femtosecond laser in ophthalmology by Dr. Hind Safwat (Al Azhr university)


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the last evolution of femtosecond laser in ophthalmic field

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femtosecond laser in ophthalmology by Dr. Hind Safwat (Al Azhr university)

  1. 1. Femtosecond Laser(FSL) in Ophthalmology By Hind M. Safwat Al Shwadfy T A ophthalmology (Al zhraa university hospital) Supervised by Assist. Prof./ Mona Farag (ophthalmology department-Al Azhar University) 2014
  2. 2. Agenda  Introduction about femtosecond laser  Femtosecond laser in the ophthalmic diagnostic tools  Femtosecond laser in the corneal and refractive surgery  Femtosecond laser in the cataract surgery  Femtosecond laser in the glaucoma surgery  Femtosecond laser in the photodynamic therapy.  Referances
  3. 3. Introduction  The development of the ruby laser almost a half century ago by Maiman opened up wide new vistas in ophthalmology, resulting in a flood of practical clinical applications of lasers in eye surgery.  The development of clinical argon, krypton, carbon dioxide, neodymium-doped yttrium aluminum garnet (Nd:YAG), and excimer laser systems in ophthalmology made it possible to treat a wide eye diseases and disorders.
  4. 4. Remember, the optically transparent refractive layers of the eye, such as the cornea and lens, do not absorb electromagnetic radiation in the visible or near-infrared spectrum at low power densities, allowing light to pass through without alteration of these tissues. However, At higher power densities; these structures do absorb the light energy, leading to plasma generation and tissue disruption.
  5. 5.  The first practical use of near-infrared lasers in clinical ophthalmology was the focused Nd:YAG laser.  The Nd:YAG laser has a pulse duration in the nanosecond (10ˉ9 second) range and produces photodisruption (photoionizing, or optical break down ).  The zone of collateral tissue damage with the nanosecond Nd:YAG laser may easily exceed 100 µm (a problem !!).
  6. 6.  By shortening the pulse duration of the near infrared laser from the nanosecond to the picosecond (10 ˉ 12 second) domain and then to the femtosecond (10 ˉ 15 second) domain, the zone of collateral tissue damage is progressively reduced (1 µm).  FSL is a focused infrared laser with a wavelength of 1053 nm that uses ultrafast pulses with a duration of 100 fs.
  7. 7.  Ultra fast, high energy, and broad waveband width, and long wave length (which can be changed).  It is a solid-state Nd:Glass laser (generated from titanium sapphire).  It can be doubled and tripled to be focused to near structures as cornea.  It’s non visible, but can be combined with helium gas to be visible.
  8. 8.  The technology of the FSL was first introduced in the labs in 1990 but commercially in late 2001, and technological evolution has resulted in a gradual increase in its higher laser firing frequency, which recently reached 500 kHz from its original 6 kHz.  The higher laser frequency permits lower energy per pulse and tighter line separation.
  9. 9. Mecanism of action Photodisruption  FSL energy is absorbed by the tissue, resulting in plasma formation.  This plasma of free electrons and ionized molecules rapidly expands, creating cavitation bubbles.  The force of the cavitation bubble creation separates the tissue.
  10. 10. FSL in the diagnostic ophthalmic instruments  Ultra high resolution OCT  Second harmonic–generation (SHG) imaging
  11. 11. Ultra High Resolution OCT (UHR - OCT)  The axial resolution of OCT depends on the bandwidth of light source used for imaging.  Compact super luminescent diodes (SLDs) have been extremely used in OCT systems.  SLDs in ophthalmic OCT are near infrared with wave length near 800 nm., and bandwidth of 20 to 30 nm. that give axial resolutions 8 – 10 µm.
  12. 12.  Multiplexing SLDs at different wavelengths around 850 nm. Can achieve bandwidth 150 nm. With axial resolution ~ 3 - 5 µm. FSL which produced from Ti : Sapphire can produce light source for UHR-OCT with multiple wave lengths (800, 1000 & 1300 nm.) with bandwidth ~ 260 nm. Achieving axial resolution ~ 1 - 3 µm.
