ANC Comment:  Nice review below borrowed from an email from Expert Review.
Thoughts – We are still lacking in our understanding of how the genetically predisposed individual develops the onset and progression of keratoconus.
Why do only 7% of patients diagnosed with this genetic condition have a positive family history?
Why are they more prone to eye rubbing, floppy eyelids, weight gain, and obstructive sleep apnea?
Is corneal crosslinking, which in effect strengthens the cornea by “aging” the tissue, going to become a standard treatment option?
Should we be putting Intacs corneal ring segments in earlier to prevent progression?
Is Keratoconus a disease, a susceptibility, or a syndrome with systemic implications?
Enjoy this work below:

From Expert Review of Ophthalmology

Advances in Keratoconus Treatment

Aylin Kılıç Uzbek; Orkun Müftüoğlu

Posted: 03/07/2011; Expert Rev Ophthalmol. 2011;6(1):95-103. © 2011 Expert Reviews Ltd.

Abstract and Introduction

Keratoconus is a noninflammatory, usually bilateral, progressive disease. It is a pathology characterized by a progressive thinning and ectasia of the stroma that results in a cone-shaped cornea. In advanced keratoconus with corneal opacities, keratoplasty was regarded as the only surgical alternative. Recently, new treatment alternatives were developed in keratoconus treatment, such as intracorneal ring segments and corneal crosslinking. Intracorneal ring segments act as spacer elements between the bundles of corneal lamellae, producing a shortening of the central arc length. Corneal crosslinking treatment increases the stiffness of the cornea. Several studies reported that collagen crosslinking can delay or stop keratoconus progression and produce a better quality of vision. A combination of crosslinking and intracorneal ring segments shows a positive, synergistic effect. Keratoconus is a disease of the corneal stroma and that usually presents itself in patients at an early age, thus the endothelial cell layer in eyes with keratoconus is young and almost healthy. Full-thickness penetrating keratoplasty has been a well-accepted surgical treatment for advanced keratoconus. Recently, great advances have been seen and new techniques of keratoplasty have been introduced in the treatment of keratoconus. These are mainly the lamellar keratoplasty techniques and the advanced shaped side-cut techniques, particularly with the use of femtosecond lasers.

Intracorneal Ring Segments for Keratoconus

The cornea is the ocular structure responsible for approximately 70% of the refraction that occurs in the optical system of the human eye. Small changes in curvature lead to great alterations of the dioptric power of the eye. Pioneering research with intracorneal implants began in the 1950s when Barraquer proposed the use of those implants with a refractive purpose.[1,2] The results brought about were satisfactory, but the segments implanted very often suffered extrusion. Since then, several studies have been developed concerning the study of corneal physiology and metabolism. The intrastromal corneal ring concept was proposed by Reynolds in 1978.[3] Intacs (Addition Technology Inc., CA, USA) intrastromal ring segments were investigated as an alternative for myopia correction. Several authors reported good outcomes with Intacs rings in low-to-moderate myopic cases.[4,5] Intacs segments for myopia received European Communauté Européenne certification in 1996 and US FDA approval in 1999.[6]

Intracorneal ring segments (ICRSs) work as spacer elements between the bundles of corneal lamellae, producing an arc-shortening effect that depends on the thickness of the device (Figures 1 & 2).[7] ICRSs cannot correct more than 4 D of myopia without significant changes in corneal asphericity, and even then without inducing spherical aberration. This means that the degree of correction was a function of both ring thickness and diameter, with minimal changes in corneal asphericity when using large diameters and thin segments.[8]

Click to zoom Figure 1. (A) A uniform corneal thickness produces a uniform stress distribution.
(B) A nonuniform corneal thickness produces a stress concentration in the thinnest region.
IOP: Intraocular pressure.
Reproduced with permission from Cynthia Roberts (Ohio University, OH, USA).

Figure 1.

(A) A uniform corneal thickness produces a uniform stress distribution.
(B) A nonuniform corneal thickness produces a stress concentration in the thinnest region.
IOP: Intraocular pressure.
Reproduced with permission from Cynthia Roberts (Ohio University, OH, USA).

