LOW FLUENCE PHOTODYNAMIC THERAPY (PDT-BF) IN CHRONIC CENTRAL SEROUS CHORIORETINOPATY (CSC): SD-OCT EVOLUTION AND ITS FUNCTIONAL IMPACT. LOW FLUENCE PHOTODYNAMIC THERAPY (PDT-BF) IN CHRONIC CENTRAL SEROUS CHORIORETINOPATY (CSC): SD-OCT EVOLUTION AND ITS FUNCTIONAL IMPACT. G.F. Pacelli, C.Pisano, L. Baraggia, B. Pacelli, V. Ferrara, V. Belloli, Arona ITALY 12th EURETINA Congress September 2012, Milan,Italy

Chronic Central Serous Chorio-Retinopathy (CSC). Chronic failure of macular Retinal Pigment Epithelium (RPE) & secondary sierous neuro-retinal detachment (SNRD) from fluid coming out through, focal or more often multifocal, permeability defects of RPE. Bilateral in 40% of cases. Disk materials accumulation

EPIDEMIOLOGY: - Higher Prevalence in male (72-88%), Peak age: 45 years. - Fourth in incidence among non surgical retinopathy. - Stress - Type A Personality. - Endogenous or exogenous hyper cortisolism (Cushing Syndrome; Sistemic Corticosteroids th. -Malignant hypertension and Toxemia in pregnancy - Renal failure (Hemodialysis) -Organ transplant - LES,. Polyarteritis nodosa - Wegener Granulomatosys -Use of Ecstasy- A S S O C I A T I O N S R Brancato et al, Graefe’s Arch 1987 R. Levine et al, Ophthalmology 1989 E. Y. Yap et al, Arch Ophthalmol Become chronic in 5% of cases - Recurrence in 45-50% of cases. - Spontaneous resolution in 3-4 months, Good visual recovery.

Acute CSC Chronic CSC years later. Guide to LASER therapy FLUORESCEIN ANGIOGRAPHY (FA): RPE INVOLVEMENT AND CLINICAL CHARACTERIZATION OF THE DISEASE

ICGa ANGIOGRAPHY : Choroideal involvement -Primary alterations of the Choroid. -Primary alterations of the Choroid. - Choroideal perfusion defects - Choroideal vascular Hyper-permeability A. Scheider et al, Am J Ophthalmol 1993 F. Cardillo Piccolino et al, Retina 1994 D. R. Guyer et al, Arc Ophthalmol, 1994 Acute CSC Chronic CSC Guide to PDT therapy

PRCL conditions directly correlated with fuctional recovery after SRD resolution. Scarso o nessun Recupero finzionale. SD-OCT: photoreceptor cell layer (PRCL) involvement. Thickening Granulation Atrofia photoreceptor Atrophy complete fuctional recovery Scarse or none functional recovery Cardillo Piccolino et al. - Am J Ophthalmol, 2005; 139:87 complete or partial functional recovery

To the current state of the art, there isn’t a “gold standard” therapy for chronic central serous chorio-retinopathy. Recently PDT proved to be effective in: reducing neuroretinal serous detachment improving BCVA. PDT cause:1) choriocapillar endothelial damage ( trombosys of the lumen). 2) choriocapillar Transient hypoperfusion. 3) Choroideal Vascular remodeling ( long term period ), 4) Reduction in congestion and secondary extravascular leakage. However described not negligible complications1) CNV development. 2) Persistent choriocapillar ischemia. 3) RPE atrophy in exposed areas. Recently developed modified protocols of PDT ( half dosage of veterporfine, reduced fluence PDT). Low fluence PDT results are surely promising as several clinic study has allready demonstrated.

Minimal Choroideal hypoperfusion in eyes treated with low fluence PDT of 25 J/cm 2. The majority of patients treated with Standard PDT (50 J/cm 2) showed an important choriocapillar hypoperfusion one week later that persisted up to three months Invest Ophthalmol Vis Sci. 2006;47:371–376

Materials and Methods: CSC: 22 eyes of 19 consecutive patientsCSC: 22 eyes of 19 consecutive patients 14 ♂ e 5 ♀; mean age 64 yrs; Mean FU: 12.5 mos).14 ♂ e 5 ♀; mean age 64 yrs; Mean FU: 12.5 mos). SRD Onset > 6 months ;SRD Onset > 6 months ; LOW-FLUENCE PDT LOW-FLUENCE PDT (25 J/cm2); Mean of treatments: 1.2 Treatment Strategy guided by: Angiography (FA&ICGa). Evaluation at baseline and quarterly later on: BCVA log (ETDRS charts).BCVA log (ETDRS charts). SD-OCT RMT ( eye tracking system ).SD-OCT RMT ( eye tracking system ). After 6 months of follow up: Microperimetry with central 20° strategy pattern.After 6 months of follow up: Microperimetry with central 20° strategy pattern. FA & ICGa repeated in case of clinical unsuccess after 3-6 months. FA & ICGa repeated in case of clinical unsuccess after 3-6 months. Statistic Significativity: calculated comparing trated area parameters with diffuse macular sensitivity with Wilcoxon Test for paired datas (reference values P=0.001).

BCVA: 0.3 logmar chronic CRC : ♂ 51 years old, SNRD for >8 months; follow-up 15 months F-U 15 months BCVA: 0.0 logmar

BCVA: 0.38 logmar BCVA: 0.2 logmar Chronic CSC : ♂ 31 years old; First episode 10 years later (5 recurrences): Macular SRD for > than 10 mos F-U 15 mos BCVA: 0.2 logmar

Chronic CSC : ♀ 76 years old, SRD for 6 months without resolution. BCVA: 0.14 logmar BCVA: 0.0 logmar 12 months later

Mean percentage increment (%) of BCVA : 58% (P<0.001*). Initial BCVA : 0.36 log.;Final BCVA: 0.21 log. Increment in 89.5 % of cases. ( 2 stable) Mean percentage Reduction of RMT: 31 % (P<0.01*). μm μm MEAN Initial RMT: 475 μm. Final mean RMT: μm. Reduction in 94 % of cases. No significant differences between sensitivity in the treated area compared to mean global sensitivity except in rare cases of preexisting alterations of RPE integrity on Autofluorescence and/or deep photoreceptor layers atrophy on SD-OCT.Results:

Conclusions: The good results of our study, even with the limitations related to the absence of a control group, confirmed the effectiveness and safety of Low Fluence PDT in the treatment of chronic CSCR. The older age of our cohort confirm the efficacy of LF- PDT even if some patients allready had important RPE distrophy. Only three patients experimented a single recurrence none of these located in the same area ( 1 treated with extrafoveal direct laser, 1 with PDT and the last one left untreated for diffuse RPE distrophy without any angiographic leakage). Thanks for your attention!!.

BCVA: 0.56 logmar BCVA: 0.7 logmar Chronic CRSC: ♂ 56 years old, SNRD for almost 1 year; follow up 6 months

Chronic CRSC: ♂ 51 yrs old, SNRD for 10 months without resolution. BCVA: 0.2 logmar BCVA: 0.02 logmar

Chronic CRSC : ♂ 59 anni, SNRD for 14 mos; follow up 20 monhts BCVA: 0.38 logmar BCVA: 0.26 logmar

Terapia delle CRSC Acetazolamide Fotocoagulazione laser Beta-bloccanti Termoterapia transpupillare (TTT) Terapia fotodinamica (PDT)

Retinal involvement -Detection of subretinal exudation. -Condition of the photoreceptor layer. SD-OCT: ELM IS/OS Disc material