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Modern Corneal and Refractive Procedures

  • Authors: Jean Chuo, MD; Sonia N. Yeung, MD, PhD; Guillermo Rocha, MD, FRCSC
  • CME Released: 4/13/2011
  • Valid for credit through: 4/13/2012
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Target Audience and Goal Statement

This activity is intended for ophthalmologists and other physicians who perform corneal and refractive surgical procedures.

The goal of this activity is to evaluate modern techniques of corneal and refractive surgical procedures.

Upon completion of this activity, participants will be able to:

  1. Analyze potential benefits of the femtosecond laser in corneal procedures
  2. Evaluate current practices in keratectomy
  3. Distinguish critical elements of corneal collagen crosslinking
  4. Describe the use of the Boston keratoprosthesis


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  • Jean Chuo, MD

    UBC Department of Ophthalmology & Visual Sciences Eye Care Centre, Vancouver, British Columbia, Canada


    Disclosure: Jean Chuo, MD, has disclosed no relevant financial relationships.

  • Sonia N. Yeung, MD, PhD

    UBC Department of Ophthalmology & Visual Sciences Eye Care Centre, Vancouver, British Columbia, Canada


    Disclosure: Sonia N. Yeung, MD, PhD, is funded by the Canadian National Institute for the Blind through the EA Baker Scholarship.

  • Guillermo Rocha, MD, FRCSC

    Department of Ophthalmology, University of Manitoba, Winnipeg, Brandon Regional Health Authority, Brandon, MB, Canada


    Disclosure: Guillermo Rocha, MD, FRCSC, has disclosed no relevant financial relationships.


  • Elisa Manzotti

    Editorial Director, Future Science Group, London, United Kingdom


    Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME Author(s)

  • Charles P. Vega, MD

    Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine


    Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

  • Nafeez Zawahir, MD

    CME Clinical Director, Medscape, LLC


    Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC


    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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Modern Corneal and Refractive Procedures: Anterior Corneal Procedures


Anterior Corneal Procedures

Excimer Laser-assisted Procedures

Photorefractive Keratectomy. Since the first excimer laser ablations were performed on human eyes by McDonald et al.[1] and Seiler et al.[2] in 1988, photorefractive keratectomy (PRK) initially became one of the most popular refractive surgeries, correcting simple and compound myopic astigmatism, and simple and compound hyperopic astigmatism (Figure 1).[3–5]

Figure 1.


Anatomic Overview of Various Corneal Procedures. (A) Layers of the cornea. (B) Location and depth of corneal involvement of various procedures. DALK: Deep anterior lamellar keratoplasty.

Like all refractive surgeries, PRK is performed using topical anesthesia. Since the precise corneal epithelial thickness is unknown, the epithelium is typically first removed either mechanically, with or without the use of alcohol, or with the excimer laser. Epithelial removal allows for accurate stromal ablation with the excimer laser, which is preprogrammed with the patient’s specific refraction and optical treatment zone. Owing to the central corneal abrasion, patients often experience significant tearing, photophobia and discomfort during the early postoperative period. Topical antibiotics, steroids and NSAIDs are used along with a bandage contact lens (BCL) that remains on the eye until the epithelial defect is healed.

Sight-threatening complications have been reported in as few as 1–2% of patients undergoing PRK.[6] Haze formation and scarring associated with regression of refractive effect, light scatter and irregular astigmatism is one of such complications[7] that has significantly decreased[8] since the use of mitomycin C was popularized by Majmudar and Epstein in 2000.[9] Although potential toxicity to the epithelial, stromal and endothelial keratocytes exists with mitomycin C use,[10–14] the use of mitomycin C in refractive surgery is supported by the current literature.[15]

Decentration of the ablation zone can lead to disturbing visual sequelae, including irregular astigmatism, persistent halo and monocular diplopia.[7] It is a rare complication now owing to the use of the eye-tracking device and the close monitoring of the patient’s fixation by the surgeon. Halos, glare and diurnal visual fluctuation were previously common occurrences that generally subsided within 6 months following the operation.[16] They are now uncommon owing to advances in techniques, especially with customized ablation.

