benefits in various macular edema central serous...
TRANSCRIPT
Prof. Dr. Emin ÖZMERT
Ankara University Faculty of Medicine, Ankara / TURKEY
Tehran - 2017, IRAN
Subthreshold 577 nm SubLiminal (= micropulse) Laser Therapy:Benefits in Various Macular Edema
Central Serous Chorioretinopathy (CSSR)
Financial Disclosure
Consulting and training agreement with “Quantel Medical, Inc.”
Protokol T: 2-year results
Wells J, Glassman A, Ayala A: Ophthalmology 2016; 27
Mild vision loss
Moderate or worse vision loss
Required at least one rescue macular laser:Aflibercept: 41 %Bevacizumab: 64 %Ranibizumap: 52 %
Suggested treatment algorithm for DME
Mitchell P: Am J Ophthalmol 157: 505-513, 2014
DME
VA ≤ 20/30
Foveal involved DME
Anti VEGF
VA > 20/30
Focal /Grid laser treatment
According to ETDRS protocol
Non-center involved DME
Non-responder
Conventional grid / focal thermal laser photocoagulation:
• The clinical endpoint is an ophthalmoscopically visible retinal burn
• About 10 to 40 % of the energy delivered damage adjacent tissues
Collateral thermal damageMainster M. Semin Ophthal 1999 Desmettre TJ, et al Br J Ophthalmol 2006
Conventional thermal laser photocoagulation
Iatrogenic collateral chorioretinal thermal damage
• Enlargement of laser scars into the fovea
• Change in contrast / macular sensitivity (microperimetry)
• Macular / peripheral scotomas
• Choroidal neovascularization, submacular fibrosis
• Loss of color vision
• Reduced night vision
• Inadvertent foveal burn
• Transient increase of edema, and decrease in VA
Suggested treatment algorithm for DME
Mitchell P: Am J Ophthalmol 157: 505-513, 2014
DME
VA ≤ 20/30
Foveal involved DME
Anti VEGF
VA > 20/30
Focal /Grid laser treatment
According to ETDRS protocol
Non-center involved DME
Non-responderSubtreshold laser modalities:
CW single spot: lightCW pattern: PASCAL, NAVILASMicropulse = Subliminal
What can be done to reduce the devastating effect of conventional thermal laser ?
• To prefer 577 nm yellow wavelenghth over532 nm green
• Light, subthreshold burns with conventional CW laser
• Modified – ETDRS protocol
• Pattern scanning (multispot) subthresholdburns with CW
( Pascal, Navilas )
• Tissue-sparing Micropulse laser stimulation:
SubLiminal laser:
pattern (multispot) + 577 nm yellow
wavelenght
SubLiminal (Easyret)
A new term “photostimulation” as opposed to “photocoagulation”
Advantages of yellow wavelenght multispot SubLiminal laser:
• Excellent combined absorption by melanin & oxyhemoglobin
* Max. absorption in RPE, choriocapillaris
* Needs less power with more uniform treatment
* Better penetration through the cataract and hazy media
• Negligible xanthophyll absorption compare to green 532nm
(Allows to treat closer to the macula)
• Reduce collateral damage, well-protected macular sensitivity
Mainster MA: Wavelength selection in macular photocoagulation.Tissue optics,thermal effects,and laser systems. Ophthalmology.1986;93:952-958
Subtreshold Micropulse(=SubLiminal) mode
From photocoagulation to photostimulation…
• CW laser emission is choped into spaced repetitive micropulses within an envelope
• Major advantages:
• No thermal damage to adjacent tissues
• Minimal energy use
• Time for tissue cooling between pulses
Continuous (CW) laser: 100 % Duty CycleLaser energy is delivered in one single laser pulse
Micropulse laserA train of ultra-short repetitive microsecond pulses
1- Yoon Hyung Kwon, Dong Kyu Lee, Oh Woong Kwon. The short-term efficacy of subthreshold micropulseyellow (577-nm) laser photocoagulation for diabetic macular edema. Korean J Ophthalmol 2014;28(5):379-385 2- Scholz P, Ersoy L, Boon CJF, FauserS. Subthreshold Micropulse Laser (577 nm). Treatment in Chronic Central Serous Chorioretinopathy. Ophthalmologica 2015 DOI: 10.1159/000439600
200 ms
MicroPulse PrincipleSubLiminal Technology
Pre-laser 4 months post laser
Traditional thermal laser treatment
8 months post laser 12 months post laser
Victor Chong MD, Oxford Eye Hospital
ExudatesLaser spots
Pre-treatment (BCVA 37 letters) 12 months post-treatment (BCVA 57 letters)
Micropulse Yellow Laser
Fong KCS, University of Malaya ( YELL-1 Study )
SubThreshold treatment modes based on a train of microsecond pulses ------------ micropulse laser
Same technology, but different trademarked names
IridexQuantel Medical
SubLiminal ? MicroPulse ?
