Corneal refractive surgery challenges

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1 Sponsored by Academy of Vision Care Corneal refractive surgery challenges Michael DelGiodice OD, FAAO and Attefa Sultani OD, FAAO Corneal refractive surgery is an ever-evolving field with over 60 years of innovation following its discovery in 1949 by Jose I. Barraquer. 1 Evolving technology has improved both safety profile and efficacy making the procedure commonplace. Nonetheless, complications are well-known and may arise after laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), or laser epithelial keratomileusis (LASEK). Early identification, judicious management and appropriate referral will allow for the best possible outcome. Thus it is imperative for practitioners to be aware of potential complications which may arise. This article addresses common clinical challenges which may arise post-operatively and reviews current treatment and management modalities. 1 Course code C Deadline: February 8, Learning objectives (Group 6, 6.1.3) Be able to understand the process of investigating and identifying presenting post-refractive surgery complications (Group 6, 6.1.3) Be able to interpret clinical findings of refractive surgery complications in order to advise patients on treatment, taking into account relevant risk factors Learning objectives (Group 2, 9.0) Know how to manage complications of refractive surgery including prescription of appropriate medication, taking account of risks About the authors Michael DelGiodice is a doctor of optometry and practices at LCA Vision in Paramus, New Jersey USA. He served a residency in primary care and ocular disease at East Orange/Lyons VA Hospital New Jersey Healthcare System. Attefa Sultani is an associate optometrist with Associated Eye Physicians in Clifton and Pompton Lakes, New Jersey USA. She served a residency in ocular disease and special testing at the State University of New York State College of Optometry.

2 48 Complications exclusive to LASIK include epithelial defects, flap striae, diffuse lamellar keratitis (DLK), flap dislocations, epithelial ingrowth and transient light sensitivity syndrome (TLSS). 1, 2 Complications exclusive to PRK and LASEK include delayed epithelial healing and corneal haze. 3 Complications common to both procedures may include overand under-correction of refractive error, irregular astigmatism, visual aberrations, dry eyes, sterile corneal infiltrates, infectious keratitis and recurrent corneal erosions. The following case studies describe typical examples of the presentation and management of such complications. Case 1: Corneal infiltrates A 40-year-old woman underwent successful Wavelight PRK with mitomycin C (MMC) 0.02% (for 30 seconds) for the in both eyes. The first day follow-up revealed well-centred bandage contact lenses, central epithelial defects in each eye and coalescent peripheral corneal infiltrates located outside the treatment zone in the right eye. The infiltrates were grey-white in colour, arcshaped and separated from the limbus by a clear zone (Figure 1). Sodium fluorescein dye testing showed mild corneal stippling over the infiltrates. Careful consideration was given to a differential diagnosis of early microbial keratitis. However, given the findings and lack of associated symptoms, a diagnosis of sterile peripheral infiltrates was made; moxifloxacin 0.5% (Vigamox) and prednisolone acetate 1% (Pred Forte) were increased from q.i.d. to every two hours in the right eye. Follow-up on day five revealed central epithelial healing in both eyes and resolving peripheral infiltrates in the right eye. Given the rate of healing, both medications were tapered to q.i.d. in the affected eye. One week later there was Figure 1: Peripheral corneal infiltrates observed one day after undergoing PRK treatment with MMC complete resolution with residual sub-epithelial scars; prednisolone acetate 1% was tapered b.i.d. for one week. Two months later, vision was 6/6 in each eye with stable corneal findings and normal intraocular pressure (IOP). Corneal infiltrates are an uncommon, but well-documented, complication following both LASIK and PRK/LASEK. Generally, corneal infiltrates have been linked to contact lens wear, surgically-induced trauma, staphylococcus hypersensitivity rising from pre-existing blepharitis, Terriens marginal degeneration, Mooren s ulcer, peripheral ulcerative keratitis and systemic autoimmune or collagen vascular disease. 4 This patient, however, presented without knowledge of current systemic autoimmunity and her corneal findings were inconsistent for autoimmune ulceration. Infectious keratitis is unlikely due to the number and location of infiltrates and due to the lack of pain, discharge, conjunctival injection and anterior chamber reaction. 