Reduced irradiation time for thin corneas
Irradiation time in mins
Stromal thickness in μm
Corneal Cross linking with Isotonic
solution*
 After epithelial removal, begin dropping PESCHKE isotonic solution:
1 drop every 2 minutes for 20 minutes (= 10 drops).
 After 20 minutes - check at slit lamp with blue light whether anterior chamber is
slightly yellow. If not, continue to drop PESCHKE isotonic solution until
anterior chamber is yellow.
 If thinnest spot is under 400 μm without epithelium, apply PESCHKE hypotonic
solution (using a 24 G cannula) to swell cornea. 1 drop every 5 seconds until
corneal thickness is at least 400 μm.
 UV-illumination treatment set to 18 mW/cm2 for 5 min (CCL-Vario illumination
device ), focus distance between beam aperture and eye ~ 45 mm – 55 mm and
adjust beam diameter.
 Instill BSS to keep cornea wet.
 Post-op check-ups: 1 day – 3 days – 1 week – 1 month – 3 months – 6 months –
yearly intervals.
Riboflavin Solutions
Standard Riboflavin Solution with Dextran
for epi-off procedure (3ml)
• The Dresden Original:Time proven Riboflavin solution with dextran
• Recommended instillation time: 20 minutes (1 drop every 2 minutes =
10 drops)
• Ingredients: 0.1 % Riboflavin (Vitamin B2), 20 % dextran 500
Standard Riboflavin Solution without Dextran
for epi-off procedure (3ml)
• Does not reduce corneal thickness
• Recommended instillation time: 20 minutes (1 drop every 2 minutes =
10 drops)
• Ingredients: 0.1 % Riboflavin (Vitamin B2), 1.1 % HPMC
Transepithelial Solution for epi-on procedure (2ml)
• Recommended instillation time: 20 minutes (1 drop every 2 minutes = 10
drops)
Significant reducation of pain and danger of post operative infection
• Ingredients: 0.25 % Riboflavin (Vitamin B2), 1.2 % HPMC, 0.01 %
Benzalkoniumchloride
Riboflavin Solutions
Hypotonic Riboflavin Solution for corneal swelling (1.5ml)
• To swell thin corneas (< 400 μ) by means of osmotic effect
• Recommended instillation time: 1 drop every 5 seconds until
corneal thickness has reached 400 μ
• Ingredients: 0.1 % Riboflavin (Vitamin B2)
•
•
Riboflavin Solution for use with LASIK procedures on thin
corneas (1.95ml)
Recommended usage: after flap preparation and excimer
treatment
Put 3 – 5 drops on stroma, put flap back, wait 3 – 4 minutes,
open flap
•
Rinse off Riboflavin, put flap back and radiate with 1/2 of the
recommended energy (1/2 of the time)
•
Ingredients: > 0.23 % Riboflavin (Vitamin B2)
Riboflavin Penetration Through Intact
epithelium
In vivo imaging of riboflavin penetration during collagen cross-linking with
hand-held spectral domain optical coherence tomography.
Malhotra C, Shetty R, Kumar RS, Veluri H, Nagaraj H, Shetty KB. J Refract Surg.2012;28(11); 776-80
 Peschke transepithelial solution Riboflavin 0.25% instilled 1 drop
every 2 minutes for 20 minutes (= 10 drops).
 If thinnest pachymetry is under 400 μm with epithelium, apply hypotonic
solution to swell cornea. 1 drop every 5 seconds until corneal thickness
is at least 400 μm.
 Position patient under illumination system. Set illumination system to 18
mW/cm2. Distance between beam aperture and eye is ~ 45 mm – 55
mm. Beam diameter adjusted to clear cornea diameter
 Instill BSS as needed to keep cornea wet. Post op medication.
 10. Post-op check-ups: 1 day – 3 days – 1 week – 1 month – 3 months –
6 months – yearly intervals.
