The Open Biomedical Engineering Journal




ISSN: 1874-1207 ― Volume 13, 2019

Radiofrequency Heating of the Cornea: An Engineering Review of Electrodes and Applicators



Enrique J Berjano*, 1, Enrique Navarro2, Vicente Ribera2, Javier Gorris2, Jorge L Alió3, 4
1 Institute for Research and Innovation on Bioengineering, Technical University of Valencia, Valencia, Spain
2 Neptury Technologies, Almassora, Spain
3 Cornea and Refractive Surgery Department, Vissum-Instituto Oftalmológico de Alicante, Alicante, Spain
4 Pathology and Surgery Department, Universidad Miguel Hernández, Elche, Spain

Abstract

This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76ºC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal).



Article Information


Identifiers and Pagination:

Year: 2007
Volume: 1
First Page: 71
Last Page: 76
Publisher Id: TOBEJ-1-71
DOI: 10.2174/1874120700701010071

Article History:

Received Date: 5/10/2007
Revision Received Date: 26/11/2007
Acceptance Date: 27/11/2007
Electronic publication date: 11/12/2007
Collection year: 2007

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2007 Bentham Science Publishers Ltd.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.


* Address correspondence to this author at the Institute for Research and Innovation on Bioengineering, Technical University of Valencia, Valencia, Spain; E-mail: eberjano@eln.upv.es




INTRODUCTION

Localized heating of the cornea has been employed since 1889 for different therapeutic and surgical objectives. The best known of these techniques is probably thermokeratoplasty (TKP), which is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature [1A Mendez-Gutierrez, "“Review of thermokeratoplasty developments,”", In: JR Pinelli, and SE Pascucci, Eds., Conductive keratoplasty. A primer, SLACK: Thorofare, 2005, pp. 3-8.]. However, the process can be used for other therapeutic objectives. TKP is a complex challenge from the engineering point of view (see Fig. 1). On one hand, it is necessary to create very localized heating in a precise location (central stroma), keeping the endothelium thermally protected (which is located no more than 300 μm distant from the central stroma). The endothelium is a mono-cellular layer in the human eye which is non regenerable, and hence the temperature at this point should always be maintained at a safe level (e.g. lower than 45ºC). Consequently, the procedure requires an extremely high spatial resolution. The temperature at the epithelium is not so critical: some TKP techniques combine surface cooling to create a temperature profile with a low temperature at the epithelium (see solid line in Fig. 1). In contrast, other techniques (like intrastromal applicators) heat both the epithelium and the central stroma (see dashed line in Fig. 1).

Fig. (1)

Left: Schematic diagram of the cornea showing the anterior layer (epithelium), the posterior layer (endothelium), separated by the stroma. The aim of the thermokeratoplasty (TKP) procedure is to create safe localized heating in the central stroma. Right: Optimum (solid line) and sub optimum (dotted line) thermal profiles in the cornea for themokeratoplasty (TKP). TKP techniques are a complex challenge from the engineering point of view, due to requiring: 1) an extremely high spatial resolution (i.e. it is necessary to create very localized heating in a precise location of the central stroma –red zone–, thermally protecting the endothelium –green zone–, which is placed no more than 300 μm distant from central stroma); and 2) a high resolution of the temperature reached at the target point (temperatures ranging from 58 to 76°C are required to shrink the collagen, and temperatures over 79°C are harmful). Since the epithelium is a layer with regeneration capability, it can stand heating during TKP(dotted line). However, in the optimum TKP technique the epithelium should be kept cool (solid line) and the heat focused on the central stroma.



Fig. (2)

RF electrodes and applicators for creating a lesion at a certain point in the cornea. A: A pair of electrodes cause a lesion by means of a bipolar application. B: The circulating saline electrode (CSE) works by delivering RF currents from the active electrode to a dispersive electrode while a flow of isotonic saline is infused over the cornea surface. C: A small surface electrode is placed on the cornea and RF currents are applied between this and a dispersive electrode. The lesion is hence confined to the cornea surface. D: An intrastromal electrode is a needle-shaped electrode which penetrates from the surface to the central stroma. The lesion has more depth than in the case of a surface electrode (C).



