Femtosecond Laser(FSL) in

Ophthalmology

By

Hind M. Safwat Al ShwadfyT A ophthalmology (Al zhraa university hospital)

Supervised by Assist. Prof./ Mona Farag

(ophthalmology department-Al Azhar University)2014

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

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.

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.

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 !!).

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.

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.

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.

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.

FSL in the diagnostic

ophthalmic instruments

Ultra high resolution OCT

Second harmonic–generation (SHG)

imaging

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.

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.

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.

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.

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.”

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.

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.

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).

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.

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.

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.

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.

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.

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”

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.

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.

FLEx

FSL in keratoplasty

1- Penetrating keratoplasty

2- Anterior lamellar keratoplasty

3- Endothelial keratoplasty

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.

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).

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.

Types of FSL cuts in PKP

Standard ''butt-joint” in traditional PKP'

Top-hat

MushroomZig zag

Christmas tree

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, ……….

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.

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, ……

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.

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.

The "zig-zag" configuration has the simplest

learning curve for suturing (inner side of Z, 50 %

of depth, and regular tensile strength).

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.

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.

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

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.

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.

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.

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.  

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:

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%).

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

FSL in prespyopia

INTRCOR (intrastromal correction of

presbyopia with femtosecond laser)

Lentotomy

Corneal inlays

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.

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.

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.

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

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).

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.

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.

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.

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.

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.

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) .

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.

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.

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.

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.

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

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).

FSL in the Glaucoma

Selective trabeculoplasty (still in vitro).

Guarded filtration surgery.

Minimal invasive glaucoma surgery (deep

sclerotomy).

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.

Histological evaluation of the tissue confirmed

the reliable creation of fistulous tracts without

collateral damage.

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.

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.

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.

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.

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