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Fundus autofluorescence and Fourier-domain optical coherence tomography imaging of 10 and 20 millisecond Pascal retinal photocoagulation treatment

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To report the evolution of pattern scanning laser (Pascal) photocoagulation burns in the treatment of diabetic retinopathy, using Fourier-domain optical coherence tomography (FD-OCT) and fundus autofluorescence (AF), and to evaluate these characteristics with clinically visible alterations in outer retina (OR) and retinal pigment epithelium (RPE). Standard red-free and colour fundus photography (FP), FD-OCT, and fundus camera-based AF were performed in 17 eyes of 11 patients following macular and panretinal photocoagulation (PRP). One hour following Pascal application, visibility of threshold burns on FP was incomplete. AF enabled visualisation of complete treatment arrays at 1 h, with hypoautofluorescence at sites of each laser burn. AF signals accurately correlated with localised increased optical reflectivity within the outer retina on FD-OCT. AF signals became hyperautofluorescent at 1 week, and corresponded on FD-OCT to defects at the junction of the inner and outer segments of the photoreceptors (JI/OSP) and upper surface of RPE. A 10 ms macular laser pulse produced a localised defect at the level of JI/OSP and RPE. Macular and 20 ms PRP burns did not enlarge at 1 year's and 18 months' follow-up respectively. We report the in vivo spatial localisation and clinical correlation of medium-pulse Pascal photocoagulation burns within outer retina and RPE, using high-resolution FD-OCT and AF. Ophthalmoscopically invisible and threshold Pascal burns may be accurately localised and mapped by AF and FD-OCT, with monitoring over time.
A, B, C) Colour and red-free fundus photographs (CFP, RFFP), and late frame fluorescein angiography of patient 1 before laser. (D) Diffuse macular oedema and fundus autofluorescence (AF) showing an increased signal at the fovea. (E, F) One hour after horseshoe-shaped grid (HSG) Pascal (100 mm spot size, 10 ms), grey-white burns visible with blurred edges on CF and RFFP. (G) Complete array of burns appearing well demarcated as hypoautofluorescent spots on AF. (H) Horizontal Fourier-domain optical coherence tomography (FD-OCT) scan at 1 h through the fovea, showing three vertical bands of increased optical reflectivity within the outer plexiform layer (OPL), extending through the thin band of high reflectivity immediately internal to the outer highly reflective layer and into the upper surface of retinal pigment epithelium (RPE). (I, J) Two weeks after Pascal, superficial nerve fibre layer reflexes masking the complete array of laser burns on CF and RFFP at the macula. (K) AF at 2 weeks demonstrating an increased signal at the site of each laser burn within the HSG array. (L) At 2 weeks, FD-OCT (horizontal, 3 mm 3D scan) demonstrating reduced optical reflectivity within the OPL with an accompanying defect at the level of the junction between the inner and outer segments of the photoreceptors (JI/OSP) and upper surface of RPE. The laser burn measures 83 mm in diameter. (M) At 4 weeks postlaser, the FD-OCT (overlapping horizontal 6 mm line scan) demonstrating the localised defects at the JI/OSP in high resolution corresponding to laser burns with sparing of photoreceptors and RPE adjacent to either side of each burn.
… 
Photograph showing diffuse exudative diabetic macular oedema that was treated with conventional (long pulse) temporal macular laser 3 months previously, and with a single intravitreal bezacizumab injection given 2 weeks prior to Pascal treatment. (A, B) Colour and red-free fundus photographs (CFP, RFFP) of patient 8, 1 h after full grid (FG) Pascal. Laser burns are visible superior to the fovea and not visible elsewhere within the FG array. (C) Horizontal Fourier-domain optical coherence tomography (FD-OCT) 3D scan performed 1 h prior to Pascal FG (10 mm spot size, 100 ms) showing sponge-like intraretinal oedema with a cystoid space. (D) FD-OCT at 1 h showing six vertical bands of increased optical reflectivity within the outer plexiform layer (OPL), extending through the thin band of high reflectivity immediately internal to the outer highly reflective layer and into the upper surface of retinal pigment epithelium (RPE). (E, F) Laser burns masked by the diffuse retinal thickening and not clearly visible on CFP and RFFP, 4 weeks after FG treatment. (G) Fundus autofluorescence (AF) performed at 4 weeks after laser showing hyperautofluorescent spots, corresponding to the complete FG array with a Pascal foveal exclusion zone of 2000 mm. The conventional laser burns are visible as mixed high and low signal spots superotemporal and inferotemporal to the Pascal FG array. (H) FD-OCT (horizontal, 6 mm 3D scan) demonstrating reduced optical reflectivity within the outer plexiform layer with accompanying defects at the level of the junction between the inner and outer segments of the photoreceptors and upper surface of RPE.
… 
Photograph showing patient 11 who received a single octant of Pascal (100 mm spot size, 10 ms) for clinically significant macular oedema. (A, B) Colour and red-free fundus photographs (CFP, RFFP) at 1 h after laser showing grey-white laser burns temporal to the fovea. (C) Fundus autofluorescence (AF) demonstrating the complete octant of burns as hypoautofluorescent spots. The two rows of titration burns are partially visible on CFP, with increasing visibility on RFFP. (C) AF clearly demonstrating the titration burns, with the power intensity varying from temporal to nasal hypoautofluorescent spots (100 mW, 125 mW, 150 mW, 175 mW, 200 mW). A power of 150 mW was used as the threshold level for the octant treatment array. (D) Horizontal Fourier-domain optical coherence tomography (FD-OCT) scan performed through the fovea before laser. (E) FD-OCT 1 h after laser demonstrating three vertical bands of increased optical reflectivity within the outer plexiform layer (OPL). (F) A horizontal FD-OCT scan through the titration zone demonstrating five vertical bands of increased optical reflectivity. Each band shows increasing reflectivity within the OPL and greater disruption of the outer highly reflective layer (HRL) as the burns move from temporal to nasal retina, and this corresponds to stepwise increases in the titration powers. (G, H) One week after laser, the grey-white burns are visible on CFP and RFFP. (I) AF demonstrating the complete octant of burns as hypoautofluorescent spots temporal to the fovea, with increased signal demonstrated with all titration burns. FD-OCT of the treatment (J) octant (horizontal, 6 mm 3D scan) and of the titration zone (horizontal 3 mm 3D scan (K), high definition overlapping horizontal 6 mm line scan (L) demonstrating reduced optical reflectivity within the OPL with an accompanying defect at the level of the junction between the inner and outer segments of the photoreceptors and upper surface of RPE. (K, L) On the titration scans, there is increasing disruption of the outer HRL with increasing power intensity. The laser burn measures 88 mm in diameter (J).