Figure 2. Once the segments are inserted, the curvature is decreased centrally, including the region of the cone. As curvature is decreased in this region, the stress is redistributed, and the decompensatory biomechanical cycle of keratoconus is broken.
Reproduced with permission from Cynthia Roberts (Ohio University, OH, USA

Figure 2.

Once the segments are inserted, the curvature is decreased centrally, including the region of the cone. As curvature is decreased in this region, the stress is redistributed, and the decompensatory biomechanical cycle of keratoconus is broken.
Reproduced with permission from Cynthia Roberts (Ohio University, OH, USA).

Two surgical procedures have been described for ICRS implantation: the mechanical method and the femtolaser method. The use of femtolaser for ICRS tunnel creation was widely accepted after FDA approval. Tunnels can be created at 70–80% of the corneal thickness within 15 s with less manipulation. The femtosecond (FS) laser provided a more accurate tunnel depth and better visual outcomes independent from surgeon skills.

Several studies have reported the outcomes following ICRS implantation in keratoconic eyes (Table 1). In almost all studies, improvement in keratometric value was statistically significant.

How ICRSs Work

  • Provide central and peripheral flattening of the cornea;
  • Preserve cornea sphericity;
  • Ring diameter determines how much the cornea will be flattened; the more increased the ring thickness and the smaller the diameter, the greater the correction that will be obtained.[1,2]

ICRS has the following advantages:

  • Provides stabilization or improvement of keratoconus progression;
  • There is no limit in routine daily life after implantation. Patients can quickly integrate themselves to their activities;
  • Low-rate complications (with femtolaser);
  • It is reversible – you can remove segments when you see adverse reactions;
  • No rejection risk – acrylic is an inert material;
  • Adjustable – after implantation, astigmatism can be managed with minimal manipulation;[9]
  • Contact lenses can be used after ring implantation;
  • It is suitable for all age groups – postponing of keratoplasty is very important for teenagers or children;[10]
  • Combining ICRS with with other procedures is possible, such as crosslinking (CXL), phakic intraocular lenses and contact lenses;
  • No interference with keratoplasty – especially in younger age groups where the postponing of keratoplasty is very important.

A clear inverse correlation between age and severity of keratoconus makes treatment of young keratoconic eyes more important. During adolescence and peak life activity, patients may be less tolerant of hard contact lenses. Contact lenses also have several disadvantages such as cornal warping, allergic reactions, dry eye and infection. Limited success of penetrating keratoplasty (PK) in younger patients can be attributed to pre-, intra- and postoperative problems.[11–14] Low scleral rigidity, increased intraoperative fibrin formation and positive vitreous pressure complicate the surgical procedure.[15] Most young patients with keratoconus wish to achieve high-quality vision with minimal risk, rapid rehabilitation and minimal discomfort and pain. Although some studies report that Intacs improves visual acuity and refractive and topographical findings in keratoconic patients, the safety and effectiveness of Intacs in different age groups remain unknown. We compared the response to Intacs treatment in different age groups of patients with keratoconus and did not find any statistically significant differences among young, middle and older age groups in visual acuity, manifest sphere, cylinder, mean refractive spherical equivalent and mean K-values (ANOVA; p > 0.05).[16] This study investigated whether an age-related increase in corneal ‘stiffness’ may induce outcomes of Intacs treatment, and found that Intacs similarly improves visual acuity, refraction and topographical findings in keratoconic patients of all ages. In adolescent patients with keratoconus, ICRSs are as safe and effective as in other age groups.

Intracorneal ring segment indications include:

  • Progressive keratoconus;
  • Contact lens intolerance;
  • Corneal ectasia postexcimer laser;
  • Corneal irregularities postradial keratotomy;
  • Corneal irregularities post-PK;
  • Pellucid marginal degeneration;
  • Corneal irregularities post-trauma;
  • Myopia/astigmatism in thin corneas.

Intracorneal ring segment contraindications include:

  • Any permanent opacification in the visual axis;
  • Unrealistic expectation;
  • Mean keratometric value more than 75 D;
  • Hydrops;
  • Very high astigmatism after PK if the donated cornea is decentralized;
  • Intense atopy that should have been treated previously;
  • Local or systemic spread of any active infection.

