Laser eye surgery: back to the future

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1 1CET POINT Refractive surgery has evolved significantly in recent years, resulting in safer and improved visual outcome for patients. This article explores the historical development of refractive techniques, current approaches with regard to patient selection and details complications that can arise. Laser eye surgery: back to the future Nadia Chaudhry FRCOphth, Alex Hamilton MPHTM and Arun Brahma MD, FRCOphth INTRODUCTION The last two decades have seen a tremendous rise in the popularity of refractive eye surgery as a means for achieving spectacle independence. Refractive correction can be achieved either by altering the refractive power of the cornea or with the help of intraocular surgery. Corneal refractive surgery includes laser eye surgery (LES) involving corneal ablation by excimer laser; corneal addition procedures such as intracorneal ring segments and epikeratophakia; corneal relaxation procedures such as radial keratotomy (RK), arcuate keratotomy (AK) limbal relaxing incisions; and thermokeratoplasty. Intraocular refractive procedures include clear lens exchange and phakic intraocular lens implantation. The focus of this article will be on laser refractive surgery, including the history, technological aspects of lasers and a brief overview of the current literature on LES. THE PAST: HISTORY OF LASER EYE SURGERY Early refractive surgery procedures Course code: C Deadline: October 10, 2015 were first carried out by Japanese ophthalmologist, Tsutomu Sato in Sato performed anterior and posterior keratotomies to treat myopia after observing that patients with keratoconus who developed breaks in Descemet s membrane had reduction in their refractive error. However, 71% of his patients developed bullous keratopathy resulting from damage to the corneal endothelium, and this procedure was eventually abandoned. In 1960 a Russian ophthalmologist, Fyodorov, modified Sato s original ABOUT THE AUTHORS Nadia Chaudhry graduated from King Edward Medical College, Lahore, Pakistan in 2002 before coming to the UK for postgraduate training. She has attained FRCOphth from Royal College of Ophthalmologists, London and is currently working as a specialist trainee in ophthalmology at Eye Hospital. 51 To be able to explain to patients about the options for refractive surgery (Group 1.2.4) To be able to advise patients on their suitability for refractive surgery based upon clinical findings (Group 2.2.5) To be able to identify post-operative symptoms following refractive surgery (Group 6.1.2) To be able to explain to patients about different types of refractive surgery (Group 1.2.4) To understand the potential post-operative complications that can arise following refractive surgery (Group 8.1.5) To understand the typical post-operative symptoms following refractive surgery (Group 1.1.1) To be able to identify post-operative symptoms following refractive surgery (Group 2.1.3) Alex Hamilton undertook his ophthalmology specialist training in Sydney. He is currently a corneal and refractive surgery fellow at Eye Hospital. Arun Brahma is a consultant ophthalmic surgeon at Eye Hospital and specialises in corneal, cataract and refractive surgery. For the latest CET visit September 12, 2015

2 // REFRACTIVE SURGERY 52 The advent of the excimer laser was the most significant advance in the history of refractive surgery as it significantly improved the safety and efficacy of refractive correction Table 1 The degree of refractive correction offered by various procedures Intraocular surgery is the option of choice for refractive errors falling outside of the treatable range for PRK/LASEK/ LASIK but is also suitable for lower prescriptions technique to make it corneal endothelium-friendly by using anterior paracentral incisions rather than peripheral scleral incisions. This formed the basis of a technique known as radial keratotomy (RK), 3 which became popular for a few years before excimer laser eye surgery took the world by storm. The history of laser eye surgery goes back to the work of Professor Barraquer of Columbia who concluded that the key to altering the refractive status of the eye was changing the curvature of the cornea by adding or removing corneal tissue while preserving corneal layers. 