UntitledREFRACTIVE SURGERY FEATURE STORY
PRK and CXL in Patients
The combined procedure strengthens the cornea and regularizes the anterior surface.
BY MIRKO R. JANKOV II, MD, PHD; SLADJANA DELEVIC, MD; VESNA JOVANOVIC, MD, MS;
EFEKAN COSKUNSEVEN, MD; AND SLOBODAN GOLUBOVIC, MD, PHD
Irregular astigmatism can occur naturally or due to maintain the existing unfavorable biomechanical status trauma or surgery. Although technological and surgi- within the underlying stroma. In cases in which the irregular cal skill improvements in modern refractive surgery astigmatism is progressive, such as keratoconus, pellucid have led to excellent outcomes, the occurrence of marginal degeneration, and laser-induced iatrogenic ectasia, corneal irregularities postoperatively has been described.1 the corneal stroma is structurally weakened, and some of Highly irregular corneas can also originate from corneal these conditions may worsen following tissue ablation pro- scars derived from injuries, previous inflammation, or sur- gical procedures such as penetrating keratoplasty, radial Hence, to correct irregular astigmatism due to a biome- keratotomy, or arcuate cuts.2 chanically unstable cornea, a coadjuvant intervention such Another more challenging cause of corneal irregulari- as CXL should be considered to potentially stabilize the ty is ectatic disease.3 Some of these diseases arise natu- cornea while regularizing the corneal surface. rally, such as keratoconus and pellucid marginal degen-eration, and others are surgically induced, such as iatro- genic ectasia after laser surgery. Common among all CXL with riboflavin and ultraviolet-A (UV-A) light admin- ectatic disesases is progression due to a previous struc- istration is a technique that strengthens corneal tissue by tural weakening and thinning of the corneal stroma.
using riboflavin as a photosensitizer and UV-A to increase Patients complain of decreased vision, glare, photopho- the formation of intra- and interfibrillar covalent bonds bia and monocular diplopia.
through photosensitized oxidation.7 This technique is simi- Once the patient is unable to use rigid contact lenses, there lar to photopolymerization in polymers, and through it bio- are few surgical alternatives for correction. Expectations are mechanical stabilization of the cornea is achieved.
limited, and consequences may be unpredictable, both The key indication for CXL is to inhibit the progression of anatomically and functionally. In recent years, however, tech- corneal ectasias, such as keratoconus and pellucid marginal nological advances have led to two approaches: (1) corneal degeneration.8 CXL may also be effective in the treatment regularization based either on intrastromal corneal ring and prophylaxis of iatrogenic keratectasia resulting from implantation4 or limited topography-guided excimer laser LASIK.9 Beyond keratectasia, the technique can also be used customized ablation treatment (T-CAT)5 or (2) corneal stabi- in treating corneal melting conditions or infectious keratitis; lization using corneal collagen crosslinking (CXL).6 CXL strengthens the collagenolytic cornea while the UV-A Vision-correcting methods, such as laser treatment or irradiation sterilizes the infectious agent.10 intrastromal corneal ring implantation, attempt to regular- In the presence of 0.1% riboflavin acting as a photosensi- ize the front surface of the irregular cornea; however, they tizer, using an irradiance of 3 mW/cm2 of UV-A, as much as 32 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I OCTOBER 2009
REFRACTIVE SURGERY FEATURE STORY
95% of UV-A light is absorbed within the cornea.7Keratocyte apoptosis in the anterior corneal stroma to adepth of approximately 300 µm has been described, and aclear demarcation line between treated and untreatedcornea has been shown.11 Confocal microscopy studies alsoshow that repopulation of keratocytes is already visible 1month after treatment, and preoperative quantity and qual-ity in terms of functional morphology is achieved within 6months after treatment.12 T-CAT can achieve the goal of regularizing a distorted cornea by significantly reducing high astigmatism.13 Figure 1. Treatment in progress; the cornea is soaked with
However, additional thinning of the already biomechanically riboflavin and irradiated by the UV lamp.
challenged cornea may be counterproductive, with the riskof worsening corneal biomechanical stability due to further inflammatory response and thus haze.
thinning after tissue ablation.
