Refractive surgery and dry eye - An update

Abstract

Dry eye disease is the most common complication and a frequent cause of patient dissatisfaction after corneal laser refractive surgery, which includes laser-assisted in situ keratomileusis (LASIK), small-incision lenticule extraction (SMILE), and photorefractive keratectomy (PRK). It has a complex, multifactorial etiology and is characterized by a highly variable clinical presentation. A detailed preoperative screening and optimization of the ocular surface prior to refractive surgery are the key to minimizing the incidence and severity of postoperative dry eye. Diagnosis of postrefractive surgery dry eye remains a challenge as no single symptom or clinical parameter is confirmative of the condition, and the symptoms and signs may not correlate well in many cases. A thorough understanding of the pathomechanism of the disease and its manifestations is essential to facilitate a treatment approach that is individualized for each patient. This article reviews various aspects of postrefractive surgery dry eye including its epidemiology, etiopathogenesis, risk factors, diagnosis, and management.

Modern corneal refractive surgery offers a choice of procedures such as laser-assisted in situ keratomileusis (LASIK), small-incision lenticule extraction (SMILE), and photorefractive keratectomy (PRK), all of which are associated with a high index of efficacy and safety. Despite its overwhelming popularity among surgeons and patients alike, it is not free of complications. Dry eye disease is the most common complication observed after corneal laser refractive surgery and one of the leading causes of patient dissatisfaction.[1] It can significantly impact the patient’s quality of life with even mild dry eye resulting in utility scores equivalent to severe migraine.[2] Postoperative dry eye also predisposes to potentially vision threatening complications such as flap folds, flap displacement, refractive regression, and microbial keratitis.[3,4] In this review, we shall elaborate upon the etiopathogenesis, epidemiology, predisposing factors, clinical manifestations, and management of postcorneal refractive surgery dry eye disease.

Methods of Literature Search

A systematic literature search was undertaken using PubMed, Google Scholar, and Cochrane Library database. The following keywords were used; “dry,” “eye,” “refractive,” “surgery,” “laser,” “LASIK,” “SMILE,” and “PRK.” All relevant review articles, original articles, case series, and case reports were reviewed. The search was conducted in October 2022. We limited our search to articles that were published from 1995 to 2022 and were written in English.

Etiopathogenesis

Dry eye disease after corneal refractive surgery has a multifactorial etiology. The primary mechanism is the transection of the corneal nerves which impacts the cornea-blink reflex and ocular surface-lacrimal gland neural loop resulting in reduced tear secretion and increased tear film instability. It also causes a disruption of the neurotrophic factors released from the corneal nerves. Reduced blinking may also adversely affect the meibomian gland function.[5-7] The degree of corneal nerve damage varies depending on the type of refractive surgery. In cornea, the stromal nerve fiber bundles run centripetally and toward the surface, perforating the Bowman layer to form the sub-basal nerve plexus. Corneal flap creation during LASIK results in transection of all sub-basal fibers throughout the flap side cut extending 300–310 degrees. Subsequent excimer laser ablation of stroma damages the deeper central corneal stromal nerves.[8] SMILE does not entail a large flap cut and the peripheral nerve fibers are resected only where the 25–50 degrees incision is placed. In addition, fibers that perforate the Bowman layer within the area of refractive lenticule are also resected; however, the fibers that had penetrated the Bowman layer outside the lenticule area may run undisturbed as sub-basal nerve plexus.[8] PRK does not require a flap creation at all. The smaller side cut in SMILE and absence of flap creation in PRK would theoretically result in better preservation of sub-basal nerve plexus.[8] This theory is supported by the less severe nerve damage and faster corneal re-innervation observed after PRK[9] and SMILE[8,10] [Fig. 1].

Figure 1.