The purpose of ICRS implantation in the management of patients with keratoconus is to defer the need for corneal transplantation and restore contact lens tolerance. The placement of Intacs generates an immediate response that interrupts the biomechanical disease progression and a biomechanical response that allows improvement of vision over 6 months.[17] Improvement in visual acuity and refraction after Intacs implantation is accomplished by shortening the path length of the portion of the collagen lamellae that are central to the segments. Redistribution of corneal curvature leads to a redistribution of corneal stress, interrupting the biomechanical cycle of the keratoconus progression, and in some cases, reversing the stress.[18]

We evaluated Intacs efficiency according to different keratoconus stages.[19] In this retrospective noncomparative case series, 306 keratoconic eyes of 255 patients who had Intacs segment implantation were reviewed. Patients were grouped according to the Amsler–Krumeich keratoconus classification (stage II: 155 eyes; stage III: 83 eyes; stage IV: 68 eyes). There was no significant difference between the three groups in the amount of change in best-corrected visual acuity (BCVA), manifest spherical refraction or manifest cylinderical refraction (p > 0.05). There was less change in uncorrected visual acuity and more improvement in mean K-values postoperatively in the stage IV group (ANOVA; p < 0.05). Segment extrusions occured in three out of 306 keratoconic eyes in the stage IV group 6 months after Intacs implantation. The patients were 18, 20 and 23 years of age.

Complications after ICRS implantation include:[17,19–22]

  • Segment extrusion;
  • Asymetry of ICRS;
  • Inadequate depth of intracorneal tunnel;
  • Bowman’s layer perforation;
  • Cornea perforation;
  • ICRS extrusion;
  • Corneal neovascularization;
  • Yellow–white deposits around segment;
  • Infectious keratitis;
  • Ring segment movement in the channel (Figure 3);
  • Epithelial plug at the incision;
  • Corneal haze;
  • Corneal melting;
  • Halos, glare;
  • Chronic pain;
  • Focal edema around segment.

Figure 3. Segment movement in the corneal channel

Figure 3.

Segment movement in the corneal channel.

Complication rates depend on the treatment method; either mechanical or femtolaser. Eyes implanted using the mechanical method had more extrusion, although three cases of ring extrusion in advanced keratoconus have been reported using the femtolaser method.[21,22] According to the published reports, ICRS can be implanted successfully in keratoconus.

CXL Treatment for Keratoconus

Recently, CXL increased as a treatment strategy for progressive keratoconus. The growing number of clinical reports suggest not only a consistent stabilizing effect of CXL, but also a variable improvement in keratometric values and visual acuity.

Optimal corneal optics requires a smooth, regular surface with a healthy tear film and epithelium. The regular arrangement of stromal cells and macromolecules is necessary for clear vision. The lattice arrangement of collagen fibrils embedded in the extracellular matrix acts as a diffraction grating to reduce light scattering by means of destructive interference.[23] In keratoconus, there are irregular fibrils, a decrease in the number of collagen lamellae and separation of collagen bundles.[24,25] This new treatment is aimed at the pathogenic cause of keratoconus and changes the intrinsic biomechanical properties of corneal collagen.

This treatment creates additional chemical bonds inside the corneal stroma by means of a photopolymerization in the anterior stroma while minimizing exposure to the surrounding structures of the eye.[26] Alternative methods of enhancing the collagen bundles of the cornea have been entertained, one of the more effective being the use of glutaraldehyde, which is toxic and has the inability to control the depth.[27] Biomechanical stress–strain tests showed an impressive increase in corneal rigidity of 71.9% in porcine and 328.9% in human corneas and Young’s modulus by a factor of 1.8 in porcine and 4.5 in human corneas after CXL.[28] The CXL effect is maximal only in the anterior 300 µm.[29] In the anterior stroma of rabbit corneas treated with riboflavin and UVA, the collagen fiber diameter was significantly increased by 12.2% (3.96 nm) and in the posterior cornea by only 4.6% (1.63 nm).[30] Similar changes have been reported due to diabetes mellitus and age-related collagen CXL.[31] There are several features that point to the anterior localization of the CXL effect. In the anterior stroma the collagen fiber diameter increased.[30] In a patient with acute keratoconus, a reccurence of acute keratoconus developed 2 years after CXL treatment, probably because the CXL treatment does not affect the posterior layers, which are mainly affected by keratoconus.[31] In normal corneas, the anterior stroma is more rigid and crosslinked because it is designed to maintain the anterior curvature.[32] The photosensitizer riboflavin has an absorption peak for UVA at a wavelength of 370 µm. Following riboflavin saturation, the cornea is exposed to UV irradiation of this wavelength, and the riboflavin molecule fluoresces and is excited into the triplet state with subsequent production of superoxide radicals (Figure 4). The same system including riboflavin is present in the human lens to protect the retina from UVA light.[33]