Fig. (3)

Two types of RF electrodes for creating a circular lesion in the cornea (both use a monopolar system, i.e. the RF current circulates between the electrode and a dispersive electrode, which is not shown). A: A circular electrode placed on the cornea provides a circular lesion pattern. B: A small circular electrode is inserted into the central stroma (red dashed line), providing a toroidal lesion.



Fig. (4)

Computer modeling of an intrastromal electrode. This kind of electrode has two important advantages: 1) the RF power is mainly deposited at the electrode tip (see Joule heat in A), and 2) the low thermal conductivity of the electrode metallic body facilitates the transmission of heat from the electrode tip to the anterior zone (see heat flux in B). Note that the maximum heat flux is located in the electrode, and in contrast, the corneal tissue shows a very low heat flux value. A high thermal gradient therefore appears between the electrode tip and endothelium, which provides thermal protection to the endothelium (see temperature in C). Scales are normalized.



Fig. (5)

Computer modeling of intrastromal electrodes. Top: Progress of the temperature profiles (assessed on the electrode axis) for an intrastromal electrode made of stainless steel (each plot represents a time step of 10 ms). Bottom: Temperature profiles at 100 ms for intrastromal electrodes with different thermal conductivity values. Note that electrodes with low thermal conductivity can remove the heat generated at the electrode tip more efficiently. All the simulations were conducted by applying a constant voltage of 10 V and the electrode tip was located at a depth of 450 µm in the cornea [41TA Silvestrini, "“Electrosurgical procedure for treatment of the cornea,”", U.S. Patent 5 766 171, Jun. 16, 1998.].



It is known that collagen shrinkage occurs at temperatures ranging from 58 to 76ºC. However, higher thermal levels, 79ºC or over, definitely lead to relaxation of the collagen and complete loss of its elasticity, inducing important keratocyte proliferation and accelerating collagen turnover (i.e. provoking a regression of the corrected refractive error) [2MM Ismail, JJ Pérez-Santonja, and JL Alió JL, "“Correction of the hyperopia and hyperopic astigmatism by laser thermokeratoplasty,”", In: ON Serdarevic, Ed., Refractive Surgery: Current Techniques and Management, Igaku-Shoin: New York, 1997, pp. 263-274.]. Therefore, the procedure also requires high resolution of the temperature reached at the target point (see Fig. 1).

In order to create corneal heating, different kinds of energy sources have been tested, such as simple thermal conduction from pre-heated probes, known as thermokeratophores [3EL Shaw, and AR Gasset, "“Thermokeratoplasty (TKP) temperature profile,”", Invest. Ophthalmol, vol. 13, pp. 181-186, 1974.,4AR Gasset, and HE Kaufman, "“Thermokeratoplasty in the treatment of keratoconus,”", A. J. Ophthalmol, vol. 79, pp. 226-232, 1975.], microwaves [5BS Trembly, N Hashizume, KL Moodie, KL Cohen, NK Tripoli, and PJ Hoopes, "“Microwave thermal keratoplasty for myopia: keratoscopic evaluation in porcine eyes,”", J. Refract. Surg, vol. 17, no. 6, pp. 682-688, Nov-Dec 2001.-7BS Trembly, and RA Crump, "“Combined microwave heating and surface cooling of the cornea,”", U.S. Patent 4 881 453, Nov. 21,1989.], laser [2MM Ismail, JJ Pérez-Santonja, and JL Alió JL, "“Correction of the hyperopia and hyperopic astigmatism by laser thermokeratoplasty,”", In: ON Serdarevic, Ed., Refractive Surgery: Current Techniques and Management, Igaku-Shoin: New York, 1997, pp. 263-274.] and ultrasound [8CA Rutzen, RW Roberts, J Driller, D Gomez, BC Lucas, FL Lizzi, and DJ Coleman, "“Production of corneal lesions using high-intensity focused ultrasound,”", Cornea, vol. 9, pp. 324-330, Oct 1990.-10PJ Klopotek, "“Meted and apparatus for generating localized hyperthermia,”", U.S. Patent 5 230 334, Jul. 27, 1993.], and radiofrequency (RF) currents. However, our interest is focused on techniques for corneal heating by means of RF currents (≈500 kHz), therefore in this review we describe the different designs of applicators (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal). Consequently, the developments are not necessarily related to either clinical procedures or trademarks.

