This article is best viewed in a PDF Format.
|
|
Keratoconus is a non-inflammatory, degenerative disorder of the cornea, characterised by stromal thinning and conical ectasia, which results in irregular astigmatism and associated visual loss. The condition typically presents in adolescence and progresses until the third and fourth decade. It is the commonest of all the corneal dystrophies, affecting approximately 1 in 2,000 of the population and all ethnic groups worldwide.
The management and treatment of patients with keratoconus depends on the degree of conical ectasia and the resultant irregular astigmatism. Early and mild cases can be treated effectively with astigmatic spectacle correction and soft toric contact lenses. As the disease progresses, rigid contact lenses become the mainstay of treatment. In the majority of eyes such lenses provide good visual rehabilitation. Unfortunately, they are not the solution in all cases. Discomfort and patient preference may limit the use of rigid contact lens wear and in advanced cases fitting may be problematic. Severe ectasia and central stromal scarring in advanced keratoconus can significantly limit the amount of visual rehabilitation achieved by rigid lenses. In addition, there is a body of evidence to suggest that repeated trauma caused by the wearing of rigid lenses may in some cases be responsible for the acceleration of the condition.1
For these reasons, between 10-25 per cent of patients with keratoconus progress to a point where surgical intervention is required.2 Surgical options include:
- Corneal transplantationPenetrating keratoplastyLamellar keratoplastyEpikeratophakia
- Intra-corneal ring segment insertIntacsFerrara rings
- Thermokeratoplasty
- Ultraviolet-A/Riboflavin corneal cross linkage (CR3)
- Lenticular refractive surgeryRefractive lens exchange withtoric intraocular lensesToric phakic intraocular lenses
- Contra-indications to surgery in individuals with pre-existing sub-clinical or overt keratoconusAstigmatic and radial keratotomiese_SFlbRefractive laser surgery.
CORNEAL TRANSPLANTATION
Penetrating keratoplasty (Figure 1)
Between 10-25 per cent of cases of keratoconus progress to the point where visual rehabilitation with rigid contact lenses is no longer possible,2 especially in those who present at a young age (less than 20) and with keratometry measurements >55 dioptres.3
In the past, such patients have had only one realistic surgical option - a full thickness corneal transplant or penetrating keratoplasty. Keratoconus is one of the most common indications for penetrating keratoplasty accounting for around 15-25 per cent of such surgeries.4,5 The procedure is generally conducted under sedation or general anaesthesia. It necessitates an experienced corneal surgeon trephining a full thickness lenticule from a donor cornea which is then sewn on to the host, with either running or individual nylon sutures, once the central diseased corneal tissue has been trephined and removed.
As the cornea is avascular, the donor and host do not have to be tissue matched and eye banks, after checking for communicable diseases and tissue quality, can provide suitable tissue within a few days or weeks. Following surgery, visual recovery typically takes several weeks/months, with full stabilisation often taking up to a year after which time the sutures can be removed.2
Corneal transplantation in keratoconus is considered relatively low risk, in terms of graft rejection and other post-operative complications, as these eyes do not typically exhibit corneal neovascularisation and other ocular pathologies. As such, the outcomes of penetrating keratoplasty for keratoconus are very favourable, with excellent long-term graft survival rates, acceptable post-operative best-spectacle corrected visual performance and good long-term stability,2, 6 with a recent follow-up study reporting 97 per cent five-year survival and 92 per cent 10-year survival in primary grafts.7 Graft rejection episodes do occur but invariably respond to medical management, with few cases resulting in graft failure.2 Iatrogenic astigmatism, however, can limit visual rehabilitation in up to 30 per cent of patients, many of whom require further keratorefractive surgical procedures such as astigmatic keratotomies, or, in more recent years, excimer laser procedures.2, 8,9 In addition, continued endothelial cell instability and loss has been reported10 as well as recurrence of the condition11 and late progression of astigmatism,12,13 with a reported mean time to recurrence of about 18 years.11
LAMELLAR ANTERIOR KERATOPLASTY
Although outcomes after penetrating keratoplasty in keratoconic eyes are favourable, with good visual rehabilitation and long-term stability, graft rejection and failure and induction of significant iatrogenic astigmatism are not infrequent occurrences.2
In keratoconus the corneal endothelium is generally intact and healthy, even after cases of acute hydrops. While corneal stromal rejection episodes can occur, it is known that with time host keratocytes migrate into and replace donor cells and that most rejection episodes (especially after 12 months) are invariably endothelial in origin.