Confocal microscopy images of preoperative and postoperative sub-basal corneal nerve fiber layer at 1 year after PRK (a and d), LASIK (b and e), and SMILE (c and f), respectively

Postoperative inflammatory response associated with wound healing after laser refractive surgery also contributes to development of dry eye. This neurogenic inflammatory response is postulated to be distinct from that of other etiologies of dry eye[11,12] as evidenced by the raised proinflammatory tear mediator levels (IL-6, MMP-9), neuropeptides (Substance P and calcitonin gene-related peptide), and neuromediators (nerve growth factor).[12-15] The upregulation is less and recovery faster with SMILE as compared to LASIK.[12,16] Direct damage to conjunctival goblet cells by the suction device during LASIK and SMILE could lead to subsequent mucin deficiency and tear film instability.[17] Greater loss of goblet cells was reported with femtosecond (FS) LASIK as compared with the use of microkeratome for LASIK.[18] In addition to these factors, the change in corneal curvature induced by laser refractive surgery can cause an abnormal distribution and instability of tear film. The central corneal flattening may cause an incongruent interaction between ocular surface and posterior lid margin to adversely affect the meibomian gland function.[19] Frequent instillation of preservative containing eye drops may also induce a toxic effect on the conjunctiva and cornea further compounding postoperative dry eye disease.[7]

Incidence

Dry eye disease is the most common complication after any corneal laser refractive surgery. Although the reported prevalence of post-LASIK dry eye ranges from 36–75%,[20,21] almost all patients experience some degree of dry eye in the immediate postoperative period.[22] The Patient-Reported Outcomes with LASIK (PROWL) studies reported that nearly one third of patients with normal Ocular Surface Disease Index (OSDI) score before surgery complained of dry eye-related symptoms 3 months after LASIK and 4% of them had severe symptoms.[23] The symptoms and signs typically peak during the first week after surgery following which it gradually recovers over 6–12 months. About 8–48% continue to be affected up to 6 months after LASIK.[4,5,24] The variability in the incidence rates reported by various studies appears to be due to use of different diagnostic criteria. The incidence of dry eye after SMILE is lower, less severe, and recovers faster than LASIK.[25-32] Denoyer et al.[8] reported that 80% of SMILE patients did not require any tear supplements at 6 months postoperatively versus 57% of LASIK patients. Few studies have evaluated the incidence of dry eye post-PRK; Hong et al.[33] reported that 37% of their patients complained of dry eye symptoms after PRK.

Predisposing Factors

Identifying patients at risk for development of dry eye after refractive surgery allows the surgeon to adopt requisite measures to optimize the ocular surface before surgery or even plan alternative procedures in the more severe cases. Several preoperative and intraoperative factors can predispose the patients to develop postoperative dry eye after corneal refractive surgery.

Preoperative factors

Pre-existing dry eye is the most important risk factor for development of dry eye after refractive surgery.[34]About 8–55% of the patients being planned for refractive surgery reportedly suffer from dry eye disease.[4,22,35,36] Schallhorn et al.[37] reported that about one-fifth of their patients with mild symptoms preoperatively progressed to develop moderate or severe symptoms after LASIK. Patients with poor tear function and stability have higher odds of developing chronic dry eye after excimer laser surgery.[9,17] Interestingly, a low TBUT among patients being planned for SMILE did not as such increase the likelihood of developing dry eye symptoms after surgery.[38]

Higher preoperative refractive error has been associated with an increased risk of dry eye after LASIK, possibly due to the increased stromal ablation in these patients.[4,21,24,39] Tuisko et al.[40] reported that more than half of the patients undergoing LASIK for high myopia complained of subjective dry eye symptoms even 2–5 years after surgery. One recent study, however, reported that lower preoperative refractive error was associated with greater risk of dry eye; the authors attributed this to the greater postoperative expectations making these patients more sensitive to the symptoms.[41] Higher refractive correction with SMILE has been associated with greater tear film instability, evidenced by decreased TBUT and abnormal tear lipid layer thickness (LLT).[42]

