Stromal Procedures

Intrastromal Corneal Ring Segments

Intrastromal corneal ring segments (ICRSs) are a relatively new form of additive keratorefractive surgery where one or two ring segments are placed symmetrically or asymmetrically into mid-peripheral corneal tunnels created by manual mechanical dissection or with FS laser, resulting in corneal flattening and a reduction in irregular astigmatism (Figure 1).^[118] The magnitude of flattening is proportional to the thickness of the implant and inversely proportional to its diameter.^[119] The main advantage over other modalities is that it is potentially reversible and adjustable, as it does not result in permanent corneal tissue destruction and distortion due to corneal wound healing.^[120] The central cornea is also preserved, maintaining its prolate shape. Despite preliminary success, this indication was overtaken by LASIK.

The Keravision INTACS implants (Kera Vision Inc., CA, USA), currently approved for use in low-to-moderate myopic patients, received European CE certification in 1996 and FDA approval in 1999.^[121] They are composed of two 150° polymethylmethacrylate (PMMA) ring segments (Figure 4). The thickness of the rings required, ranging from 0.21 to 0.45 mm, depend on the level of the myopia. Currently, this method has FDA approval for the correction of low-to-moderate myopia (-1.00 to -3.00 D, with less than 1.00 D of coexisting astigmatism).

Figure 4.

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Image of 5-months Post-intrastromal Corneal Ring Segments Insertion (Symmetric Placement). Courtesy of Allan Slomovic (University of Toronto, ON, Canada).

In 2000, Colin et al. reported the use of INTACS in keratoconus with an aim to delay or even avoid corneal grafts in ectatic corneal disease.^[122] Since then, several studies have reported variable visual, refractive and keratometric changes (2.14–9.60 D) following INTACS implantation in keratoconic eyes.^[122–125] Corneal irregularity is also reduced with INTACS, which may be reflected by reduction in HOAs and a corresponding improvement in BCVA.^[124] ICRS in keratoconus have also been useful for improving contact lens tolerance.^{[123,126,127]}

The indications for ICRS in general (INTACS, Ferrara rings [Ferrara Ophthalmics, Brazil] and Kerarings [Mediphacos, Belo Horizonte, Brazil]) have since transitioned to the correction of ectatic corneal disorders such as keratoconus, pellucid marginal degeneration and post-LASIK ectasia. Ferrara et al. reported good outcomes for myopia with a different ring segment design called Ferrara rings, which has subsequently been adopted for use in ectatic corneal disorders.^[128]

Few cases of ICRS in pellucid-marginal degeneration have been reported. Central corneal flattening and reduction in spherocylindrical error has been demonstrated, along with improved contact lens tolerance.^[129–131] Similar refractive changes have been noted in keratoconus and post-LASIK ectatic corneas following ICRS implantation. Central corneal flattening and reductions in spherocylindrical error have also been noted (Figure 5), with a corresponding improvement in BCVA.^[132,133] Pinero also noted a reduction in coma-like aberrations and astigmatism, which led to a significant improvement in BCVA during a 2-year follow-up period.^[119] This group also found more HOAs in eyes that underwent the mechanical procedure compared with a FS-assisted procedure in the initial postoperative period.

Figure 5.

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Ultrasound Biomicroscopy View of the Anterior Segment (A) Pre- and (B) Post-intrastromal Corneal Ring Segment Insertion.

Collagen Crosslinking

Until recently, treatments for conditions affecting the biomechanical strength of the cornea, namely ectatic corneal disorders, have been limited to ICRS and corneal grafting. Both treatments address only the consequences of progressive corneal weakening but not the basic defect within the cornea.

In 1997, early in vitro studies by Spoerl et al. showed the potential and advantages of a new technique, involving riboflavin (vitamin B2) and UVA (370 nm), to safely increase the stability of the cornea by artificially crosslinking corneal fibers without disadvantages such as scarring, decompensation and toxicity.^[134,135] Corneal crosslinking (CXL) has since been shown clinically to increase the rigidity and structural integrity of the cornea, preventing progression to end-stage disease in various ectasias (Figure 1).^[136–141]

As riboflavin is poorly absorbed through the corneal epithelial tight junctions,^{[139,142,143]} the cornea is generally de-epithelialized out to 7–9 mm. Ultrasound pachymetry is then performed at the thinnest point of the de-epithelialized cornea, to ensure a minimal corneal thickness of 400 µm. Riboflavin 0.1% solution is then applied to the cornea every 2–3 min for 30 min. Corneal saturation with riboflavin and its presence in the anterior chamber is monitored by slit-lamp biomicroscopy with cobalt blue light, where it is visible as a yellow flare (Figure 6A). The eye is then irradiated for 30 min with UVA (Figure 6B) with the continual application of riboflavin solution every 2–3 min.

Figure 6.

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Collagen Crosslinking. (A) Following epithelial debridement with riboflavin in the cornea (seen in the anterior chamber as yellow flare. (B) Irradiation with UV light. Courtesy of Jeffrey Judelson (SK, Canada).