Laser-assisted in situ Keratomileusis. Initially described by Pallikaris et al. in 1990, laser-assisted in situ keratomileusis (LASIK) has become the most commonly performed corneal refractive surgical procedure (Figure 1). It combines photoablation using the excimer laser and an intrastromal surgical technique that preserves the integrity of the outer cornea.[17]

In LASIK, a corneal flap consisting of the epithelium and part of the stroma is made with either the microkeratome or the femtosecond (FS) laser. With the microkeratome, the flap can range from 130 to 160 µm deep,[3] depending on the degree of refractive correction required. With the FS laser, the flap is created by delivering laser pulses at a predetermined stromal depth, usually between 100 and 110 µm deep. The flap is hinged in both cases.

After the corneal flap is made and flipped back to expose the stroma, the excimer laser beam is applied to the stromal bed in a fashion similar to that in PRK. The corneal flap is replaced after the ablation by accurately realigning the fiduciary lines made with radial keratotomy or custom LASIK markers prior to the procedure,[18] although this is now less frequently performed with the use of the FS laser.

The advantages and limitations of LASIK are well documented, especially in comparison to PRK. A Cochrane collaboration methodology meta-analysis/systemic review conducted by Shortt et al.[19,20] concluded that LASIK is safer and more accurate than PRK, with less postoperative pain and more rapid visual recovery (2–3 days with LASIK and 4–15 days with PRK).[21] The amount of haze and regression is also less with LASIK, especially in patients with severe myopia.[22] However, some studies found LASIK to be associated with more complaints of dry eye, worse contrast sensitivity and night vision, inferior correction of high-order aberrations (HOAs), flap complications and, arguably, an increased risk of corneal ectasia.[23–26]

Flap complications caused by the microkeratome are well documented, occurring in up to 3% of cases, and are related to the surgeon’s experience with using a microkeratome.[27,28] Incomplete flap creation or failure of the microkeratomes to stop at the hinge results in a free flap.[29] Other complications include buttonholes, short flaps, blade marks and irregular cuts. These can mostly be managed by repositioning the flap and deferring photoablation, with no significant loss of best-corrected visual acuity (BCVA). The most devastating complication is intraocular penetration from a misassembled microkeratome.[30] Postoperative flap-related complications include loss or dislocation of the flap, which can result from incomplete adherence of the flap to the stromal bed, leading to significant haze formation. Other flap-related complications include diffuse lamellar keratitis (‘shifting sands of the Sahara’),[31] epithelial ingrowth (Figure 2) and wrinkling of the flap.

Figure 2.


Post-laser-assisted in situ Keratomileusis Epithelial Ingrowth at the Flap–stromal Interface. Courtesy of Allan Slomovic (University of Toronto, ON, Canada).

Many refractive surgeons have turned to the FS laser for flap creation to minimize complications and improve surgical outcome. A poll taken in 2006 found that over 30% of all LASIK flaps were made with the FS laser under such monikers as ‘IntraLASIK’, ‘all-laser LASIK’ and ‘bladeless LASIK’.[32] The major advantages of FS laser flap creation over the mechanical microkeratome are:

  • Reduced intraoperative flap complications;
  • Stronger flap adhesion, which is likely to reduce trauma-associated flap dislocation and, possibly, the risk for corneal ectasia;
  • Improved flap strength and less variable central corneal thickness;
  • Capability of cutting thinner flaps (90 µm) to accommodate thin corneas and/or high refractive errors;
  • Fewer induced HOAs;
  • Reduced LASIK-related dry eyes.[32–46]

Corneas that underwent FS laser-assisted LASIK have also been found to be biomechanically similar to those that underwent PRK.[47]

The use of FS lasers in LASIK is not without complications. Earlier models have been shown to lead to an increased incidence of diffuse lamvellar keratitis[48] and a greater risk for haze development,[49] which is likely to result from the induced inflammatory response.[50] More recent models, such as the 60- and 150-kHz lasers, induce a much smaller inflammatory response.[51]

A unique side effect of the FS laser is transient light-sensitivity syndrome, which is known for intense photophobia with good uncorrected distance visual acuity and an unremarkable slit-lamp examination at 2–6 weeks after uneventful LASIK.[52] Similarly, it is associated with the earlier models but rarely with the later models, and is postulated to have an inflammatory origin with a good response to steroid treatment.[45,52]