Demographic factors such as gender, age, and race may also influence the development of dry eye postsurgery. Female patients are at an increased risk[4,24,37,41] and have greater odds of developing more severe and chronic symptoms.[37,43] Older age has been reported as a risk factor by some authors[24,41] while others found no such association[4,21,37,39] Asian patients are at greater risk for developing chronic dry eye post-LASIK as compared with Caucasians.[44] Contact lens users also have a higher risk of developing postrefractive surgery dry eye.[39,45]

Intraoperative factors

Surgery-related factors which can influence corneal denervation and hence the development of postoperative dry eye include the surgical technique, amount of stromal ablation or tissue removal, ablation profile, flap diameter, thickness, and hinge position. SMILE has been found to have a more favorable response in terms of corneal sensitivity and dry eye manifestations as compared to LASIK.[10,30,31,46] Surface ablative procedures such as laser-assisted subepithelial keratectomy (LASEK) and PRK have also been found to be associated with less tear dysfunction and dry eye symptoms as compared to LASIK.[19,41,47,48] Schallhorn et al.,[37] however, observed that PRK patients complained of more dry eye-related symptoms as compared to LASIK at 3 months. The authors attributed this to the more severe neurotrophic effect induced by LASIK resulting in reduced corneal sensitivity and hence, greater comfort among the patients. Postoperative dry eye incidence following SMILE was found to be comparable with PRK at 3 months[49] and higher than LASEK at 6 months.[50]

In LASIK patients, flap size, thickness, hinge location as well as the ablation profile and depth can impact the incidence of dry eye. Larger flaps and greater depth of ablation are associated with higher risk of postoperative dry.[21,24] Furthermore, hyperopic ablation leads to greater denervation due to the increased nerve density in the periphery as compared to central cornea.[51] Thinner flaps are associated with faster recovery of dry eye symptoms[52] and corneal sensation,[53] possibly because shallower lamellar dissection results in a less volume of tissue through which the corneal nerves must regenerate.[54] FS lasers allow creation of thinner flaps with more consistent dimensions which results in less damage to anterior stromal nerves.[55] Salomão et al.[56] reported a lower incidence of dry eye with FS LASIK as compared to LASIK with microkeratome (9% vs 46%). Other studies found no such difference.[57-59] Nasal hinge flap has been reported to produce less dry eye symptoms in early postoperative period[60] and faster recovery of corneal sensation,[60,61] possibly due to better preservation of the long ciliary nerves which enter the cornea at the 3 o’clock and 9 o’clock positions. The difference, however, was not evident on long-term follow-up at 6 months.[54] Narrower hinge has also been associated with a greater loss of corneal sensation and more dry eye symptoms.[62] Interestingly, the incision size in SMILE (2 mm, 3 mm, or 4 mm) did not impact the incidence of postoperative dry eye.[63] Further studies are required to explore the influence of factors such as lenticule thickness or diameter on the incidence of dry after SMILE.

Clinical Manifestations

Postcorneal refractive surgery dry eye is a spectrum of disease that includes tear dysfunction, neurotrophic epitheliopathy, and dysesthetic cornea.[64] The manifestations are typically more severe and prolonged after LASIK as compared to SMILE or PRK.

Clinical symptoms

Patients may present with symptoms such as ocular dryness, pain, stinging, photophobia, redness, and visual fatigue.[5,22,43,58] Complaints of fluctuating vision and impaired functional vision due to irregular astigmatism induced by an unstable tear film are not uncommon.[65] The intensity and duration of these symptoms are highly variable due to the complex, multifactorial etiology with an often poor correlation between subjective symptoms and objective signs.[7] The symptoms are most bothersome during the first month, following which they gradually improve over 3–12 months.[5] Various questionnaires such as Ocular Surface Disease Index (OSDI), Impact of Dry Eye on Everyday Living (IDEEL), and Dry Eye Questionnaire (DEQ-5) may be used to quantify the symptom severity in these patients.[66]

