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Saturday / June 15.
HomemiophthalmologyRefractive Surgery: Articles Review

Refractive Surgery: Articles Review

The following articles explore: comparisons between corneal laser techniques, combining techniques to improve safety and patient outcomes plus factors contributing to dry eye and ocular discomfort following LASIK.

LASIK Vs LASIK-Xtra

Researchers have described the application of prophylactic high-fluence cross-linking (CXL) concurrently with high myopic femtosecond laser in situ keratomileusis (LASIK) has been described as a “pivotal biomechanical enhancement of a LASIK procedure in… any patient who is younger than 30 years with myopia more than 6 D, with astigmatism more than 1 D, and any patient with a difference in the amount of astigmatism between the two eyes of more than 0.5 D”.

The rationale for LASIK-Xtra is to strengthen the cornea, particularly in patients with high myopia with thin residual stroma and in younger patients, prior to any indication of ectasia. The researchers wrote that LASIK-Xtra may be justified because without any such preventive application, a long-term, corneal steepening trend may occur, that results in a refractive shift.

The findings were presented following research that evaluated the possible topographic epithelial profile thickness changes after stand-alone LASIK with concurrent prophylactic CXL (LASIK-Xtra) in patients with high myopia. The researchers found that LASIK-Xtra resulted in a statistically significant reduced epithelial increase in comparison with stand-alone LASIK. Their findings were published in Cornea Journal.

…how much XL do you need for prophylactic treatment of these normal, albeit high risk, corneas?

One hundred thirty-nine consecutive eyes were enrolled for this prospective, observational, longitudinal study. All eyes were enrolled for primary myopic LASIK correction and had no other previous ocular surgery. They had no present or past ocular pathology other than refractive error, no epithelial defects, irritation or dry eye disorder.

During the last six years of the study, patients with high myopia (more than – 5 D spherical equivalent) and / or high keratometric preoperative astigmastism (more than 1.5 D on the Scheimpflug-derived simulated keratometry) who were being treated with LASIK, were randomised to receive LASIK-Xtra.

Post-operatively, patients were evaluated for dry eye, indications of epithelial ingrowth, corneal haze or ectasia, and measurement of the best-spectacle corrected distance visual acuity.

No Statistical Difference

The researchers found no statistically significant difference in post-operative epithelial thickness changes between the two moderate myopia subgroups (up to -7.00 D). There was no statistically significant increase in epithelial thickness in the high myopic patients who were treated with LASIK-Xtra. They identified a significant increase in the epithelial thickness change in the high myopic patients who received stand-alone
LASIK treatment, of average magnitude between +8 and =9 µm.

They proposed a number of factors that may explain this increase in epithelial thickness, among them “that the amount of epithelial thickening is determined by the rate of change of the curvature of the stromal surface”; and that “a thinned cornea (especially in large myopic ablation) might become biomechanically less stable, thus oscillate more because of external factors and / or be more susceptible to aqueous pulsing, and as a result, induce epithelial hyperplasia”.

The researchers noted that theories resulting from the study findings were important because over the past two decades myopic regression after LASIK
has been treated by retreating the cornea with a new excimer laser ablation. They said this had the potential to exaggerate epithelial hyperplasia.

Comment
Basically, refractive surgeons are very interested in understanding corneal ectasia and preventing post-LASIK corneal ectasia. Although the pathogenesis is not fully understood, there are many patient factors that have been identified as “high risk”. Namely, young patients with thin corneas, high ablations and inferior steepening are approached with caution. The few that actually develop ectasia are possibly in the genetic spectrum of keratoconic predisposition and the laser ablation “hastens the process” so watch this space: exciting research is looking to understand this pathology and I wonder how it will be classified in future…Connective tissue disorder? Collagen vascular disease? Post-infective? I digress.

