Ira Seibel

Does ocriplasmin affect the RPE–photoreceptor adhesion in macular holes?

Background To evaluate the anatomical outcome of patients after vitrectomy due to persisting symptomatic vitreomacular traction (VMT), including full-thickness macular holes (FTMHs) of less than 400 µm, after ocriplasmin treatment. Methods Retrospective, single centre, consecutive interventional case series. Patients were treated with a single intravitreal injection of ocriplasmin (Jetrea, Thrombogenics Inc, USA, Alcon/Novartis EU). Main outcome measures: resolution of VMT, closure of FTMH and anatomical outcome of vitrectomy after unsuccessful treatment with ocriplasmin. Results Five patients were treated with ocriplasmin injection. VMT persisted in all but one case. Four patients underwent pars-plana vitrectomy (PPV) for treatment of persistent VMT and FTMH (n=2, size of macular hole <400 µm) in spectral-domain optical coherence tomography (SD-OCT). FTMHs were closed in both cases within the first week postoperatively. After PPV, in three eyes newly developed subretinal fluid was detected, which persisted up to several months postoperatively. Conclusions Data on ocriplasmin remain controversial. We report on four cases with resolution of VMT following PPV after unsuccessful ocriplasmin treatment. Newly developed subretinal fluid has been described after ocriplasmin treatment, predominantly in cases with resolution of VMT. We also detected this newly developed subretinal fluid after vitrectomy, which persisted for several weeks up to 7 months in two cases with FTMHs. This may be attributable to loosening of the photoreceptor complex due to enzyme activity of ocriplasmin. Long-term effects of ocriplasmin are still to be evaluated using SD-OCT.

Proton Beam Therapy of Parapapillary Choroidal Melanoma

PURPOSE To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy. DESIGN Clinical case series, retrospective study. METHODS We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups. RESULTS The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects. CONCLUSION Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients.

Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome

PURPOSE To evaluate the risk factors, recurrence rates, retreatments, and long-term patient outcomes following proton beam therapy for uveal melanoma. DESIGN Retrospective interventional case series. METHODS All patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charité-Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken. RESULTS Of 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals. CONCLUSIONS This study showed that each globe-retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured.

Salvage proton beam therapy in local recurrent uveal melanoma.

PURPOSE To evaluate survival and ocular outcome in recurrent uveal melanoma treated with proton beam therapy as salvage therapy. DESIGN Retrospective, interventional case series. METHODS We evaluated 48 patients with local recurrence of uveal melanoma after primary treatment with brachytherapy, transpupillary thermotherapy, proton beam therapy, laser photocoagulation, CyberKnife radiation, or photodynamic therapy. All patients received proton beam therapy as a salvage therapy at the Helmholtz Zentrum Berlin between July 2000 and December 2010. Kaplan-Meier analysis was used to obtain survival rates. RESULTS The Kaplan-Meier estimator for local tumor control was 92.1% at 10 years after secondary treatment with proton beam therapy. Local recurrence developed in 3 patients; 1 of them underwent enucleation. During follow-up, 20.8% of the patients died (16.7% of metastasis, 4.1% of other causes or not specified). The most frequent surgical interventions were phacoemulsification (20.8%) and pars plana vitrectomy (10.4%). The Kaplan-Meier estimators were 77.4% for survival and 70.1% for the absence of metastasis 10 years after the primary treatment. CONCLUSIONS Proton beam therapy as a salvage treatment resulted in high local tumor control rates in recurrent uveal melanoma, especially if the primary therapy was transpupillary thermotherapy or plaque brachytherapy. Preservation of the globe was possible in most patients. Enucleations were indicated only in case of re-recurrences of uveal melanoma, but not because of secondary complications like intractable pain or secondary glaucoma. Retreatment was associated with vision deterioration, but loss of vision remained exceptional. Further larger prospective studies are needed to confirm the presented results of our retrospective analysis.

Long-term results after proton beam therapy for retinal papillary capillary hemangioma.