5 According to Donshik and others, 5 peripheral corneal infiltrates associated with contact lenses have a variable presentation. The clinical characteristics important for differentiating sterile from infectious aetiologies include: size, location, number, shape, appearance of the overlying epithelium, presence or absence of surrounding cellular stromal inflammation and amount of anterior chamber reaction. Furthermore, infiltrates less than 1.5mm in size, with intact epithelium, and moderate conjunctival injection do not require cultures and can be treated empirically with topical antibiotic and corticosteroid medication. The case presented here represents sterile corneal infiltrates following refractive surgery. Both topical antibiotic and corticosteroid therapy are paramount at reducing the risk of both infection and inflammation. Caution should be taken with regards to any corneal infiltrate following laser vision correction and eyes should be closely monitored for signs and symptoms consistent with infection. Case 2: Flap macrostriae A 39-year-old woman underwent successful Wavelight femtosecond LASIK in each eye for in both eyes. The first day follow-up revealed vision of 6/9-2 in the right eye and 6/6 in the left eye. Corneal flap evaluation revealed macrostriae with 1mm of flap recession in the right eye (Figure 2) and a well-positioned flap in the left eye. The patient was diagnosed with macrostriae. She was brought into the operating theatre the same day and the flap was refloated, stretched, smoothed, and a

3 Sponsored by bandage contact lens was applied. The patient was instructed to continue with moxifloxacin 0.5% q.i.d. but to increase prednisolone acetate 1% to every one hour for one day then to four times daily for one week. Follow-up revealed a wellpositioned flap with 6/6 vision and mild central microstriae. The contact lens was removed and topical medication was discontinued. Three months later, vision was 6/6 in each eye with a stable corneal appearance. Corneal flap striae are classified into two types: microstriae and macrostriae. Microstriae are related to flap setting, typically located centrally, associated with myopic ablation, and rarely have an effect on vision. Macrostriae represent a displacement of the flap edge, involves multiple bands of folded tissue and generally affects vision and causes discomfort. Flap striae are a well-known complication and can be caused by misalignment of the corneal flap after replacement, flap desiccation and contraction during laser ablation, flap wrinkling during stretching, movement of the flap on the first postoperative day, or the tenting effect of the flap over the ablated stromal bed. 6 In the case of the patient described here, she failed to wear the protective eye shields the night before and this was the cause of her macrostriae. When observing the flap post-surgically, it is helpful to utilise both indirect and retro-illumination to determine whether microstriae or macrostriae are present. 7 Decreased VA, reduced quality of vision or induction of irregular astigmatism indicates the need for urgent repositioning of the flap. As noted by Steinert, 8 striae that are not urgently attended to may result in progressive fibrosis within Bowman s layer and cause loss of best corrected VA. Surgical management is aimed at dissecting the flap from the stromal bed, refloating it back into position and stretching the striae in a down and out position for three to five minutes on each side. The eye may be taped shut for 20 minutes and re-examined or a bandage contact lens may be inserted and removed within one to seven days. This case illustrates the importance of careful examination of the flap edge, especially inferiorly Figure 2: Corneal flap macrostriae following femtosecond LASIK with superior hinge placement, as a delay in diagnosis may result in irregular astigmatism and loss of best corrected vision. 6 Case 3: Diffuse Lamellar Keratitis (DLK) A 20-year-old woman underwent uncomplicated bilateral Wavelight LASIK for treatment of compound myopic astigmatism. The first day follow-up revealed VA of 6/6 in the right eye and 6/4.5 in the left eye. Corneal evaluation revealed 2+ DLK in the right eye and 1+ DLK in the left eye (Figure 3). Moxifloxacin 0.5% (Vigamox) was continued q.i.d. along with difluprednate 0.05% (Durezol) every hour and loteprednol etabonate 0.5% (Lotemax) ointment at night in each eye. Given the day of discovery and egregious nature of the condition, oral corticosteroids (ie Medrol Dosepak 4mg) were prescribed. Follow-up two days later revealed mild resolution in each eye. Topical corticosteroids were tapered every two hours and ointment was continued at bedtime. The one week follow-up revealed complete resolution. The two-week follow-up revealed 6/4.5 vision, normal IOP and clear corneae in each eye. Topical corticosteroids were tapered over several weeks and the ointment was discontinued. First described by Smith and Maloney, 9 DLK represents a diffuse inflammatory infiltration of mononuclear cells and granulocytes within the stromal interface following LASIK. 9,10 Because of its white granular appearance with waves of increasing density, the condition has also been referred to as Shifting Sands or Sands of Sahara. 6 Prior studies reported the incidence of DLK to range from 0.4% to 29% While DLK is typically observed within the first week post-surgically, isolated cases in the late postoperative period have been reported to occur following epithelial trauma. 