We don’t know too much yet but it has been proposed that combining collagen cross-linking with LASIK in high-risk individuals may aid in maintaining structural stability of the cornea. The technique described in this paper seems to affect a change i.e. less epithelial hyperplasia occurred after LASIK plus a short burst of XL “LASIK-Xtra” in high myopes compared to stand alone LASIK. However, the only proven method found to stabilise progressive ectasia is substantially more involved than the riboflavin/UV delivery of LASIK-Xtra so the question is, how much XL do you need for prophylactic treatment of these normal, albeit high risk, corneas? A measureable difference in epithelial thickness tells us that something is happening but only time will tell whether this technique statistically improves the risk of ectasia for these patients.

The authors propose that the LASK-Xtra technique may enhance corneal stability (as indicated by less compensatory epithelial hyperplasia), which in turn may reduce the potential for ectasia and also that of myopic regression. Should this be proven, it would be an excellent advance towards improving safety in high-risk individuals.

Reference:

Anastasios J. Kanellopoulos, MD and George Asimellis PhD. Epithelial Remodelling After Femtosecond Laser-assisted High Myopic LASIK: Comparison of Stand-alone With LASIK Combined with Prophylactic High-fluence Cross-linking. Cornea, Volume 33, Number 5, May 2014.

Excimer Laser Surface Ablation

An article by Dr. David P.S. O’Brart reviewed recent published literature of excimer laser surface ablation procedures, concluding that modern excimer laser surface treatments deliver excellent refractive and visual outcomes that are comparable with those after LASIK, even in complex cases characterised by previous corneal surgery. Studies show that “long-term stability and safety appear to be extremely satisfactory” following this technique.

Dr. O’Brart reported that limitations of early excimer laser refractive surgery have been overcome with “the development of large optical zone treatments, smooth ablation profiles with flying spot laser technology and modulation of wound healing with adjunctive medications such as Mitomycin-C”. The DNA alkylating agent, Mitomycin-C, has long been used as an adjunctive medication intraoperatively immediately after laser ablation to “suppress wound healing and thereby reduce haze and regression of correction”. He noted that long-term studies are needed to determine “the precise influence many decades after PRK of intra-operative mitomycin-C on the health and functioning of the cornea and its endothelium”.

Among others, Dr. O’Brart highlighted a randomised bilateral study by Wallau and Campos which found that eyes treated with PRK reported statistically better uncorrected vision and visual acuity, improved post-operative contrast sensitivity and less induction of high-order aberrations than eyes treated with LASIK. A study by Moshirfar and colleagues found that while efficacy, predictability, safety and contrast sensitivity showed so statistical difference between the two procedures, PRK treated eyes had significantly less higher-order aberrations.

The author outlined a number of studies comparing outcomes achieved using different techniques to remove epithelial; i.e. mechanically using blades and brushes as in the original PRK; LASEK using alcohol, where the epithelium can be removed and replaced as a single sheet; with modified micro-keratomes (epi-LASIK) and trans-epithelial PRK, (by blade). The author concluded that studies to date have revealed conflicting outcomes and further randomised clinical trials are necessary to be able to choose between the various methods. “The technique for epithelial removal can be left to the preference of the individual surgeon,”
he wrote.

On the basis of recently published literature, the author suggested that combined collagen cross-linking and topographic-PRK treatments may be considered. Dr. O’Brart wrote that “riboflavin / ultraviolet corneal collagen cross-linking is the first treatment that seems to arrest the evolution of keratoconus and even to enhance refractive and topographic parameters… As well as an isolated treatment, collagen cross-linking has been used in combination with other procedures such as topography-guided PRK, to optimise visual and refractive outcomes in keratoconus and even post-LASIK ectasia. Combined collagen cross-linking and limited topography guided PRK with ablation depths generally less than 50um, in eyes with moderate keratoconus and post LASIK-ectasia, is effective with reported significant improvements in visual, refractive and topographic parameter and stabilisation of the ectactic process in the vast majority of eyes.”