  13. 13. Second harmonic–generated (SHG) imaging  Development of nonlinear optical (NLO) imaging techniques such as second harmonic–generated (SHG) imaging has emerged as a powerful new tool for investigating collagen organization.  Briefly, during SHG the extremely high field strengths associated with ultra short laser pulses cause an oscillating polarization in certain molecules, such as collagen, that results in the emission of light at exactly half the wavelength of the laser beam.
  14. 14. o Finally, because of the high axial & lateral resolutions and the increased penetration depth of infrared light, it allows for 3-D image acquisition through the full thickness of the cornea. o Using this imaging paradigm, SHG studies showed that collagen is arranged in a more complex fashion than previously thought.
  15. 15. FSL in the Corneal & Refractive Surgery Born of a Workplace Accident : “The medical use of the FSL at the University of Michigan: A graduate student in the ultrafast lasers lab had sustained a well-defined laser burn on his retina. The examination of this burn by a second-year resident [Ron M. Kurtz, MD] led to collaborative research between the department of ophthalmology and the school of engineering, and ultimately to the original femtosecond medical laser, marketed as (with FDA approval) IntraLase in 2001.”
  16. 16. Why FSL in the refractive & corneal surgery? 1) Ultra-short pulse duration (10 ˉ 15 sec.) has the ability to deliver laser energy with minimal collateral damage to the adjacent tissue (1µm). 2) It can be focused anywhere within or behind the cornea.
  17. 17. 3) It is capable, to a certain extent, of passing through optically hazy media, such as an edematous cornea. 4) The laser may be applied in multiple geometric patterns including vertical, spiral, or zig-zag cuts.
  18. 18. FSL systems used in the corneal and refractive surgery:  1st released commercial device was: Intralase FS™ (Abbott Medical Optics, Abbott Park, Illinois);  Femtec® (20/10 Perfect Vision, Heidelberg, Germany);  VisuMax Femtosecond System® (Carl Zeiss Meditec, Jena, Germany);  Femto LDV™ (Ziemer Group, Port, Switzerland); and  Wavelight FS200® (Alcon, Fort Worth, Texas).
  19. 19. Femto-LASIK (Intralase) Technique:  The suction ring is centered over the pupil.  The docking procedure is then initiated while keeping the suction ring parallel to the eye.  An applanating glass contact lens is used to stabilize the globe and to flatten the cornea.  The surgeon administers the FS laser treatment. Each pulse of the laser generates microscopic gas bubbles dissipating into surrounding tissue.
  20. 20.  Multiple pulses are applied next to each other to create a cleavage plane and ultimately the LASIK flap.  Suction is then released.  A spatula is carefully passed across the flap starting at the hinge and sweeping inferiorly to lift the flap for excimer laser ablation.
  21. 21. Advantages: 1. Reduced incidence of flap complications like buttonholes, free caps, irregular cuts etc. 2. Control over flap diameter and thickness, side cut angle, hinge position and length. 3. Increased precision with improved flap safety and better thickness predictability. 4. Capability of cutting thinner flaps to accommodate thin corneas and high refractive errors.
  22. 22. 5. Stronger flap adherence. 6. Better contrast sensitivity. 7. Decreased incidence of epithelial ingrowth. 8. Less increase in IOP required. 9. Lesser incidence of dry eye. 10. Lesser hemorrhage from limbal vessels. 11. The ability to retreat immediately if there is incomplete FS laser ablation.
  23. 23. Disadvantages: 1. Opaque bubble layer (OBL): Gas bubbles routinely accumulate in the flap interface during FSL treatment, but occasionally they may dissect into the deep stromal bed(obscuring excimer laser tracker), reaching AC, or escape to subepithelial (resulting in button hole). 2. Transient light sensitivity syndrome (TLSS): Also called as good acuity plus photosensitivity (GAPP). Occurs days to weeks after FS - LASIK.
