Dr. G. F. Pacelli 1, L. Baraggia 1, Dr.ssa B. Pacelli 2, Dr. V. Ferrara 1, Dr. V. Belloli 1 Microperimetric follow-up (FU) of clinical significant diabetic macular edema (CSDME) after modified grid laser (MGL) treatment with Pascal laser (PL). 1 Polo Ospedaliero SS. Trinità Arona (No). Italy 2 Agenzia sanitaria e sociale. Regione Emilia Romagna. Unità Epidemiologia. Italy

CSDME: Increased Macular Thickness (MT) within 500 μm from the fovea, that often leads to an irreversible deterioration of visual acuity. CSDME: Increased Macular Thickness (MT) within 500 μm from the fovea, that often leads to an irreversible deterioration of visual acuity. Laser still remains the standard treatment and the only one with proven longstanding efficacy as shown by E.T.D.R.S. Studies. The Main limit of conventional ETDRS laser treatment is the potential impact on Macular Sensitivity (MS). Recently new laser treatment modalities have been developed in order to minimize the impact on deeper retinal layers (Among these PL seems to be promising ). Introduction:

Index of efficacy: Reduction in Retinal Thickness of the treated and the foveal area (SD-OCT RMT analysis). Reduction in Retinal Thickness of the treated and the foveal area (SD-OCT RMT analysis). The improvement of Foveal Sensitivity (FS). (MP1 analysis). The improvement of Foveal Sensitivity (FS). (MP1 analysis). Index of Safety: Improvement/stability of Retinal Sensitivity (RS) in the macula and particularly in the quadrant mainly exposed to PL. Improvement/stability of Retinal Sensitivity (RS) in the macula and particularly in the quadrant mainly exposed to PL. Main goal: To assess the efficacy of PASCAL MGL in the treatment of CSDME and its relative impact on MS. Microperimetry (MP1) is an optimal tool to assess the impact of laser on macular function. Secondary aim : To compare PL structural and functional effects with those shown by a similar previous study (28 eyes of 27 patients; mean FU 7 mos) conducted with conventional Longer Pulse Duration Laser (LPDL) using light treshold parameters (540 nm diode). Objective:

Side effects of Laser Photocoagulation are: Scotoma V-R Interface wrinkling Epiretinal pathology of vitreomacular traction syndrome A Gandorfer, M Rohleder, A Kampik Br J Ophthalmol 2002 Damage to the neurons (photoreceptors, bipolar and ganglions cells)

Effect of Pulse Duration on Size and Character of the Lesion in Retinal Photocoagulation. ATul Jain et al. Arch. Ophthalmol The Pascal® Sistem: Reduced Fluence (thermal energy delivered) Laser light is converted into heat, as it’s absorbed by the melanin and hemoglobin, in its tissutal target that is Retina Pigment epithelium (RPE). Combination of short duration and uniform pulses, typical of PL, has important effects in sparing photoreceptorial cells (PRC). With PL, less thermal energy spreads in all directions, heating less volumes of tissue as demonstrated by histology: 1.Less lateral heat diffusion: Less RPE and PRC damage. 2.Decreased anterior spread of heat: Less damage to inner retina and nerve fiber layer. Conventional Laser 200 ms;Ø 200 µm Power 175 mW = Fluence 84 J/cm 2 PASCAL ® 20 ms;Ø 200 µm Power 300 mW = Fluence 19 J/cm2 Histological appearance of lesions.

Materials and Methods: CSDME: 31 eyes of 26 consecutive patients (onset < 6 months ; 14 ♂ e 12 ♀ ; mean age 66 yrs; Mean FU: 8,3 mos). CSDME: 31 eyes of 26 consecutive patients (onset < 6 months ; 14 ♂ e 12 ♀ ; mean age 66 yrs; Mean FU: 8,3 mos). 2 groups ( Hba1c cut-off value: 9% ). 2 groups ( Hba1c cut-off value: 9% ). Group 1 ( Hb> 9% ): 11 patients (7 ♀ 4 ♂ ). Group 2 ( Hb<9% ): 15 patients (6 ♀ 9 ♂ ). Basal and quarterly evaluation of: BCVA log (ETDRS charts). BCVA log (ETDRS charts). SD-OCT RMT Spectralis (Heidelberg ing. Germany) SD-OCT RMT Spectralis (Heidelberg ing. Germany) MP1 central 20° (Nidek Tech., Vigonza PD, Italy). MP1 central 20° (Nidek Tech., Vigonza PD, Italy). Fluorescein angiography Spectralis (Heidelberg Ing. Germany). Fluorescein angiography Spectralis (Heidelberg Ing. Germany). PASCAL laser using single spot modality (Mean of 2 treatments). PASCAL laser using single spot modality (Mean of 2 treatments). Statistical significance (SS*) of trend comparing the initial with the very last control value Wilcoxon test for related samples.For each FU step, mean values for all parameters have been compared Mann Withney Test for independent sample. Statistical significance (SS*) of trend, overall and for each group, evaluated comparing the initial with the very last control value for each patient, applying Wilcoxon test for related samples. For each FU step, mean values for all parameters have been compared between groups by performing Mann Withney Test for independent sample. (*SS evaluated at α level of 0.05 and of 0.001).

Pseudophakic/mild lens opacities eyes* were included (eyes recently operated of phacoemulsification were excluded). Pseudophakic/mild lens opacities eyes* were included (eyes recently operated of phacoemulsification were excluded). Eyes affected by other chronic diseases were obviously excluded. Eyes affected by other chronic diseases were obviously excluded. Materials and Methods: * In case of cataract worsening follow-up was interrupted at the previous control.