The author reviewed several studies of treatment on post-corneal surgery eyes and said the results were “very encouraging and comparable to published series treated with LASIK but without any of the attendant flap complications”. Dr. O’Brart noted his preference for trans-epithelial, corneal wave-front topography-guided PRK augmented with Mitomycin-C to address and correct both low and higher-order aberrations for these complex cases, even though haze may still occur.

He concluded that long term stability and safety appear to be extremely satisfactory for eyes treated with modern excimer laser surface treatments.

Comment
PRK preceded LASIK as a revolutionary surgery used to treat refractive error by altering the corneal shape. Over the last decades, technologies have continued to improve and parameters are better understood. Modern day PRK, usually now called ASLA: Advanced Surface Laser Ablation, is a wonderful procedure with results comparable to LASIK and some studies show potentially better visual outcomes with surface laser. Certainly, this article points out that higher order aberrations are worse after LASIK compared to PRK but surgical technique is not uniform amongst surgeons and factors such as flap size, flap centration, flap striae, treatment zone over pupil, femto vs. microkeratome cut and so on, all determine the likelihood of problematic HOA after LASIK.

Certainly there are cases for which LASIK is preferable over PRK e.g. higher scripts. LASIK also offers a faster recovery with almost no discomfort post-operatively. However, judicial use of analgesia, sedation and bandage contact lenses may make the post PRK journey more comfortable.

In terms of techniques used to remove epithelium, surgeons have different preferences. I personally find the latest model brushes to be precise, smooth and accurate. Alcohol can create a lovely round debridement, but if the patient suddenly moves and the alcohol leaks across the surface of the eye, chemical irritation may occur. Peeling the epithelium off and then replacing it, such as with LASEK or epi-LASEK, makes little sense to me as the tissue is a single layer of avascular cells and is more likely to necrose and fall off than integrate with surrounding tissue. Also, as epithelium replicates so quickly, I prefer to see a fresh layer regenerate within a couple of days rather than trying to salvage the amputated tissue. Excimer laser removal of epithelium is limited to certain laser platforms and is a more recently devised method of debridement, favoured by some….Yes there are many ways to “skin a cat”, as the saying goes, and probably many of the techniques out there are equally best. As mentioned above, what really matters is what the surgeon feels works best in his/her hands.

Intraoperative Mitomycin C is an excellent anti-scarring agent and is commonly used with high success in ablations of 70 micron or more, or with cylinder corrections. Some surgeons use it routinely and some not at all. I find it an excellent adjuvant agent in terms of preventing haze in patients who have a higher risk of scarring.

Combining collagen cross-linking with surface laser is a point of contention and is not yet a mainstream procedure. Cross-linking alone has been well established in terms of stabilising corneal ectasia but one of the characteristics of a post cross-link cornea is that it usually changes shape (reduction of steep K’s is common) and this changes the refractive error. It is not uncommon to see visual improvement in the majority of post cross-linked eyes. Therefore, if any type of effective cross-linking is used in conjunction with refractive surgery, the patient needs to be counselled in regards to a possible “refractive surprise” i.e. the outcome is difficult to predict. It makes sense to me to cross-link first, gauge the stabilisation and refractive change, and then if necessary, do the excimer ablation 12 months (approx.) later.

Reference:

David P S O’Brart. Excimer Laser Surface Ablation: A Review of Recent Literature. Clinical and Experimental Optometry. May 2013

Dry Eye and LASIK

Researchers have proposed that rather than treating post-LASIK dry eye with tear supplements and punctal plugs, a better approach would be “to direct management towards the possible neural mechanisms underlying the dry eye symptoms and associated changes to the ocular surface after LASIK”.

Dry eye syndrome is common among patients who undergo laser in situ keratomileusis (LASIK) with approximately half of all patients undergoing the procedure reporting symptoms of dry eye up to six months after surgery, peaking one week to three months after LASIK. The incidence of chronic dry eye increases by 18–41 per cent after LASIK.