Ocular surface pain that variably overlaps with the dry eye symptoms is another important manifestation of dry eye disease after laser ablative surgery.[67] A subset of patients complain of persistent and disabling pain which may be accompanied by hyperalgesia and allodynia and is termed as neuropathic ocular pain or corneal neuralgia. It attributed to the dysfunctional recovery of trigeminal nerve after surgery-induced damage, but the typical clinical signs of dry eye are often lacking.[43] Levitt et al. reported that 20–55% of their LASIK patients had at least mild symptoms of dry eye or persistent ocular pain, whereas Moshirfar et al. reported that only one patient per 900 undergoing LASIK developed corneal neuralgia.[64,68] Among post refractive surgery patients with persistent dry eye, ocular pain was reported by up to 78.8% patients, of which 63.5% was neuropathic in origin.[43] Onset of neuropathic ocular pain may be observed in the immediate postoperative period in nearly half of the patients while others may show a later presentation.[43,64] Risk factors identified for developing neuropathic pain after refractive surgery include neuropsychiatric conditions and central sensitization syndromes. The proparacaine challenge test can help distinguish between central or peripheral pain origins for ocular neuropathic pain.[43]

Clinical signs

Postrefractive surgery dry eye patients exhibit signs of dysfunctional tear syndrome with decreased tear film stability and reduced tear secretion evidenced by positive vital staining of ocular surface, reduced TBUT, and decreased Schirmer test values.[5,7] Laser-induced neurotrophic epitheliopathy (LINE), first described by Wilson,[69] is a dry eye like condition that is primarily characterized by epithelial erosions with normal tear production manifesting a few days to weeks after surgery. Decreased supply of neurotrophic factors to epithelial cells, reduced tear production, and infrequent blinking may contribute to its development. It is observed in 4–14% of cases and usually resolved within the first 6 months of surgery. Various objective parameters such as the ocular surface staining score, TBUT, Schirmer test, and tear meniscus height assessment can help quantify the severity of disease. More advanced diagnostic modalities that may employed for better characterization of the disease include in vivo confocal microscopy, meibography, tear film interferometry, and tear analysis for osmolarity and inflammatory mediator measurement. Table 1 details the important clinical manifestations of dry eye disease and their course following corneal laser refractive surgeries.[7,9,16,25,27,33,42,51,52,59,70-76]

Table 1.

Clinical manifestations after corneal laser refractive surgery and their salient characteristics

Clinical Manifestations	Salient Characteristics
Vital staining of cornea	Positive vital staining at 1 week; predominantly involving the flap in LASIK, less severe in SMILE
	Symptoms less severe due to reduced sensitivity
	Resolves by 6-12 months after LASIK[7]
	Resolves by about 1-3 months after SMILE[16]
	Resolves by about 3 months after PRK[9]
Tear breakup time	Reduced; most severe at 1 week
	Normalizes by about 6-12 months post-LASIK[16,27,70]
	Normalizes by about 3-6 months after SMILE[42,70]
	Normalizes by about 3 months after PRK[9]
Schirmer test	Reduced after surgery; maximally during first month
	Normalizes by 6-9 months after LASIK[7,59]
	Normalizes by about 3 months after SMILE[42]
	Normalizes by about 3-6 months after PRK[9,33]
Corneal sensitivity	Greater reduction after LASIK; decreased maximally at 1-2 weeks
	Recovers by about 12 months after LASIK[7]
	Recovers faster, by 3-6 months after SMILE[16,71,72]
	Recovers in 3-12 months after PRK[51,73,74]
Lipid layer thickness	Reduced after SMILE by 1 week, recovers by 3 months[16,42]
	No significant change reported by one study after LASIK[76]
Tear osmolarity	Increased; more after LASIK than PRK and SMILE
	Levels raised for up to 3-6 months after LASIK and SMILE[25]
	Levels raised for up to 4 months after PRK[75]
Nerve morphology on confocal scanning	Sub-basal nerve density, stromal nerve cells reduced after surgery; other features include nerve beading, irregular branching,
	microneuromas and increased dendritic cells.
	Microneuroma in post-LASIK neuropathic corneal pain.[64]
	Recovery may take up to 24-60 months after LASIK[74]
	Recovery by about 12 months after SMILE[25,51]
	Recovery by about 24 months after PRK[51]