It is for these reasons that there has been a trend over recent years to perform lamellar (partial thickness), rather than full thickness, penetrating techniques. Such procedures offer replacement of the diseased (stromal) part of the keratoconic cornea, while leaving the healthy non-diseased endothelial cells relatively intact. This negates the risk of endothelial rejection and theoretically improves the post-operative mechanical stability of the cornea, with less chance of wound dehiscence and possibly less induction of iatrogenic astigmatism.
Early results in such procedures were rather ambivalent, however, as techniques and experience has developed, outcomes have improved.14-16 Lamellar keratoplasty has been shown to result in less endothelial cell loss, less intraocular pressure problems than full thickness techniques, a reduction in rejection episodes and, in some cases, a reduction of induced astigmatism.17-19
However, while some series have achieved comparable visual outcomes, others have demonstrated that in terms of best spectacle corrected visual acuities of 6/6 or better, penetrating techniques slightly out-perform deep lamellar procedures19 and that while endothelial rejection is negated, stromal rejection very rarely can occur.18, 20
Further refinements in operative techniques, together with improvements in technologies, such as the implementation of femto second lasers and microkeratomes for lamellar keratoplasty, will allow for further refinement of lamellar techniques and improve the ease of performing these procedures for both surgeons and patients alike. Lamellar keratoplasty, if not already so, (in the author's opinion) will become the surgical intervention of choice in keratoconus, providing an effective, technically easy-to-perform, out-patient, local anaesthetic procedure with fairly rapid visual recovery and excellent visual outcomes and long-term graft survival and stability.
EPIKERATOPHAKIA
This procedure involves removing the corneal epithelium from the host keratoconic cornea and then sewing onto the corneal stromal bed a previously cryolathed lenticule of donor cornea.21
The procedure has generally resulted in less favourable outcomes than penetrating keratoplasty and while implementation of more advanced technologies has helped improve outcomes, it has been largely replaced by deep anterior lamellar techniques.
INTRA-CORNEAL RINGSEGMENT INSERTS
(Intacs and Ferrara rings)
A recent surgical alternative to corneal transplantation to correct irregular astigmatism in keratoconus has been the insertion of intra-corneal ring segments.
The technology has been available for over 10 years for the correction of low degrees of myopia (up to -3.0 dioptres).22 More recently, these ring segments have been used to reduce the irregularity of the cornea and flatten the apex of the cone in mild to moderate cases of keratoconus with some success.23, 24
Two types of intra-stromal rings are available: Intacs (Figure 2), which have a hexagonal cross-section and are placed more peripheral than Ferrara rings which are triangular/prismatic in shape. Intacs were approved by the FDA in 1994 for low myopic corrections and extended to treatment of keratoconus in July 2004.25 The rings can be inserted into the mid/deep stroma as a quick and painless out-patient technique performed under topical anaesthesia, either using a specially designed vacuum lamellar dissector to create the circular pockets for the rings, or more recently with femtosecond laser technology. The precise mode of action of the rings is unknown, but it is assumed that the ring segments push out against the curvature of the cornea, flattening the peak of the cone and returning the cornea to a more natural shape. Studies have in the past also suggested an important role for the epithelium, with hyperplastic changes adjacent to the segments having an important refractive effect.26
Results have generally been favourable, with most eyes achieving a significant reduction in astigmatism post-operatively, accompanied by an improvement in best- spectacle corrected and uncorrected visual acuity.27-31 While most series remain small, favourable outcomes of up to 24-36 month follow-up have been achieved.27-31 The results seem to be best in eyes with mild to moderate keratoconus, with mean keratometric readings of less than 53 dioptres.32 Perforation of the anterior chamber is a small risk during the procedure and lack of efficacy, infection, sterile keratitis and late ring extrusion account for a number of failures.27-31, 33 Removal of problematic ring segments can easily be performed and has been shown to allow the cornea to return to its preoperative state.34 In addition, it is still possible to perform both lamellar and penetrating keratoplasty techniques following ring removal.