… 
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Fundus autofluorescence and Fourier-domain optical
coherence tomography imaging of 10 and
20 millisecond Pascal retinal photocoagulation
treatment
M M K Muqit,
1
J C B Gray,
1
G R Marcellino,
2
D B Henson,
1
L B Young,
1
S J Charles,
1
G S Turner,
1
P E Stanga
1
1
Manchester Royal Eye
Hospital, Oxford Road,
Manchester, UK;
2
OptiMedica
Corporation, Santa Clara,
California, USA
Correspondence to:
Mr P E Stanga, Consultant
Ophthalmologist and
Vitreoretinal Surgeon,
Manchester Royal Eye Hospital,
Oxford Road, Manchester
M13 9WH, UK;
retinaspecialist@btinternet.com
Accepted 22 November 2008
Published Online First
15 December 2008
ABSTRACT
Aim: To report the evolution of pattern scanning laser
(Pascal) photocoagulation burns in the treatment of
diabetic retinopathy, using Fourier-domain optical coher-
ence tomography (FD-OCT) and fundus autofluorescence
(AF), and to evaluate these characteristics with clinically
visible alterations in outer retina (OR) and retinal pigment
epithelium (RPE).
Methods: Standard red-free and colour fundus photo-
graphy (FP), FD-OCT, and fundus camera-based AF were
performed in 17 eyes of 11 patients following macular and
panretinal photocoagulation (PRP).
Results: One hour following Pascal application, visibility
of threshold burns on FP was incomplete. AF enabled
visualisation of complete treatment arrays at 1 h, with
hypoautofluorescence at sites of each laser burn. AF
signals accurately correlated with localised increased
optical reflectivity within the outer retina on FD-OCT. AF
signals became hyperautofluorescent at 1 week, and
corresponded on FD-OCT to defects at the junction of the
inner and outer segments of the photoreceptors (JI/OSP)
and upper surface of RPE. A 10 ms macular laser pulse
produced a localised defect at the level of JI/OSP and
RPE. Macular and 20 ms PRP burns did not enlarge at
1 year’s and 18 months’ follow-up respectively.
Conclusions: We report the in vivo spatial localisation and
clinical correlation of medium-pulse Pascal photocoagulation
burns within outer retina and RPE, using high-resolution FD-
OCT and AF. Ophthalmoscopically invisible and threshold
Pascal burns may be accurately localised and mapped by AF
and FD-OCT, with monitoring over time.
Laser photocoagulation remains the gold standard
treatment for diabetic macular oedema (DMO) and
proliferative diabetic retinopathy (PDR). The Early
Treatment Diabetic Retinopathy Study (ETDRS)
recommends visible end point (VEP) laser photo-
coagulation, although subthreshold and modified
laser strategies are being frequently reported.
1–4
The
original ETDRS used long pulse duration, 100–
200 ms, burns for macular and panretinal photo-
coagulation (MP, PRP). It is well recognised that
conventional (long pulse) laser scar expansion may
be associated with photoreceptor loss, retinal
pigment epithelium (RPE) hypertrophy, subfoveal
fibrosis and paracentral scotomas.
5
Recently, selective retina therapy (SRT) demon-
strates therapeutic effects using short pulse dura-
tions.
3
Micropulse and non-VEP photocoagulation
have been reported to produce visual outcomes
that are equally effective or better than modified
VEP laser.
46
However, ophthalmologists have
found laser titration difficult in the absence of
visible laser uptake, with risks of overlapping
retreatment burns.
For new laser technology, the goal of retinal
photocoagulation is to target the RPE with
minimal photoreceptor damage and RPE cell loss,
and perhaps barely visible scar formation.
The Pascal (pattern scanning laser) photocoagu-
lator is a new laser delivery system introduced in
2005.
7
It semiautomates the procedure and can
deliver single applications of multiple laser burns to
the retina. Pascal uses medium-pulse duration, 10–
30 ms, burns for either PRP or MP. Importantly,
this results in less destruction within the outer
retina than with conventional burns, presumably
due to less thermal diffusion to the choroid.
8
Despite recent knowledge of Pascal therapeutic
parameters,
9
Pascal uptake may be difficult to
quantify in clinical practice. Assessment of laser
burns may be even more challenging in the
presence of retinal thickening of varied topogra-
phy, or poorly pigmented RPE with low contrast.
It is important to determine the in vivo effects on
tissue across a range of therapeutic parameters, for
laser application to be safe and well tolerated by
patients.
In this article, we describe a pilot study of in vivo
retinal imaging of medium-pulse Pascal burns using
Fourier-domain optical coherence tomography
(FD-OCT) and fundus autofluorescence (AF) in a
cohort of patients with diabetes. The main aim of
our study was to assess the visibility and morphol-
ogy of Pascal lesions within outer retina and RPE
and better understand the laser–tissue interaction.