Tissue-Sparing Subthreshold Micropulse Laser (= SubLiminal Laser)
EASYRET: 577 nm Yellow, multispotsSUPRA SCAN 577: Yellow, multispots
How does micropulse laser therapy work ?
Heated sublethal tissue that remains viable after MPL, stimulates the RPE, and triggers a stress response
Over-express more than 25 genes. These genes represent diverse biological functions:
* Modulates beneficial intracellular biological factors ( PEDF, TSP1, SDF1, ß-Actin, VEGF )
* Alteration and normalization of cytokine expression
* Heat Shock Proteins:
- Inhibit protein aggregation
- Guide proteins to the correct organe
These factors are primarily anti-angiogenic and restorative
1. Shafiee A, IOVS 2000; Figueroa J, BJO 2009; Vojosevic S, Retina 2010
2. Lavinsk D, Retina 2014Wilson AS,et al: Invest Ophthalmol Vis Sci. 2003; 44:1426-1434.
3. Wilson AS,et al: Invest Ophthalmol Vis Sci. 2003; 44:1426-1434.
4. Sramek C, et al: Invest Ophthalmol Vis Sci. 2011; 52:1780-7.
Terminology on Micropulse(=SubLiminal) Technology
• Pulse ON time: Duration of each micropulse
• Pulse OFF time: Interval between micropulses
• Period ( T ): ON time + OFF time
• Exposure duration ( Envelope ): no of micropulses X T
• Duty Cycle ( % ): ON time / T X 100
Expression of the energy delivered on tissues ( 5, 10, 15 % )
LOW DUTY CYCLE
Low thermal diffusion due to the long “OFF” time
between each Pulse
HIGH DUTY CYCLE
More energy is delivered with more thermal diffusion
during the “ON” time
Micropulse(=SubLiminal) / Multispot ( pattern ) laser stimulation: Parameters
- Duration: 200 ms =0,2 s- Spot size:160 microns- Duty Cycle: % 5- Power: MPL, barely visible spot / 2- Various pattern choice: Multispot delivery
Since the laser spots are not visible, this pattern ensuresa homogenous application and a dense placement of the subthreshold laser spots
Low intensity: % 5 Duty CycleHigh dansity : contiguous ( confluent ) applications (no overlapping burns )
More RPE cells are exposed to thermal stress which improve its efficacy
Customizable macular grid
Fovea landmark
Non-treatment area (blue circle)
Treatment area (spots)
Treatment area (spots)
Laser aiming beam OCT
Laser aiming beam OCT
Square
SubLiminal Treatment Guidelines
DME: OCT- guided SubLiminal (=micropulse) treatment
Pre op OCT - BCVA 20/40
Post op OCT - BCVA 20/20
160 μm spot size / DC 5% / 200 msTitrate Power: Single spot outside arcades until bare visible burn Treatment Power: 50% of the power level obtained during the titrate step
- No visible reaction must be observed - There is no need to change power with
different degrees of edema
Wait for min 3 months
0,5 0,8 0,4 0,7
Pattern scan Subliminal laser applied on thickened area of OCT
- No visible reaction must be observed - There is no need to change power with different degrees of edema
Mİ: MPL applied on both eyes
24.02.2016 24.02.2016 /15.03.20171xMPL: 2xMPL:
26.07.201726.07.2017
Cataract developed Hard exudates increased
RE LE
SS: 71 years old, BRVO
CMT:483 µm
3 months later CMT: 272 µm
Parafoveal macular edema
Retinal arterial macroaneurism – CMEYellow MPL applied into the macroaneurism
FAF: CME,premacular hem.VA: 20/200
After MPL
Test spots2 years later after MPLVA: 20/20
Radiation retinopathy / 2xMPL
4 months later after the last application
Idiopathic Macular Telengiectasia- Type 2Intraretinal melanin clumping
Hypofl. dots due to melanin
clumping in retina
Melanin is black on both
FFA and FAF
SO: Idiopathic Parafoveal Telengiectasia / MPLThere is no proven therapyRestorative effect of MPL ??