There is some debate among the ophthalmic community whether one or two intact segments should be inserted.35-36 Certainly, most practitioners would agree that a thicker segment should be inserted inferiorly around the base of the cone, with the incision for insertion of the ring generally being located temporally.37 An increasing number of practitioners are now advocating insertion of only a single intact segment inferiorly, with studies suggesting the results are comparable, if not better, than two ring insertion.35-36 Refinement in ring technology, in terms of diameter, shape, thickness and width, a greater understanding of corneal biomechanics and further development of treatment algorithms should, in the future, allow more predictable refractive outcomes and the increased use of intracorneal ring technology for the treatment of mild to moderate keratoconus. Certainly, it is this author's opinion that Intacs are the treatment of choice in the contact lens intolerant eye, with keratometry less than 53 dioptres and no central corneal scarring and that this should be attempted before considering keratoplasty techniques.
It must be stressed, however, that at present intracorneal ring technology does not offer a cure for the condition but can very often produce a marked improvement in unaided and best-corrected visual acuity and allow eyes to be corrected with spectacles and/or soft rather than rigid lenses. There is also no evidence that it halts the progression of the condition and long-term follow-up studies are required.
RIBOFLAVIN/ULTRAVIOLET A CORNEAL CROSS LINKAGE (CR3)
Riboflavin (vitamin B2)/ultraviolet A (370nm) corneal collagen cross linkage is a new treatment modality, the early results of which indicate that it may be the first treatment available to actually stabilise the keratoconic process.38
The aims of the treatment are to increase the biomechanical stability of the corneal stroma and its resistance to enzymatic digestion, by inducing cross linkage between the stromal collagen molecules. Photochemical collagen cross-linking by riboflavin/UVA appears to provide a simple, safe and technically easy-to-perform outpatient surgical procedure. The riboflavin has the dual function of acting as a photosynthesiser for the production of oxygen-free radicals, as well as absorbing the UVA irradiation and preventing damage to deeper ocular structures such as the corneal endothelium, the lens and the retina. The production of oxygen-free radicals by this photochemical process is thought to induce collagen cross-linkage by the natural lysyl oxidise pathway.
The technique is performed as an outpatient procedure under topical anaesthesia (Figure 3). As riboflavin does not penetrate the epithelium, it is removed using a blunt spatula (although some surgeons advocate the use of minor epithelial trauma only, as sufficient to allow riboflavin penetration into the corneal stroma).
Following anaesthetic eye drop administration, riboflavin eye drops 0.1 per cent are applied to the stromal surface five minutes prior to the procedure and then every five minutes during the procedure, which involves exposing the corneal stromal surface to ultraviolet A radiation (370nm) at a radiance of 3mW/cm2 for 30 minutes. At this low energy level, UV wavelength and using this concentration of riboflavin, the technique has been shown to be safe with no endothelial damage, provided the cornea is thicker than 400µm, with no loss of corneal stromal transparency and no damage to deeper ocular structures.39, 40
In laboratory studies, riboflavin/UVA cross linkage has been shown to improve stress-strain measurements, reduce the swelling rate, increase shrinkage temperature and increase the resistance against enzymatic degeneration of corneal stromal tissue.41-43 It has also been shown to increase the diameter of the collagen fibres following the procedure with most changes occurring in the anterior 200µm without any damage to the corneal endothelium.44, 45 Clinical studies have demonstrated stabilisation of keratoconic eyes, with no evidence of progression with up to five years follow-up and some slight regression of the ectasia by an average of 2 dioptres.40, 46 No long-term problems in terms of loss of transparency of the cornea or lens have occurred and endothelial counts have been unchanged post-operatively.
While this technique is still under laboratory and clinical evaluation, it does appear to offer great promise and is the first treatment to stabilise the keratoconic process allowing treatment of the cause, not just the symptoms and end result of the condition. The ability to halt disease progression at the earliest stages of the condition, when full visual rehabilitation can still be achieved with spectacles and soft contact lenses, offers great hope for future generations suffering with this not infrequent and often visually devastating condition.
THERMOKERATOPLASTY
Johan Horner, described attempts to reshape the cornea by chemical cauterisation as early as 1869.47 In 1928 Knapp documented improvements in visual acuity after thermal cauterisation in keratoconic eyes and in the mid 1970s Gassett and Kaufman and Arentsen and Laibson published encouraging results with thermokeratoplasty applied to the apex of the cone.48, 49 However, generalised problems with thermokeratoplasty procedures including limited efficacy, predictability and long-term stability, together with post-operative scarring have until recently limited its usage.