Pre
Endprocedure
of 5 mins
Transepithelial cross linking
Transepithelial Crosslinking
Comparing protocols
Group1
A standard CXL
treatment
isotonic
 20%with
dextran
led
Riboflavin in 20%
to a
Group 2
Lid speculum removed
during the reduction
30 minutes of
significant
in
saturation with isotonic
Riboflavin.
Group 3
Received hypotonic
Riboflavin without
corneal pachymetry
dextran
dextran
 Closed
eyelids during the riboflavin saturation phase significantly
reduced the number of eyes requiring swelling before irradiation.
Pachymetry
15%
loss of
Pachymetry
increasedsolutions with
 Need
forcorneal
the development
of new riboflavin
isooncotic
increased
by 11%
thickness
after 30
properties
by 1% at 30mins
after 30 minutes
minutes
90% needed
swelling with
hypoosmolar
Riboflavin
Only 13% needed
swelling with
hypoosmolar
None required
swelling with
hypoosmolar
Riboflavin
Riboflavin
Intraoperative optical coherence tomography
using RESCAN 700:
Preliminary results in collagen cross linking
Natasha Pahuja
Fellow & PhD Cornea & Refractive Surgery
Natasha Pahuja, Vishal Arora, Rohit Shetty, Chaitra Jayadev,
Rudy Nujits, Bharat Hegde.
Financial disclosure: Nil
before riboflavin soaking
after crosslinking
• Purpose - To evaluate the
effectiveness and safety of
accelerated corneal collagen crosslinking (ACXL) in patients below 14
years of age with progressive
keratoconus.
HOW SAFE IS CROSSLINKING ??
65
Data transfer
ALLEGRO
Topolyzer
&
Topolyzer Vario
WaveLight EX500
or
ALLEGRO
Oculyzer
&
Oculyzer II
ALLEGRETTO WAVE® portal
software/Eye-Q laser system
TP PRK + KXL CASE 1
How to Avoid ectasia ???
Many factors are yet unknown
Take all precautions
Be prepared for post operative surprises




LASIK XTRA
High refractive error (> 8D )
Steep K on topography
Thin cornea
Poor biomechanics
ORBSCAN
PENTACA
M
POST-OP
KERATOMETRY
ORBSCAN
PENTACA
M
OD
PRE-OP POSTERIOR
ELEVATION
ORBSCAN
PENTACAM
Right Eye
Left Eye
LASIK xtra pre and post operative
LASIK
Preoperative
Postoperative
Riboflavin in
Saline
90 seconds soak
30mW/cm2 for 90
seconds
SIMPLIFIED 5 POINT MANAGEMENT
ALGORITHM
77
CASE #1: 35yr / F, for routine check up, Keratoconus detected incidentally, no risk factors for Keratoconus
LOW RISK/ MODERATE RISK/ HIGH RISK
BCVA: -4.50DS -3.00DC @ 40- 6/6
78
CASE #4: 22yr/ F, planning for Pregnancy, K/C/O Keratoconus
OS: Pachymetry 496 Micron
LOW RISK/ MODERATE RISK/ HIGH RISK
BCVA: -2.50 DS -2.00 DC @ 50- 6/6
Collagen Crosslinking
79
CASE #2: 27yr/ M, No Atopic Eye disease, contact lens intolerant, thinnest cornea 419
LOW RISK/ MODERATE RISK/ HIGH RISK
BCVA: -10.00 DS -5.00 DC @ 35- 6/12P
BCVA: -5.00/-1.00 @10- 6/9
80
INTRASTROMAL CORNEAL RING SEGMENTS (ICRS)
MODERATE TO ADVANCE
KERATOCONUS
THICKNESS OF >450 MICRONS
IN THE CENTRAL 6MM
SINGLE 0.45 SK RING INFERIORLY
81
CASE #3: 21yr/ F, Active atopic eye disease, k/c/o Keratoconus since
4 years: OS Pachymetry: 493 microns
LOW RISK/ MODERATE RISK/ HIGH RISK
BCVA: +1.5/-3.00@100°
6/9
BCVA: -0.75/-1.5@130° 6/9
82
TOPOGRAPHY GUIDED PRK (TPRK)
CENTERED CONE
DECENTERED CONE
CASE #5: 32yr/ M, Central Corneal Scarring,Refraction not recordable
LOW RISK/ MODERATE RISK/ HIGH RISK
Penetrating Keratoplasty
84
REHABILITATION
KERATOPLASTY (DALK/FEK)
Treat the allergy aggressively to
reduce the chances of failure of CXL
Steroid
Cyclosporine
Persistent eye rubbing may “nullify”
the effect of CXL
Paradox of Cross linking and Infectious
keratitis: To do or no to do?