  24. 24. Patients present with extreme photophobia and good visual acuity with paucity of clinical findings on exam. It resolves without sequel but requires aggressive topical steroids for weeks. Proposed mechanism is either an inflammatory response of the surrounding tissue to the gas bubbles or biochemical response of the keratocytes to the near-infrared laser energy. 3. Micro-irregularities on the back surface of the FSL LASIK flap can cause “rainbow glare”
  25. 25. 4. Photodisruption-induced microscopic tissue injury and ocular surface inflammatory mediators may cause lamellar keratitis in the flap interface. 5. Increased difficulty in lifting the flap if retreatment is required after that (because of good adherence). 6. Increased cost. 7. Moving the patient between 2 laser instruments.
  26. 26. Femtosecond lenticule extraction (FLEx) & Small-incision lenticule extraction (SMILE) Femtosecond-only vision correction is now available for myopia under Carl Zeiss Meditec’s ReLEx umbrella, which comprises both femtosecond lamellar extraction (FLEx) and small-incision lamellar extraction (SMILE). Using a curved applanation plate, the Zeiss VisuMax precisely cuts and removes a lenticule, rather than ablating.
  27. 27. FLEx
  28. 28. FSL in keratoplasty 1- Penetrating keratoplasty 2- Anterior lamellar keratoplasty 3- Endothelial keratoplasty
  29. 29. FSL in penetrating keratoplasty  Penetrating keratoplasty (PKP) was under evolution from manual blade → trephination → laser assisted.  (FLEK) is femtosecond laser-enabled keratoplasty. Advantages: I. General; 1- Cuts are at a precise depth which is consistent and reproducible with limited damage to surrounding tissue.
  30. 30. 2- Wound configurations create more surface area for healing, improve tissue alignment and distribution, require less suture tension for alignment of tissue, and have superior biomechanical strength, rapid visual recovery and less astigmatism. II. Specific; according to type of cuts (see later).
  31. 31. Disadvandages (or contra indication): * Absolute: any condition preventing proper laser docking such as severe ocular surface irregularity, elevated glaucoma filtering bleb or glaucoma shunt implant, small orbits, extremely narrow palpebral fissures, and recent corneal perforations. * Relative: prior PKP or globe trauma because of the risk of corneal/globe rupture and expulsive hemorrhage(controverse), severe peripheral corneal neovascularization.
  32. 32. Types of FSL cuts in PKP Standard ''butt-joint” in traditional PKP' Top-hat Mushroom Zig zag Christmas tree
  33. 33. Top – hat:  The first FSL customized trephination pattern used.  This cut possesses the advantages of improved wound seal (7 folds less leak),and stability due to its internal flange.  Replacement of a greater amount of endothelial cells that may be beneficial in endothelial diseases such as Fuchs' dystrophy. However, ……….
  34. 34.  The "top-hat" incision suture placement can vary as precision is required to pass the suture through the posterior wing, leading to the possibility of tissue misalignment and posterior wound gape that may impact refractive outcomes.  The larger posterior corneal diameter of the "top-hat" configuration brings the donor tissue closer to the angle, and could theoretically increase the risk of endothelial rejection and glaucoma.
  35. 35. Mushroom:  Provide greater anterior stromal replacement and therefore may be more advantageous in diseases such as keratoconus or pathologies involving primarily the anterior cornea.  Less topographic astigmatism, and time to complete suture removal outcomes. However, ……
  36. 36.  A water-tight seal of the graft-host interface was easier to achieve in the "top-hat" profile compared with the "mushroom”, due to the contribution of the force of the IOP on the inner lamella of the "top-hat" cut graft, pressing it against the host cornea.  Ring-shaped microcystic edema over the interface of the graft-host overlap zone and protrusion of the anterior lamella between sutures associated with ointment deposits and bacterial infiltrates.
