Ring electrode for radio-frequency heating of the cornea: modelling and in vitro experiments

[EN] Radio-frequency thermokeratoplasty (RF-TKP) is a technique used to reshape the cornea curvature by means of thermal lesions using radio-frequency currents. This curvature change allows refractive disorders such as hyperopia to be corrected. A new electrode with ring geometry is proposed for RF-TKP. It was designed to create a single thermal lesion with a full-circle shape. Finite element models were developed, and the temperature distributions in the cornea were analysed for different ring electrode characteristics. The computer results indicated that the maximum temperature in the cornea was located in the vicinity of the ring electrode outer perimeter, and that the lesions had a semi-torus shape. The results also indicated that the electrode thickness, electrode radius and electrode thermal conductivity had a significant influence on the temperature distributions. In addition, in vitro experiments were performed on rabbit eyes. At 5 IN power the lesions were fully circular. Some lesions showed non-uniform characteristics along their circular path. Lesion depth depended on heating duration (60% of corneal thickness for 20s, and 30% for 10s). The results suggest that the critical shrinkage temperature (55-63degreesC) was reached at the central stroma and along the entire circular path in all the cases.Berjano, E.; Saiz Rodríguez, FJ.; Alió, J.; Ferrero, JM. (2003). Ring electrode for radio-frequency heating of the cornea: modelling and in vitro experiments. Medical & Biological Engineering & Computing. 41(6):630-639. https://doi.org/10.1007/BF02349970S630639416Alió, J. L., Ismail, M. M., Artola, A., andPérez-Santonja, J. J. (1997a): ‘Correction of hyperopia induced by photorefractive keratectomy using non-contact Ho: YAG laser thermal keratoplasty’,J. Refract. Surg.,13, pp. 13–16Alió, J. L., Ismail, M. M., andSanchez, J. L. (1997b): ‘Correction of hyperopia with non-contact Ho: YAG laser thermal keratoplasty’,J. Refract. Surg.,13, pp. 17–22Alió, J. L., andPérez-Santonja, J. J. (1999): ‘Correction of hyperopia by laser thermokeratoplasty (LTK)’ inPallikaris, I., andAgarwal, S. (Eds): ‘Refractive Surgery’ (Jaypee Brothers Medical Publishers Ltd, New Delhi, 1999), pp. 583–591Alió, J. L., andPérez-Santonja, J. J. (2002): ‘Correction of hyperopia by laser thermokeratoplasty (LTK)’ inAgarwal, S., Agarwal, A., Apple, D. J., Buratto, L., Alió, J. L., Pandey, S. K., andAgarwal, A. (Eds): ‘Textbook of ophthalmology’ (Lippincott Williams & Wilkins, Philadelphia, 2002), pp. 1331–1337Ayala, M. J., Alió, J. L., Ismail, M. M., andSánchez-Castro, J. M. (2000): ‘Experimental corneal histological study after thermokeratoplasty with holmium laser’,Arch. Soc. Esp. Oftalmol.,75, pp. 619–626Asbell, P. A., Maloney, R. K., Davidorf, J., Hersh, P., McDonald, M., Manche, E., andConductive Keratoplasty Study Group (2001): ‘Conductive keratoplasty for the correction of hyperopia’,Tr. Am. Ophtalmol. Soc.,99, pp. 79–87Avitall, B., Mughal, K., Hare, J., Helms, R., andKrum, D. (1997): ‘The effects of electrode-tissue contact on radiofrequency lesion generation’PACE,20, pp. 2899–2910Avitall, B., Helms, R. W., Koblish, J. B., Sieben, W., Kotov, A. V., andGupta, G. N. (1999): ‘The creation of linear contiguous lesions in the atria with an expandable loop catheter’,J. Am. Coll. Cardiol.,33, pp. 972–984Berjano, E. J., Saiz, J., andFerrero, J. M. (2002): ‘Radio-frequency heating of the cornea: Theoretical model andin vitro experiments’,IEEE Trans. Biomed. Eng.,49, pp. 196–205Brickmann, R., Kampmeier, J., Grotehusmann, U., Vogel, A., Koop, N., Asiyo-Vogel, M., Kamm, K., andBirngruber, R. (1996): ‘Corneal collagen denaturation in laserthermokeratoplasty’,SPIE Proc.,2681, pp. 56–63Choi, B., Kim, J., Welch, A. J., andPearce, J. A. (2002): ‘Dynamic impedance measurements during radio-frequency heating of cornea’,IEEE Trans. Biomed. Eng.,49, pp. 1610–1616Curley, M. G., andHamilton, P. S. (1997): ‘Creation of large thermal lesions in liver using saline-enhanced RF ablation’. Proc. 19th Ann. Int. Conf. IEEE Eng. Med. Biol. Soc., Chicago, pp. 2516–2519Doss, J. D., andAlbillar, J. I. (1980): ‘A technique for the selective heating of corneal stroma’,Contact Intraocular Lens Med.,6, pp. 13–17Doss, J. D. (1982): ‘Calculation of electric fields in conductive media’,Med. Phys.,9(4), pp. 566–573Gruenberg, P., Manning, W., Miller, D. andOlson, W. (1981): ‘Increase in rabbit corneal curvature by heated ring application’,Ann. Ophthalmol.,13, pp. 67–70Hata, C., andRaymond Chia, W.