4 He first used the term keratomileusis, derived from two Greek words, keras (hornlike, cornea) and mileusis (carving). The advent of the excimer laser was the most significant advance in the history of refractive surgery as it significantly improved the safety and efficacy of refractive correction. The term excimer describes ultraviolet lasers that generate nanosecond pulses with wavelengths between 157 and 351nm. The ultraviolet beam of light then vaporises tissues precisely by breaking up molecules without collateral damage to adjacent tissue; this pioneering work was carried out by IBM researcher, September 12, 2015 For the latest CET visit Srinivasan, who worked on interaction of 193nm with organic materials and used the term photoablative decompensation (photoablation) to describe this process. 5 The term excimer is derived from excited dimer, an interaction of argon and fluoride, emitting UV radiation with a wavelength of 193nm, removing on average, 0.25μm of corneal tissue per pulse. Stephen Trokel and Francis L Esperance further expanded on the interaction between excimer laser and the cornea and then filed for separate patents for photorefractive keratectomy (PRK). 6 Theo Seiler of Germany first performed excimer laser phototherapeutic keratectomy in a sighted eye in 1985, whereas Francis L Esperance performed the first PRK in the US on a blind eye in PRK was then followed by the development of LASIK (laserassisted in situ keratomileusis), which has now become the most commonly performed refractive procedure worldwide. Pallikaris and colleagues coined the term LASIK in 1988, a procedure involving corneal ablation by excimer laser under a hinged corneal flap created by an automated keratome. 8 It was thought that by creating an anterior lamellar corneal flap, the integrity of Bowman s layer and corneal neural net is preserved resulting in better healing and predictability, along with reduced pain and corneal haze. In 1989, the first LASIK was performed on a blind human eye in the University of Crete, and in 1992, Stephen Slade performed the first LASIK in the US. The initial clinical trials on LASIK began in 1996 and culminated in FDA approval for Refractive procedure Myopia Hyperopia Astigmatism PRK/LASEK <-6.00D <+4.00D <4.00D LASIK <-10.00D <+6.00D <4.00D Intraocular refractive surgery >-10.00D >+6.00D <6.00D LASIK in the US in 1999, nearly a decade after other parts of the world. 9 In the late 1990s, other variants of PRK were introduced including LASEK (laser assisted sub-epithelial keratomileusis) and EpiLASIK. 10,11 The latest advance in refractive surgery has been the use of femtosecond (FL) laser to create lamellar corneal flaps with a degree of precision and safety not possible with the automated microkeratome used in traditional LASIK. Dr Juhsaz and Dr Kurtz at the University of Michigan designed the first femtosecond laser system for use in ophthalmology in the early 1990s. 12 FL is increasingly used in LES to create anterior corneal flaps; 30% of LASIK procedures used a FL in 2006 with the number increasing to more than 55% by ,14 THE PRESENT: CURRENT STATUS OF LASER EYE SURGERY LES currently involves the use of both excimer laser and femtosecond laser to achieve the desired refractive correction. The frequency of the beam determines which biological tissues it will target, with lasers used in LES having a wavelength of around 193nm in the UV-C range of the electromagnetic spectrum. Their main target in the cornea is the peptide bond, linking the adjacent amino acids in collagen. When the laser beam strikes the cornea, it breaks these bonds and imparts kinetic energy to the resulting fragments. This results in highspeed ejection of material from the corneal surface, a process referred to as photochemical ablation. 15 There are three main approaches to photochemical ablation; wide area, scanning slit and flying spot: Wide area ablation uses a wide diameter beam and treats the entire operating field simultaneously, obviating the need for eye tracking. However, creating a wide diameter stable laser beam is costly and technically difficult Scanning slit ablation uses a

3 //REFLECTIVE LEARNING Having completed this CET exam, consider whether you feel more confident in your clinical skills how will you change the way you practise? How will you use this information to improve your work for patient benefit? rectangular beam of light, which passes over the corneal surface unidirectionally, remodelling the cornea over a course of several pulses; this smaller beam requires lasers with less output and ensures a uniform action with no limitation of the ablation area The flying spot ablation uses a tightly focused beam of light, which concentrates on a small corneal area at a time and moves rapidly in multiple directions. This technique needs lasers with low output, reducing the maintenance needs. Also, with the flying spot versatility, ablation can be carried