ETDRS modified technique”: direct FL of microaneurisms and a MGL applied to the whole area of thickened retina.* (Mean Ø spot 65 μm) with a power limited to obtain a mild whitening effect (mean 60 m.W), 0.2 m.sec* ( Olk et al.Ophthalmology 90). ETDRS modified technique”: direct FL of microaneurisms and a MGL applied to the whole area of thickened retina.* (Mean Ø spot 65 μm) with a power limited to obtain a mild whitening effect (mean 60 m.W), 0.2 m.sec* ( Olk et al.Ophthalmology 90). Conventional LPDL (540 nm diode, 0.2 msec)

Short pulse duration PL (0.02 msec) ETDRS modified technique”: direct PL of microaneurisms and a MGL applied to the whole area of thickened retina.* (Mean Ø spot 60 μm) with a power limited to obtain a mild whitening effect (mean 175 m.W), 0.02 m.sec* ( Olk et al. Ophthalmology 90). ETDRS modified technique”: direct PL of microaneurisms and a MGL applied to the whole area of thickened retina.* (Mean Ø spot 60 μm) with a power limited to obtain a mild whitening effect (mean 175 m.W), 0.02 m.sec* ( Olk et al. Ophthalmology 90).

SD OCT ( LPDL ETDRS versus PL spots). LPDL PL

Conventional laser scar “Pascal” Laser scar “Pascal” Laser scar “Pascal” laser Scars Conventional L scar SD OCT ( LPDL ETDRS versus PL spots).

Pre PL CRT map Pre PL FA Post PL CRT map & Autofluorescence Short pulse duration PL (0.02 msec) Short pulse duration PL (0.02 msec) PL scar after 6 months

MP1 follow up (8 mos) of DME treated with PL.

Mean % increment in BCVA: 59 % (P<0.001). Increment in 93,5% of cases. Mean % increment in BCVA: 59 % (P<0.001). Initial BCVA: 0.32 log.;Final BCVA: 0.12 log. Differences between groups don’t achivies SS; Increment in 93,5% of cases. BCVA variations (ETDRS Chart) Foveal Sensitivity (Db). Mean % increment of FS: 21%. (P<0.001). Increment in 77,42 % of cases Mean % increment of FS: 21%. (P<0.001). Initial FS: 10,92 db; Final FS: 12,58 db. Differences between groups don’t achivies SS at 9 mos. Increment in 77,42 % of casesResults:

Results: Mean % increment of RS in the quadrant: 13% (P<0.001) Initial Mean RS: 11,24 db.; Final mean RS:12.42 db. Increment in 77,42 % of cases After 9 mos the differences between groups don’t achivies SS. Increment in 77,42 % of cases Mean % increment of RS: 8%. (P<0.002). Initial mean RS is 10.6; final 11.8 db. After 9 mos the differences between groups don’t achivies SS. Increment :64,5% of cases. RS in the area mainly exposed to PL RS in the central 20° macula

Central 20° RT Central RT (3 mm) Mean % decrease of MT: 17 % (P<0,001) Initial MT: 406,1 micron.;Final MT: 359,3 micron Differences between groups don’t achivies SS Decrement in 90,3% of cases. Mean % decrease of CRT: 15 %. (P<0,001) Initial MT: 436,86 micron; Final MT: 383,2 micron Differences between groups don’t achivies SS Decrement in 93,5% of cases. Mean % decrease of sectorial RT :17% (P<0,001). Initial MT: 406,1 micron; Final MT: 359,3 micron Decrement in 93,5% of cases Differences between groups don’t achivies SS Decrement in 93,5% of cases. Results: RT of sector mainly exposed to PL

Conventional LPDL SPDL (Pascal) FS 30% Initial Value (IV):11.4 Db; Final value (FV):14.9 Db 21% (IV:10.9 Db; FV:12.5 Db). RS sector 24% IV: 10.6 Db; FV: 11.8 Db. 13% IV: 11,24 Db.; FV:12.42 Db. CRT 9% IV: 330,8; FV: 285,4 micron. 15% IV: 436,86; FV: 383,2 micron SRT 14% IV: 343,7 FV:286,2 micron. 17% IV: 406,1; FV: 359,3 micron BCVA 36% IV: 0,19; FV:0,03 logmar 59% (IV: 0.32; FV :0.12 logmar Finally comparing PL (0,02 msec) results at 9 months with those of a previous study conducted in Focal diabetic macular edema treated with LPDL (diode: 540 nm 0,2 msec) using light parameters, we have to puntualize that macular edema were less diffuse (sectorial) and less intense than in this new study and this might explain the better result of the former study on FS evolution. PL versus 540 nm longer pulse duration laser (LPDL):

Conclusions: In the Era of anti-VEGF therapies, FL treatment remains the only with proven longstanding efficacy in the management of DME, expecially if light sub-threshold parameters are employed as with PL. ( Always a better trend in G2 for each parameter even if not always SS). In the Era of anti-VEGF therapies, FL treatment remains the only with proven longstanding efficacy in the management of DME, expecially if light sub-threshold parameters are employed as with PL. ( Always a better trend in G2 for each parameter even if not always SS). MP1 FU shows the absence of any MS impairment. MP1 FU shows the absence of any MS impairment. PL, minimizing laser scar, can be considered effective and safe. PL, minimizing laser scar, can be considered effective and safe. Concluding PL is a valid instrument to perform MGL: results similar to LPDL with less structural and functional impact on photoreceptorial layers. Concluding PL is a valid instrument to perform MGL: results similar to LPDL with less structural and functional impact on photoreceptorial layers. Limits of this study: The Difference in baseline severity of CSDME in our two studies doesn’t allow a reliable direct comparison beetwen PL and LPDL.The Difference in baseline severity of CSDME in our two studies doesn’t allow a reliable direct comparison beetwen PL and LPDL.

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