APPLICATORS WITH SURFACE COOLING

The first applicator designed for applying RF currents in the human cornea was described by Doss and Albillar [11JD Doss, and JJ Rowsey, "“A technique for the selective heating of corneal stroma,”", Contact Intraocul. Lens Med. J, vol. 6, pp. 13-17, Jan-Mar 1980.] in 1980. Since it was developed at Los Alamos Scientific Laboratory (NM, USA), the device was named the Los Alamos Keratoplasty probe [1A Mendez-Gutierrez, "“Review of thermokeratoplasty developments,”", In: JR Pinelli, and SE Pascucci, Eds., Conductive keratoplasty. A primer, SLACK: Thorofare, 2005, pp. 3-8.]. However, Doss and Albillar called it the circulating saline electrode (CSE), since, while the active electrode delivered RF currents (1.6 MHz) a flow of isotonic saline (at 37ºC) was infused over the cornea surface [11JD Doss, and JJ Rowsey, "“A technique for the selective heating of corneal stroma,”", Contact Intraocul. Lens Med. J, vol. 6, pp. 13-17, Jan-Mar 1980.,12JD Doss, and RL Hutson, "“Corneal-chaping electrode,”", U.S. Patent 4 326 529, Apr. 27, 1982.] (see Fig. 2B).

The basic idea of the CSE was to improve the temperature profile obtained by the thermokeratophore during thermokeratoplasty (TKP). The thermokeratophore was a metallic probe preheated to a specific temperature range (90-130ºC) and placed on the cornea surface, i.e. the thermal lesion was created by thermal conduction from the thermokeratophore towards the corneal stroma. Consequently, the maximum temperature was reached at the cornea surface (≈75ºC), while the central stroma remained at ≈45ºC [11JD Doss, and JJ Rowsey, "“A technique for the selective heating of corneal stroma,”", Contact Intraocul. Lens Med. J, vol. 6, pp. 13-17, Jan-Mar 1980.]. In contrast, using the CSE, the maximum temperature in the cornea was reached at the central stroma (≈70ºC), both epithelium and endothelium remaining at a temperature lower than 50ºC. The applicator had a monopolar system, i.e. the RF currents were delivered between the CSE (active electrode) and a large dispersive electrode placed away from the CSE. This technique was first tested on excised pigs’ eyes [11JD Doss, and JJ Rowsey, "“A technique for the selective heating of corneal stroma,”", Contact Intraocul. Lens Med. J, vol. 6, pp. 13-17, Jan-Mar 1980.], later on an in vivo model with dogs’ eyes (sacrificed within minutes of the treatment) [13JJ Rowsey JJ, JR Gaylor, R Dahlstrom, and JD Doss, "“Los Alamos keratoplasty techniques,”", Contact Intraocul. Lens Med. J, vol. 6, pp. 1-12, Jan-Mar 1980.], and finally some preliminary clinical trial were conducted on patients to treat keratoconus [14JJ Rowsey, and JD Doss, "“Preliminary report of Los Alamos Keratoplasty Techniques,”", Ophthalmol, vol. 88, pp. 755-760, Aug 1981.-16JJ Rowsey, "“Electrosurgical keratoplasty: update and retraction,”", Invest. Ophthalmol. Vis. Sci, vol. 28, p. 224, 1987.]. Although the CSE was very effective right away (the corneas were flattened), it was also a common experience that the flattening of these diseased corneas tended to diminish significantly within a few weeks. Unfortunately, the protocol did not allow performing re-treatments to determine whether longer term stability could be achieved (Doss, personal communication, Oct. 11, 1995). It is also important to point out that this technique has never been employed on relatively “normal” human corneas such as those found in astigmatism and hyperopic conditions (in contrast, in keratoconus the cornea has abnormal morphology and is also very thin).