out in a customised manner, increasing the indications for such lasers. The major disadvantage of flying spot technique is the longer ablating time, which in turn necessitates the use of eye-tracking device EXCIMER LASER Conventional excimer laser surgery is based on the patient s refractive status, and has good predictability for low to moderate myopia and low hyperopia. However, after LASIK, the optical quality is sub-optimal in some patients who complain of glare, haloes and problems with night vision due to higher order aberrations. This led to the development of optimised and customised wavefront-guided (WFG) LASIK, which aimed at correcting these aberrations by taking into account a wavefront map generated by the optical system of the eye. FDA approved this technique, called custom- LASIK in 2002 in the US, later than the rest of the world. 16 WFG LASIK has excellent outcomes and its efficacy in treating primary myopia and astigmatism was analysed in a report by American Academy of Ophthalmology. 17 This metaanalysis looked at available evidence on WFG LASIK in 2008 and found significant evidence that this technique is extremely efficacious with a high level of patient satisfaction. As compared to conventional LASIK, this technique has similar or better refractive accuracy and uncorrected visual acuity, improved contrast sensitivity, and less high-order aberrations. Most of the studies included in the metaanalysis did have a relatively short follow-up of 12 months or less. Excimer laser-based refractive procedures Surface procedures: PRK, LASEK and Epi-LASIK The first procedure, which involved the use of excimer laser, was PRK. This technique involves removing the corneal epithelium mechanically. The laser is applied to Bowman s layer to remodel the surface, with the epithelium growing back after a week or so. 18 The major disadvantages of PRK are pain, delayed visual recovery, corneal sub-epithelial haze and regression. In LASEK, a 20% diluted ethanol is used to loosen the corneal epithelium, which is reflected back on a hinge before excimer laser application to Bowman s layer. The epithelial sheet is then repositioned post-laser, theoretically reducing the pain and discomfort involved with PRK. In epi-lasik, an epikeratome is used to separate the corneal epithelium from the Bowman s layer before laser application. Despite LASEK being dubbed as painless PRK, many prospective studies have not shown any advantage of LASEK over PRK in terms of patient pain and ocular surface healing. 19,20 Lamellar procedure: LASIK LASIK is a lamellar procedure where an anterior corneal flap is made either with the help of a microkeratome or now increasingly with a femtosecond laser, and then application of an excimer laser to the corneal bed to remodel the refractive status of the eye. LASIK can be used to correct myopia, myopic astigmatism and hyperopia. However, the efficacy and safety of this procedure decreases with increasing preoperative refractive error Table 1 summarises the extent of refractive error correction offered by the different refractive procedures. With LASIK, the corneal epithelium and corneal nerve endings are protected; hence this procedure is patient-friendly with minimal pain. In addition, there is less sub-epithelial scarring and anterior stromal haze. However, the creation of a corneal flap can lead to a subset of related complications including corneal scarring and reduction in bestcorrected visual acuity. FEMTOSECOND LASER Femtosecond laser (FL) is a 1,053nm infrared laser, which works by photo-disruption of its target tissue. 24 FL is unique in that it has an extremely short pulse duration resulting in minimal collateral damage making it ideal for corneal surgery (see Figures 1 and 2). FL is increasingly being used in LASIK, astigmatic keratotomy, and channel creation for intrastromal corneal ring 14, 25 segments. The major use of FL in LASIK is flap creation, a procedure termed intralasik. Each pulse of FL Figure 1 Femtosecond laser used for corneal refractive surgery 53 For the latest CET visit September 12, 2015

