Resumen de Computational planning tools in ophthalmology: instrastromal corneal ring surgery

Julio Flecha Lescún

• SUMMARY This thesis addresses the problem of the simulation of intrastromal corneal ring segment surgery for the reduction of myopia and astigmatism, as well as the stabilisation of keratoconus (KC). This disease causes high myopia, irregular astigmatism and reduction of the patient's visual acuity to the point of blindness. Therefore there are several techniques to try to stabilise it and, thus, prevent its progression. For mild keratoconus, it is enough to use special spectacles or lenses to try to correct it, but in more advanced cases it would be necessary to use refractive surgery to try to stop the progression of the disease. The most common ones to avoid the cornea transplant (PK) are the cross-linking and the additive surgery of intrastromal rings.

  The current planning tools are empirical, based on the nomograms of the ring manufactures, and rely on the experience of the surgeon. Unfortunately, deterministic tools able to estimate the postsurgical visual results of this treatment do not exist. Therefore, the aim of the current thesis is to establish a realistic numerical framework to simulate intrastromal ring surgeries and estimate the mechanical and optical postsurgical outcomes.

  There are different types of rings depending on their angle and cross-section. There are two large groups of rings: segments which have an angle of less than 360º and those that cover the entire circumference. In the first group we find rings of triangular section such as the Keraring (Mediaphacos, BeloHorizonte, Brazil) and the Ferrara (AJL Ophthalmic Ltd, Spain) and rings of hexagonal section like the Intacs (Additional Technology Inc.). In the second group we can find the MyoRing (Dioptex, GmbH.) whose cross-section is the combination of a parabola and a circumference and the Intacs SK whose section is oval.

  Due to the complexity of the simulation, since multiple variables are involved, such as the type of rings, the model of the corneal material, the contact conditions between them, etc., two methodologies arised which simulated the insertion of the rings. Both are based on generating a hole in the corneal stroma, introducing the ring and closing the hole with the ring inside, establishing contact until the simulation is completed. In the first of the methodologies the hole was generated by introducing a pressure, while the second was used to an auxiliary tool, such as balloon angioplasty to introduce endovascular stents, which is displaced generating enough hole to insert the rings. As with all numerical simulations, they were not exempt of limitations, although with the first of the methodologies only circular cross--section rings were simulated and in some configurations, there was pressure inside the hole, so it was decided to focus on the second. Nevertheless, interesting conclusions were obtained: the greatest correction was obtained by placing the rings with the largest section near the apex, and whether the ring is located near the epithelium, the stresses generated in the stroma can cause the ring to extrude.

  With the second methodology based on a displacement control, it was possible to simulate most of the cross-sections and very interesting studies were carried out that gave conclusive results. The most important were: i) the most influential parameter is the depth of insertion; ii) considering the physiological depth of the surgery, the greater optical change is provided by the diameter of the ring, and the fine adjusted is reached with the size of the implant cross--section, i.e the diameter of the implant and the size of the cross--section are the key on regulating the refractive correction; iii) the friction between ring and stroma is important to consider it because a prediction of 2 or 3 diopters could be lost; iv) whether the KC progression is stress-driven, only MyoRing can stop its progression; v) when the covered arc of the segments is more than 320º, axisymmetric model could be used instead of tridimensional model, saving computational time; vi) the anisotropy of the model does not play an important role because the rings are much stiffer than corneal tissue; vii) the implants cannot consider such as second limbus since they act as a dynamic pivot that moves along the circadian cycles of intraocular pressure (IOP); viii) preliminary nomograms is built which allow the estimation of the optical outputs according to the size and typology of the ring and optical zone of implantation.

  Additionally, a characterisation of ring material was carried out by means two complementary methods: uncertainty analysis and iFEM optimisation, concluding that the manufacturing process of the rings could be the cause of the alteration of the material between the raw PMMA and the ring already prepared for its insertion.

  REFERENCES M. M. Abdellah and H. G. Ammar. Femtosecond laser implantation of a 355-degree intrastromal corneal ring segment in keratoconus: a three year follow up. J. Ophthalmol., 2019(6783181):1–7, Oct 2019. ISSN 2090–0058. DOI: https://doi.org/10.1155/2019/6783181.