The CSE technique was also proposed using a bipolar system (i.e. without using a dispersive electrode). Several arrangements with a variable number of electrodes were proposed [17JD Doss, "“Multipolar corneal-shaping electrode with flexible removable skirt,”", U.S. Patent 4 381 007, Apr. 26, 1983.] but never tested. The most novel idea of CSE was to cool the cornea surface during heating. In fact, the same idea was later employed in microwave thermal keratoplasty [5BS Trembly, N Hashizume, KL Moodie, KL Cohen, NK Tripoli, and PJ Hoopes, "“Microwave thermal keratoplasty for myopia: keratoscopic evaluation in porcine eyes,”", J. Refract. Surg, vol. 17, no. 6, pp. 682-688, Nov-Dec 2001.-7BS Trembly, and RA Crump, "“Combined microwave heating and surface cooling of the cornea,”", U.S. Patent 4 881 453, Nov. 21,1989.], and more recently, a system for surface cooling of the cornea during TKP has been patented, especially for electrical-induced techniques such as RF or microwave TKP [18BS Trembly, "“Thermokeratoplasty systems,”", U.S. Patent 7 192 429, Mar. 20, 2007.].

APPLICATORS WITHOUT SURFACE COOLING (DRY APPLICATORS)

Prior to the development of the CSE, some experimental studies were conducted by using a two-electrode applicator for delivering RF currents (2 MHz) in a bipolar system (see Fig. 2A). The applicator, known as the localized current field (LCF) device, was also developed at Los Alamos Scientific Laboratory [19JD Doss, "“Electrothermal treatment of cancer eye,”", Los Alamos Scientific Laboratory Mini-review, pp. 77-14.]. It was employed in the veterinary field for hyperthermic therapy for neoplasia or degenerative corneal diseases [20SM Neumann, RA Kainer, and GA Severin, "“Reaction of normal equine eyes to radio-frequency current-induced hyperthermia,”", A. J. Vet. Res, vol. 43, pp. 1938-1944, 1982.,21MB Glaze, and MA Turk, "“Effects of radiofrequency hyperthermia on the healthy canine cornea,”", A. J. Vet. Res, vol. 47, pp. 913-918, 1986.]. A similar probe, i.e. based on a bipolar RF application, was later proposed for refractive surgery [22RJ Fugo, "“Method of ocular refractive surgery,”", US. Patent 5 423 815, Jun. 13, 1995.]. It consisted of a bipolar forceps which created thermal lesions in segments of perilimbal corneal tissue. To our knowledge it has never been tested.

Around 1993, Mendez and Mendez-Noble [23A Mendez, and A Mendez Noble, "“Conductive keratoplasty for the correction of hyperopia,”", In: NA Sher, Ed., Surgery for hyperopia and presbyopia, Williams & Wilkins: Baltimore, 1997, pp. 163-171.] proposed using a small surface application electrode to create small lesion spots (see Fig. 2C). The aim was the correction of hyperopia by producing steeping of the cornea by means of creating a series of eight spots of one millimeter in diameter distributed symmetrically around a seven millimeter diameter ring in the mid-periphery of the cornea. The electrode played the role of an active electrode, and a large-area disk was the dispersive electrode. In addition, a more complex applicator including up to eight electrodes was proposed to simultaneously create the circular lesion pattern [24L Hood, and AG Mendez, "“Method and apparatus for modifications of visual acuity by thermal means,”", U.S. Patent 5 533 999, Jul. 9, 1996.]. Our group also conducted computational and experimental research to characterize the corneal lesions created by this kind of surface electrode application [25EJ Berjano, J Saiz, and JM Ferrero, "“Radio-frequency heating of the cornea theoretical model and in vitro experiments”", IEEE Trans. Biomed. Eng, vol. 49, pp. 196-205, Mar 2002.,26ME Mulet, JL Alió, TF Salem, and EJ Berjano, "“Corneal thermal lesions with radiofrequency currents for thermokeratoplasty,”", Invest. Ophthalmol. Vis. Sci, vol. 41, p. S919, 2000.]. In a retrospective study of 166 cases Mendez and Mendez-Noble [23A Mendez, and A Mendez Noble, "“Conductive keratoplasty for the correction of hyperopia,”", In: NA Sher, Ed., Surgery for hyperopia and presbyopia, Williams & Wilkins: Baltimore, 1997, pp. 163-171.] found some cases of regression due to surface application. They considered that during the surface application, tear film or balanced salt solution on the cornea might cause a dissipation of the energy. In 1994 they therefore proposed the intrastromal application of RF energy by means of penetrating electrodes (see subsequent section).