LASIK-laser-assisted in situ keratomileusis; SMILE- small-incision lenticule extraction; PRK-photorefractive keratectomy

Preoperative Considerations

Identifying patients with pre-existing dry eye during the preoperative evaluation is crucial to ensure optimal outcomes after any corneal refractive procedure. A detailed history and meticulous ocular surface examination can help detect the high-risk cases who then require to be treated aggressively to optimize the ocular surface.[77] Moreover, special attention should be paid to the possibility of co-existent ocular allergies and systemic disorders such as diabetes or collagen vascular diseases.[7,78] Corneal refractive surgery should not be performed in patients with uncontrolled systemic disorders or active ocular involvement. Surgery in systemic conditions that are well controlled with a normal tear function has been found to be fairly safe without serious complications.[79-81] There are reports of severe refractory dry eye and necrotizing keratitis postrefractive surgery in well-controlled Sjogren syndrome and Crohn’s disease patients indicating that these patients are not well suited for refractive surgery.[82,83] Ocular allergies are a known risk factor for dry eye and both often co-exist, which may complicate the outcomes of laser refractive surgery. Chronic inflammation of the ocular surface in allergic disorders impairs the tear film stability, conjunctival goblet cells, and meibomian gland function which contributes to dry eye disease.[84] Moreover, ocular surface inflammation induced by corneal laser refractive surgery may be exacerbated in atopic patients.[85] Laser refractive surgery is contraindicated in cases with active ocular allergic disease but may be considered after adequately treating the allergic condition.

Management

Management approach for postrefractive surgery dry eye aims to stabilize the tear film, increase aqueous production, and control ocular surface inflammation. Depending on the severity and nature of manifestations various agents including topical lubricants, anti-inflammatory drugs, punctal plugs, mucin secretagogues, and autologous serum may be employed in a step ladder approach. Table 2 details the different management options and their outcomes in postcorneal refractive surgery dry eye disease.

Table 2.

Management options and outcomes of postcorneal refractive surgery dry eye disease