Our secondary aims were to investigate the effects
of different Pascal thresholds on retinal autofluor-
escence and to evaluate the evolution of Pascal
burns over time.
MATERIALS AND METHODS
Subjects
A consecutive series of patients with diabetes
undergoing routine unilateral or bilateral Pascal
for macular oedema and PDR were studied. Ocular
comorbidity included high myopia, cystoid macu-
lar oedema secondary to branch vein occlusion and
diffuse DMO.
All patients gave informed consent, and all
investigations were performed as part of routine
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care at Manchester Royal Eye Hospital, UK. FD-OCT and AF
were performed before laser treatment, and 1 h, 1 week,
2 weeks, 1 month and 1 year after MP. In the PRP group, AF
was performed after 1 h, 1 month, 3 months and 18 months.
However, it was not possible for all patients to undergo all tests
at the previously mentioned time-points.
Pascal photocoagulation system
This is a frequency-doubled neodymium-doped yttrium alumi-
nium garnet (Nd: YAG) solid-state laser with a wavelength of
532 nm, using a 630–650 nm diode laser aiming beam.
7
Photocoagulation is applied in a rapid raster sequence with a
pattern array. In order to achieve this, the pulse duration of each
burn is reduced to 10–20 ms. Squares are available in adjustable
262, 363, 464 and 565 arrays. The 565 array was used for PRP
in two patients.
In full grid treatment, the A plus B pattern consisted of four
concentric rings with 112 spots encircling the fovea. Each octant
of the array contains 14 spots, and focal macular MP may
comprise single or multiple octants. Photocoagulation of the
papillomacular bundle may have the potential to produce
centrocaecal scotomas over time. The papillomacular bundle
may be spared by using a horseshoe-shaped grid (HSG) array.
To configure an HSG, the superonasal and inferonasal octants
were excluded to give a total array of 84 spots. The diameter of
the innermost ring is 2000 mm (‘‘safety zone’’), and this inner
ring of 12 spots is delivered in 132 ms, which is theoretically
below a patient’s reaction time. The 100 mm spots were placed
one and a half burn widths apart.
Ocular imaging
Fundus autofluorescence
AF intensity is determined by the quantity and distribution of
lipofuscin.
10
We used a fundus flash-camera system (Topcon
TRC-50DX, type IA) with an imaging field of 50u. The AF
exciter filter has a 30 nm bandwidth and central wavelength of
580 nm, with 60% transmission. The barrier filter has a 40 nm
Table 1 Pascal photocoagulation parameters
Case Pascal type
Energy
(mW) Duration (ms)
Spot size
(mm)
Spot
spacing
(spots)
1 HSG 100 10 100 1.5
2 FG 125 10 100 1.5
3 FA 100 10 100 1.5
4 HSG 150 10 100 1.5
5 FA 150 10 100 1.5
6 HSG 125 10 100 1.5
7 FG 150 10 100 1.5
8 FG 200 10 100 2.0
9 TG 150 10 100 1.5
10 TG 150 10 100 1.5
11 FA 150 10 100 1.5
12 HSG 150 10 100 2.0
13 FA 125 10 100 1.5
14 FA 125 10 100 1.5
15 HSG 100 10 100 1.5
16 PRP 300 20 400 2.0
17 PRP 400 20 400 1.5
CRT, central retinal thickness; FA, focal array; FG, full grid; HSG, horseshoe grid; PRP,
panretinal photocoagulation; TG, temporal grid.
Table 2 Ocular imaging classifications
Case Diagnosis Snellen visual acuity
Optical coherence
tomography
macular oedema
patterns
Clinical visibility of laser
uptake at 2 weeks
Laser masking
features
1 CSMO 6/5 Sponge-like Y SRNFLR
2 Diffuse 6/5 Sponge-like N SRNFLR
DMO
3 CSMO 6/18 Sponge-like Y Choroidal folds
4 Diffuse 6/9 Sponge-like N Myopic RPE attenuation
DMO
5 CSMO 6/9 Sponge-like N Myopic RPE attenuation
6 Diffuse 6/36 Sponge-like N SRNFLR
DMO
7 Diffuse 6/24 Sponge-like N SRNFLR
DMO
8 Diffuse 6/60 Cystoid+N Exudates
DMO Sponge-like
9 Diffuse 6/12 Cystoid+N Diffuse retinal
DMO Sponge-like thickening
10 Diffuse 6/9 Cystoid+N Diffuse retinal
DMO Sponge-like thickening
11 CSMO 6/5 Sponge-like Y Nil
12 Diffuse 6/6 Sponge-like N Diffuse retinal
DMO thickening
13 CSMO 6/9 Sponge-like N Exudates
14 BVO+6/18 Chronic cystoid N Hypoxic
CMO RPE attenuation
15 Diffuse 6/12 Cystoid+N Diffuse retinal
DMO Sponge-like thickening
16 PDR 6/6 NA Y NA
17 PDR 6/6 NA Y NA
BVO, branch vein occlusion; CMO, chronic macular oedema; CSMO, clinically significant macular oedema; DMO, diabetic macular
oedema; PDR, proliferative diabetic retinopathy; RPE, retinal pigment epithelium; SRNFLR, superficial retinal nerve fibre layer reflexes.
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bandwidth and central wavelength of 695 nm. AF images show
the spatial distribution of signal intensities for each pixel in grey
values. Dark signals correspond to low pixel values and blocked
autofluorescence, and bright signals correlate with high pixel
values and increased autofluorescence due to a window-type
effect.
11
Fourier domain optical coherence tomography
FD-OCT (Topcon, 3D OCT-1000) allows non-contact, in vivo
visualisation of the retina. Image detection is based on retrieval
of an optical A-scan from interferometric signals as a function of
spectral fringe patterns.