PACK - CXL
Term Photoactivated Chromophore for infectious
keratitis - created at 9th cross-linking congress in
Dublin, Ireland, 2013
To distinguish - CXL for infectious keratitis
CXL for progressive keratoconus
Said DG et al.Collagen Cross-Linking with Photoactivated Riboflavin (PACK-CXL) for the Treatment of
Advanced Infectious Keratitis with Corneal Melting. Ophthalmology 2014
Mechanism of Action
‘Fortified
stroma’
Apoptosis
Resists proteolysis by
enzymes from PMN
participating in
inflammation
Not only kills
keratocytes but
also microbes
May block
penetration/effect of
toxins from
pathogenic organism
Decelerates
infectious process
Said DG et al.Collagen Cross-Linking with Photoactivated Riboflavin (PACK-CXL) for the Treatment
of Advanced Infectious Keratitis with Corneal Melting. Ophthalmology 2014;article in press:1-6
PACK-CXL
Bactericidal activity in vitro
• Pseudomonas aeruginosa
• Staphylococcus aureus
• Staphylococcus epidermidis
• Methicillin-resistant S. aureus
• Multidrug resistant P.
aeruginosa
• Drug-resistant Streptococcus
pneumoniae
Fungal pathogens in vitro
• Candida albicans
• Fusarium species
• Aspergillus fumigatus
Said DG et al.Collagen Cross-Linking with Photoactivated Riboflavin (PACK-CXL) for the Treatment of
Advanced Infectious Keratitis with Corneal Melting. Ophthalmology 2014
Literature search*
Studies
Eyes that improved with CXL
Percentage (%)
Makdoumi et al.
6/7
86
Makdoumi et al. (2011)
15/16
94
Morén (2008)
1/1
100
Iseli et al. (2008)
4/5
80
Micelli Ferrari et al. (2009)
1/1
100
Khan et al. (2011)
3/3
100
Anwar et al. (2011)
1/2
50
Price et al. (2012)
34/40
85
Panda et al. (2012)
7/7
100
Sorkhabi et al. (2013)
Müller et al. (2012)
Skaat et al. (2011)
Our study
8/10
80
4/6
67
5/6
83
9/16
56
Alio et al. Corneal cross linking and infectious keratitis: a systematic review with a meta-analysis
of reported cases.Journal of Ophthalmic Inflammation and Infection 2013, 3:47
CXL for infectious keratitis
Questions to be answered:
•
•
•
•
Indications
Protocol
Safety
Primary treatment/ non-healing
keratitis
Procedure
• 0.1% Riboflavin drops (MedioCross D) every 2 min for 30
mins.
• Riboflavin + UV-A (365 nm)
irradiation:
– Conventional CXL- 15 patients
• 3 mW/cm2 for 30 minutes
– Accelerated CXL in 3 patients
• 9mw/cm2 for 10 minutes
Results and discussion
• 1st POD- significantly reduced/ no pain in all
patients
– ‘Chemical denervation’
• Appearance (3/11 patients) / increase (4/7
patients) in hypopyon
– Jarisch- Herxheimer reaction
• Mean time for epithelial healing- 23 days
• Mean time for resolution of corneal infiltrate was 33 days