-K. (2001): ‘Catheter for circular tissue ablation and methods thereof’. US Patent 2001/0044625 A1Jain, M. K., andWolf, P. D. (1998): ‘Effect of electrode contact on lesion growth during temperature controlled radiofrequency ablation’, Proc. 20th Ann. Int. Conf. IEEE Eng. Med. Biol. Soc. Hong Kong (IEEE, Piscataway NJ) pp. 245–247Jain, M. K., andWolf, P. D. (1999): ‘Temperature controlled and constant power radiofrequency ablation: what affects lesion growth?’,IEEE Trans. Biomed. Eng.,46, pp. 1405–1412Krasteva, V. Tz., andPapazov, S. P. (2002): ‘Estimation of current density distribution under electrodes for external defibrillation’,Biomed. Eng. OnLine,1, 7Labonté, S. (1992): ‘A theoretical study of radio-frequency ablation of the myocardium’,PhD dissertation, Department of Electrical Engineering, University of Ottawa, CanadaLabonté, S. (1994): ‘Numerical model for radio-frequency ablation of the endocardium and its experimental validation’,IEEE Trans. Biomed. Eng.,41, pp. 108–115Mannis, M. J., Segal, W. A., andDarlington, J. K. (2001): ‘Making sense of refractive surgery in 2001: Why, when, for whom, and by whom?’,Mayo Clin. Proc.,76, pp. 823–829McCally, R. L., Bargeron, R. A., andGreen, W. R. (1983): ‘Stromal damage in rabbit corneas exposed to CO2 laser radiation’,Exp. Eye Res.,37, pp. 543–550McDonald, M. B., Hersh, P. S., Manche, E. E., Maloney, R. K., Davidorf, J., andSabry, M. (2002): ‘Conductive keratoplasty for the correction of low to moderate hyperopia: U.S. clinical trial 1-year results on 355 eyes’,Ophthalmol.,109, pp. 1978–1989McRury, I. D., Mitchell, M. A., Panescu, D. andHaines, D. E. (1997): ‘Non-uniform heating during radiofrequency ablation with long electrodes: monitoring the edge effect’,Circ.,96, pp. 4057–4064Méndez-g, A., andMéndez-Noble, A. (1997): ‘Conductive keratoplasty of the correction of hyperopia’ inSher, N. A. (Ed.) ‘Surgery for hyperopia and presbyopia’ (Williams & Wilkins, Baltimore, 1997), pp. 163–171Miller, D., andManning, W.J. (1978): ‘Alterations in curvature of bovine cornea using heated rings’,Invest. Ophthalmol., p. 297Mirotznik, M. S., andSchwartzman, D. (1996): ‘Nonuniform heating patterns of commercial electrodes for radiofrequency catheter ablation’,J. Cardiovasc. Electrophysiol.,7, pp. 1058–1062Nakagawa, H., Yamanashi, W. S., Pitha, J. V., Arruda, M., Wang, X., Ohtomo, K., Beckman, K. J., McClelland, J. H., Lazzara, R., andJackman, W. M. (1995): ‘Comparison ofin vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation’,Circ.,91, pp. 2264–2273Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., andWebster, J. G. (1995): ‘Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation’,IEEE Trans. Biomed. Eng.,42, pp. 879–890Plonsey, R., andHeppner, D. B. (1967): ‘Considerations of quasistationarity in electrophysiological systems’,Bull. Math. Biophys.,29, pp. 657–664Rowsey, J. J. (1987): ‘Electrosurgical keratoplasty: Update and retraction’,Invest. Ophthalmol. Vis. Sci.,28, p. 224Rutzen, A. R., Roberts, C. W., Driller, J., Gomez, D., Lucas, B. C., Lizzi, F. L., andColeman, D. J. (1990): ‘Production of corneal lesions using high-intensity focused ultrasound’,Cornea,9, pp. 324–330Schwan, H. P., andFoster, K. R. (1980): ‘RF-fields interactions with biological systems: electrical properties and biophysical mechanism’,Proc. IEEE,68, pp. 104–113Seiler, T., Matallana, M., andBende, T. (1990): ‘Laser thermokeratoplasty by means of a pulsed Holmium:YAG Laser for the hyperopic correction’,Refrac. Corneal Surg.,6, pp. 335–339Silvestrini, T. A. (1998): ‘Electrosurgical procedure for the treatment of the cornea’. US Patent 5,766,171Simmons, W. N., Mackey, S., He, D. S. andMarcus, F. L. (1996): ‘Comparison of gold versus platinum electrodes on myocardial lesion size using radiofrequency energy’,PACE,19, pp. 398–402Stringer, H., andParr, J. (1964): ‘Shrinkage temperature of eye collagen’,Nature,204, p. 1307Trembly, B. S., andKeates, R. H. (1991): ‘Combined microwave heating and surface cooling of the cornea’,IEEE Trans. Biomed. Eng.,38, pp. 85–91Trembly, B. S., Hashizume, N., Moodie, K. L., Cohen, K. L., Tripoli, N. K., andHoopes, P. J. (2001): ‘Microwave thermal keratoplasty for myopia: keratoscopic evaluation in porcine eyes’,J. Refract. Surg.,17, pp. 682–688Tungjitkusolmun, S., Woo, E. J., Cao, H., Tsai, J. Z., Vorperian, V. R., andWebster, J. G. (2000): ‘Thermal-electrical finite element modelling for radio frequency cardiac ablation: effects of changes in myocardial properties’,Med. Biol. Eng. Comput.,38, pp. 562–568Wiley, J. D., andWebster, J. G. (1982): ‘Analysis and control of the current distribution under circular dispersive electrodes’,IEEE Trans. Biomed. Eng,29, pp. 381–38

Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes

The authors thank Dr. John M Asara, Min Yuan, and Susanne Breitkopf for their technical help with metabolomics experiments, Dr. Ben Fowler for his technical help with TEM experiments and also Tina B McKay for many thoughtful discussions and scientific insights during the study.Purpose To establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients. Methods Human corneal fibroblasts from Healthy (HCFs), Type 1DM (T1DM) and Type 2DM (T2DM) donors were isolated and cultured for 4 weeks with Vitamin C stimulation in order to allow for extracellular matrix (ECM) secretion and assembly. Results Our data indicated altered cellular morphology, increased cellular migration, increased ECM assembly, and severe mitochondrial damage in both T1DM and T2DMs when compared to HCFs. Furthermore, we found significant downregulation of Collagen I and Collagen V expression in both T1DM and T2DMs. Furthermore, a significant up regulation of fibrotic markers was seen, including α-smooth muscle actin in T2DM and Collagen III in both T1DM and T2DMs. Metabolic analysis suggested impaired Glycolysis and Tricarboxylic acid cycle (TCA) pathway. Conclusion DM has significant effects on physiological and clinical aspects of the human cornea. The benefits in developing and fully characterizing our 3D in vitro model are enormous and might provide clues for the development of novel therapeutics.Yeshttp://www.plosone.org/static/editorial#pee

Late Development of Ulcerative Keratitis in Radial Keratotomy Scars

• We describe three patients in whom ulcerative keratitis developed seven months to 2½ years after uncomplicated radial keratotomy. All ulcers occurred along keratotomy scars within the interpalpebral fissure or inferiorly. At least one case developed spontaneously; another patient may have sustained an unrecognized corneal injury. The third patient was using an extended-wear soft contact lens for correction of residual myopia. Bacteria were isolated from two of the ulcers. With therapy, all ulcers healed without reducing visual acuity. We hypothesize that the altered structure of the slowly healing keratotomy incisions coupled with redistribution of the tear film due to changes in corneal topography may result in intermittent epithelial irregularities. Alone or in conjunction with any form of mechanical or hypoxic corneal injury, these changes along keratotomy incisions may predispose to corneal infection