Vitreoretinal surgical management In ocular oncology

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www.ophtalmique.ch Vitreoretinal surgical management In ocular oncology Pournaras Jean-Antoine C Vitreoretinal Surgery Unit

1. Surgical resection after proton beam therapy 2. Ocular Biopsy 3. RD in advanced Retinablastoma

www.ophtalmique.ch Surgical tumor resection after proton beam therapy

Conservative treatment of uveal melanomas COMS study 1986-2001 Enucleation : 660 cases 125 I brachytherapy : 657 cases Absence of similar study on surgical management

Three lines treatment 1. Tumor Control 2. Eye retention probability 3. Functional result

1. Sterilization of tumor site Proton Beam Radiotherapy Local tumor control 91% before 1993 96% 1989-1993 98.8% after 1998 n = 2435 MM Egger et al. Int J Radiat Oncol Biol Phys 2001

Proton beam irradiation 10 years Local tumor control 98.8 % Eye retention probability 95.6 % 94-05 94-05 88-93 88-93 84-87

Complications Radiation induced retinopathy and maculopathy Secondary Neovascular Glaucoma

Toxic Tumor Syndrome caused by the presence of a large volume of irradiated tumor either because it becomes ischemic or because it causes extensive retinal detachment or both Inflammatory cytokines release Exudation from irradiated / incompetent vessels VEGF from ischemic tissue

2. Management of complications Panphotocoagulation Anti-VEGF, Corticosteroids Secondary enucleation VR surgery exoresection / endoresection of toxic tumor

Exoresection Indications: large tumor size, anterior location, exudative retinal detachment Two matched group studies have reported that with large tumors, better results after exoresection than after iodine plaque radiotherapy Kivelä et al. Ophthalmology 2003;Bechrakis et al. Ophthalmology 2002 Complex surgery; rarely use Adjunctive brachytherapy or proton beam therapy Excision of tumor with internal scleral lamellae Risk of recurrence 50% in external scleral lamellae Damato et al. 2012

Primary Endoresection Endoresection Damato et al. BJO 1998; Garcia-Arumi et al. Retina 2001; Garcia-Arumi et al. BJO 2008; Konstantinidis et al. BJO 2014 small case series short follow-up period recent study concern <12mm in 90 % cases observation required Impossible to attest complete resection If tumor recurrence, higher mortality rate Neoadjuvant combined radiotherapeutic-surgical approach Bornfeld et al. 2002; Bechrakis et al.2006

Endoresection: Surgical technique 1 23 G pars plana vitrectomy 2 retinotomy over the tumor 3 piecemeal tumor removal (increased intraocular pressure) 4 endodiathermy to the margins 5 fluid air exchange to flatten the retina 6 endolaser retinopexy to attach retina around tumor site 7 air silicone exchange to maintain retinal flattening and to prevent postoperative hemorrhage Peyman et al. 1988; Damato et al. BJO 1998

Case 1. Toxic tumor syndrome Complex surgery Common retinectomy and tumorectomy 1 or more surgeries Phtisis

Case 2: Massive ischemia, extensive exudative RD Man, 44 yo Thickness 8.2 60Gy in 4 fractions (2.2012) Indication: progression exsudative RD Intravitreal hemorrhage 2.2013

Surgery 2.2013

9.2013

Case 3: Knapp- Ronne type Man, 48 yo 60Gy in 4 fractions Indication: Risk progression exsudative RD Risk Intravitreal hemorrhage Tumorectomy +Silicon oil 5.2013 Silicon oil removal 8.2013

Case 4: Recurrent vitreous hemorrhage Woman, 42 yo Thickness 6.1mm Vx silicon oil 25-28.1.2012 60Gy in 4 fractions (27.2-2.3.2012) Tumorectomy 12.6.12 Phaco + silicon oil removal 23.10.12 VA 0.8 cc 2014

Endoresection: Indications Risk of hemorrhage, pigment dispersion, retinal infiltration early tumorectomy Risk of hemorrhage, pigment dispersion, retinal infiltration Without previous episode No changes at 3 or 6 months: wait for tumor regression 3 to 6 months tumorectomy Any tumor with diffuse exudative RD, lipid deposits, necrosis, excessive inflammation early tumorectomy