It is probable that the ablation rate on a cornea previously Our surface ablation protocol is intended to reduce treated with CXL would not be significantly altered in com- postoperative pain and haze by minimizing the inflamma- parison with that of the normal cornea. Even if it were differ- tion reaction and minimizing increased sensitivity to UV- ent, one would expect slight overcorrection, as the corneal radiation injury.14 A 50-µm phototherapeutic keratecto- collagen seems to be more compact in the first 6 months my (PTK) at a 6.5-mm optical zone is used to remove the after the CXL treatment. This is the reason we recommend epithelium. Afterward, PRK with a minimal amount of tis- that approximately 80% of the refraction (mainly cylinder) sue removal (less than 50 µm) and optical zones as small should be treated at an optical zone of 6 or 5.5 mm and a as 5.5 mm is planned, aiming at maximum cylinder reduc- transitional zone of 9 mm. One must also be sure not to tion with minimal tissue removal to regularize the cornea.
surpass 50 µm of ablation depth at the deepest point.5 A single procedure, meaning an immediate sequence of T-CAT transepithelial PRK and CXL, would be without The key indications for use of this combined treatment doubt more comfortable for both the patient and the method are to regularize distorted corneal optics, halt the surgeon. It is also easy to predict what the ablation out- progression of keratoconus, and achieve lasting visual reha- come would be, as one would be applying the laser to bilitation. The goal is to synergize the effects of the two virgin corneal tissue and there would be no need to treatments. When planning combined sequential treat- remove the crosslinked cornea. Moreover, there would be ments, two main questions arise: (1) Which is the correct less chance of PRK-induced scarring because the CXL treatment order? (2) What is the right time interval would induce apoptosis of the keratocytes and thus between the treatments? eliminate the agents that would theoretically produce Regarding treatment sequence, concerns include whether the cornea pretreated with CXL will react to T-CAT PRK the However, corneal thickness becomes crucial in this case, expected way, or whether the effect will be altered because as an excimer laser treatment, even with stromal removal it is being applied now to a stiffer cornea. On the other limited to 50 µm, would additionally decrease the thickness hand, will CXL be safe when applied over a cornea addition- of an already thin cornea. To avoid the danger of endothelial ally thinned by laser ablation? damage, we recommend intraoperative ultrasound contact If the plan is to first stabilize the cornea with CXL and pachymetry immediately after T-CAT PRK and the use of later apply limited T-CAT transepithelial PRK, one should hypotonic riboflavin to expand the corneal thickness wait at least 6 months in between procedures, as by this throughout the procedure.
time the cornea will have completed the repopulation and Moreover, CXL alone additionally changes the corneal deactivation of keratocytes.12 It is essential to wait past this shape by flattening it up to 2.00 D of the keratometry value period, as it is likely that a cornea with still activated kerato- over several years,6,8,15-18 meaning that a planned laser treat- cytes during the first few months after CXL will react exces- ment may be enhanced or even overflattened by additional sively to excimer laser injury, resulting in an exaggerated CXL treatments later on. This is another reason why we rec- OCTOBER 2009 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I 33
REFRACTIVE SURGERY FEATURE STORY
defining a horizontal line, are placed with help of a slit lamp,using the light slit rotated into horizontal position. Beforesetting the marks, the patient's head tilt is adjusted so thatboth pupils are level (ie, positioned along the same horizon-tal line). The second drop of anesthetic is applied beforeintroduction of the eye speculum under the laser micro-scope. Chilled balanced salt solution is applied to the corneafor 60 seconds to slow corneal metabolism.
Ablation using the Allegretto Wave excimer laser (WaveLight AG, Erlangen, Germany) is aligned onto thecenter of the pupil. A 50-µm PTK at a 6.5-mm opticalzone is applied to remove the epithelium uniformly.
Immediately afterward, T-CAT PRK ablation of up to 50µm depth at a 5.5- to 6-mm optical zone is applied, fol-lowed by irrigation with chilled balanced salt solution foranother 60 seconds. Immediately after the transepithelial PRK and before CXL treatment, ultrasound pachymetry is performed over thedeepithelialized cornea at approximately the thinnest pointto ensure a minimal corneal thickness of 400 µm. Riboflavin Figure 2. Serial computerized corneal topography: at the
0.1% solution in 20% dextran (Peschkemed, Huenenberg, time of examination, right after the removal of the rigid gas
Switzerland) is applied to the cornea every 3 minutes for 30 permeable contact lens (upper left); 1 month after contact
minutes. For corneas thinner than the safety limit, 30- lens removal and the day of the CXL treatment (upper right);
minute instillation of hypotonic riboflavin 0.1% without 5 months after CXL treatment and the day of T-CAT transep-
dextran is applied until the cornea has reached at least 3 ithelial PRK (lower left); 2 weeks after the T-CAT transepithe-
80 µm thickness.
lial PRK treatment (lower right).