Tear Supplements
Author/Year	Study Details	n	Duration of therapy	Outcomes Measures	Results
Durrie et al. (2008)[86]	Evaluated PEG + PPG vs placebo in a randomized comparative contralateral eye study in post-LASIK patients	30 patients	1 month	TBUT Corneal & conjunctival staining	TBUT significantly longer in PEG+PPG group at 2 weeks, but comparable at 1 month
Astakhov et al. (2013)[87]	Evaluated 0.15% hyaluronate (PF) vs PEG+PPG in a randomized comparative study in post-LASIK patients	54 patients	3 months	Corneal fluorescein staining	Similar efficacy with both medications; PF hyaluronate showed a trend for more rapid improvement
Fouda et al. (2017)[88]	PEG+PPG vs intraoperative botulinum toxin A (BTA) injection below lower puncta vs punctal plugs	70 patients	6 months	ST, TBUT, OSDI score	All parameters better for the BTA and punctal plug group than the tear substitute only group up to 3 months after surgery. Fewer complications in BTA than plug group
Wallerstein et al. (2018)[89]	Evaluated CMC+HA vs CMC in a randomized comparative study in post-LASIK patients	148 patients	3 months	ST, TBUT, OSDI, corneal staining	CMC-HA-was non inferior to CMC alone, with incremental benefit in uncorrected vision
Topical Cyclosporin
Author/Year	Study Details	n	Duration of therapy	Outcomes Measures	Results
Hessert et al. (2013)[90]	Topical cyclosporin (0.05%) therapy after LASIK and PRK evaluated in a randomized comparative study	124 eyes	3 months	Ocular symptoms, tear inflammatory mediators	No significant benefit observed with prophylactic topical cyclosporin therapy
Salib et al. (2006)[91]	Evaluated topical cyclosporin therapy in dry eye patients undergoing LASIK in a randomized clinical trial	42 eyes	6 months	ST, OSDI, corneal staining	Cyclosporine offered significant improvements in tear volume at more study visits than artificial tears (statistically insignificant) Better refractive predictability 3 and 6 months after surgery with topical cyclosporine 0.05%
Kanellopoulos (2019)[92]	Evaluated topical 0.05% cyclosporine A therapy in post-LASIK dry eye patients in a retrospective study	145 eyes	12 months	ST, TBUT, OSDI, corneal epithelial thickness	A significant improve in all metrics observed at 12 months
Mucin Secretagogoues
Author/Year	Study Details	n	Duration of therapy	Outcomes Measures	Results
Mori et al. (2014)[93]	Evaluated topical diquafosol tetrasodium in persistent post-LASIK dry eye patients in a prospective study	15 patients	12 weeks	ST, TBUT, corneal and conjunctival staining, symptom score	Improvement in ocular surface staining, TBUT, and symptom score observed
Toda et al. (2014)[94]	Prospective randomized study compared artificial tears, 0.3% sodium hyaluronate, diquafosol tetrasodium, and a combination of hyaluronate and diquafosol in post-LASIK patients	206 eyes	1 month	ST, TBUT, corneal and conjunctival staining, symptom score, corneal sensitivity	Hyaluronate and diquafosol combination therapy was beneficial for early stabilization of visual performance, tear secretion, and improvement of subjective dry eye symptoms
Igarashi et al. (2015)[95]	Rebamipide ophthalmic suspension in post-LASIK/ReLEx dry eye patients in a randomized comparative study	30 patients	4 weeks	ST, TBUT, corneal staining, subjective symptoms, objective scattering index	Rebamipide therapy significantly improved dry eye parameters such as tear volume, TBUT, fluorescein score, and subjective symptoms while reducing the intraocular scattering of light
Autologous Serum
Author/Year	Study Details	n	Duration of therapy	Outcomes Measures	Results
Noda-Tsuruya, et al. (2006)[96]	Randomized study evaluated topical autologous serum therapy in post-LASIK patients	27 patients	6 months	ST, TBUT, corneal staining scores, subjective symptom score	Autologous serum group showed prolongation of TBUT and reduction in rose bengal staining score
Javaloy et al. (2013)[97]	Prospective randomized study evaluated the effect of platelet-rich plasma (PRP) on corneal nerve regeneration and sensitivity after LASIK	108 eyes	3 months	Corneal sensitivity Corneal staining Sub-basal nerve density	PRP drops promoted epithelial status but had no positive effect on corneal sensitivity or nerve regeneration
Lin et al. (2015)[98]	Retrospective review evaluated the efficacy of autologous serum eye drops in recalcitrant LASIK-induced neurotrophic epitheliopathy	10 patients	8.26±11.87 weeks	Corneal and conjunctival staining, Schirmer, TBUT, TMH,	Autologous serum was effective in improving corneal surface conditions and postoperative visual acuity
Alio et al. (2017)[99]	Prospective study evaluated PRP in post-LASIK moderate–severe persistent dry eye patients unresponsive to artificial tears	156 eyes	6 weeks	Corneal staining, OSDI, conjunctival hyperemia	Improvement in dry eye symptoms (85%), corneal staining (90%), and conjunctival hyperemia (94%)
Punctal Plugs
Author/Year	Study Details	n	Duration of therapy	Outcomes Measures	Results
Yung et al. (2012)[100]	Randomized comparative study evaluated punctal plus in post-LASIK dry eye patients	25 eyes	2 months	ST, TBUT, ocular surface staining, symptom score, FVA, SRI	Punctal plugs significantly improved the symptoms, tear function, and quality of vision
Nemet et al. (2020)[101]	Retrospective comparative study evaluated the effect of preventive intraoperative punctal plug implantation during LASIK	345 eyes	3-6 months	Presence of dry eye disease, superficial punctate keratitis	Preventive temporary punctal plug placement reduced dry eye symptoms by 13%, reduced SPK by 12%, and delayed dry eye disease by more than 30 days
Oral Supplements
Author/Year	Study Details	n	Duration of therapy	Outcomes Measures	Results
Goyal et al. (2017)[102]	Evaluated ω3FA supplementation in post-LASIK patients in a randomized controlled study	60 eyes	3 months	ST, TBUT, OSDI, corneal staining scores	Supplementation with ω3FA had a positive influence on tear secretion (Schirmer); tear film stability remained unaffected
Lin et al. (2022)[103]	Oral Vitamin D3 supplementation in post-LASIK dry eye in a randomized controlled study	90 patients	3 months	ST, TBUT, OSDI, tear , inflammatory mediators	Significantly better OSDI score, tear production and TBUT in study group