  37. 37. Zig – zag:  Its angled anterior side cut creates a precise donor- host transition with less potential for tissue misalignment and overall optical distortion.  The greater surface area of donor-host contact allows for improved seal of the incision site, improved tensile strength of the wound, and faster wound healing.
  38. 38.  The "zig-zag" configuration has the simplest learning curve for suturing (inner side of Z, 50 % of depth, and regular tensile strength).
  39. 39. FSL in the deep anterior lamellar keratoplasty (DALK) The use of the FSL in DALK was first described by Drs Farid and Price in 2009 using the "zig-zag" incision profile. Advantages:  Better donor-host fit, increased surface area, faster wound healing promoting earlier suture removal, and reduced astigmatism, resulting in overall increased success of the procedure.
  40. 40.  In addition, FS-assisted DALK is technically easier to perform compared with manual DALK. Technique: Customized FS trephinations (zig-zag or mushroom) create a posterior cut whose depth is about 50 to 100 μm from the endothelium, allowing the needle or a blunt cannula to be passed easily and more accurately just anterior to Descemet membrane and thereby facilitating a successful big-bubble dissection.
  41. 41. FSL in anterior lamellar keratoplasty (ALK)  Yoo et al described a sutureless technique for FS-assisted ALK (FALK) to create smooth lamellar dissections just deep to the corneal pathology.  smoother stromal bed.  Less astigmatism
  42. 42. FSL in Descemet stripping assisted endothelial keratoplasty (DSAEK)  Still under trials with doubt in its result.  Interface haze resulting from the roughened collagen fibrils produced by the FSL.  High rates of graft dislocation and loss of endothelial cells when the FSL was used to prepare the endothelial graft tissue.
  43. 43. FSL in Astigmatic Keratotmy (AK)  AK is the most commonly used method for the reduction of high amounts of astigmatism in postoperative PK patients.  The technique is similar to limbal relaxing incisions, with incisions placed inside the donor-recipient junction as it behaves like a new limbus due to a fibrotic ring formed as part of the healing response.  Astigmatic keratotomy should only be performed after all corneal sutures are removed.  Astigmatic keratotomy may be performed manually with a diamond knife as well as with a femtosecond laser.
  44. 44.  Major limitations of manual AK are technical difficulties (especially in non orthogonal astigmatism), unpredictability, and complications such as wound dehiscence, epithelial abrasions, and perforation.  Compared with the mechanical method, the use of FSL offers the advantages of higher precision and stability as well as more accurate planning of the length, depth, and optical zone of the cuts.
  45. 45. FSL in Intrastromal corneal ring segments implantation  Intrastromal corneal ring segments are implants originally designed to correct low to moderate myopia. Currently, they are used to treat postoperative LASIK corneal ectasia, pellucid marginal degeneration, and keratoconus.  Intrastromal corneal ring segments are inserted in intrastromal channels (created either manually or using a femtosecond laser) at 75% depth of the thinnest pachymetry.  This results in an arc shortening effect and redistribution of corneal peripheral lamellae to produce flattening of the central cornea.
  46. 46. Advantages:  Compared to the manual technique, FSL makes tunnel creation faster, easier, and more reproducible and offers accurate tunnel dimensions (width, diameter, and depth).  But, with mechanical dissectors, segment depth may be shallower at positions further from the incision but depth is consistent throughout when using FSL. Technique:
  47. 47. Complications:  Intraoperative incomplete channel creation (2.7%)  Postoperative segment migration (1.3%)  Intraoperative adverse events such as endothelial perforation (0.6%), and vacuum loss (0.1%).  Postoperative complications such as superficial movement of the segments (0.1%), corneal melting (0.2%), and infection (0.1%).