12
High acquisition speeds (25 000 A-
scan/s) permit visualisation of retinal morphology up to an axial
resolution of 5 mm. Important reflective signals within the outer
retina include the outer highly reflective layer (HRL). The thin
band of high reflectivity immediately internal to the outer HRL
is believed to correspond to the junction between the inner and
outer segments of the photoreceptors (JI/OSP), and the outer
HRL has been reported to represent the melanin in RPE.
13–15
We
used three acquisition modes, namely 6 mm/6 mm size retina
and choroidal 3D-scans, overlapping line scans with averages
taken of five high-resolution images and retina 3D scans with a
3 mm/3 mm acquisition area.
RESULTS
Seventeen eyes of 11 patients with diabetes (mean age 54 years
(median 54, range 26–76); 15 (88%) males; 15 (88%) Caucasian
and two (12%) Asian) were treated. Fifteen eyes received MP,
and two eyes underwent PRP (table 1). Within the MP group,
five patients received a HSG, four had full grid, four eyes
received a focal macular pattern, and the remaining two eyes
underwent temporal grid. Visual acuity was 6/5 to 6/9 in 10
Figure 1 (A, B, C) Colour and red-free fundus photographs (CFP, RFFP), and late frame fluorescein angiography of patient 1 before laser. (D) Diffuse
macular oedema and fundus autofluorescence (AF) showing an increased signal at the fovea. (E, F) One hour after horseshoe-shaped grid (HSG) Pascal
(100 mm spot size, 10 ms), grey-white burns visible with blurred edges on CF and RFFP. (G) Complete array of burns appearing well demarcated as
hypoautofluorescent spots on AF. (H) Horizontal Fourier-domain optical coherence tomography (FD-OCT) scan at 1 h through the fovea, showing three
vertical bands of increased optical reflectivity within the outer plexiform layer (OPL), extending through the thin band of high reflectivity immediately
internal to the outer highly reflective layer and into the upper surface of retinal pigment epithelium (RPE). (I, J) Two weeks after Pascal, superficial nerve
fibre layer reflexes masking the complete array of laser burns on CF and RFFP at the macula. (K) AF at 2 weeks demonstrating an increased signal at
the site of each laser burn within the HSG array. (L) At 2 weeks, FD-OCT (horizontal, 3 mm 3D scan) demonstrating reduced optical reflectivity within
the OPL with an accompanying defect at the level of the junction between the inner and outer segments of the photoreceptors (JI/OSP) and upper
surface of RPE. The laser burn measures 83 mm in diameter. (M) At 4 weeks postlaser, the FD-OCT (overlapping horizontal 6 mm line scan)
demonstrating the localised defects at the JI/OSP in high resolution corresponding to laser burns with sparing of photoreceptors and RPE adjacent to
either side of each burn.
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(59%) eyes, 6/12 to 6/24 in five (29%) eyes and worse than 6/36
to 6/60 in two (12%).
Postoperative laser parameters
Laser spot arrays were more easily visible after 1 h on
ophthalmoscopy and colour fundus photography (CFP). With
red-free photography (RFP), burn edges were blurred, and overall
spot sizes were smaller than expected (fig 1). In the presence of
choroidal folds, high myopia, and exudative DMO, the visibility
of burns was difficult at 1 h, becoming even more difficult after
1 week (fig 2). Young patients with diabetes have bright
superficial RNFL reflexes, and this appearance may mask the
underlying laser–tissue interaction signs. The laser spots became
less visible on CFP and RFP in four eyes (fig 1) 4 weeks after laser.
AF imaging demonstrated hypoautofluorescence at 1 h
postlaser in the 15 MP eyes studied. The size and shape of each
Pascal spot and hypoautofluorescent signal were altogether
similar within the designated treatment array. HSG and full grid
configurations, and also titration spots were clearly delineated
with hypoautofluorescent spots (fig 1).
In a single patient, all burns appeared hyperautofluorescent at
1 week, and it is possible that AF signals increased with higher
laser power used from 100 mW up to 200 mW observed within
the titration scale (fig 3).
The CFP and RFP visibility of complete Pascal arrays was
incomplete in 12 eyes after 2 weeks, but increased AF signals
accurately mapped laser burns in 15 eyes over 4 weeks (figs 1, 2).
A single patient in the MP group had 1 year’s follow-up, and the
macular lesions were hypoautofluorescsent. In comparison with
Figure 2 Photograph showing diffuse exudative diabetic macular oedema that was treated with conventional (long pulse) temporal macular laser
3 months previously, and with a single intravitreal bezacizumab injection given 2 weeks prior to Pascal treatment. (A, B) Colour and red-free fundus
photographs (CFP, RFFP) of patient 8, 1 h after full grid (FG) Pascal. Laser burns are visible superior to the fovea and not visible elsewhere within theFG
array. (C) Horizontal Fourier-domain optical coherence tomography (FD-OCT) 3D scan performed 1 h prior to Pascal FG (10 mm spot size, 100 ms)
showing sponge-like intraretinal oedema with a cystoid space. (D) FD-OCT at 1 h showing six vertical bands of increased optical reflectivity within the
outer plexiform layer (OPL), extending through the thin band of high reflectivity immediately internal to the outer highly reflective layer and into the
upper surface of retinal pigment epithelium (RPE). (E, F) Laser burns masked by the diffuse retinal thickening and not clearly visible on CFP and RFFP,
4 weeks after FG treatment. (G) Fundus autofluorescence (AF) performed at 4 weeks after laser showing hyperautofluorescent spots, corresponding to
the complete FG array with a Pascal foveal exclusion zone of 2000 mm. The conventional laser burns are visible as mixed high and low signal spots
superotemporal and inferotemporal to the Pascal FG array. (H) FD-OCT (horizontal, 6 mm 3D scan) demonstrating reduced optical reflectivity within the
outer plexiform layer with accompanying defects at the level of the junction between the inner and outer segments of the photoreceptors and upper
surface of RPE.