Figure 4. Crosslinking treatment

Figure 4.

Crosslinking treatment.

Several animal studies have examined the various tissue effects of CXL. Laboratory studies summary:

  • Keratocyte death at 300 µm, no observable toxic effect of CXL at a depth beyond this level;[34]
  • Increased tissue stiffening;[29]
  • Increase in Young’s modulus by factor of 4.5 (human cornea);[29]
  • Alteration in the swelling properties of the porcine cornea;[35]
  • Doubled collagenase digestion time.[36]

In the first 6 months following CXL, the majority of cases show some corneal flattening, with an average reduction of corneal curvature of approximately 2 D. As a result, there is usually an improvement in maximal and average keratometry (K) readings, uncorrected visual acuity and BCVA. After the first 6 months, there is stabilization of cornea topography, without progression of the disease. Recently, El Raggal reported a statistically significant reduction in the mean K-value reading in his series – a decrease of 1.63 ± 0.17 D.[37] This finding was also addressed by Caporossi et al., who reported a topographic mean reduction in dioptric power of 2.1 ± 0.13 D in the central 3 mm.[38] Flattening of the cornea with or without a reduction in the magnitude of the astigmatism is usually accompanied by an improvement in uncorrected visual acuity. In 2008, Raiskup-Wolf et al. published a series comprising 241 eyes followed up to 6 years after CXL.[39] This uncontrolled, retrospective study confirmed earlier findings, with statistically significant improvements in astigmatism, BCVA and maximum simulated keratometric values at 12 months. A Kmax of −1.91 D flattening was observed in 54% of eyes (p < 0.01). The effects of CXL were maintained over the duration of follow-up, with progression of the disease documented in only two cases. Vinciguerra et al. reported the less affected fellow eye used as the control.[40] This study demonstrated a statistically significant improvement in both uncorrected and BCVA at 12 months, along with a reduction in the steepest simulated K-value of as much as 6.16 D (p < 0.0011). Improvements were also observed in topographic indices and high-order aberrations. In another study, statistically significant differences were observed between the treatment and control groups in terms of both changes in maximum (steepest) and simulated K-values and best spectacle – corrected visual acuity at 3.6 and 12 months following CXL, respectively.[41]

In rabbits, a cytotoxic level for the endothelium was found to be 0.36 mW/cm2, which would be reached in human corneas with a stromal thickness of less than 400 µm.[42] To avoid danger to the endothelium, lens or retina, it is important to measure the preoperative corneal thickness for each patient.

This new treatment modality can be used in several other corneal diseases. The safety and effectiveness of CXL require further research to understand and long-term follow-up will be required. Different CXL devices and riboflavin solutions in the market will show an effect on keratoconus treatment.

Combination of CXL & ICSR

Crosslinking and ICRS have a synergistic effect on keratoconus treatment, and can be performed simultaneously or sequentially.

Chan and Sharma showed that the combination of collagen CXL with Intacs led to better results than Intacs insertion alone, as proved by greater reductions in manifest cylinder and keratometric readings, which were thought to be the result of biomechanical coupling from local collagen changes around the Intacs segment.[43]

The authors also reported on the efficacy of transepithelial CXL in keratoconic eyes after Intacs implantation.[44] Intacs resulted in an improvement of 1.9 Snellen lines (p < 0.05) of uncorrected visual acuity and 1.7 Snellen lines (p < 0.05) of BCVA. CXL performed after Intacs treatment yielded an additional 1.2 Snellen lines (p < 0.05) of uncorrected visual acuity and 0.36 Snellen lines (p < 0.05) of BCVA. The decrease in spherical, cylinder, mean K-values and steepest K-values were 2.08 D (p < 0.05), 0.47 D (p > 0.05), 2.22 D (p < 0.05) and 1.27 D (p < 0.05), respectively, after Intacs treatment with an additional 0.5 D (p < 0.05), 0.15 D (p > 0.05), 0.35 D (p > 0.05) and 0.76 D (p < 0.05) of improvement gained after CXL in each respective parameter. We concluded that Intacs implantation with transepithelial CXL was effective in eyes with keratoconus. Collagen CXL has an additive effect on Intacs implantation in these eyes and may be considered as an enhancement/stabilizing procedure.