  48. 48. FSL in cross linking  Traditionally, riboflavin is applied to a debrided cornea (epith. off), followed by ultraviolet exposure for 30 minutes.  An innovative approach to this procedure using FSL spares the epithelium, thus reducing post-treatment pain and providing a more rapid visual rehabilitation.  Intrastromal pockets can be created with FSL, which then allows for the direct injection of riboflavin with subsequent ultraviolet exposure
  49. 49. FSL in prespyopia  INTRCOR (intrastromal correction of presbyopia with femtosecond laser)  Lentotomy  Corneal inlays
  50. 50. INTRACOR  It depends on monovision idea for correction of prespyopia.  The surgeon uses the laser to create five concentric rings of different depths, centered on the pupil, in the cornea of the patient’s non-dominant eye. The inner ring is approximately 0.9 mm in diameter and the outer ring is 3.2 mm.
  51. 51. FSL Lentotomy  FSL lentotomy may offer a viable new approach to treating presbyopia.  The basis for this treatment relates to the idea that nuclear sclerosis is the main contributor to presbyopia. Therefore, a cure for improving near vision function would be to increase the flexibility of the nucleus of the crystalline lens.  FSL lentotomy involves creation of intra lenticular incisions to result in additional gliding planes within the lens substance, thereby increasing its flexibility.
  52. 52.  The results of ex vivo studies show that with use of appropriately selected cutting parameters, an increase in flexibility of up to 73 % can be achieved in human globes.  The FSL was chosen for this technique since its ultrashort pulse profile allows for precision cutting within the lens without causing damage to the surface.
  53. 53. FSL in corneal inlays  FSL may be used to create intrastromal pockets for insertion of biocompatible corneal inlays for ttt of presbyopia.  Corneal inlays are disc shaped corneal implants work by changing the refractive index of the cornea.  The central zone of the implant is neutral or plano, and has no refractive power. It allows light rays from distant source to focus on the retina, preserving
  54. 54. distance vision.  The central neutral zone is surrounded by one circular zone of additional positive power, which focus light rays from near objects on the retina, and improve near vision (their design is similar to multifocal contact lens or intraocular lens).
  55. 55. Inlays: 1- Hydrogel; as Presbylens & Flxivue microlens. 2- Non Hydrogel AutoFocus Kamara inlay Slit-lamp photograph (left) & Retro illumination appearance of intracorneal inlay (Flexivue Microlens; Presbia Cooperatief UA, Amsterdam, The Netherlands) implantation (arrow) in a pocket created with a femtosecond laser.
  56. 56. FSL assisted biopsy (FAB)  Corneal biopsy consists of an option adopted in patients in which corneal scraping does not provide a diagnostic result.  Until recently, corneal biopsies have been performed manually using diamond knifes, beaver blades or microtrephine.  Among the disadvantages of the manual technique are imprecision of incision depth, inadequate tissue removal, corneal scarring and perforation.
  57. 57.  The introduction of FSL technology in ophthalmology has provided surgeons with the ability to perform biopsies in a safer and more accurate way.  The predictability of cutting with the FS in predetermining depth without scarring and inducing irregular astigmatism are the main benefits that encourage the use of FSL.
  58. 58. FSL in the Cataract Surgery (FLACS)  FDA-approval for FSL assisted cataract surgery was in 2010 for cataract surgery.  There are the most common laser plateforms in the cat. surgery; 1- OptiMedica Catalys (Santa Clara, CA) >>> is currently seeking FDA approval and is already available outside of the United States. 2- LenSx (recently acquired by Alcon, Fort Worth, TX) >>> approved for lens fragmentation, anterior capsulotomy, and corneal incisions. 3- LensAR (Winter Park, FL) >>> recently received FDA approval for lens fragmentation and anterior capsulotomy.
  59. 59. Indication: Any patient with cataract either associated with astigmatism or other refractive errors or not ! However, it’s also contraindicated in: 1. Patients who have deep set orbits or those with tremors or dementia may do poorly with the initial docking of the lens that requires patient cooperation. 2. Anterior basement membrane dystrophy, corneal opacities (such as arcus senilis, corneal dystrophies, and trauma- or contact lens- induced scars), ocular surface disease, pannus with encroaching blood vessels, or recurrent epithelial erosion syndrome.