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100 ms conventional MP scars, Pascal burns appeared uniform in
shape with no coalescence of scars at 1 year’s follow-up.
Macular oedema was classified using OCT before laser
intervention
16
(table 2): sponge-like (10/15 eyes), sponge-like
and cystoid (4/15 eyes) and chronic cystoid (1/15 eye).
At 1 h, vertical bands of moderate and high reflectivity
(VBMHR) were observed within the outer nuclear layer (ONL),
with extension from the inner HRL through the outer plexiform
layer (OPL). These VBMHR corresponded to Pascal burns (figs 1,
2). The OPL showed slight thickening, and the inner retinal
architecture remained intact. The basal border of the outer HRL
showed no signs of disruption.
At 1 week, there were localised areas of hyporeflectivity at the
level of JI/OSP and apical RPE that corresponded to laser burns.
The VBMHR showed reduced hyper-reflectivity within the OPL.
At 2 weeks, different stages of Pascal burn development were
represented. Patients with an underlying thin outer HRL (fig 2)
developed visible pigmentation and hypertrophy, observed as a
tiny cleft of hyper-reflectivity at the centre of the burn protruding
into the OPL. In other cases, the VBMHR had resolved to varying
degrees with an intact OPL layer that corresponded to non-
pigmented lesions. Overlapping FD-OCT may demonstrate JI/
OSP and outer HRL defects in high definition (fig 3).
We observed that 10 ms burns remained highly localised,
with no significant reflectivity changes in adjacent RPE or
neuroretina. Although the laser spot size delivered was 100 mm,
the burns were measured on FD-OCT in three patients at 79 mm
(patient 1), 83 mm (patient 3) and 88 mm (patient 11).
At 1 year, macula burns appeared as square-edged foci of
hyporeflectivity within the JI/OSP and apical RPE. On 3D
Figure 3 Photograph showing patient 11 who received a single octant of Pascal (100 mm spot size, 10 ms) for clinically significant macular oedema.
(A, B) Colour and red-free fundus photographs (CFP, RFFP) at 1 h after laser showing grey-white laser burns temporal to the fovea. (C) Fundus
autofluorescence (AF) demonstrating the complete octant of burns as hypoautofluorescent spots. The two rows of titration burns are partially visible on
CFP, with increasing visibility on RFFP. (C) AF clearly demonstrating the titration burns, with the power intensity varying from temporal to nasal
hypoautofluorescent spots (100 mW, 125 mW, 150 mW, 175 mW, 200 mW). A power of 150 mW was used as the threshold level for the octant
treatment array. (D) Horizontal Fourier-domain optical coherence tomography (FD-OCT) scan performed through the fovea before laser. (E) FD-OCT 1 h
after laser demonstrating three vertical bands of increased optical reflectivity within the outer plexiform layer (OPL). (F) A horizontal FD-OCT scan
through the titration zone demonstrating five vertical bands of increased optical reflectivity. Each band shows increasing reflectivity within the OPL and
greater disruption of the outer highly reflective layer (HRL) as the burns move from temporal to nasal retina, and this corresponds to stepwise increases
in the titration powers. (G, H) One week after laser, the grey-white burns are visible on CFP and RFFP. (I) AF demonstrating the complete octant of
burns as hypoautofluorescent spots temporal to the fovea, with increased signal demonstrated with all titration burns. FD-OCT of the treatment (J)
octant (horizontal, 6 mm 3D scan) and of the titration zone (horizontal 3 mm 3D scan (K), high definition overlapping horizontal 6 mm line scan (L)
demonstrating reduced optical reflectivity within the OPL with an accompanying defect at the level of the junction between the inner and outer
segments of the photoreceptors and upper surface of RPE. (K, L) On the titration scans, there is increasing disruption of the outer HRL with increasing
power intensity. The laser burn measures 88 mm in diameter (J).
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mapping with FD-OCT, fresh Pascal burns appeared columnar
in shape (fig 4). The outer HRL remained intact on either side of
each burn, together with basal aspects of outer HRL.
For the two cases of PRP, AF showed hypoautofluorescence at
1 h postlaser, with hyperautofluorescence at 4 and 12 weeks’
follow-up. Regarding laser-burn evolution, a patient treated
with Pascal PRP in November 2006 was investigated (fig 5). The
patient had 2 weeks previously undergone conventional 50 ms
PRP. Over 18 months’ follow-up, both conventional laser and
Pascal burns appeared as hypoautofluorescent spots. However,
on comparison of serial CFP and AF imaging, Pascal burns
remained non-pigmented and unchanged in size and shape over
this period. Conventional 100 ms laser burns appeared variable
in size, shape and pigmentation.
DISCUSSION
In this study, we aimed to investigate AF and FD-OCT
appearances of medium-pulse Pascal photocoagulation.
Controversy exists in clinical practice as to whether Pascal
burns within PRP or macular arrays are uniform in uptake,
based on clinical biomicroscopy. The higher power intensity of
VEP burns originally described by the ETDRS in DMO may
increase the risk of paracentral scotomas, choroidal rupture and
choroidal neovascularisation. However, these risks are now
more rarely associated with modified ETDRS MP regimens.
2
In order to understand the evolution of Pascal MP burns, we
investigated a range of patients with diabetes with variable
retinal morphology. Laser photocoagulation in diffuse DMO
may result in excessive laser power due to masking of burns by
retinal thickening and exudates. It is possible that increasing
pulse durations may lead to suprathreshold burns that evolve
over time to produce zonal photoreceptor loss and macular
capillary loss.
In experimental work with rabbit retina, medium pulse
demonstrated localised homogenous burns.
17
In rabbit eyes, the
power required to produce ophthalmoscopically visible spots
was shown to decrease with increasing pulse duration, but the
cumulative pulse energy increased with pulse duration.