This eye disease affects patients whether or not they had dry eye prior to LASIK, though those who had dry eye prior report worse dry eye and report more frequently than those who had not previously experienced dry eye. Additionally females, patients of Asian descent and patients undergoing procedures in which flaps are created using a microkeratome, reported dry eye more frequently that other patient groups.

Despite the prevalence of dry eye among people who have been treated for LASIK, the etiology of LASIK-induced dry eye is unclear and the clinical indicators were not consistent with the changes in dry
eye symptoms.

Cecelia Chao; Professor Blanka Golebiowski and Professor Fiona Stapleton have reviewed the current evidence surrounding post-LASIK dry eye, focussing on ocular surface sensitivity and corneal innervation. They noted that post-LASIK dry eye was most likely to be caused by corneal flap formation, photoablation and disturbance to corneal homeostasis and lacrimal functional unit, which together disrupts a patient’s corneal nerves.

Signs of Dry Eye

The researchers identified the signs of dry eye after LASIK as:

A significant decrease of tear secretion and volume immediately after LASIK. Tear secretion returned to pre-operative levels one to six months after LASIK while volume returned approximately three months after LASIK.

LASIK-induced neurotropic epitheliopathy – or corneal epithelial erosion – between the first week and third month post LASIK (experienced by 4 to 14 per cent of LASIK patients). This was more commonly associated with a superior flap hinge and most likely due to the severing of corneal nerves during the procedure.

Increased conjunctival staining in the first week, possibly a result of denervation which increased tear osmolarity and decreased goblet cell density.

Reduced production of mucin due to the significant decrease in goblet cell density for six months post-LASIK. Mucin plays an important role in the stabilisation of the tear film. The authors noted that goblet cell density reduction occurred both after photorefractive keratectomy (PRK) and after LASIK, suggesting this may be a secondary effect of corneal nerve damage and subsequent inflammation.

They noted that patient demographics and hinge characteristics might also be important signs of post-LASIK dry eye. Additionally, tear neurotransmitters and neuropeptides play a role.

Importantly, the authors noted that changes in the clinical indicators of dry eye after LASIK were not consistent with the changes in dry eye symptoms. Additionally, patents who had undergone LASIK reported different symptoms when compared to patients who had undergone PRK. “LASIK patients tend to report ocular dryness while the patients who underwent PRK do not habitually report dryness but other sensations, including soreness to touch and sharp pain,” they wrote.

Nerve Recovery Post-LASIK

Several studies have provided evidence of corneal nerve damage and disruption after LASIK. Although current technology makes the extent of damage or repair difficult to detect, the authors wrote that the central subbasal corneal nerves start to regenerate about two weeks post LASIK then increase significantly from the sixth month and within two to five years have returned to pre-operative levels. Nerve reduction and regeneration levels varied in different regions within the LASIK flap.

The authors wrote “the current body of evidence suggests that flap creation causes significant damage to corneal nerves irrespective of the flap size or method of flap creation, but the nerves are still disrupted more severely at higher correction range (cut-off point: -6.00 D).” They noted that ablation depth is the only surgical factor proven to affect initial corneal nerve regeneration, with a lower myopic cornea, which requires a small ablation depth, having a greater number of long subbasal nerves than a higher myopic cornea, which requires a greater ablation depth.

Corneal Sensitivity

According to the authors, “corneal sensitivity is a measure of corneal nerve function and indicates the integrity of the protective mechanisms of the ocular surface.” While this sensitivity decreases by about 50 per cent of the Cochet-Bonnet filament length after LASIK, it recovers gradually to almost pre-operative levels between six months and one year. The impact of surgical factors – such as the size of the flap, the way in which it was created; hinge position and diameter; and the level of refractive correction – on corneal sensitivity are as yet unclear. The authors note that “the recovery of sensitivity appears faster with nasal hinge flaps for up to three months after LASIK, although the sensitivity with nasal hinge LASIK flaps did not return to pre-operative levels in two studies”. Additionally they note that “refractive correction may play a role in the recovery of corneal sensitivity”. They noted the recovery in corneal sensitivity and corneal nerve morphology after LASIK do not occur over the same time frame, with sensitivity returning to pre-operative levels within less than a year and corneal nerve parameters (NBD and density) taking a year to return to half their respective pre-operative values. Corneal nerve density takes two to five years to almost return to pre-operative levels.