Finally, we also conducted experimental research to assess the performance of a ring applicator for the rapid creation of a circular lesion pattern [27EJ Berjano, J Saiz, JL Alio, and JM Ferrero, "“Ring electrode for radio-frequency heating of the cornea: modelling and in vitro experiments,”", Med. Biol. Eng. Comput, vol. 41, pp. 630-639, Nov 2003.] (see Fig. 3A). The results suggested that the contact conditions between applicator and cornea surface should be balanced along the circular path in order to avoid zones with different lesion characteristics. In fact, it has been recognized that manual placement of the probe may involve human error, and hence the problem of controlling the contact between applicator and cornea has been broadly investigated in RF heating [28PR Goth, D Panescu, and S Khalaj, "“Thermokeratoplasty system with a guided probe tip,”", U.S. Patent 2005/0245949 A1, Nov. 3, 2005.-30L Hood, "“Thermokeratoplasty system with a power supply that can determine a wet or dry cornea,”", US Patent 6,673,069 B1, Jan. 6, 2004.].

INTRASTROMAL APPLICATORS

The electrodes most frequently employed in clinical practice for RF heating of the cornea are the intrastromal electrodes. They were initially proposed by Mendez and Mendez-Noble in 1994 in order to improve the results obtained by surface application electrodes [23A Mendez, and A Mendez Noble, "“Conductive keratoplasty for the correction of hyperopia,”", In: NA Sher, Ed., Surgery for hyperopia and presbyopia, Williams & Wilkins: Baltimore, 1997, pp. 163-171.]. Briefly, the active electrode has a very fine tip that measures between 350 and 400 μm in length and ≈100 μm in diameter. It is inserted into the cornea and then the RF energy is directly applied into the stroma. Typical values are a frequency of 330-350 kHz [31LV Paulino, E Paulino, RA Barros, AG Salles, and JR Rehder, "“Corneal topographic alteration after radiofrequency application to an animal model,”", Arq. Bras. Oftalmol, vol. 68, pp. 415-456, Jul-Aug 2005.-33B Choi, J Kim, AJ Welch, and JA Pearce, "“Dynamic impedance measurements during radio-frequency heating of cornea,”", IEEE Trans. Biomed. Eng, vol. 49, pp. 1610-1616, Dec 2002.], and a power of ≈600 mW delivered for ≈600 ms.

The electrical-thermal behavior of this kind of electrode has been extensively studied using computer modeling [34JA Pearce, and C Ikei, "“Increasing corneal curvature by RF current: numerical model studies of governing physical processes,”", Proc. SPIE, p. 6640, 2007.-38EJ Berjano, JL Alio, and J Saiz, "“Modeling for radio-frequency conductive keratoplasty: implications for the maximum temperature reached in the cornea,”", Physiol. Meas, vol. 26, pp. 157-172, Jun 2005.]. The same kind of electrode has also been employed in other RF heating techniques such as ablation of cardiac arrhythmias [39EJ Woo, S Tungjitkusolmun, H Cao, JZ Tsai, JG Webster, VR Vorperian, and JA Will, "“A new catheter design using needle electrode for subendocardial RF ablation of ventricular muscles: finite element analysis and in vitro experiments,”", IEEE Trans. Biomed. Eng, vol. 47, pp. 23-31, Jan 2000.]. It is known that RF power is mainly deposited at the electrode tip (see Fig. 4A). This behavior is especially advantageous for heating the cornea, since it allows direct heating of the central stroma. However, this electrode design offers additional advantages for cornea heating; since the electrode body is usually made of a conducting metal (e.g. stainless steel), the low thermal conductivity of this element compared to the thermal conductivity of the cornea facilitates the transmission of heat from the electrode tip to the anterior cornea (see Fig. 4B). As a result, a high thermal gradient appears between the electrode tip and endothelium, which provides thermal protection to the endothelium (see Fig. 4C).

We studied the effect of the thermal conductivity of the intrastromal electrode on the temperature profile in the cornea by means of theoretical modeling [40EJ Berjano, J Saiz, JM Ferrero, and J Alió, "“Effect of the termal conductivity of the intra-tissue active electrode during RF electrocoagulation,”", In: Proc XVI Annual Congress Spanish Soc. Biomed. Eng, 1998, pp. 23-25.]. Fig. 5 shows the temperature profiles for intrastromal electrodes made from different materials, confirming the importance of the electrode body in diffusing the heat created at the electrode tip.