8
We
observed no complications within the outer retina at 10 ms and
20 ms.
9
AF is a non-invasive tool to investigate the in vivo effects of
laser photocoagulation on RPE metabolism. Framme has
reported AF signals following SRT to remain hyperautofluor-
escent for up to 3 years.
18
Framme and coworkers described
difficulty in visualisation of AF signal changes with the
Heidelbergh angiograph (confocal scanning laser ophthalmo-
scopy system) in DMO patients treated by SRT.
18
Immediate
hypoautofluorescence was not observed in these patients, and
laser burns could not be visualised over time.
In contrast, we found AF to be a reliable method of detecting
the totality of Pascal burns at all time points, whether
Figure 4 (A, B) Colour and red-free fundus photographs (CFP, RFFP) of patient 15, 1 year following horseshoe-shaped grid (HSG) Pascal for diabetic
macular oedema. Focal spots of hypopigmentation in the parafoveal macular region are visible. (C) Fundus autofluorescence (AF) demonstrating
hypoautofluorescence within the macular treatment array. The burns appear round and uniform in size and shape, with no coalescence of burns. In the
temporal macula, previous conventional laser burns are visible as larger hypoautofluorescence lesions with varying shapes of burns and coalescence of
burns. (D, E) FD-OCT (horizontal, 6 mm 3D scan) of a single burn demonstrating sparing of the inner neuroretina and an accompanying defect at the
level of the junction between the inner and outer segments of the photoreceptors and upper surface of retinal pigment epithelium (RPE). The outer highly
reflective layer on either side of the Pascal burn demonstrates normal reflectivity.
Clinical science
Br J Ophthalmol 2009;93:518–525. doi:10.1136/bjo.2008.148833 523
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ophthalmoscopically visible, barely visible or invisible. None of
our patients required a retreatment with Pascal for subther-
apeutic laser uptake. In the presence of exudative, cystoid and
sponge-like DMO, we were able to accurately locate laser burns
with AF. We used alterations in AF and changes in reflectivity
on FD-OCT to verify then monitor burns over time. PRP lesions
were visualised successfully in our two patients.
In DMO, we started titration at 100 mW, and a barely visible
burn was designated as threshold. Interestingly, the totality of
titration burns used in our patients showed hypoautofluores-
cence after 1 h. In one case, five laser spots of increasing
intensity were required to establish threshold. The selected
threshold was 150 mW; however all burns from 100 mW
(invisible) up to 200 mW (white grey burn, suprathreshold)
produced hypoautofluorescence at 1 h, followed by hyperauto-
fluorescence. In the MP group, all titration spots showed
increased AF signal over 2 to 4 weeks.
In the last decade, Toth et al have demonstrated argon blue-
green laser lesions in Macaca mulatta retina using time-domain
OCT.
19
With FD-OCT, we can evaluate alterations in retinal
architecture in greater detail. After 1 h, each Pascal burn
produced a VBMHR that corresponded spatially with blockage
of background signal on AF. Disruption of the JI/OSP suggests
that each VBMHR may consist of coagulated photoreceptor
elements and Muller cells within the OPL. VBMHR appeared
surrounded by vacuoles of hyporeflectivity, and this suggests
oedema within the OPL. We observed localised proliferation
within the apical RPE with no morphological alterations within
inner retina, and this correlates with reported histopathological
work.
7
The observed hyperautofluorescence was associated with a
window defect and increased lipofuscin production at sites of
photocoagulation. This phenomenon occurred at both invisible
and barely visible Pascal intensities. The 100 mm burns produced
at 10 ms duration appear to result in a burn size smaller than
the original laser spot size by approximately 15%.
In the long term, FD-OCT evaluation of macular scars
showed hyporeflective defects at the JI/OSP and apical RPE.
Scars appeared barely visible, with no full-thickness extension
through outer HRL, or any significant expansion.
19 20
The
adjacent HRL was unaffected on both sides of the Pascal scar.
In Pascal 20 ms PRP, initial hyperautofluorescence appears to
fade by 6 months, and hypoautofluorescence remained up to
18 months in one patient with no significant laser scar
enlargement.
Laser-induced alterations in RPE function and morphology
are linked to progressive photoreceptor apoptosis. The initial
acumulation of lipofuscin may be the by-product of therapeutic
metabolic effects within outer retina. However, evolution of AF
signals over time suggests that an increased load of lipofuscin
may result from the coagulated photoreceptors and/or RPE cells.
We have demonstrated with AF and FD-OCT that 10–20 ms
Pascal produces well-circumscribed and highly localised burns.
Individual spots of Pascal arrays result in uniform laser uptake
within the outer retina.. Threshold (barely visible) Pascal burns
may always result in RPE alterations, even if the complete array is
not immediately clinically visible. AF may be used as a monitoring
tool after laser photocoagulation, either to confirm successful
placement of burns or to target future retreatments especially
when using ophthalmoscopically invisible or threshold burns.
Figure 5 Photograph showing patient 17 who received conventional (50 ms pulse) panretinal photocoagulation (PRP) to the retinal periphery 2 weeks
prior to Pascal. (A, B) Colour and red-free fundus photographs (CFP, RFFP) of the superonasal retinal quadrant 1 h after Pascal PRP (565 spot array,
400 mm spot size, 20 ms). (C) Pigmented, conventional PRP burns in the retinal periphery, and Pascal PRP burns within the treatment arrays. The
conventional PRP burns show hyperpigmentation and coalescence of laser burns in the periphery. (D, E) After 18 months, Pascal PRP burns unchanged
in size and shape on CFP and RFFP. Fundus autofluorescence (AF) demonstrates hypoautofluorescence within the PRP array, and there is no significant
expansion of the Pascal burns in comparison with initial fundus photography (A, B).