16,17 DLK may occur in clusters or as isolated cases. While there is no definitive aetiology, various causes may include: talc from gloves, oil, wax, metallic fragments, silicates, bacterial endotoxins, epithelial defects, substances produced by laser ablation, particles from eye drape, meibomian gland secretions and povidone iodine. The first step to proper management of DLK involves staging the degree of inflammation. According to Linebarger and others, 18 there are four stages of DLK. Stage 1 appears as white granular cells located to the periphery of the flap. In Stage 2 DLK, white granular cells migrate centrally and involve the visual axis; more frequently this is seen on day two or three postoperatively. Stage 3 DLK appears as Figure 3: Stage 2 DLK following LASIK 49 Find out when CET points will be uploaded to the GOC at For the latest CET visit

4 50 dense, white, clumped cells located at the visual axis with relative peripheral clearing and decreased VA by 1 or 2 lines. Stage 4 represents severe lamellar keratitis with hyperopic shift in refractive error, decreased vision, stromal melting and permanent scarring. Current treatment recommendations for Stage 1 and 2 DLK include high-dose topical corticosteroid drops every hour with a slow taper over several weeks once the inflammation begins to subside. Follow-up is initiated within the first hours until day five to identify possible progression. Typically detected within 72 hours, the treatment of Stage 3 DLK includes lifting the flap and irrigating the interface to debulk the inflammatory cells and collagenases to prevent progression to Stage Hoffman and others 20 reported successful treatment of DLK Figure 4: Grade 3 corneal haze following PRK with a combination of oral and topical with MMC corticosteroids for early-onset Stage 2 extreme photophobia, a diagnosis of bilateral and Stage 3 DLK; no patients in their study TLSS was made and prednisolone acetate 1% required a flap lift and none developed Stage was prescribed q.i.d. for two weeks. Follow-up 4 disease. 20 In those rare corneae that go on revealed 6/6 vision, unremarkable anterior to Stage 4 DLK (1 in 5,000 eyes), the prognosis segment findings and complete resolution is poor. In addition, lifting the flap is of little of symptoms. Prednisolone acetate 1% was benefit and may add to further stromal discontinued and loteprednol etabonate 0.5% volume loss. 21 (Lotemax) was prescribed t.i.d. and tapered over a month without incident. Case 4: Transient Light Sensitivity Syndrome (TLSS) A 47-year-old woman underwent uncomplicated bilateral Wavelight LASIK for in each eye. At her four-week post-operative follow-up she complained of extreme light sensitivity and pain in both eyes. Her VA was 6/6 in each eye. Evaluation with a bright light source was difficult due to her intense photophobia but revealed normal anterior segment findings in each eye. Given her recent history of femtosecond LASIK, unremarkable anterior segment findings and TLSS is an unusual complication after LASIK with the femtosecond laser and carries an incidence of %. 22 It is clinically characterised by extreme photophobia, normal VA, and unremarkable anterior segment findings. Its onset is typically two to eight weeks after treatment with no signs to explain the cause of photosensitivity. While no definitive aetiology has been determined, proposed mechanisms include: interface inflammation secondary to necrotic cell debris, cytokine migration, or activated keratocytes in the interface. Studies have shown that a reduction in laser energy and an increase in postoperative steroid regimen account for an overall drop in the incidence of TLSS. Furthermore, according to Munoz et al., 23 postoperative interface inflammation may increase the probability of developing TLSS. According to Binder, 24 the gas from the evaporated cornea escapes into the episclera over the ciliary body and creates irritation through the ciliary body. Patients who present within the critical postoperative time eliciting extreme photophobia should be assessed for interface inflammation and likely considered to have TLSS based upon normal VA and normal anterior segment findings. The mainstay of treatment includes aggressive topical corticosteroid therapy, and in severe cases, oral treatment as well. All eyes receiving treatment should be monitored for elevated IOP due to this well-known side effect of steroids. Case 5: Epithelial ingrowth A 52-year-old man underwent bilateral CustomVue LASIK for treatment of compound myopic astigmatism. At six months postoperatively, he showed myopic regression and had a flap lift enhancement in the right eye. Four years postoperatively he returned for comprehensive evaluation and was noted to have two loci of epithelial ingrowth at the 4 and 7 o clock position in the right eye. Both loci contained a nest of epithelial cells that measured 2.0mm and caused mild recession of the flap edge. Given the peripheral location and size of the ingrowth, he was instructed to follow up in six months for re-evaluation. The next visit revealed documented growth to 3.0mm. Referral was made for surgical intervention and the patient had the cells successfully debrided.