They said it is important to understand the relationships between clinical indicators of dry eye, corneal sensitivity, and corneal nerve morphology as well as dry eye symptoms after LASIK. This is because, “the evidence… supports a relationship between dry eye signs and corneal sensitivity after LASIK because both return to pre-operative levels at the same time point. However there is no similar association between either the signs of dry eye or corneal sensitivity and dry eye symptoms after LASIK. Dry eye symptoms or ectopic pain may be due to either damaged nerve axons or subclinical inflammation in the presence of normal tear secretion and normal corneal sensitivity.

“…there is often a lack of evidence that dry eye is, in fact, dry. This apparent dichotomy between morphology and function is conceivably due to abnormal sensations resulting from damaged nerves.”

Comment
Early in medical school we were taught that “pain is good”. Let me qualify that:

Pain is a warning to us that danger is present and alerts us to remove ourselves promptly from the stimulus causing pain. For example, hold your finger in a flame and pretty quickly the finger will be burnt if you don’t pull it away. Pain allows us to do that and people with abnormal sensation do not enjoy the same
protective mechanism.

Surgery without anaesthesia is, of course, painful in patients with normal sensation. Postoperative pain is also normal as wounds heal. However, the issue of “pain after the wounds have healed” is intriguing and in the case of the cornea, what happens to the damaged corneal nerves down the track is of great interest. We tend to blame any long term ocular discomfort on “dry eye”… but is it?

“Dry eye” after LASIK is a well-known, well-accepted and earnestly treated complication. Despite the high incidence of dry eye after LASIK, it does not by and large put patients off from having a surgery which literally can be life changing. Clinically, it is actually fairly uncommon (thankfully) that the dry eye becomes a real problem to the patient and a course of lubricating drops will usually assist the patient adequately until the problem recovers naturally.

The interesting point that this article makes is that there is little correlation between dry signs and the patient’s level of discomfort so possibly the patients with significant symptoms are not the same patients showing clinical signs of dry eye. Whilst dry signs tend to recover at the same time as corneal sensitivity (after nerves have been severed and then repair), the symptoms seem to be a separate story altogether. So the question is: when patients experience ocular discomfort after LASIK, does it have anything at all to do with corneal sensitivity and dry signs?… This article suggests quite logically that there is more to it. Neuropathic pain and inflammatory cascades following nerve damage may be the prime suspects in
terms of causing patient discomfort, rather than the dry eye per se, and lubrication and punctual plugs minimally improve these factors. Enter the conceivable players of new anti-inflammatory therapies that potentially could be in the form of topical medications, autologous products (e.g. serum or blood extracts, systemic therapy or other modalities that may alter neural function). Certainly neuropathic pain is not news to the surgical world, and most people have heard of phantom limb pain but it would seem that we have not fully explored this issue with corneal LASIK. I find it exciting to think how we may be approaching this issue differently in years to come.

Reference

Cecelia Chao, MOptom, Blanka Golebiowski, PhD, and
Fiona Stapleton, PhD. The Role of Corneal Innervation in LASIK-induced Neuropathic Dry Eye. The Ocular Surface, January 2014, Vol 12, No. 1

Dr. Abi Tenen specialises in refractive and cataract surgery. She is expert in laser eye surgery and was the first Australian female surgeon to qualify in the use of femtosecond laser technology.

Her areas of specialty are LASIK, ASLA, implantable contact lens surgery, refractive lens exchange, keratoconus, collagen cross-linking, intracorneal rings, pterygium surgery with conjunctival autografting and cataract surgery with premium intraocular lens implants.

Dr. Tenen is in private practice at the Vision Eye Institute in Victoria and holds a senior lecturer position with the medical faculty, Monash University.