  L. Akaishi, P. F. Tzelikis, and I. M. Raber. Ferrara intracorneal ring implantation and cataract surgery for the correction of pellucid marginal corneal degeneration. J. Cataract. Refract. Surg., 30(11):2427–2430, Nov 2004. ISSN 0886–3350. DOI: http://dx.doi.org/10.1016/j.jcrs.2004.04.047.

  W. S. Al-Tuwairqui, U. L. Osuagwu, H. Razzouk, A. AlHarbi, and K. C. Ogbuehi. Clinical evaluation of two types of intracorneal ring segments (ICRS) for keratoconus. Int. Ophthalmol., 37(5):1185–1198, Nov 2016. ISSN 1573–2630. DOI: http://dx.doi.org/10.1007/s10792-016-0385-2.

  J.L. Alió, A. Artola, A. Jassanein, H. Haroun, and A. Galal. One or 2 Intacs segments for the cor- rection of keratoconus. J. Cataract. Refract. Surg., 31:943–953, May 2005. ISSN 0886–3350. D O I : https://doi.org/10.1016/j.jcrs.2004.09.050.

  J. L. Alió, D. Piñero, and A. Daxer. Clinical outcomes after complete ring implantation in corneal ectasia using the femtosecond technology. Ophthalmology, 118(7):1282–1290, Jul 2011. ISSN 0161–6420. D O I : http://dx.doi.org/10.4103/2008-322X.180713.

  M. Á. Ariza-Gracia, J. Zurita, D. P. Piñero, J. F. Rodríguez-Matas, and B. Calvo. Coupled biomechanical response of the cornea assessed by non–contact tonometry. A simulation study. PLoS One, 10(3):1–10, Mar 2015. ISSN 1932–6203. DOI: https://doi.org/10.1371/journal.pone.0121486.

  M. Á. Ariza-Gracia, J. Zurita, D. P. Piñero, B. Calvo, and J. F. Rodríguez-Matas. Automatized patient–specific methodology for numerical determination of biomechanical corneal response. Ann. Biomed. Eng., 44 (5):1753–1772, Aug 2016. ISSN 1573–9686. DOI: https://doi.org/10.1007/s10439-015-1426-0.

  M. Á. Ariza-Gracia, A. Ortillés, J. Cristóbal, J. F. Rodríguez-Matas, and B. Calvo. A numerical–experimental protocol to characterize corneal tissue with an application to predict astigmatic keratotomy surgery. J. Mech. Behav. Biomed. Mater., 74(2017):304–314, Oct 2017a. ISSN 1751–6161. D O I : https://doi.org/10.1016/j.jmbbm.2017.06.017.

  M. Á. Ariza-Gracia, S. Redondo, D. P. Llorens, B. Calvo, and J. F. Rodriguez-Matas. A predictive tool for deter- mining patient-specific mechanical properties of human corneal tissue. Comput. Methods. Appl. Mech. Eng., 317(Supplement C):226–247, Apr 2017b. ISSN 0045–7825. DOI: https://doi.org/10.1016/j.cma.2016.12.013.

  R. Barbara, A. Barbara, and M. Naftali. Depth evaluation of intended vs Intacs intrastromal ring seg- ments using optical coherence tomography. Eye, 30(1):102–110, Oct 2016. ISSN 1476–5454. D O I : http://dx.doi.org/10.1038/eye.2015.202.

  G. Bikbova, G. Kazakbaeva, M. Bikbov, and E. Usumov. Complete corneal ring (MyoRing) implantation versus MyoRing implantation combined with corneal collagen crosslinking for keratoconus: 3–year follow–up.Int.Ophthalmol.,38(3):1285–1293,Jun2018.ISSN1573–2630. DOI: https://doi.org/10.1007/s10792- 017-0593-4.