4 // REFRACTIVE SURGERY 54 Figure 2 Flap creation by femtosecond laser on striking the corneal tissue generates ionized molecules, which in turn forms microscopic gas bubbles spreading to adjacent corneal tissue. Thus, pulses of FL create a cleavage plane leading to the formation of a precise LASIK flap; this flap is lifted with the help of a spatula before corneal remodelling by excimer laser. FL offers numerous advantages over the flap creation by microkeratomes, including high precision and safety, greater surgeon flexibility in creating corneal flaps, and reduced flaprelated complications. 26,27 FL is especially advantageous in very steep corneas (>48D) and in very flat corneas (<40D) by reducing the risk of flap buttonholes and free caps, respectively. Also, FL allows sparing of corneal tissue permitting treatment of higher degrees of myopia. Studies have shown that FL flaps in LASIK are associated with better visual outcomes, although many corneal surgeons prefer microkeratomes based on their own experience. 28,29 The major limiting factor in the use of FL in LES is the cost of the laser. There are complications unique to FL-associated flaps including: formation of an opaque bubble layer in the flap interface that may interfere with the working of the excimer laser eye tracking device and rarely even cause flap buttonhole; 30 transient light sensitivity syndrome resulting in extreme photophobia requiring intensive topical steroids; 31 and lamellar keratitis in the flap interface caused by FL-induced microscopic tissue injury. 32 INDICATIONS AND SUITABILITY OF LES The major contraindications of LES are: Systemic Autoimmune diseases such as lupus and rheumatoid arthritis Immunodeficiency Unstable diabetes mellitus Severe atopy Ocular Unstable refractive errors, keratoconus or suspect keratoconus Untreated severe blepharitis and dry eyes Uncontrolled uveitis Uncontrolled glaucoma Corneal scarring and herpetic eye disease Cataract An ideal candidate for refractive surgery will have the following characteristics: Desire to achieve spectacle independence and aware of the pros and cons of LES Stable refractive error over the last two years Over 18-years-of-age No significant ocular or systemic problems Not pregnant or breastfeeding Preoperatively, the patient should have a thorough ocular examination to ensure that none of the above mentioned contraindications are present. For contact lens wearers, the prelaser evaluation should be carried out two weeks after discontinuation of soft contact lenses and three weeks after hard or rigid gas permeable lenses. Uncorrected and best-corrected visual acuity and accurate refraction should be carried out. A complete work-up includes slit lamp examination with fundus visualisation, corneal topography and pachymetry. Pupils should be assessed using a pupil gauge or an infrared pupillometer. Patients with high degrees of refractive error and large pupils are at a higher risk of night glare and haloes. Corneal topography is essential prior to LES especially to identify patients with latent keratoconus. COMPLICATIONS OF LES With modern LES and the use of FL to create corneal flaps, the incidence of complications has significantly reduced but can still arise. Intraoperative complications The most important intraoperative complications are flap-related and include incomplete or irregular flap, thin flaps, free cap, buttonholes and full thickness corneal perforation. 33,34 Corneal perforation is a rare complication and occurs due to improper assembly of microkeratomes. 35 Modern microkeratomes with fixed depth plates have made this complication extremely unlikely. When flap-related complications develop and laser ablation is not performed, most patients return to their preoperative refractive status. 36 It is considered prudent to wait a period of three months before repeating LES, although the associated risks are higher at 12.5% as compared to 0.66% with flap-related problems in primary refractive surgery. 36,37 Corneal epithelial defects can develop especially in older patients, and they not only cause discomfort but are a risk factor for epithelial ingrowth and diffuse lamellar keratitis (DLK). 38,39 Early postoperative complications Flap dislocation can occur in the first 24 hours after LES requiring flap repositioning and sometimes a bandage contact lens. A microkeratome flap is more likely to dislocate than a FL flap. 40 Epithelial trauma during LES can result in epithelial ingrowth and again this complication is less common with the use of FL. 41 Diffuse lamellar keratitis (DLK) is a sterile inflammation of the interface without a microbial cause. It generally occurs in the first few days after surgery and is believed to be a nonspecific inflammatory response to a variety of stimuli including meibomian gland secretions, microkeratome blade debris, povidone-iodine solution, September 12, 2015 For the latest CET visit