UV-A irradiation is performed using an optical system (Koehler illumination) consisting of an array of seven UV-A ommend treating the spherical component of the refraction diodes with a potentiometer in series to allow regulation of only partially and planning 80% of the cylinder correction.
voltage (UV-X; Peschkemed; Figure 1). Irradiance is per-formed for 30 minutes at 3 mW/cm2, corresponding to a surface dose of 5.4 J/cm2. During treatment, riboflavin solu- The procedure is conducted under sterile conditions in tion and topical anesthetic proparacaine 0.5% are applied an operating theater. Our surface ablation protocol aims every 2 to 3 minutes to saturate the cornea with riboflavin to reduce postoperative pain and haze by minimizing the inflammation reaction and minimizing increased sensibility After the treatment, dexamethasone with tobramycin to UV-radiation injury. Vitamin C for protection against UV ointment (Tobradex; Alcon Laboratories, Inc.) and topical damage and haze formation18 and omega-3 fatty acids for ofloxacin 0.3% (Floxal; Bausch & Lomb, Rochester, New improvement of the tear film, both 1 g daily, are given for York) are applied. A bandage contact lens is fitted to the 3 days before surgery and 6 months after the surgery. NSAID corneal surface and removed after reepithelialization, typi- treatment with ibuprofen (Brufen; Galenika, Belgrade, cally on day 3 postoperative. The patient is given the topical Serbia) 600 mg four times daily is started 2 days before sur- steroid dexamethasone phosphate 0.1% (Maxidex; Alcon- gery and continued through day 3 postoperative. A pred- Couvreur, Belgium) four times daily, with gradual decrease nisolone 50 mg (Pronison; Galenika) tablet is given orally as of dosage over the following 2 months. a single dose 30 minutes before the surgery. Diclofenac 0.1%(Voltaren; Novartis, Basel, Switzerland) and ciprofloxacin 0.3% (Marocen; Hemofarm, Vrsac, Serbia) eye drops are Case 1: CXL first, T-CAT transepithelial PRK later. A 36-
administered 15, 10, and 5 minutes before surgery. year-old woman who had worn rigid gas permeable contact The first drop of anesthetic, proparacaine 0.5% (Alcaine; lenses for 20 years reported to our service because of con- Alcon Laboratories, Inc., Fort Worth, Texas) is applied dur- tact-lens intolerance. Her BCVA with contact lenses was 1.0 ing the preparation of the eyelids and the surgical field.
in both eyes. Papillary reaction was observed on the upper Scleral (perilimbal) marks at the 3- and 9-o'clock positions, tarsal conjunctiva, with red eye and corneal punctate ero- 34 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I OCTOBER 2009
REFRACTIVE SURGERY FEATURE STORY
Figure 3. Computerized corneal Scheimpflug tomography: (left) before and (center) after the combined T-CAT transepithelial
PRK-CXL treatment. Difference map is at right.
sions. At the examination, her BCVA in the right eye was 0.6 ago. She had been treated at another center with succes- with refraction of -2.00 -1.50 X 90º and in the left was 0.4 sive CXL and implantation of Ferrara Rings (Ferrara with refraction of -2.50 -1.75 X 100º. Ultrasound pachyme- Ophthalmics, Belo Horizonte, Brazil) 1 year ago in her right try was 493 and 474 µm in the right and left eyes respective- eye. This resulted in UCVA in the right of 0.3 and BCVA of ly, and her computerized corneal topography can be seen in 0.6 with refraction of -0.75 D sphere, which did not improve with pinhole. Her left eye had UCVA of 0.1 and After 1 month of contact lens abstinence, a typical pat- BCVA of 0.3+ with refraction of -1.75 -1.75 X 150º, achiev- tern of keratoconus could be appreciated on corneal topog- ing 0.6 with pinhole. raphy. At that time bilateral CXL treatment was performed.