  E. Coskunseven, G. D. Kymionis, N. S. Tsiklis, S. Atun, E. Arslan, M. R. Jankov, and I. G. Pallikaris. One–Year results of intrastromal corneal ring segment implantation (Keraring) using femtosecond laser in patients with keratoconus. Am. J. Ophthalmol., 145(5):775–779.e1, May 2008. ISSN 0002–9394. D O I : https://doi.org/10.1016/j.ajo.2007.12.022.

  A. Daxer. Corneal intrastromal implantation surgery for treatment of moderate and high myopia. J. Cataract. Refract. Surg., 34(2):94–198, Feb 2008. ISSN 0886–3350. D O I : https://doi.org/10.1016/j.jcrs.2007.10.011.

  A. Daxer. Biomechanics of Corneal Ring Implants. Cornea, 34(11):1493–1498, Sep 2015. ISSN 1536–4798. DOI: http://dx.doi.org/10.1097/ICO.0000000000000591.

  A. Daxer. MyoRing treatment of myopia. J. Optom., 10(3):194–198, Jul–Sep 2017. ISSN 1888–4296. D O I : https://doi.org/10.1016/j.optom.2016.06.003.

  A. Daxer, A. Ettl, and R. Hörantner. Long–term results of MyoRing treatment of keratoconus. J. Optom., 10 (2):123–129, Feb 2016. ISSN 1888–4296. DOI: http://dx.doi.org/10.1016/j.optom.2016.01.002.

  A. Ebrahimian, P. Mosaddegh, N. M. Bagheri, and S. Pirhadi. A simple numerical approach to mimic MyoRing surgery in keratoconus corneas based on optical coherence tomography. EC Ophthalmol., 10(5):345– 356, Apr 2019.

  J. Flecha-Lescún, B. Calvo, J. Zurita, and M. Á. Ariza-Gracia. Template–based methodology for the simulation of intracorneal segment ring implantation in human corneas. Biomech. Model. Mechanobiol., 17(4):923– 938, Aug 2018. ISSN 1617–7940. DOI: https://doi.org/10.1007/s10237-018-1013-z.

  J. Flecha-Lescún#, M. Á. Ariza-Gracia#, P. Büchler, and B. Calvo. Corneal biomechanics after intrastromal ring surgery: opto–mechanical in–silico assessment. Transl. Vis. Sci. Technol., 9(11):26: 1–16, Oct 2020. ISSN 2164–2591. DOI: https://doi.org/10.1167/tvst.9.11.26.

  Z. Gatzioufas, A. Khine, M. Elalfy, I. Guber, C. McLintock, F. Sabatino, S. Hamada, and D. Lake. Clinical out- comes after Keraring implantation for keratoconus management in patients older than 4 years: a retrospective, interventional, cohort study. Ophthalmol. Ther., 7(1):95–100, Mar 2018. ISSN 2193–6528. DOI: http://dx.doi.org/10.1007/s40123–017–0117–3.

  C. Gökgöl, N. Diehm, and P. Büchler. Numerical Modeling of Nitinol Stent Oversizing in Arteries with Clinically Relevant Levels of Peripheral Arterial Disease: The Influence of Plaque Type on the Outcomes of Endovascular Therapy. Ann. Biomed. Eng., 45(6):1420–1433, Jun 2017. ISSN 1573–9686. DOI: https://doi.org/10.1007/s10439-017-1803-y.

  M. Hosny, E. El-Mayah, M. K. Sidky, and M. Anis. Femtosecond laser–assisted implantation of complete versus incomplete rings for keratoconus treatment. Clin. Ophthalmol., 9:121–127, Jan 2015. ISSN 1177– 5483. DOI: https://doi.org/10.2147/OPTH.S73855.

  K. Jadidi, S. A. Mosavi, F. Nejat, M. Naderi, L. Janani, and S. Serahati. Intrastromal corneal ring regment implantation (Keraring 355º) in patients with central keratoconus: 6–month follow–up. J. Ophthalmol, 2015(916385):1–8, Jan 2015. ISSN 2090–0058. DOI: http://dx.doi.org/10.1155/2015/916385.