Laser Subepithelial Keratomileusis & Epipolis Laser in situ Keratomileusis. Laser subepithelial keratomileusis (LASEK) emerged as an alternative to PRK and LASIK.[53–55] In 1996, Azar et al. performed the first LASEK procedure, termed ‘alcohol-assisted flap PRK’.[56] It was later renamed by Cimberle and Camellin.[57]

An alternative approach termed epipolis LASIK (epi-LASIK) was introduced by Pallikaris et al.[58] It involves epithelial separation by mechanical means using a subepithelial separator similar to a blunt microkeratome. The theoretical advantage of epi-LASIK over LASEK is that the epithelial layer is separated from the stroma without the use of alcohol, which is potentially toxic to the epithelium and corneal stroma.[59–61]

By creating a corneal epithelial flap, LASEK/epi-LASIK can be seen as a hybrid of PRK and LASIK that may address the discomfort and delayed recovery associated with PRK while eliminating virtually all flap-related complications of LASIK.[56,62–66] Some studies have found less corneal haze[67,68] and decreased levels TGF-β1.[67] However, other investigators found no difference between PRK and LASEK with regards to pain, recovery time, final visual outcome and patient preference.[69] When compared with LASIK, patients who underwent LASEK had more pain with the early postoperative period and an increased time to visual stabilization.[70]

Phototherapeutic Keratectomy. Phototherapeutic keratectomy (PTK) has been investigated since 1988 and was approved by the US FDA in 1995 for the treatment of anterior corneal disorders. It is best suited to pathological processes in the anterior 10–20% of the corneal stroma, specifically anterior stromal scars, dystrophies, elevated corneal lesions and infectious keratitis.[71,72] PTK can be an alternative to lamellar keratoplasty or penetrating keratoplasty (PKP) in many cases.[72]

Simple PTK, or PTK without the use of adjuncts, is very similar to PRK. Corneal thickness and the depth of pathology are estimated preoperatively using various techniques. The epithelium and anterior stroma are ablated with an excimer laser up to a certain percentage of this estimated depth. The effect of the laser treatment is then assessed using a slit-lamp microscope and ablation is repeated if necessary. This shoot-and-check technique is continued until the bulk, but not necessarily all, of the pathological process is removed. The tendency is to keep ablating until all the opacities have been removed, but that often results in a deep ablation with significant induced corneal flattening and excessive corneal haze.[73] BCL is applied immediately post-treatment.

Simple PTK is a safe procedure that is most effective for those with a smooth corneal surface.[74–77] For those with an irregular corneal surface, this surface contour is duplicated deeper into the corneal tissue with simple PTK, owing to the flat-beam profile and beam homogeneity of the excimer laser. A variety of techniques are used to overcome this hurdle. If the epithelium is loose and irregular, it is removed mechanically. Elevated lesions may be debulked with a blade or ‘chipped away’ with the laser using small spot sizes.

The use of masking/modulating agents can also be helpful. These substances protect depressions on the corneal surface so that elevations are ablated preferentially. Some of these agents, such as artificial tears and tetracaine,[78–80] are simply applied frequently onto the corneal surface during treatment. Others, such as BioMask[81,82] and Photo-Ablatable Lenticular Modulator,[83] are applied to the cornea in situ and moulded with a rigid contact lens in its liquid state. As the agent solidifies, its bottom surface fills the corneal surface irregularities while its upper surface reproduces the inner surface of the contact lens.[81,84] Most recently, wavefront or topography-guided corneal ablation has become a popular means of reducing or eliminating corneal surface irregularity.[85,86] PTK is also successful in treating recalcitrant, recurrent corneal erosions.[87] After all the loose epithelium is debrided, the Bowman’s layer is ablated uniformly to just 5–6 µm deep.

In summary, PTK is a very safe and versatile technique that is quite effective at treating a wide variety of anterior corneal lesions. Moreover, if unsuccessful, an anterior lamellar graft can often be performed. For these reasons, PTK is frequently the procedure to attempt before going onto a corneal transplant.