Postop 2 months BCVA:0,3 CMT:102 µm
Preop BCVA: 0,3 CMT: 120 µm
HT: Idiopathic Parafoveal Telengiectasia / MPL
5 months later after MPL
Diminishing in size of neurodegenerative area
Cavitation within the retina due toneural dejeneration
Central Serous ChorioretinopathyTreatment options: No proven standard thraphy established
• Observation without treatment for 6-8 weeks for spontaneous resolution
• Conventional argon laser treatment extrafoveal RPE leakage, associated with inevitable collateral damage
• Intravitreal Anti-VEGF injection: Poor evidence, needs frequent injections, local / systemic side effects
• Half-dose PDT: effective, invasive, risk of RPE atrophy, CNV and choroidal ischemia
• Subthreshold Micropulse (=SubLiminal) : effective, non-invasive, no side effects
Acute CSCR: FA / ICGA Guided SubLiminal Treatment
- Hyperfluorescent areas on mid-phase ICGA
- Hot spots on mid-phase FA
- 500µm distance from foveal center
FA ICGA SubLiminal Laser Treatment
160 μm spot size / DC 5% / 200 msTitrate Power: Single spot outside arcades until bare visible burn Treatment Power: 50% of the power level obtained during the titrate step
Wait for min 6 weeks
AK: A 42 year-old female, micropulse laser therapy
VA: 0.2
VA: 1.012th month
TŞ: Parafoveal focal leaking point lasting 6 months
5 month later after MPL: VA 1.0
MPL was applied to the area of focal angiographic leakage: VA 0.8
CHRONIC CENTRAL SEROUS CHORIORETINOPATHY
• Usually seen in patients aged > 50
• Persistent subretinal fluid
accumulation for at least 6 months
• Irreversible visual loss due to
widespread areas of pigment
mottling, atrophic changes,
staining and leaks of RPE
• Rarely, CNV developes as a
complication
Chronic CSCR-FAF
Multiple mottled FAF:
* Leakage points, RPE atrophy, photoreceptor damage -------- black dots
* Increased RPE activity, pholorophore in subretinal fluid ----- white dots
• FAF is useful to differantiate acute and choronic SSCR
• If there is no fluid on OCT, diagnosis of chr. SSCR is difficult
There is mottled FAF ( aggregates ) on the area of attached serous retinal detachment , which was previously detached
SY : 56 years old, female, Chr. CSCR
4 months later
VA: 0.4 ----- 1.0
Sometimes it resembles AMD
and adult-onset vitelliform lesions
IB: 46 years old, male, Chr. CSCR
Preoperative, BCVA:0.7
Preoperative SRF: 394 µm
1 month later, BCVA: 0.8 SRF: 259 µm 3 months later, BCVA:1.0 SRF: 32 µm
28.2.2014
20.3.2014
11.03.2015
1 year after one session MPL VA: 10/10, no distortion
MPL
Z.Ş. Right Eye
Differential Diagnosis:Pachychoroid Spectrum Disease
• Pachychoroid pigment epitheliopathy
• Pachychoroid neovasculopathy
• Polypoidal choroidal neovasculopathy
• Chronic Central Serous Chorioretinopathy + CNV
PCV + CNV
Chronic CSC+ CNV
- Chronic subfoveal fluid accumulation- Flat (Shallow) -irregular Pigment Epithelial Detachment- Thick choroid or large choroirdal vessels on EDI-OCT
OCT-Angiography: CNV, feding vessel
Pachychoroid neovasculopathy
ICG: RPE atrophyCNV ? Large choroidal vessels?
