take between six to nine months for pre-operative levels to return.53

No difference in the reduction of goblet cell density has been found when comparing femtosecond laser and mechanical microkeratome surgical methods.52

Treatment of dry eye

Dry eye symptoms following laser refractive surgery vary from patient to patient, and the severity of these symptoms can have a significant effect on post-operative level of satisfaction and quality of life.32 Reduced tear break-up time can decrease visual acuity and cause ocular discomfort.33 Following LASIK, the topical administration of artificial tears can reduce dry eye symptoms. The use of 3% Diquafosol tetrasodium (DQS) ophthalmic solution has been gaining interest as an effective post-LASIK topical method of treatment for dry eye disease.35 DQS stimulates mucin and tear fluid production by acting as a P2Y2 receptor agonist.36,37 The use of DQS in the treatment of dry eye disease following LASIK has been found to stabilise the tear film by restoring both mucin and tear fluid levels within the tear film.38 Use of DQS over a six-month period can significantly increase tear break-up time and reduce patient reported symptoms of ocular irritation associated with dry eye disease.39 Additionally, 3% DQS ophthalmic solution can increase tear meniscus height for up to 30 minutes in normal human eyes.40 Sodium hyaluronate, which is found in ocular tissues such as the lacrimal gland, cornea and conjunctiva, as well as in the tear film itself, has high levels of water retention, anti-inflammatory and wound healing properties, and as such can be beneficial in the treatment of aqueous deficient dry eye.41 The action of binding with water and resisting evaporation gives sodium hyaluronate a higher level of fluid retention when compared with carboxymethyl cellulose and hydroxypropyl methylcellulose.42,43 The recovery time to normal tear fluid levels following refractive surgery has also been found to improve if patients are treated pre-operatively with artificial tears containing sodium hyaluronate when compared with patients not receiving any pre-operative treatment.44

Further advancement of these ophthalmic solutions, resulting in a combination treatment of both sodium hyaluronate and DQS, has been found to increase tear secretion, reduce dry eye symptoms and stabilise vision following LASIK when compared with topical treatment of each ophthalmic solution individually.45 For dry eye patients using sodium hyaluronate, but still reporting dry eye symptoms, the addition of DQS can improve both objective and subjective results by enhancing tear fluid secretion and increasing retention of tear fluid on the ocular surface.46

Figure 2

Effect of nerve growth factor

Nerve growth factor (NGF) is a soluble protein released by corneal and conjunctival cells and secreted basally by the lacrimal gland.54,55 It is a signalling molecule that plays a major role in the healing of corneal wounds, heightening corneal sensitivity and maintenance of tear film homeostasis.54,56,57 There have been numerous studies investigating NGF levels concerning a variety of ocular surface diseases. NGF has been found to increase proliferation of corneal epithelial cells, advance corneal nerve regeneration and has an increased concentration in the tear film of patients with dry eyes.58,59 A direct correlation between NGF tear film levels and the degree of corneal damage in patients with dry eye disease has been found. 59 NGF has also demonstrated effective healing properties in patients with persistent epithelial defects and neurotrophic corneal ulcers.60–62 It is now believed that NGF also improves the recovery of corneal sensitivity after surgery.56,58 In PRK and LASIK, the pre-operative tear film NGF concentrations have been recorded as being lower than the post-operative levels – LASIK eyes had lower NGF levels, corneal sensitivity and greater ocular surface dryness than PRK eyes post-operatively.63 Topically administered NGF has been found to decrease corneal healing times following refractive surgery resulting in a more rapid recovery of corneal sensitivity with no ocular or systemic side effects being found.54,57,60,64

Conclusion

LASIK is the most common form of laser refractive surgery,1,2 and the majority of patients who undergo the procedure will experience some degree of dry eye symptoms post-operatively.3,4 This is largely due to stromal nerve fibre bundles being severed during flap creation and further nerve fibre damage as a result of the laser ablation.13,21 The denervation of the cornea during the procedure is the cause for the post-operative decrease in corneal sensitivity and results in the disruption to the tear reflex arc.17,21,22 During recovery, a decrease in lacrimal gland secretion results in dry eye symptoms for the patient.29 These dry eye symptoms are compounded further by the loss of goblet cells thought to be a result of damage caused by the suction ring during flap creation.47 Reduced mucin secretion destabilises the tear film further enhancing the symptoms of dry eye.49

Management of dry eye post-LASIK is typically performed with the use of artificial tears.34 Advancements in our understanding of both the tear film and ocular surface hydration has resulted in the development of new solutions designed to provide a stable tear film after surgery. An increasing knowledge of the soluble nerve growth factor protein is also assisting developments in topical treatments aimed to improve recovery following refractive surgery by reducing corneal healing times and returning corneal sensitivity to pre-operative levels at a faster rate.54,57,60,64

Many patients consider that the benefits of reduced refractive error following LASIK outweigh the potential complications. However, severe and prolonged dry eye syndrome can have a significant impact upon quality of life and level of post-operative satisfaction.2 It is paramount that careful screening of potential dry eye patients is conducted pre-operatively with a thorough battery of tear film tests and use of dry eye questionnaires. Patients deemed at risk of dry eye post-LASIK should be advised of the seriousness of symptoms, and higher risk patients should potentially not be treated.

About the authors

Duncan Stevens is currently working as a locum optometrist within independent and multiple practice settings, participating in shared care schemes and the supervision of pre-registration optometrists. He worked for two years in the Caribbean within a private ophthalmology practice specialising in corneal pathology and sports vision. He is currently enrolled on the postgraduate study programme at Aston University.

Dr Shehzad Naroo is a reader at Aston University in the School of Life Ind Health Sciences. He is Editor-in-Chief of the journal Contact Lens and Anterior Eye and the Global President of the International Association of Contact Lens Educators. He is a visiting professor at the King Saud University in Riyadh. In 2015 he was given the International Optometrist Award by the World Council of Optometry.

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