  60. 60. 3. Additionally, the level of increase in IOP induced by the docking may be a significant contraindication for patients with glaucoma, optic neuropathies, or borderline endothelial pathology. 4. Diabetics may have undiagnosed epithelial disease. 5. Patients with poor dilation. 6. Relative contraindication in dense PSC with vacoules (interrupt proper posterior capsule mapping) .
  61. 61. Techinque:  Pupillary dilatation and topical anesthesia.  Applanation of the cornea with a docking system (OptiMedica platform has a liquid optics interface which increases IOP only by 15 mmHg).  Anterior segment imaging is then performed. LenSx and OptiMedica utilize (FD-OCT), while LensAR utilizes Scheimpflug imaging technology. This step is required to find anatomical landmarks(especially iris & posterior capsule) for laser pattern mapping.
  62. 62.  Preprogrammed corneal incisions for temporal wound, paracentesis, and any optional limbal-relaxing incisions (LRIs) can be adjusted at this point. N B; If a corneal incision is created, not open until the patient is moved to the operating room (fear of infection).  The pattern is then centered and the laser is activated. Laser- assisted capsulotomy is performed, followed by lens fragmentation. N B; This sequence is justified (not as LensAR) because lens fragmentation causes release of gas bubbles, which can distort the anatomy and affect capsulotomy planning.  Now, Patient then undergo removal of the anterior capsulotomy, followed by standard phacoemulsification.
  63. 63. Advantages: 1. FSL performs corneal incisions allowing for more square architecture, which has proven more resistant to leakage. 2. FSL systems can also create LRIs to treat astigmatism. Since the FSL systems are capable of delivering cuts to precise depths and lengths, these LRIs may be more accurate and standardized compared to manual techniques. 3. Manual capsulorhexis is known to be the most technically difficult part of cataract surgery for trainees, leads to tears.
  64. 64. So the smooth, regular edges by FSL may offer superior capsular strength and resistance to capsular tears. 4. The FSL may be able to deliver a more circular, stronger, precisely planned and executed capsulorhexis, which could afford more control over capsulotomy unpredictability (as in manual) and offer less PCO & more accurate refractive outcomes. 5. With consideration to a reduction in ultrasound energy and instrumentation during fragmentation, FSL may show improved safety and decreased complications.
  65. 65. Disadvantages: 1. The high cost. 2. Moving the patient between 2 rooms(laser instrument room to surgical microscope room), may increase(or at least the same) post operative endophthalmitis although the water tight squared CCI. 3. Limitations of FSL use in very high-grade opacifications have not yet been delineated in published studies
  66. 66. 4. Diabetics may have persistent epithelial defects from the trauma of docking. 5. Need a steady lens, so cannot be applied for phacodonesis. 6. Laser mapping image cannot be done in cases of poor dilatation as posterior synechiae, intraoperative floppy iris syndrome suspects, or those on chronic miotic medications. 7. Contra indications (see before).
  67. 67. FSL in the Glaucoma  Selective trabeculoplasty (still in vitro).  Guarded filtration surgery.  Minimal invasive glaucoma surgery (deep sclerotomy).
  68. 68. FSL in selective trabeculoplasty  In 2005, Toyran et al used an FSL to perform photodisruption of human trabecular meshwork(TM) strips ex vivo.  Unlike the minimal disruption of tissue produced by selective laser trabeculoplasty, FSL can make full- thickness ablation channels through the TM.  Theoretically, these tracts could permit direct access of aqueous humor from the anterior chamber to Schlemm canal.
  69. 69.  Histological evaluation of the tissue confirmed the reliable creation of fistulous tracts without collateral damage.
  70. 70. Advantages: 1- FSL photodisruption is very specific with minimal scarring. 2- In addition, a few small channels should be more than enough to increase the outflow facility to therapeutic levels.