Submacular fluidFlat-irregular PEDDilated choroidal vessels
Central Serous Chorioretinopathywith serous PED
Polypoidal Choroidal Vasculopathy (PCV)
MPL is not useful,
Low-fulence PDT Treatment is preferred
PCV
Chronic Central Serous Chorioretinopathy + CNVAnti-VEGF injections and MPL are not useful
Unresponsive to Anti-VEGF After PDT
In 30 % of Chr. CSCR cases, type 1 CNV developes during the follow-up period
Marco Antonio Bonini Filho et al. JAMA Ophthalmol 2015
Hage R , Mrejen S, Krivosic V, et al. A. Am J Ophthamol 2015
Clinical Studies
Purpose:
To compare the efficacy and safety of:
• 577 nm yellow wavelength multispots MPL
and
• Low-fluence photodynamic therapy (PDT)
in the treatment of chronic central serous chorioretinopathy
Journal of Ophthalmology, Vol: 2016Article ID: 3513794
Treatment parameters:
• Micropulse yellow wavelength (577 nm) laser ------ (15 eyes)
Tissue-Sparing /Subthreshold Micropulse(=SubLiminal) Laser Stimulation
• Low-fluence PDT group ------------(18 eyes)• Verteporfin: 6 mg/m2 over ten minutes
• 689 nm laser for 83 seconds,
reduced light dose of 25 J/cm2,
intensity of 300 mW / cm2
Results-1
The changes in ETDRS letters throughout the follow-up
0
10
20
30
40
50
60
70
80
baseline 1st month 3rd month 6th month 9th month 12th month
ETD
RS
lett
ers
Micropulse laser
Photodynamictherapy
Results-2
Final best corrected visual acuity changes: improvement rate is higher with MPL
BCVA change Low-fluence PDT
n (%)
MPL
n (%)
Increase ≥ 5 ETDRS letters 6 (33.3%) 10 (66.7%)
Stable (within ± 4 ETDRS letters) 6 (33.3%) 1 (6.7 %)
Decrease ≥ 5 ETDRS letters 6 (33.3%) 4 (26.7%)
Total 18 15
p=0,101
Results-3The changes in subretinal fluid height throughout the follow-up:
The resorption rate of subretinal fluid is slower with MPL
0
20
40
60
80
100
120
140
baseline 1stmonth
3rdmonth
6thmonth
9thmonth
12thmonth
Su
bre
tin
alF
luid
He
igh
t(µ
m)
Micropulse laser
Photodynamic therapy
Results-4
Treatment response of subretinal fluid: There is no unresponsive case with MPL
Treatment response Low-fluence PDT
n (%)
MPL
n (%)
Complete resolution of SRF 13 (72.2%) 12 (80.0%)
Incomplete resolution of SRF 1 (5.6%) 1 (6.7%)
Unresponsive 3 (16.7%) None
Recurrence 1 (5.6%) 2 (13.3%)
Total 18 15
p=0,486
Recurrence rate is higher with MPL, because we could not differentiate the Pachychoroid Spectrum Diseasebefore the invention of OCT-Angiography
Conclusion: 577 nm SubLiminal micropulse multispots laser
• As effective as low-fluence PDT in providing resorption of SRF
with some additional benefits
• A non-invasive procedure
• Tissue-sparing effect without termal damage
• Ensure safe re-treatment after 3 months
Further investigation of macular function by
microperimetry, ERG and FAF may provide additional
useful information on MPL
THANK YOU