Nonexcimer Laser Procedures

Bowman’s Layer Transplantation. The development of haze in the anterior corneal stroma following surface ablation with an excimer laser is likely to result from an abnormal wound-healing response. Since subepithelial stromal scarring does not occur in the presence of the Bowman’s layer, Melles and colleagues hypothesized that scar excision followed by isolated Bowman’s layer transplantation would restore a clear cornea and improve visual acuity.[88] He recently reported the first isolated donor Bowman’s layer transplantation and concluded that persistent subepithelial haze after excimer laser surface ablation unresponsive to retreatment may be effectively managed with superficial scar dissection followed by Bowman’s layer transplantation. No recurrent scarring was noted over 6 months in their published case. This technique may be an alternative to antiproliferation agents, deep anterior lamellar keratoplasty (DALK) or PKP for this particular indication.

Automated Anterior Lamellar Keratoplasty. By contrast with PKP,[87] automated anterior lamellar keratoplasty (ALK) is a procedure in which only part of the cornea anterior to the Descemet’s membrane (DM) is replaced by donor corneal tissue.[89,90] Over the past decade, lamellar keratoplasty has gained a renewed interest owing to advances in microkeratomes and FS lasers.[91]

Indications for automated ALK are opacities or irregularities in the anterior to mid-stromal region of the cornea, ranging from herpetic scarring to anterior stromal dystrophies.[92] Lamellar keratoplasty has many advantages over PKP.[92] First, the anterior chamber is not entered in lamellar keratoplasty, reducing the risk of expulsive hemorrhage or endophthalmitis. Second, the corneal endothelium is not transplanted, decreasing the risk of graft rejection. Last, the recovery is shorter postoperatively, and visual rehabilitation is faster. When compared with other lamellar techniques, automated ALK is a procedure of relative ease with rapid visual recovery.[91]

Deep Anterior Lamellar Keratoplasty. In situations where the pathological process is in the deep stromal area but does not affect the endothelium, one must increase the depth of the keratectomy (Figure 1). In DALK, the recipient is prepared by excising a corneal disc spanning the thickness of the entire stroma, without DM. A donor button with its DM stripped off is sutured into the recipient bed (Figure 3).

Figure 3.


Post-deep Anterior Lamellar Keratoplasty. (A) 6 weeks post-deep anterior lamellar keratoplasty. (B) Post-deep anterior lamellar keratoplasty with Descemet’s membrane detachment. Courtesy of Jeffrey Judelson (SK, Canada).

It is not easy to dissect the cornea down to the DM since the depth of dissection, relative to the corneal thickness, is difficult to visualize, resulting in possible DM microperforation.[93] Several techniques have been advocated to overcome this hurdle. All of them focus on facilitating the identification of DM and/or the predescemetic plane to obtain a smooth deep surface with uniform thickness. Sugita and Kondo proposed the use of hydrodelamination, whereby a saline solution is injected into the stroma with a blunt needle.[94] The stroma whitens when the solution penetrates between the collagen fibers, allowing for easy identification and removal. Melles and Manche both proposed a technique where viscoelastic material is forced through the posterior stromal lamellae, causing the DM to separate and the overlying tissue is then excised.[95–99] Alternatively, several authors,[90,100–102] including Anwar and Teichmann who ultimately modified it,[103,104] proposed the so-called big-bubble technique using air to delaminate the corneal stroma and to separate it from the DM.

Deep anterior lamellar keratoplasty was historically associated with poor postoperative visual acuity. Causes included graft–host interface haze and/or vascularization, graft-surface irregularities and/or astigmatism, and persistent epithelial defects.[105] Graft–host interface haze is especially problematic when DM visualization was inadequate intraoperatively and a layer-by-layer dissection was necessary,[103] leaving the host bed with too much residual stroma.[106] With recent surgical advances, DALK has been shown to offer functional results comparable with, or better than, those with PKP, while avoiding the problems associated with transplanted donor endothelium.[107–115]

The popularization of DALK has also opened up the possibility of using only the stromal layer of a donor cornea, hence reducing dependence on a donor with a high endothelial cell count.

Last, FS lasers have recently been employed in a variation of the big-bubble technique. In separate studies, Farid et al.[116] and Price et al.[117] used the FS laser to create a zigzag incision in the donor cornea and recipient bed during the step of partial trephination instead of a calibrated guided trephine system as originally described by Anwar and Teichmann.[104] Theoretically, this technique minimizes the risk of DM perforation by allowing for precise depth visualization for air-needle placement in the posterior stroma based on the lamellar and posterior laser cuts. The use of FS laser in DALK needs to be evaluated further.