Clinical science
524 Br J Ophthalmol 2009;93:518–525. doi:10.1136/bjo.2008.148833
group.bmj.com on December 1, 2013 - Published by bjo.bmj.comDownloaded from
Funding: This study was sponsored/funded by OptiMedica Corporation.
Competing interests: GRM is employed by the OptiMedica Corporation and has a
proprietary interest in the Pascal Photocoagulator.
Patient consent: Obtained.
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doi: 10.1136/bjo.2008.148833
December 15, 2008
2009 93: 518-525 originally published onlineBr J Ophthalmol
M M K Muqit, J C B Gray, G R Marcellino, et al.
treatment
millisecond Pascal retinal photocoagulation
tomography imaging of 10 and 20
Fourier-domain optical coherence
Fundus autofluorescence and
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... After conventional photocoagulation, there is early-on (within one week of laser) decreased FAF, which then turns into spots of increased FAF, most of which remain stable over months, or, less frequently, may progress to spots of decreased FAF [48]. The increased FAF may be explained by the accumulation of lipofuscin from the photoreceptors and RPE cells disrupted by the laser treatment [49]. In contrast to the conventional laser group, in the micropulse group, the FAF pattern remained unchanged even one year after the treatment. ...
... This may suggest that the subthreshold laser does not alter the photoreceptor and RPE cells and their function [48]. The evolution of scars after panretinal photocoagulation was also evaluated using FAF [49]. The scars made using a short-pulse laser displayed a slower evolution and a significantly lower expansion rate when compared to conventional laser [50]. ...
... The scars made using a short-pulse laser displayed a slower evolution and a significantly lower expansion rate when compared to conventional laser [50]. FAF may be useful in assessing photocoagulation scar placement, especially in cases where these are not visible ophthalmoscopically, in order to guide retreatment [49]. ...
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Diabetic retinopathy is a leading cause of visual morbidity worldwide. Fundus autofluorescence is a rapid, non-invasive imaging modality that has gained increased popularity in recent years in the multimodal evaluation of diabetic retinopathy and, in particular, of diabetic macular oedema. Acquired using either a fundus camera or the confocal scanning laser ophthalmoscope, short-wavelength and near-infrared autofluorescence are the most used techniques in diabetic retinopathy. In diabetic macular oedema, short-wavelength autofluorescence, in its cystoid pattern, is useful for detecting cystoid macular oedema. Increased spot hyperautofluorescence in short-wavelength and granular changes in near-infrared autofluorescence correlate well with other imaging findings, indicating photoreceptor and retinal pigment epithelium damage and being associated with decreased visual acuity. While also being a marker of oxidative stress, increased short-wavelength autofluorescence in the setting of diabetic macular oedema appears to be a prognostic factor for poor visual outcome, even after the resolution of the intraretinal fluid. Autofluorescence also helps in the assessment of diabetic retinal pigment epitheliopathy and choroidopathy. Fundus autofluorescence is an evolving technology that will assist in gaining further insight into the pathophysiology of diabetic retinopathy and allow for a more comprehensive evaluation of these patients.
... [11][12][13][14] The multispot pattern uses a brief pulse duration (20 ms) combined with rapid raster scan and may be less damaging to the inner retina, with reduced collateral thermal diffusion, compared with conventional exposure of 100 to 200 ms in the single-spot technique. 15 Hence, it is hypothesized that this new technology may be less painful and timeconsuming. ...
... 5 Owing to the use of shorter pulses, thermal damage is reduced, limiting the damage to the retinal pigment epithelium and preserving the inner retinal layers and sensory-rich chorioretinal tissues. 18 When combined with rapid raster scan, these models may be even less damaging to the inner retina, 15 allowing the patient to experience a more comfortable, faster, and less painful procedure. Hence, despite the higher intensity, less exposure time with multispot technique was still able to result in lower pain perception. ...
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Background and objective: To compare pain intensity with single-spot versus multispot technique in laser panretinal photocoagulation, using a 532-nm, solid-state laser system. Materials and methods: This was a prospective, interventional, randomized, single-masked comparison trial. Patients received two types of intervention: conventional single-spot technique, with an exposure time of 150 ms, and multispot technique, done with an exposure time of 20 ms, Both techniques used power sufficient to produce visible gray-white burns, and spot size of 20 μm. Participants received both treatments in the same eye, each one in one hemiretina, and were randomized to receive first single- or multispot technique and to the initial site of treatment. We assessed pain intensity using a numerical pain scale immediately after completion of each treatment. Results: A significantly lower pain scale was observed with the multispot when compared with the single-spot technique (coefficient [Coef]: -1.61; 95% CI, -2.49 to -0.74; P < .001), which was not affected by treatment order, the hemiretina treated, or treatment duration (P > .05). Among demographic characteristics, multiracial patients had a pain scale 1.25 greater than that of White patients (Coef: 1.25; 95% CI, 0.47 to 2.04; P = .002), but there is no effect of age or sex on the pain scale (P > .05). Regarding treatment duration, a shorter procedure was also observed in the multispot technique (Coef: -1.13; 95% CI, -1.43 to -0.82; P < .001), and it was not affected by order of treatment (P = .098), hemiretina (P = .327), pain (P = .141), or demographic data, such as age, sex, and race (P > .05). Conclusion: The use of the multispot technique, with a short pulse duration (20 ms), is significantly less painful and less time-consuming for patients with proliferative retinopathy compared with the conventional single-spot technique using an exposure time of 150 ms. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:40-45.].
... The findings are consistent with previous studies that reported similar changes in CMT after PRP laser treatment [9][10][11]. The mechanism of CMT increase after PRP is not fully understood, but it may be related to inflammatory cytokines, vascular endothelial growth factor, or mechanical stress induced by laser burns [12][13][14]. ...