5 Sponsored by Epithelial ingrowth describes aberrant epithelial cells that have migrated under the flap and into the interface. The most accepted theory proposes that active proliferation of conjunctival or corneal epithelium results in migration between the flap and the interface. Current reports describe the incidence to range from 1-10%. 21 Clinical associations such as flap dislocation, epithelial defects, flap relifts, and large ablation profiles have been noted to increase the risk of ingrowth. 21 Clinically, epithelial ingrowth may occur in two forms: (a) white grey small spots or lines located at the periphery that may be diffuse or localised and; (b) white or grey elevated colonies, sheaths, cysts or strands that adopt a more diffuse form. The first is considered a benign form that remains stationary and may Figure 5: Improvement in corneal haze to grade disappear over a period of four months; 1, of the eye shown in Figure 4, following PTK this might result in residual haze. The treatment second describes a more aggressive form of the condition with central progression and for two weeks then slowly tapered over the often keratolysis of the flap. The importance following four months. At the six-month of monitoring ingrowth is important for postoperative visit, his best corrected vision preventing advanced keratolysis that tends was 6/12 (part) with grade 3 haze (Figure to spread over the entire flap, resulting in 4) and complaints of poor vision, light hyperopia, irregular astigmatism and decreased sensitivity and ghosting. Given his subjective vision. 21 complaints and evidence of progressive haze that was refractory to topical corticosteroid Case 6: Corneal haze therapy, he was referred for transepithelial A 40-year-old man underwent bilateral phototherapeutic keratectomy (PTK); all CustomVue PRK with MMC 0.02% (for 30 laboratory tests for systemic autoimmune seconds) for the treatment of moderate disease were negative. Following PTK, his compound myopic astigmatism. Pre-operative cornea revealed grade 1 haze and 6/6 vision evaluation was normal with the exception of (Figure 5). dense corneal scars located outside the visual axis in both eyes. Over the first week after treatment, he experienced two episodes of Corneal haze is a well-known complication corneal erosion and grade 2 haze was noted following PRK and LASEK. A review of the in the left eye. Prednisolone acetate 1% (Pred literature suggests that corneal haze may Forte) was initially started every two hours occur as early as two weeks after treatment, peaks at nine months, and takes years to completely resolve. Surgical injury to the basement membrane and stroma results in abnormal collagen deposition, altered extracellular matrix and myofibroblast formation contributing to fibrosis, reduced transparency, regression and decreased vision. Risk factors include: ablation depth, slope of wound surface, volume of stromal tissue removed, level of correction, healing time, basement membrane integrity, Bowman s layer ablation and tear film transforming growth factor. 21 According to Netto et al., 25 two types of corneal haze exist: (a) typical transitory haze without visual compromise and; (b) lateonset haze that occurs two to six months postoperatively and may result in severely compromised vision. Fantes and others 27 went a step further and classified haze into 5 stages: 1) trace haze seen with oblique illumination; 2) haze not interfering with fine iris detail; 3) mild obscuration of iris detail; 4) moderate obscuration of iris detail; 5. complete opacification within the area of haze in which the anterior chamber is completely obscured. The best treatment for corneal haze is prevention. 26,27 MMC is an antibiotic derived from Streptomyces caespitosus and is a chemotherapeutic agent which modulates wound healing. 21 First suggested by Talamo in 1991, 28 intraoperative MMC 0.02% for up to two minutes has been shown to prevent haze formation after PRK (and LASEK) for high myopia. 21 Patients who develop visually significant haze require a trial with topical corticosteroids to control the immune response and limit the extension of haze. A slow steroid taper up to six months after treatment should be considered for aggressive cases. In eyes that are refractory to topical therapy, PTK may be considered and this has been found to be highly successful. 51 MORE INFORMATION References Visit click on the article title and then on references to download. Exam Questions Under the new Enhanced CET rules of the GOC, MCQs for this exam appear online at Please complete online by midnight on February 8, You will be unable to submit exams after this date. Answers will be published on co.uk/cet/exam-archive and CET points will be uploaded to the GOC on February 18, You will then need to log into your CET portfolio by clicking on MyGOC on the GOC website (www.optical.org) to confirm your points. Reflective learning Having completed this CET exam, consider whether you feel more confident in your clinical skills how will you change the way you practice? How will you use this information to improve your work for patient benefit? Find out when CET points will be uploaded to the GOC at For the latest CET visit

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