Advances in temperature regulation and depth of thermal injury with the advent of holmium and diode lasers and conductive keratoplasty technologies now offer greater precision. Published results have indicated encouraging outcomes for the correction of low degrees of hyperopia. This has allowed investigators to re-consider thermokeratoplasty for keratoconus. Recent case series have indicated some success with both diode lasers and conductive keratoplasty in steepening areas of corneal flattening in ectatic eyes.50, 51 Further studies may clarify the role of thermokeratoplasty in the management of keratoconus.
REFRACTIVE LENS EXCHANGE
(Phakic/toric intraocular lenses)
Corneal surgery in keratoconic eyes can be problematic, require specialised equipment and be technically difficult to perform. It may also be associated with further destabilisation of the cornea and worsening of the ectatic process as in the case of laser refractive and incisional surgery.
While not addressing the correction of irregular astigmatism, refractive lens exchange and toric phakic intraocular lens insertion may be of some benefit in selected patients with early/mild keratoconus and functional best spectacle corrected visual acuities. Clinical studies have demonstrated significant improvements in unaided visual performance with good safety and efficacy indices both for refractive lens exchange and toric phakic intraocular lens insertion.52-54
Such treatment modalities are relatively easy to perform and may offer an alternative in selected contact lens intolerant keratoconic patients for treating astigmatism and myopia before considering keratoplasty techniques.
Further refinements in positioning and implantation of toric intraocular lenses and biometry techniques in these problematic eyes may allow the greater use of lenticular refractive techniques for the future management of some keratoconic eyes.
KERATOCONUS AS A CONTRA-INDICATION TO CORNEAL SURGERY
The advent of excimer laser refractive surgery has heralded a new era in ophthalmology.
Such techniques have been shown to be safe and effective for the correction of low to moderate degrees of myopia, hyperopia and astigmatism with millions of procedures being performed worldwide.
However, one of the major contra-indications to such surgeries is the presence of overt or even sub-clinical keratoconus. An association between development/acceleration of corneal ectasia in such eyes and laser in situ keratomileusis (Lasik) has been clearly established with keratoconus both overt and 'forme fruste' being an absolute contraindication to Lasik surgery.55
While a number of investigators have proposed excimer laser phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) as possible treatment modalities for keratoconus,52 recent reports of corneal ectasia following PRK56-58 suggest that such procedures are not advisable in these eyes and that keratoconus in all its forms should be regarded as a relative, if not an absolute, contraindication.
Similarly, some surgeons have advocated the use of radial keratotomy techniques for the correction of selective patients with mild to moderate keratoconus.59
Such techniques, which are known to mechanically destabilise the cornea, are probably not advisable and must have the potential to exacerbate the ectatic process in the medium to long-term. Indeed, ectasia has been reported after radial keratotomy.60
While many surgical interventions for keratoconus are still at a developmental stage, the use of techniques which are additive (such as Intacs), mechanically and chemically stabilise the cornea (riboflavin/UVA corneal collagen cross linkage) or that replace the diseased corneal tissue (keratoplasty techniques) must be deemed preferable to procedures that remove tissue (excimer laser) and mechanically destabilise the cornea (astigmatic and radial keratotomies), this is particularly in a condition where the cornea is known to be thin, ectatic and mechanically unstable.
CONCLUSIONS
Keratoconus is a fairly common condition with severe ocular morbidity. It particularly affects young individuals and can significantly limit lifestyle choices as a result of visual handicap. The development of new surgical treatment modalities and the refinement of older techniques, with the introduction of new technologies, offer the promise of improved visual outcomes for future generations with this condition.
References
A full list of references is available on request from william.harvey@rbi.co.uk
- David O'Brart is a consultant anterior segment and refractive ophthalmic surgeon at Guy's and St Thomas' NHS Foundation Trust and in private practice. He is currently undertaking the first UK Ethics Committee Approved clinical trial of riboflavin/UVA corneal collagencross linkage and is in the process of recruiting patients with mild to moderate kerataconus for enrolment into this study. Robert Petrarca is a medical student at Guy's, Kings, and St Thomas' Medical School and an optometrist in private practice