LASIK-laser-assisted in situ keratomileusis; SMILE- small-incision lenticule extraction; PRK-photorefractive keratectomy; ReLEx-refractive lenticule extraction; PPG-Polypropylene glycol; PEG-Polyethylene glycol, TBUT-tear breakup time, OSDI-Ocular Surface Disease Index, FVA-functional visual acuity; SRI-surface regularity index; CMC-carboxymethyl cellulose; HA-hyaluronic acid; ω3FA-omega-3-fatty acid; TMH-tear meniscus height; ST-Schirmer test

Tear substitutes

Tear substitutes, preferably preservative free, are the first line of treatment for postoperative dry eye after refractive surgery. They are routinely prescribed post surgery for about 4–6 weeks and often suffice for the management of transient dry eye in majority of patients. Non-preserved carboxymethylcellulose (CMC)-based artificial tears have been shown to be more effective in stabilizing the ocular surface after laser refractive surgery as compared to saline drops or 0.3% hydroxypropyl methylcellulose owing to its greater muco-adhesive properties.[104,105] Other formulations such as hyaluronic acid (HA), polyvinyl alcohol, and polyethylene glycol may be used depending on the severity and type of dry eye.[86,87] Hyaluronic acid is available in preservative-free formulation and has intrinsic properties of water retention, viscoelasticity, and promotion of corneal epithelial wound healing.[87] More recently, a multi-ingredient formulation containing CMC 0.5% and HA 0.1% was found to promote visual recovery faster after LASIK as compared to CMC alone possibly due to the HA-mediated epithelium recovery which improved the surface optics.[89]

Topical anti-inflammatory therapy

Postoperative inflammation is an important contributor to development of dry eye and can be controlled using anti-inflammatory agents such as topical steroids and cyclosporin. Topical steroids are a part of routine postoperative regimen, tapered over 4–6 weeks. Topical cyclosporin is effective in optimizing dry eye patients before laser refractive surgery as well the treatment of new onset dry eye postsurgery.[91,106] It is effective in improving the tear secretion and stability for up to 1 year in patients with symptomatic dry eye after LASIK[92] Several weeks of treatment may be required before any effect is apparent, with a maximum effect reached at about 6 months.[92] The benefit of incorporating topical cyclosporin in the routine postoperative regimen; however, remains unclear. While one study reported improved visual outcomes with reduced recovery time when topical cyclosporine was prescribed in routine post-LASIK patients,[107] another found no significant benefit in terms of improving the dry eye-related signs, symptoms, and tear inflammatory mediators.[90] Topical cyclosporine has also been reported to enhance corneal nerve regeneration and improving corneal sensitivity in post-LASIK patients.[108] More recently, a newer formulation of Cyclosporin A Cationic Emulsion 0.1% has shown promising results in moderate to severe dry eye patients with improvement in clinical signs evident as early as 4 weeks, though, up to 12 months of treatment is recommended for more sustained effects.[109] Further studies are required to assess its efficacy in postrefractive surgery dry eye patients.