Finally, regarding intrastromal electrodes, it is interesting to note Silvestrini’s proposal [41TA Silvestrini, "“Electrosurgical procedure for treatment of the cornea,”", U.S. Patent 5 766 171, Jun. 16, 1998.] for an RF applicator circular in shape (or semicircular or any other appropriate form) which is placed on the central stroma and inserted into the inner cornea through at least one access (see Fig. 3B). To our knowledge this device was never experimentally assessed.

COMPUTER MODELING STUDIES

During the study and development of applicators for RF heating of the cornea, theoretical models and computer simulations have played an important role. This methodology is advantageous, being both fast and cheap, for assessing the electrical and thermal behavior of RF applicators [42EJ Berjano, "“Theoretical modeling for radiofrequency ablation: state-of-the-art and challenges for the future,”", Biomed. Eng. Online, vol. 18, no. 5, p. 24, 2006.]. For instance, computer modeling studies have been developed for surface applied monopolar electrodes, both for single [25EJ Berjano, J Saiz, and JM Ferrero, "“Radio-frequency heating of the cornea theoretical model and in vitro experiments”", IEEE Trans. Biomed. Eng, vol. 49, pp. 196-205, Mar 2002.] and circular lesion patterns [27EJ Berjano, J Saiz, JL Alio, and JM Ferrero, "“Ring electrode for radio-frequency heating of the cornea: modelling and in vitro experiments,”", Med. Biol. Eng. Comput, vol. 41, pp. 630-639, Nov 2003.]. Likewise, many computer modeling studies have been carried out on intrastromal electrodes, especially for those employed in Conductive Keratoplasty (CK) [34JA Pearce, and C Ikei, "“Increasing corneal curvature by RF current: numerical model studies of governing physical processes,”", Proc. SPIE, p. 6640, 2007.-38EJ Berjano, JL Alio, and J Saiz, "“Modeling for radio-frequency conductive keratoplasty: implications for the maximum temperature reached in the cornea,”", Physiol. Meas, vol. 26, pp. 157-172, Jun 2005.].

CLINICAL RELEVANCE

Even though numerous RF applicator designs for cornea heating have been proposed and experimentally tested, to date only the needle-shaped intrastromal applicators have achieved clinical success [31LV Paulino, E Paulino, RA Barros, AG Salles, and JR Rehder, "“Corneal topographic alteration after radiofrequency application to an animal model,”", Arq. Bras. Oftalmol, vol. 68, pp. 415-456, Jul-Aug 2005.,32JM Lyra, FC Trindade, D Lyra, and A Bezerra, "“Outcomes of radiofrequency in advanced keratoconus,”", J. Cataract. Refract. Surg, vol. 33, pp. 1288-1295, Jul 2007.,43JL Alio, PJ Claramonte, A Caliz, and MI Ramzy, "“Corneal modeling of keratoconus by conductive keratoplasty,”", J. Cataract. Refract. Surg, vol. 31, pp. 190-197, Jan 2005.]. For instance, they were initially employed for the correction of low to moderate hyperopia [44MB McDonald, PS Hersh, EE Manche, RK Maloney, J Davidorf, and M Sabry, "“Conductive Keratoplasty United States Investigators Group. Conductive keratoplasty for the correction of low to moderate hyperopia: U.S. clinical trial 1-year results on 355 eyes,”", Ophthalmol, vol. 109, pp. 1978-1989, Nov 2002.], and to correct residual hyperopia after corneal surgery [45IF Comaish, and MA Lawless, "Conductive keratoplasty to correct residual hyperopia after corneal surgery", J. Cataract. Refract. Surg, vol. 29, pp. 202-206, Jan 2003.]. Subsequently, clinical trials were carried out on correcting hyperopic astigmatism [46IG Pallikaris, TL Naoumidi, and NI Astyrakakis, "“Conductive keratoplasty to correct hyperopic astigmatism,”", J. Refract. Surg, vol. 19, pp. 425-432, Jul-Aug 2003.] and presbyopia [47MB McDonald, D Durrie, P Asbell, R Maloney, and L Nichamin, "“Treatment of presbyopia with conductive keratoplasty: six-month results of the 1-year United States FDA clinical trial,”", Cornea, vol. 23, pp. 661-668, Oct 2004.]. Corneal modeling of keratoconus has recently been conducted by means of this type of electrode [43JL Alio, PJ Claramonte, A Caliz, and MI Ramzy, "“Corneal modeling of keratoconus by conductive keratoplasty,”", J. Cataract. Refract. Surg, vol. 31, pp. 190-197, Jan 2005.].