  L. Janani, K. Jadidi, S. A. Mosavi, F. Nejat, M. Naderi, and K. Nourijelyani. MyoRing implantation in keratoconic patients:3yearsfollow–updata.J.Ophthalmic.Vis.Res.,11(1):26–31,Aug2016.ISSN2008–322X. DOI: http://dx.doi.org/10.1016/j.ophtha.2010.12.012.

  S. Kling and S. Marcos. Finite–element modeling of intrastromal ring segment implantation into a hyperelastic cornea. Invest. Ophthalmol. Vis. Sci., 54(1):881–889, Jan 2013. ISSN 1552–5783. D O I : http://dx.doi.org/10.1167/iovs.12-10852.

  M. Lago, M. Rupérez, C. Monserrat, F. Martínez-Martínez, S. Martínez-Sanchís, E. Larra, M. Díez-Ajenjo, and C. Peris-Martínez. Patient–specific simulation of the intrastromal ring segment implantation in corneas with keratoconus. J. Mech. Behav. Biomed. Mater., 51:260–268, Nov 2015. ISSN 1751–6161. DOI: https://doi.org/10.1016/j.jmbbm.2015.07.023.

  H. Lubatschowski, G. Maatz, A. Heisterkamp, U. Hetzel, W. Drommer, H. Welling, and W. Ermer. Application of ultrashort laser pulses for intrastromal refractive surgery. Graefes Arch. Clin. Exp. Ophthalmol., 238(1): 33–39, Jun 2000. ISSN 1435–702X. DOI: https://doi.org/10.1007/s004170050006.

  A. Pandolfi and G. A. Holzapfel. Three–dimensional modeling and computational analysis of the human cornea considering distributed collagen fibril orientation. J. Biomech. Eng., 130(6):1–11, Dec 2008. ISSN 1528–8951. DOI: https://doi.org/10.1115/1.2982251.

  D. P. Piñero, J. L. Alio, B. E. Kady, E. Coskunseven, H. Morbelli, A. Uceda-Montanes, M. J. Maldonado, D. Cuevas, and I. Pascual. Refractive and aberrometric outcomes of intracorneal segments for Keratoconus: mechanical versus femtosecond–assited procedures. Ophthalmology, 116(9):1675–1687, Jul 2009. ISSN 0161–6420. DOI: http://dx.doi.org/10.1016/j.ophtha.2009.05.016.

  D. P. Piñero, J. L. Alió, R. I. Barraquer, R. Michael, and R. Jiménez. Corneal biomechanics, refraction, and corneal aberrometry in keratoconus: an integrated study. Invest. Ophthalmol. Vis. Sci., 51(4):1948–1955, Apr 2010. ISSN 1552–5783. DOI: http://dx.doi.org/10.1167/iovs.09-4177.

  Rabinowitz. Keratoconus. Surv. Ophthalmol., 42(4):297–319, Jan–Feb 1998. ISSN 0039–6257. D O I : http://dx.doi.org/10.1016/S0039-6257(97)00119-7.

  S. A. Rattan. Continuous intracorneal ring impltantation for treatment of myopic astigmatism. International Medical Case Reports Journal, 2018(11):217–220, Sep 2018. ISSN 1179–142X. D O I : https://doi.org/10.2147/IMCRJ.S173167.

  M. H. Shabayek and J. L. Alio. Intrastromal corneal ring segment implantation by femtosecond laser for keratoconus correction. Ophthalmology, 114(9):1643–1652, Sep 2007. ISSN 0161–6420. D O I : http://dx.doi.org/10.1016/j.ophtha.2006.11.033.

  A. Vega-Estrada and J. Alio. The use of intracorneal ring segments in keratoconus. Eye Vis., 3(8):1–7, Mar 2016. ISSN 2326–0254. DOI: https://doi.org/10.1186/s40662-016-0040-z.

  M. O. Yousif and A. M. A. Said. Comparative study of 3 intracorneal implant types to manage central keratoconus. J. Cataract. Refract. Surg., 44(3):295–305, Mar 2018. ISSN 0886–3350. D O I : http://dx.doi.org/10.1016/j.jcrs.2017.12.020.