Mucin secretagogues

Tear mucin plays an important role in maintaining tear film stability owing to its hydrophilicity and lubricating properties. Diquafosol tetrasodium (DQS) is a P2Y2 receptor agonist that facilitates mucin production and tear secretion from conjunctival epithelial cells and goblet cells.[110] Addition of DQS 3% solution improved tear film stability and alleviated symptoms in post-LASIK dry eye patients who were unresponsive to artificial tears and topical sodium hyaluronate therapy.[93] Combination therapy with DQS and hyaluronate after LASIK has been found to act synergistically and improve functional visual acuity, tear secretion, and dry eye symptoms faster than monotherapy with either agent.[94] However, it remains unclear if these improvements are maintained after termination of the DQS treatment. Another mucin secretagogue, Rebamipide 2% solution, has been reported to alleviate dry eye-related signs and symptoms, as well as improve the optical quality in post-LASIK dry eye patients.[95]

Autologous serum

Autologous serum is rich in neurotrophic and epitheliotropic factors such as nerve growth factor and substance P, epidermal growth factor (EGF), transforming growth factor (TGF), vitamin A as well as anti-inflammatory factors and matrix metalloproteinase inhibitors.[111] It has been reported to improve tear film stability demonstrated by prolongation of TBUT and reduction of ocular surface staining in post-LASIK patients.[96] Recalcitrant cases of LASIK-induced neurotrophic epitheliopathy have been found to benefit from autologous serum therapy with significant improvement in ocular surface parameters and visual acuity.[98] Platelet-rich plasma (PRP) and plasma rich in growth factors (PRGF) are considered to have advantages over autologous serum due to a higher concentration of growth factors, anti-inflammatory cytokines, and other platelet derivatives.[99] Autologous PRGF and PRP have been found to be efficacious in improving persistent dry eye symptoms and corneal staining in post-LASIK patients unresponsive to conventional therapy.[99,112] Platelet-rich plasma has been found to promote epithelial growth but did not have a significant positive effect on corneal nerve regeneration and recovery of corneal sensitivity after surgery.[97] Limitations of autologous serum or plasma drops include the need for its preparation from the patient’s own blood and a limited shelf life of up to a week when stored at 4⁰ C and 3 months when stored at -20⁰ C.

Punctal plugs

Punctal plugs help in retaining patient’s own tears as well as instilled tear supplements for longer time. Preventive implantation of punctal plugs during LASIK was found to reduce dry eye symptoms, improves tear function, and decreases the need for frequent lubricant instillation during the early postoperative period and may be considered in high-risk cases.[88,101,113] Yung et al.[100] observed that punctal occlusion with silicone plugs was effective in treating refractory post-LASIK dry eye for up to 3 months after surgery. Loss of plugs, epiphora, and granuloma formation are some of the complications associated with use of punctal plugs.[88]

Other measures

Supportive measures such as lid hygiene, heated eye mask, eyelid thermal pulsation therapy, and oral doxycycline therapy should be prescribed to treat co-existing anterior blepharitis or meibomian gland dysfunction which can contribute to postoperative dry eye.[114,115] Oral Omega-3 fatty acid and vitamin D3 supplementation may also have role in improving tear secretion and visual quality in post-LASIK patients.[102,103] Newer treatment agents such as topical nerve growth factor (NGF) have been found to stimulate corneal sensitivity, nerve regeneration, and tear film stability in animal studies, making it a promising option for postrefractive surgery dry eye patients in future.[116]

Conclusion

Postoperative dry eye has a high prevalence among post corneal refractive surgery patients and can significantly impact their quality of life. The severity and duration of disease may be highly variable and is determined by factors including but not limited to surgical variables, presence of pre-existing dry eye, and magnitude of refractive error. Proper preoperative evaluation and counseling can help detect the high-risk cases and minimize postoperative dissatisfaction. The management of postrefractive surgery dry eye follows a step ladder approach and comprises tear supplements, topical anti-inflammatory agents, mucin secretagogues, punctal plugs, and autologous serum drops in the more refractory cases. While most cases resolve within the first year, a small subset may progress to chronic dry eye warranting more aggressive therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.