... 11 For new laser technology, the goal of retinal photocoagulation is to target the RPE with minimal collateral nerve fiber layer damage and perhaps barely visible scar formation. 12 A new semiautomated photocoagulator, pattern scan laser is becoming increasingly popular in practice as it delivers laser in different desired patterns and the laser sessions are relatively painless for the patient. It uses mediumpulse duration, 1030 ms, burns for either PRP or macular photocoagulation. ...
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Laser photocoagulation in a grid pattern is effective in many eyes in resolving diffuse diabetic macular edema and stabilizing vision. We retrospectively studied 203 eyes of 203 patients, all of whom had diabetic macular edema treated with grid laser photocoagulation. During the follow-up period, 11 of these 203 eyes developed enlargement of the laser scars that progressed into the central fovea. Each of the 11 eyes experienced loss of vision, and in five, the visual loss was significant. Five of these eyes also developed a retinal pigment hyperplastic scar. After the laser treatment, but before the scars enlarged, the visual acuity of these eyes was unchanged from that before treatment. But after the atrophic scars enlarged into the central fovea, visual acuity in one eye decreased from 20/40 to 20/100, and the other 10 eyes had visual acuities of 20/200 or worse.
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We describe a new technique for investigating laser-tissue interactions based on the use of an interferometric laser exposure pattern. A Michelson interferometer is used to generate a sinusoidal fringe exposure pattern. The periodicity of the fringe pattern may be adjusted from macroscopic dimensions to a scale of microns without the need for an imaging plane. Since fringe pattern periodicity is more adjustable and directly measureable than laser spot size, this technique offers significant advantages for studying the effects of thermal damage and diffusion in the irradiated tissue. In addition, the comparison of tissue response with theoretical models is simplified since the sinusoidal fringe pattern is itself an eigenfunction of the thermal diffusion equation. This technique is demonstrated for argon laser photocoagulation in the rabbit retina. Exposures at durations comparable to the thermal relaxation time produced spatially confined lesions, while those at much longer durations resulted in significant diffusion of the thermal damage beyond the primary targeted regions. The role of thermal diffusion can thus be assessed directly from the ophthalmoscopic and histologic appearances of the lesions. This technique can be employed to study thermal diffusion and other transport phenomena occurring in laser-tissue interactions for a variety of laser sources and tissue targets.
Article
To assess the in vivo evolution of argon laser retinal lesions by correlating the cross-sectional structure from sequential optical coherence tomography with histopathologic sectioning. Argon laser lesions were created in the retinas of Macaca mulatta and evaluated by cross-section optical coherence tomography, which was compared at selected time points with corresponding histopathology. Argon laser lesions induced an optical coherence tomography pattern of early outer retinal relative high reflectivity with subsequent surrounding relative low reflectivity that correlated well with histopathologic findings. The in vivo optical coherence tomography images of macular laser lesions clearly demonstrated differences in pathologic response by retinal layer over time. The novel sequential imaging of rapidly evolving macular lesions with optical coherence tomography provides new insight into the patterns of acute tissue response by cross-sectional layer. This sequential imaging technique will aid in our understanding of the rapid evolution of retinal pathology and response to treatment in the research and clinical setting.
Article
We report cross-sectional images of diabetic macular edema and correlation between tomographic features and visual acuity with best correction by means of optical coherence tomography. In a prospective study, optical coherence tomography was performed in 59 eyes of 42 patients with diabetic macular edema and in 10 eyes of 10 normal control subjects. Optical coherence tomography showed three patterns of structural changes in diabetic macular edema: sponge-like retinal swelling (52 [88%] of 59 eyes), cystoid macular edema (28 [47%] of 59 eyes), and serous retinal detachment (9 [15%] of 59 eyes). Some eyes had more than one pathologic change. Retinal swelling was more pronounced in the outer rather than the inner retinal layers. Cystoid macular edema was located mainly in the outer retinal layers. In eyes with long-standing cystoid macular edema, cystoid spaces had fused, resulting in a large cystoid cavity involving almost the entire retinal layer. Hard exudates were seen as highly reflective areas located in the outer retinal layers. The retinal thickness at the central fovea and the visual acuity with best correction showed an intermediate negative correlation in eyes without cystoid macular edema (correlation coefficient: -0.61, P < .01). Diabetic macular edema involved three structural changes, including sponge-like retinal swelling (88%), cystoid macular edema (47%), and serous retinal detachment (15%). Visual acuity with best correction moderately correlated with retinal thickness regardless of the different tomographic features.
Article
To evaluate the efficacy of the Iris Oculight MicroPulse 810 nm diode laser in the treatment of macular oedema secondary to either branch retinal vein occlusion (BRVO) or diabetic maculopathy and in the treatment of proliferative diabetic retinopathy. The specific advantages of this type of laser delivery are greater retinal pigment epithelial specificity and less damage to the inner retina, thus preserving visual field and colour contrast sensitivity. Fifty-two eyes of 33 consecutive patients were treated over a 6-month period. Thirteen eyes had proliferative diabetic retinopathy and 39 had macular oedema secondary to BRVO or diabetic maculopathy. Panretinal and grid pattern photocoagulation were performed using the micropulse mode with the laser on for 100-300 microseconds and off for between 1900 and 1700 microseconds repeatedly in a pulse envelope of 0.1-0.3 s duration. Microaneurysms were not treated directly. Patients were assessed clinically and angiographically at 3 and 6 months. Ten eyes (77%) with proliferative disease showed some regression of new vessels at 6 months. Twenty-two eyes (57%) showed resolution of macular oedema at 6 months. Visual acuity was maintained in 27 eyes (69%) and improved in 11 eyes (28%). Diode laser in micropulse mode is effective in the management of diabetic and occlusive macular oedema and proliferative diabetic disease.