After the treatment, antibiotic drops are instilled and a BCL is placed over the cornea until complete re-epithelialization, which is usually on day 3 post-treatment. Some authors advocate the use of a tapering regimen of topical steroids,^[144] while others believe steroids inhibit the crosslinking process.^[145]

Corneal crosslinking is a photochemical reactive process. The corneal stroma is saturated with riboflavin, which collects alongside the collagen to be crosslinked. Riboflavin absorbs UV light at 370 nm (absorption maxima of the riboflavin chromophore) in the presence of oxygen and induces new chemical bonds in the stromal collagen by the creation of free radicals. Riboflavin has two functions in the process of chemical crosslinking. First, it facilitates UVA absorption, absorbing approximately 95% of UVA^[139] and thereby preventing damage to deeper ocular structures. Second, it produces oxygen free radicals, which are thought to induce collagen crosslinkage by increasing the formation of intrafibrillar and interfibrillar covalent bonds through the natural lysyl oxidize pathway.^[135] Initially, CXL was thought to induce crosslinkage between the stromal collagen molecules, which subsequently increases the biomechanical stability of the corneal and its resistance to enzymatic digestion.^[146] Recent studies suggest that, instead, CXL increases the number of crosslinking sites within the collagen molecule.^[147] This process produces a rearrangement of corneal lamellae and a relocation of the surrounding matrix, which, in turn, results in the reduction of the central corneal curvature.

The major indication for the use of CXL is to halt or reduce, but not reverse, the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration.^{[135,137–140,148–150]} Clinical studies have shown stabilization of keratoconic eyes with no evidence of progression with up to 6 years follow-up and some slight regression of the ectasia by an average of 2D.^[138,139] CXL is also effective in the treatment and prophylaxis of iatrogenic ectasia, resulting from excimer laser ablation.^[136,151] For corneal edema due to endothelial decompensation, CXL has been reported to reduce corneal thickness and improve epithelial changes when used in combination with a dehydration agent such as 40% glucose.^[152–154] Studies have also suggested that it may be used with success in bullous keratopathy.^{[153,155–157]} CXL has been used in some cases to treat infectious keratitis or corneal ulceration with progressive melting unresponsive to medical treatment with good success.^[158–161] Some success has been reported for combination therapy using ICRS implantation or limited topography-guided photoablation to reshape the cornea.^[162–166]

Corneal crosslinking has not been shown to induce endothelial injury. There has been no loss of corneal stromal transparency and no damage to deeper ocular structures provided the cornea is thicker than 400 µm.^{[139,167,168]} A corneal thickness of less than 400 µm is, therefore, regarded as the absolute contraindication for the procedure.

After crosslinking, a transient loss of visual acuity with haze can be observed in some cases, which usually subsides completely during the first postoperative year. A loss of two or more Snellen lines at 6 months or 1 year after treatment is considered a complication, with a rate ranging from 1 to 3%.^[169] Age over 35 years and BCVA better than 6 out of 7.5 are reported risks factors. Several cases of infectious keratitis have been reported post-CXL.^[170–172] It is generally thought that the infectious agents were contracted in the early postoperative, rather than intraoperative, period as CXL kills bacteria and fungi. Pre-existing ocular surface conditions such as blepharitis should be aggressively treated before surgery to avoid such complications.

The use of CXL has become much more widespread and versatile as it emerges as a promising treatment for many corneal conditions. However, concerns regarding certain aspects of CXL have been raised. In particular, its effect on other ocular parameters such as tear function, corneal sensitivity, properties of conjunctival epithelium and goblet cells, and ocular surface limbal stem cell viability has been questioned. The long-term effect of UVA irradiation in possibly increasing the occurrence of metaplastic disorders of the ocular surface should also be further studied.

Thermal Correction of Presbyopia

Holmium: YAG Laser Thermal Keratoplasty. Laser thermal keratoplasty (LTK) is a form of refractive surgery directed at the corneal stroma that is based on biomechanical principles very similar to conductive keratoplasty (CK; see later).^[173,174] Instead of delivery of heat by electrical conduction, a laser delivers the heat by thermal conduction. Otherwise, the objective of LTK is to stimulate shrinkage of the stromal collagen in a concentric pattern around the central cornea by the creation of leukoma footprints and thus achieve corneal steepening. Unlike CK, these footprints are in a conical shape, as thermal conductivity (unlike direct electrical conductivity) is attenuated as it passes from the corneal surface into the stroma.^[175] The use of LTK has not been widespread owing to the significant regression of effect observed.

Conductive Keratoplasty. Approved by the FDA for usage in 2002, CK is a laserless, non-lamellar modality for refractive surgery, primarily indicated for the management of low-to-moderate hyperopia (+0.75 to +3.00 D, with less than +0.75 D of coexisting astigmatism).^[176] By applying this outside of the visual axis, steepening of the central cornea is achieved to correct the hyperopia.^[177,178] This has largely been replaced by newer techniques secondary to induced irregular astigmatism and regression of effect.

New Approaches to the Correction of Presbyopia

Intrasomal Correction of Presbyopia. Intrasomal correction of presbyopia (INTRACOR) refers to a developing technique using FS to correct presbyopia in a minimally invasive manner.^[179,180] In this procedure, FS pulses are delivered intrastromally, avoiding any disruption of Bowman’s layer and DM, with the objective of creating five concentric cylindrical rings around the line of sight. The intended result is to create a multifocal hyperprolate cornea by steepening the anterior corneal surface centrally, while flattening the cornea more peripherally. This procedure is indicated mainly for patients with only low hyperopia, myopia or astigmatism; the number, size and shape of the INTRACOR rings are determined based on the level of ametropia or cylinder. The benefits of this procedure are many, as it is fast and painless, with procedure time ranging from 18 to 30 s, and it is associated with very low intraoperative risk and postoperative complications, as it avoids the need for surface ablation or flap creation.

Since the introduction of this technique, only two studies evaluating the short-term outcome of the procedure have been published.^[179,180] Each series reported uneventful surgeries for all cases, with no significant postoperative complications aside from slight disturbance in visual acuity in the immediate postoperative period. Long-term follow-up is required for its proper evaluation.