There is no report that compares sequential and simultaneous treatment but it seems logical to first use ICRS followed by CXL as a second procedure. As it is easy to reshape a weak cornea by using ICRS and the ICRS effect progresses up to 6 months, CXL will provide corneal stiffness as a second procedure.

Recently, Kanellopoulos reported on outcomes using a combination of CXL and topography-guided photorefractive keratectomy.[45] He compared sequential and same-day simultaneous CXL and topography-guided photorefractive keratectomy for the treatment of keratoconus.

New System Microwave Treatment for Keratoconus

Microwave keratoplasty uses microwaves to elevate the temperature of corneal stromal collagen. Positive and negative ring applicator electrodes generate electrical field lines with a concentration of energy specifically within the stroma. Very rapid vibration of water molecules results, causing frictional heat energy.[46] The medical device company Avedro, Inc. (MA, USA) is developing the science of thermobiomechanics for corneoplastic applications. Keraflex is the first technology that Avedro, Inc. has developed from its platform, and is currently under clinical investigation in Europe for keratoconus treatment. The Keraflex procedure combines refractive correction and corneal collagen CXL stabilization.

Advances in Keratoplasty

Keratoconus is a disease of the corneal stroma that first presents at a relatively young age, thus the endothelial cell layer eyes with keratocouns is young and almost healthy. Full-thickness PK has been a well-accepted surgical treatment for advanced keratoconus.[47–49] However, it can be complicated by allograft endothelial rejection that can lead to endothelial cell loss with subsequent risk of graft failure.[47–49] Therefore, replacement of a healthy endothelial cell layer with PK with subsequent risk of rejection and rejection-related (either by itself or by treatment with steroids) complications such as glaucoma can be a major problem in patients with keratoconus. In addition, the integrity of the ocular surface would be compromised with the full-thickness PK.[47–49] Recently, advances have been seen and new techniques of keratoplasty have been introduced in the treatment of keratoconus.[50] These are mainly lamellar keratoplasty techniques and the advanced-shaped side-cut techniques, particularly with the use of FS lasers.[50–54]

Deep Anterior Lamellar Keratoplasty

The concept of anterior lamellar keratoplasty (ALK) is that of targeted lamellar replacement of stromal corneal tissue while retaining Descemet’s membrane and endothelial cell layer.[50,51] Despite the distinct advantages of ALK surgery in reducing the risks of graft rejection and intraocular complications, PK remains the most common procedure at present, largely because lamellar surgery is more technically demanding and time consuming, and interface irregularity that can arise from manual lamellar dissection often results in suboptimal visual outcomes unable to match PK visual quality.[50,51] Recent improvements in surgical technique and advances in instrumentation have contributed to improved visual quality with lamellar keratoplasty surgery, and studies report that lamellar keratoplasty visual outcomes are comparable with those of PK surgery.[55–60] The advent of microkeratome- and FS-assisted lamellar transplantation surgeries are such technologies that have allowed this to occur.[50]

The traditional advantages of ALK over conventional PK are well recognized.[60,61] Since ALK is a largely nonpenetrating extraocular technique, it reduces the incidence of intraocular complications such as glaucoma, cataract formation, retinal detachment, cystoid macular edema, endophthalmitis and expulsive hemorrhage. In addition, leaving an intact and healthy recipient endothelial bed layer reduces the problems of endothelial rejection. Therefore, it may be possible to do this surgery with worse endothelial donor quality and less immunosuppression. Furthermore, as the integrity of the Descemet’s membrane is not violated, a tectonically stronger corneal wound with a lesser degree of suture-related postoperative astigmatism can be achieved.[58–62]