From the clinical and manufacturing point of view, these electrodes were initially manufactured by Refractec (Irvine, CA, USA). This company currently develops and markets electrodes and an RF generator under the trade name of ViewPoint® CK System. The surgical procedure is known as Conductive Keratoplasty® (CK). In general, for the treatment of hyperopia, the lesion spots (which shrink corneal collagen in the treatment zone) are created following a full circular pattern (6, 7 and/or 8 mm diameters). This lesion pattern acts like a belt, tightening the peripheral region of the cornea so that the central cornea becomes slightly raised [48GH Strauss, "“Mechanism of Conductive Keratoplasty,”", In: JR Pinelli, and SE Pascucci, Eds., Conductive keratoplasty. A primer, SLACK: Thorofare, 2005, pp. 11-19.].

The Brazilian company Loktal Medical Electronics (Butantã, São Paulo, Brazil) has also developed similar electrodes (stainless steel tip of 90 µm in diameter and 350 µm in length) which are employed with an RF generator (Wavetronic Genius). To date, this equipment has been employed in a clinical study for treatment of advanced keratoconus [32JM Lyra, FC Trindade, D Lyra, and A Bezerra, "“Outcomes of radiofrequency in advanced keratoconus,”", J. Cataract. Refract. Surg, vol. 33, pp. 1288-1295, Jul 2007.]. In this case, the thermal spots were created in optical zones of 4.0 and 5.0 mm (the exact number of spots and their location were determined by the degree of corneal curvature) [32JM Lyra, FC Trindade, D Lyra, and A Bezerra, "“Outcomes of radiofrequency in advanced keratoconus,”", J. Cataract. Refract. Surg, vol. 33, pp. 1288-1295, Jul 2007.].

Both technologies (Refractec and Loktal) are based on delivering RF energy for a total time of 600 ms (typical value). During this period, the RF generator emits a train of pulses consisting of exponentially damped sinusoidal waves (350 kHz) [31LV Paulino, E Paulino, RA Barros, AG Salles, and JR Rehder, "“Corneal topographic alteration after radiofrequency application to an animal model,”", Arq. Bras. Oftalmol, vol. 68, pp. 415-456, Jul-Aug 2005.,32JM Lyra, FC Trindade, D Lyra, and A Bezerra, "“Outcomes of radiofrequency in advanced keratoconus,”", J. Cataract. Refract. Surg, vol. 33, pp. 1288-1295, Jul 2007.,38EJ Berjano, JL Alio, and J Saiz, "“Modeling for radio-frequency conductive keratoplasty: implications for the maximum temperature reached in the cornea,”", Physiol. Meas, vol. 26, pp. 157-172, Jun 2005.]. The typical value of delivered power is 600 mW, however other power values can be employed. On this topic, Choi et al [33B Choi, J Kim, AJ Welch, and JA Pearce, "“Dynamic impedance measurements during radio-frequency heating of cornea,”", IEEE Trans. Biomed. Eng, vol. 49, pp. 1610-1616, Dec 2002.] have studied in depth the effect of programmed power on impedance progress during heating.

CONCLUSION

This paper has reviewed the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Taking into consideration the extensive number of cornea heating techniques for purposes of refractive surgery proposed and tested to date (thermokeratophores, laser, microwave, ultrasound, radiofrequency), we believe that the problem has not yet been solved. Therefore, a great deal of research effort should be focused on finding the optimum RF applicator for cornea heating.

ACKNOWLEDGMENTS

This work was partially supported by the “Programa de Investigación y Desarrollo Tecnológico 2007 (Ref: IMIDTA/2007/586)” of the Institut de la Petita i Mitjana Indústria de la Comunitat Valenciana (IMPIVA-Generalitat Valenciana), and by the "Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Educación y Ciencia" of Spain (TEC 2005-04199/TCM). We would like to thank the R+D+i Linguistic Assistance Office at the Technical University of Valencia for their help in revising this paper.

REFERENCES

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