Heating of the CorneaWord下载.docx

1、 An Engineering Review of Electrodes and ApplicatorsEnrique J Berjano,*1 Enrique Navarro,2 Vicente Ribera,2 Javier Gorris,2 and Jorge L Ali3,41Institute for Research and Innovation on Bioengineering, Technical University of Valencia, Valencia, Spain2Neptury Technologies, Almassora, Spain3Cornea and

2、Refractive Surgery Department, Vissum-Instituto Oftalmolgico de Alicante, Alicante, Spain4Pathology and Surgery Department, Universidad Miguel Hernndez, Elche, Spain*Address correspondence to this author at the Institute for Research and Innovation on Bioengineering, Technical University of Valencia

3、, Valencia, Spain; E-mail: eberjanoeln.upv.es AbstractThis 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 an

4、d 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 v

5、iew, 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 76C）. Secondly, we describe the different applicator designs （i.e. RF electrodes） proposed and tested to date. This review is planned from

6、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 applic

7、ation placement （surface versus intrastromal）.INTRODUCTIONLocalized 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 tiss

8、ue （particularly the central part of the corneal tissue, i.e. the central stroma） causes collagen to shrink, and hence changes the corneal curvature 1. However, the process can be used for other therapeutic objectives. TKP is a complex challenge from the engineering point of view （see Fig. 11）. On o

9、ne 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 m distant from the central stroma）. The endothelium is a mono-cellular layer in the human eye which is non regenerable, and

10、 hence the temperature at this point should always be maintained at a safe level （e.g. lower than 45C）. 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

11、 profile with a low temperature at the epithelium （see solid line in Fig. 11）. In contrast, other techniques （like intrastromal applicators） heat both the epithelium and the central stroma （see dashed line in Fig. 11）.Fig. （1）Left: Schematic diagram of the cornea showing the anterior layer （epitheli

12、um）, 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 tech

13、niques 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 n

14、o more than 300 m distant from central stroma）; and 2） a high resolution of the temperature reached at the target point （temperatures ranging from 58 to 76C are required to shrink the collagen, and temperatures over 79C are harmful）. Since the epithelium is a layer with regeneration capability, it c

15、an 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.It is known that collagen shrinkage occurs at temperatures ranging from 58 to 76C. However, higher thermal levels, 79C or over, d

16、efinitely 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） 2. Therefore, the procedure also requires high resolution of the temperatur

17、e reached at the target point （see Fig. 11）.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 3,4, microwaves 5-7, laser 2 and ultrasound 8-10, and radiofrequency （RF） currents

18、. 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 technica

19、l 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

20、）. Consequently, the developments are not necessarily related to either clinical procedures or trademarks.APPLICATORS WITH SURFACE COOLINGThe first applicator designed for applying RF currents in the human cornea was described by Doss and Albillar 11 in 1980. Since it was developed at Los Alamos Sci

21、entific Laboratory （NM, USA）, the device was named the Los Alamos Keratoplasty probe 1. 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 37C） was infused over the cornea surfac

22、e 11,12 （see Fig. 2B2B）.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 dis

23、persive 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

24、-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）.The basic idea of the CSE was to improve the temperature profile obtained by the thermokeratophore during thermokeratoplasty （TKP）. The thermokeratophore w

25、as a metallic probe preheated to a specific temperature range （90-130C） 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 （75C）, wh

26、ile the central stroma remained at 45C 11. In contrast, using the CSE, the maximum temperature in the cornea was reached at the central stroma （70C）, both epithelium and endothelium remaining at a temperature lower than 50C. The applicator had a monopolar system, i.e. the RF currents were delivered

27、between the CSE （active electrode） and a large dispersive electrode placed away from the CSE. This technique was first tested on excised pigs eyes 11, later on an in vivo model with dogs eyes （sacrificed within minutes of the treatment） 13, and finally some preliminary clinical trial were conducted

28、on patients to treat keratoconus 14-16. 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

29、 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 （i

30、n 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 17 but never tested. The most novel ide

31、a of CSE was to cool the cornea surface during heating. In fact, the same idea was later employed in microwave thermal keratoplasty 5-7, 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 TK

32、P 18.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. 2A2A）. The applicator, known as the localized current field （LCF） device, was also developed at Los Alamos Scientific Laboratory 19. It was employed in the veterinary field for hyperthermic therapy for neoplasia or degenerative corneal diseas