  71. 71. FSL in guarded filtration surgery The precision of scleral incisions created with the FSL has great potential to standardize portions of guarded filtration surgery. Limitation: * Inherent light-scattering properties of the sclera, which could lead to imprecise incisions and collateral damage. * Although longer laser wavelengths (to 1.7 μm) might overcome this problem, current hardware and software platforms used in cataract surgery are not equipped for higher wavelengths.
  72. 72. FSL in minimal invasive glaucoma surgery(deep sclerotomy)  Initial attempts at deep sclerectomy using the FSL occurred in 2007.  Bahar et al used the IntraLase FSL to create both superficial and deep partial-thickness scleral flaps in human cadaveric eyes. After amputating the deep flap, they observed aqueous percolating through the exposed Descemet window.  Further testing is required to optimize the laser settings, and no human trials have been published to date.
  73. 73. FSL in the photodynamic therapy (PDT)  High peak power pulse energy by femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800 nm wavelength(after trippling to be in ultraviolet region) for corneal neovascularizatin mediated by indocyanine green (ICG).  Application FSL - PDT in AMD and melanomas is still under research.
  74. 74. References  Fujimoto J.G., Aguirre A.D., Chen Y. et al. Ultrahigh-Resolution Optical Coherence Tomography Using Femtosecond Laser. In “Braun M., Gilch B ., and Zinth W. ; Ultra Short Laser Pulses in Biology and Medicine”. Springer 2008; pp: 3-13.  Stuart A, A Femtosecond Quest For Surgical Perfection. At www.eyenet.com. Feb. 2011.  Asota I, Farid M, Garg S, and Steinert R F. Femtosecond Laser-enabled Keratoplasty. Int Ophthalmol Clin. 2013;53(2):103-114.  http://eyewiki.aao.org/Femtosecond_lasers_and_laser_assisted_in_situ_keratomileusis_(LASIK); access on 17/03/14  Review of Ophthalmology® > Refractive Surgery Goes Intrastromal(Jul 5 – 2012).  Georg G. Femtosecond lentotomy increases presbyopic lens deformability. The XXIV Congress of the ESCRS.  Peter K, Gerard S, and David R S. Applications of the femtosecond laser in corneal refractive surgery. Current Opinion in Ophthalmology Issue: Volume 22(4), July 2011, p 238–244.  Kymionis, George D , Karavitaki , et al . Current corneal femtosecond laser techniques. Expert Review of Ophthalmology5.2(Apr 2010): 143-146.  Kymionis, George D, Kankariya, Vardhaman P, et al. Femtosecond Laser Technology in Corneal Refractive Surgery: A Review Journal of Refractive Surgery28.12(Dec 2012): 912-20.
  75. 75.  http://eyewiki.aao.org/Corneal_inlays; access on 28/03/14  Moshirfar M, Churgin D S, and Hsu M. Femtosecond Laser-Assisted Cataract Surgery: A Current Review. Middle East Afr J Ophthalmol. 2011 Oct-Dec; 18(4): 285–291.  Seibold L K, and Kahook, M Y. cond Lasers in Glaucoma. Glaucoma today; march/april 2012  Sawa M, Awazu K, Takahashi T, et al. Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green. Br J Ophthalmol 2004;88:826–831  Winkler M, Dongyul Chai D, Kriling S, et al. Nonlinear Optical Macroscopic Assessment of 3-D Corneal Collagen Organization and Axial Biomechanics. Invest Ophthalmol Vis Sci. 2011;52:8818–8827)  Donaldson K E, Braga-Mele R, Cabot F, et al. Femtosecond laser–assisted cataract surgery. J Cataract Refract Surg 2013; 39:1753–1763.  SOONG H K & MALTA. J B. PERSPECTIVE Femtosecond Lasers in Ophthalmology. Am J Ophthalmol 2009;147:189 –197