5 red blood cells under the flap, and bacterial endotoxins. The patient presents with decreased visual acuity, pain and alterations in corneal topography including a hyperopic shift. Patients with mild DLK are treated with intensive topical steroids with antibiotic prophylaxis. Severe DLK requires lifting and irrigation of the flap with balanced salt solution, in addition to intensive topical steroids. 42 Infectious keratitis under the flap is rare, but potentially vision threatening, with incidence varying from 0 1.5%. 43 Early infectious keratitis within two weeks is caused by common bacterial pathogens such as Staphylococcus and Streptococcus, whereas lateonset infection is caused by opportunistic organisms like fungi, Nocardia and mycobacteria. 44 The treatment involves intensive topical antimicrobial antibiotics with discontinuation of topical steroids. Corneal haze after LASIK is minimal or absent especially when compared to PRK. 45 The addition of antimetabolite mitomycin C to LES, applied after excimer laser ablation at a concentration of 0.02% for 10 to 30 seconds, can further reduce the incidence of corneal haze as well as treatment regression. 46 Late postoperative complications Post-LES dry eye is a common problem, especially after LASIK, due to damage to the surface corneal nerves resulting in a neurotrophic cornea, which in turn leads to reduced lacrimal gland secretion. 47 A serious complication of LASIK is corneal ectasia due to weakening of the collagen lamellar structure of cornea. The major risk factors for corneal ectasia are thin cornea preoperatively, high myopic correction and leaving a postoperative stromal bed of less than 250µm. 48 The treatment of progressive corneal ectasia is complex and involves the use of rigid gas permeable contact lenses, intrastromal corneal rings and collagen cross-linking. 49,50 Problems with night vision including glare and haloes are also seen after LES. Glare is caused by optical aberrations and haloes can occur when the pupil size in the dark is greater than the treatment zone. The use of FL and WFG excimer laser has reduced the incidence of these complications. Patient expectations have dramatically increased Retinal detachment has been reported after LASIK, either due to peripheral retinal breaks in myopic patients or by pressure on the vitreous base caused by sudden compression and decompression of the eye due to the placement of suction ring. 51 THE FUTURE OF LES The major future goal of LES is to achieve vision better than 6/6 and to improve the quality of vision by completely eliminating optical aberrations. The increasing use of custom ablation to remove optical aberrations and FL to reduce flap-associated complications has helped refractive surgery take a giant leap forwards, and research is continuing in this area. Small incision lenticule extraction (SMILE) is a promising new flapless keratomileusis technique to correct myopia, and early results are encouraging. 52 It involves using a femtosecond laser to cut a lenticule of corneal stromal tissue, which is then removed through a small pocket incision made by the FL. Increasing developments in the field of corneal imaging are helping in preoperative selection of patients who want to undergo LES, hence reducing the incidence of post-lasik ectasia. Another field of interest is the use of collagen cross-linking and intrastromal corneal rings in combination with LASIK. Collagen cross-linking strengthens the cornea. When combined with refractive surgery it may reduce the risk of post-lasik ectasia in patients with thin corneas. A concept of photoablative inlay has been introduced called PAI-LASIK, where a hydrogel inlay is sculpted and placed between the flap and stroma. 53 This technique can be used to treat high degrees of refractive error without the risk of corneal ectasia, and is reversible. Early animal studies have shown that this material is biocompatible. CONCLUSION LES surgery has come a long way from RK to intralasik, greatly increasing in efficiency, predictability and safety. At the same time, patient expectations have dramatically increased and in this respect, refractive surgery is a victim of its own success. On-going developments in the field of corneal imaging and laser technology will lead to further improvements in the technique of LES in this rapidly evolving field. 55 Exam questions Under the enhanced CET rules of the GOC, MCQs for this exam appear online at Please complete online by midnight on October 10, You will be unable to submit exams after this date. Answers will be published on and CET points will be uploaded to the GOC every two weeks. You will then need to log into your CET portfolio by clicking on MyGOC on the GOC website ( to confirm your points. References Visit click on the article title and then on references to download For the latest CET visit September 8, 2015