In her left eye, we performed T-CAT transepithelial Almost 5 months after the CXL treatment, BCVA in the PRK followed by immediate application of CXL. Three right eye was 1.0+ with refraction of -3.25 -1.00 X 90º and in months after treatment, her UCVA was 0.5 and BCVA the left eye 0.6 with -3.50 -1.50 X 100º. As the patient was was 0.6 with refraction of -0.50 -1.25 X 155º. Topography contact-lens intolerant, T-CAT transepithelial PRK was per- can be seen in Figure 3.
formed in the left eye. After 2 weeks, UCVA reached 0.8, andBCVA was 1.0+ with refraction of -0.75 -0.50 X 90º.
Case 2: T-CAT transepithelial PRK followed immedi-
Treatment of keratoconus with a combination of ately by CXL. A 26-year-old woman with a 10-year history
CXL and excimer laser topography-guided transepithe- of keratoconus became contact-lens intolerant 1.5 years lial PRK is possible. The aim of this combined treat-ment is regularization of the cornea and significant reduction of irregular astigmatism rather than com- • In patients with irregular astigmatism due to keratoconus, plete elimination of spherical refractive error. Thus, an treatments such as PRK or corneal rings can regularize the ablation depth of up to 50 µm with small optical front surface of the cornea, but they do not address the zones (6 or 5.5 mm) and larger transition zones (9 underlying unfavorable biomechanical status of the stroma.
mm) is recommended. • A coadjuvant intervention with CXL can potentially stabi- With sequential CXL followed by T-CAT transepithe- lize the cornea and regularize the corneal surface. lial PRK, an interval of at least 6 months should beallowed between the two treatments. Coadjuvant T- • With combined CXL and topography-guided CAT transepithelial PRK immediately followed by CXL transepithelial PRK, Dr. Jankov and colleagues aim to is more comfortable for the patients; however, it is regularize the cornea and reduce irregular astigmatism, rather suitable for thicker corneas or earlier stages of kerato- than completely eliminating spherical refractive error.
36 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I OCTOBER 2009
Mirko R. Jankov II, MD, PhD, practices at LaserFocus Centre for Eye Microsurgery, Belgrade,Serbia. Dr. Jankov states that he is a paid consult-ant to WaveLight Laser Technologie AG. He maybe reached at e-mail: firstname.lastname@example.org. Sladjana Delevic, MD, is with Oculus Specialized Hospital for Ophthalmology, Belgrade, Serbia. Dr. Delevic states that shehas no financial interests in the products or companies men-tioned. Vesna Jovanovic, MD, MS, practices at LaserFocus Centre for Eye Microsurgery, Belgrade, Serbia. Dr. Jovanovic states thatshe has no financial interests in the products or companiesmentioned. Efekan Coskunseven, MD, is with the Dunya Eye Hospital, Istanbul, Turkey. Dr. Coskunseven statesthat he has no financial interests in the products orcompanies mentioned. Slobodan Golubovic, MD, PhD, is with Oculus Specialized Hospital for Ophthalmology, Belgrade, Serbia. Dr.
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5. Kanellopoulos AJ, Binder PS. Collagen cross-linking (CCL) with sequential topography-guided PRK: atemporizing alternative for keratoconus to penetrating keratoplasty. Cornea. 2007;26(7):891-895. 6. Coskunseven E, Jankov MR, Hafezi F. Contralateral eye study of corneal collagen cross-linkingwith riboflavin and UVA irradiation in patients with keratoconus. J Refract Surg. 2009;25(4):371-376.
7. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res.
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2006;25(9):1057-1059. 12. Mazzotta C, Balestrazzi A, Traversi C, et al. Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomo-graph II in vivo confocal microscopy in humans. Cornea. 2007;26(4):390-397.
13. Jankov MR, Panagopoulou SI, Tsiklis NS, Hajitanasis GC, Aslanides IM, Pallikaris IG. Topogra-phy-guided treatment of irregular astigmatism with the WaveLight excimer laser. J Refract Surg.
14. Stojanovic A, Wang L, Jankov MR, Nitter TA, Wang Q. Wavefront optimized versus custom-Qtreatments in surface ablation for myopic astigmatism with the WaveLight Allegretto Laser. J RefractSurg. 2008;24(8):779-789.
15. Jankov MR, Hafezi F, Beko M, et al. Corneal cross-linking for the treatment of keratoconus: pre-liminary results. [Article in Portuguese] Arq Bras Oftalmol. 2008;71(6):813-818.
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