The traditional ALK technique is that of manually dissecting the stromal layers with the use of various lamellar dissectors. However, it is not easy to obtain a precise and smooth lamellar dissection with this manual procedure. Therefore, the visual outcome after manual ALK surgery is generally suboptimal because of interface irregularity and residual scarring.[63–66] Additional techniques have been reported to aid in the lamellar separation, which enable surgeons to approach the deeper stromal layers with greater safety and consistency. This form of surgery may now be termed deep anterior lamellar keratoplasty (DALK). These techniques involve the use of manual dissection, deep stromal injection of air, saline injection, or the use of viscoelastics (Figure 5).[63–66] In addition, others described careful manual peeling techniques and the use of Trypan blue to aid in visualization of the Descemet’s membrane.[67,68] However, as histologic evidence suggests that the cleavage plane does not occur between stroma and the Descemet’s membrane, clear separation of stroma from the Descemet’s membrane has recently been brought into question.[69]

Figure 5. Anterior segment optical coherence tomography scan after air injection showing big-bubble formation (arrows) together with intrastromal accumulation (arrowheads).

Figure 5.

Anterior segment optical coherence tomography scan after air injection showing big-bubble formation (arrows) together with intrastromal accumulation (arrowheads).

If sufficiently directed posteriorly, the force of injecting substances will enter the plane between the Descemet’s membrane and the posterior stroma. This may result in clean separation within this potential space. Studies indicate that DALK has outcomes comparable to the standard penetrating graft,[53–56] and endothelial cell loss is less than or at least equal to that of penetrating grafts.[50,58–61] An important advantage of this technique is that for the donor, one may simply strip off the Descemet’s membrane and avoid the need for lamellar dissection of the donor buton. In addition, repeat grafting entails simply peeling off the previous graft and replacing the donor. However, the depth of dissection may be difficult to assess under the operating microscope, and even among the most experienced surgeons perforation rates may be as high as 39%.[59–61] To improve visual outcome the deep dissection should reach the Descemet’s membrane. The advantage of deep lamellar keratoplasty is the elimination of a graft–host stromal interface and the associated problems of irregularity and scarring, leading to faster visual rehabilitation and improved visual outcomes.[59–61] The surgical challenge is to reach the level of the Descemet’s membrane and achieve entire removal of the corneal stroma without perforating the Descemet’s membrane.

FS-enabled Keratoplasty (FS-enabled Keratoplasty or Intralase-enabled Keratoplasty)

Corneal transplantation has developed into a relatively high level of graft survival rate in low-risk cases.[47,48] However, postoperative astigmatism remains a major obstacle in the functional rehabilitation of patients with clear corneal transplants.[70,71] Possible sources of optical distortion include misalignment of the anterior surface of the donor and host; rotational misalignment, where the tissue is not precisely distributed; excess and uneven suture tension; and postoperative slow and uneven wound healing. Recipient and donor corneas are usually trephined with suction-assisted, freestanding, unguarded or handle-mounted disposable trephines, or on punch blocks. However, these procedures can create different angles and degrees of uniformity of sidewall cuts. After trephination, the two straight-walled tissues are sutured together, forming a butt joint and with little alignment control other than visualization through an operating microscope.

The wound-healing advantages of a stepped incision for PK were recognized as long ago as 1950 by Barraquer[72] and were recently demonstrated by Busin[73] to decrease postoperative astigmatism. This stepped corneal button configuration provided a lamellar rim to facilitate healing and allowed transplantation of a relatively large diameter of healthy endothelial cells while keeping the anterior edge of the graft a safe distance from the limbus. Achievement of such a wound by hand dissection is not only difficult and arduous, but also unpredictable and imprecise in a procedure where only microns of irregularity can affect good wound structure and optical integrity.