Diagnosis and Prognosis Primary vitrectomy Transillumination gives information about basal infiltration in order to define tumor borders, impeded by vitreous hemorrhage 1. US of tumor with AL calculation. 2. Vx + silicon oil (particles speed modified in silicon oil) 3. Proton beam therapy 4. Silicon removal + Vx + tumorectomy + silicon oil 5. Removal of silicon oil

Conclusions 1. Local tumor control Primary vitrectomy may be discussed in vitreous hemorrhage cases without tumorectomy 2. Secondary Endoresection Development of VR instrumentation Surgery may become essential in tumor management Oncologists decision with high variability among centers

Ocular biopsy www.ophtalmique.ch

Role of biopsy Diagnostic tool when all investigations failed and if management may be influenced Biospy reveals 50% Choroidal melanoma 50% uveal metastasis Molecular and genomic analysis Characterisation of the tumor (cell type, mutational status) Prognostic information monosomy 3 + 8q gain in choroidal melanoma are clinically relevant and strongly associated with metastatic disease and death Prescher et al. Lancet 1996; White et al. Cancer 1998; Scholes et al. IOVS 2003; Cassoux et al. 2013 Targeted therapy

Biopsies Transcleral choroidal biopsy Transvitreal choroidal biopsy Fine Needle Aspiration Biopsy

Transcleral biopsy Indications: If access to the tumor (avoid VR complications) Benign tumor or adjuvant radiotherapy should be performed Do D, Nguyen QD. In Ryan, Retina, 5th.

Transcleral biopsy Dissection of 6 6 mm scleral flap, nearly full-thickness and hinged (usually posteriorly) Near Full-thickness scleral flap is retracted biopsy specimen is grasped at one edge Incision of choroidal tissue with a sharp blade. Scissors may be used to complete the dissection Careful separation of the retina from the choroid Suture of the scleral flap Pericard patch Do D, Nguyen QD. In Ryan, Retina, 5th. Vitrectomy reduces bulging of the retina during procedure Peyman et al. 1978

Transvitreal biopsy Indications: no access by transcleral route posterior plan tumor malign tumor lead directly to enucleation / RX / Chimioth without dispersion by transcleral approach

Transvitreal biopsy Pars plana vitrectomy Endolaser around the margins of the intended biopsy site Increased intraocular pressure Retinotomy Biopsy of the tumor Fluid/gas exchange, 20% SF6 A newly developed instrument, the Essen biopsy forceps was reported to be effective in the diagnosis of choroidal tumors in 20 patients Bechrakis et al. 2002; Akgul et al. BJO 2011

photo

Photo avant après

Film 1

Intraocular metastasis of pulmonary adenocarcinoma (cords and ductal structures; TTF1 +; naspin A +)

Film 2

Marginal zone B cell lymphoma

Fine-needle biopsy Extensively used in the diagnostic evaluation including tumors of the orbit and eye Major concern about risk of dissemination No tumor dissemination along the needle track, no such occurrence has been documented with a needle of 25G or finer McCannel et al. Ophthalmology 2012 As diagnostic tool, no histological information, only cytology Prognostic informations

Fine-needle biopsy: surgical technique 22G 30G needles for intraocular aspiration Jakobiec et al. 1979; Augsburger JJ, Shields JA, et al. 1985 Needle length depends on tumor intraocular location of the tumor and planned biopsy route Biopsy needle is connected to a plastic disposable aspirating syringe via a standard plastic tubing

Complications Usual vitreoretinal surgery complications increased intraocular pressure Cataract progression Peripheral retinal tears Retinal detachment Choroidal hemorrhage Vitreous hemorrhage Endophthalmitis Exacerbation of the underlying inflammatory disease Proliferative vitreoretinopathy Young TA, et al. AJO 2008

Conclusions No diagnosis by current modalities (clinical observation, angiogram, ulttrasonography) Biopsy is recommended if there is substantial likelihood that the results will improve patient management These procedures can be safely performed by retina surgeons according to experienced oncologists