The FS-pulsed laser can cut corneal tissue through the application of numerous adjacent pulses.[74] Compared with conventional blade trephination, the goal of a laser incision for PK is the creation of a more structurally stable and predictable wound configuration. It is also possible to create an infinite variety of nonplanar patterns for corneal transplantation incisions with the use of the FS lasers. Earlier laboratory investigations and recent studies demonstrated that PK incisions created by the FS laser can lead to a sevenfold increase in resistance to wound leakage and possibly less astigmatism.[52,53,75] With the FS laser cuts, better alignment of the donor and host anterior surface reduces distortion and the increased surface area of the shaped incision, such as zigzag incisions, may lead to improved tensile strength of the incision as it heals.[52,54,75] An incision pattern of two intersecting angled side cuts connected by a ring cut in the mid-stroma seems to have intrinsic biomechanical advantages in obtaining a watertight seal with enhanced tissue alignment and apposition. Anterior segment Visante optical coherence tomography images showed excellent approximation of corneal tissues as well as strong wound healing in the early postoperative period with the FS zigzag cut.[52,54,75]

In addition, the Visante optical coherence tomography images show increased signal return from the incisions over time, consistent with wound healing. In recent series, average postoperative astigmatism of 3D was achieved by postoperative month 1 and maintained by postoperative month 9. Early results are encouraging that interlocking incisions, creating both structural alignment and a leak-resistant valve with less need for tight suturing, does result in less irregular astigmatism.[52,54,75]

FS-enabled DALK

For patients with ectatic diseases a technique that can maintain the patient’s healthy endothelial layer and replace the entire anterior stromal layer with the addition of superior wound-edge healing and minimal induced astigmatism is ideal. The combination of the big-bubble DALK technique and the FS laser-assisted zigzag cut achieves such a goal. It also preserves the option of a full-thickness PK with the benefits of FS laser incision if the dissection of Descemet’s membrane fails. Recent preliminary studies showed promising results with FS–DALK in eyes with ectatic diseases.[76]

The FS laser, an infrared laser, has the ability to ablate tissue with less interference from optical haze, and it has been shown to be capable of performing posterior lamellar surgery with preparation of the donor corneal lamella (femto-DALK or FS-enabled DALK).[52,74] However, it should be noted that the deep lamellar ablations created with FS lasers currently do not produce smooth lamellar beds as seen after laser-assisted in situ keratomileusis flap formation.[77–79] This may be because of the increased levels of, and scatter of, laser energy needed in the deeper cuts and the inherently looser lamellar fibrillar configuration of deep stroma. In addition, specific nomograms for depth and energy settings have yet to be worked out for deep ablations.[77]

The advancement of the FS laser to produce corneal cuts and the recent lamellar keratoplasty techniques have allowed corneal transplantation in keratoconus patients to become precise, with the goals of visual performance parallel to those of refractive surgery. With the goals of faster rehabilitation and higher quality visual acuity, a theoretically infinite number of shapes and designs will allow further exploration of optimal incision configurations, the use of corneal welding techniques with diode lasers, corneal glues, or alternative minimal suturing styles for transplantation of the cornea.

Expert Commentary

Within the last decade, ICRS technology proven itself as a safe and effective treatment option in corneal ectatic disease that allows refractive rehabilitation. The reversibility of the procedure as well as low complication rates are the greatest advantages of ICRS implantation. The last 5 years has seen a marked increase in the prominence of corneal collagen CXL as a treatment strategy. Clinical reports shows not only the stabilizing effect of CXL but also a variable improvement in corneal shape and visual function. These recent advancements in the minimally invasive procedures in the treatment and rehabilitation of the corneal ectatic disease allowed safer and more comfortable options for these patients, particularly those that have no scarring in the cornea and that are resistant to contact lenses. The classical treatment of corneal transplantation is still an important option but more so in the advanced ectatic disease. The recent improvements in lamellar keratoplasty and FS laser-assisted incisions definitely increased the safety of corneal transplantation, but they remain technically demanding and time consuming.

Five-year View

In the next 5 years, long-term results of CXL and the results of microwave keratoplasty should provide insights regarding the treatments of the corneal ectatic disease. If they prove their safety, it would be possible to offer these treatment options for younger patients before the significant progression of the ectatic disease. In addition, combination of different treatments would be crucial. Despite improvements, the development of new treatments targeting the molecular basis of the ectatic disease still seems to be less likely in the next 5 years. Future advances in lamellar keratoplasty and FS laser-assisted corneal cuts, as well as more experienced surgeons, can improve the results of corneal transplantation, which may become an important treatment option and rival for minimally invasive procedures.