PURPOSE To evaluate the potential benefit and risk of proton beam therapy in the treatment of symptomatic retinal papillary capillary hemangioma. DESIGN Retrospective interventional case series. METHODS This study included patients presenting with symptomatic exudative retinal papillary capillary hemangioma with or without association with von Hippel-Lindau disease. All patients were treated either as a first or a secondary treatment option by proton beam therapy between 2001 and 2009. The minimum follow-up was 30 months. RESULTS Eight eyes of 8 patients (3 male and 5 female, with a mean age of 36 years [range 22-80 years]) were treated for symptomatic papillary retinal hemangioma. The median interval between onset of macular edema and proton beam therapy was 1.7 months (range 0.5-3.3 months). The median follow-up period was 84 months (range 32-106 months) between proton beam treatment and last follow-up. Exudation completely resolved in all but 1 patient after 4.2 months on average (range 2.8-7.2 months). Mean visual acuity prior to proton beam irradiation was 0.7 logMAR (0.2 DIN (DIN 58220 norm)) (range 2-0.3 logMAR) and declined to 0.8 logMAR (0.16 DIN; range 2-0.1 logMAR) at last follow-up examination (no statistical significance, P=.071). CONCLUSION The anatomic outcome after proton beam therapy for retinal papillary hemangioma is convincing, whereas functional outcome may be compromised because of tumor location, long-persisting macular edema, extensive exudation, and poor initial visual acuity. In patients with extended retinal detachment surgical intervention was still necessary. Although proton beam therapy is proven to be a therapeutic option, treatment will remain challenging.

Magnetic resonance safety and compatibility of tantalum markers used in proton beam therapy for intraocular tumors: A 7.0 Tesla study.

Proton radiation therapy (PRT) is a standard treatment of uveal melanoma. PRT patients undergo implantation of ocular tantalum markers (OTMs) for treatment planning. Ultra‐high‐field MRI is a promising technique for 3D tumor visualization and PRT planning. This work examines MR safety and compatibility of OTMs at 7.0 Tesla.

Proton Beam Therapy Leads to Excellent Local Control Rates in Choroidal Melanoma in the Intermediate Fundus Zone

PURPOSE To evaluate long-term outcomes of proton beam radiotherapy in the treatment of choroidal melanoma of the intermediate zone of the fundus. DESIGN Retrospective interventional single-center study. METHODS The study was a retrospective analysis with long-term follow-up of 62 patients with a minimum tumor-to-disc and tumor-to-fovea distance of 2 mm of choroidal melanoma in the intermediate zone of the fundus. Mean values of tumor prominence, largest basal diameter, and tumor distances to the optic disc and fovea were 7.6, 12.8, 5.2, and 4.6 mm, respectively. All patients were irradiated with a total proton dose of 60 cobalt gray equivalents. RESULTS After proton beam radiotherapy, 71.0% of the patients received subsequent endoresection of the tumor. Only 18 patients (29.0%) did not require additional tumor resection and were analyzed as a separate group. For the total of patients, the median follow-up time was 70.3 months. The 5-year Kaplan-Meier rates of local tumor relapse, enucleation, and distant metastasis were 3.9%, 3.7%, and 13.4%, respectively. Cataract surgery was the most frequent secondary treatment in our cohort. CONCLUSIONS In this study we demonstrate the effectiveness of proton beam irradiation in tumor control and preservation of the globe in the analyzed patients. The rate of metastasis was not higher than previously described. Nevertheless, consecutive tumor surgery is frequently required to maintain the eye in patients with large-sized choroidal melanomas. In conclusion, proton beam radiotherapy allows preservation of the eye in mid-zone choroidal melanomas.

Endodrainage, Tumor Photocoagulation, and Silicone Oil Tamponade for Primary Exudative Retinal Detachment due to Choroidal Melanoma Persisting after Proton Beam Therapy

Background: Choroidal melanoma is frequently accompanied by an exudative retinal detachment that can persist after proton beam therapy. This study investigates whether vitrectomy without tumor resection improves the clinical outcome. Methods: This is a retrospective interventional case series. Twenty patients with choroidal melanoma with exudative retinal detachment involving the macula were treated by vitrectomy, endodrainage, photocoagulation, and silicone oil tamponade after proton beam therapy. Results: The mean follow-up was 38.4 months (median 21.5, range 12.0-122.0). The mean time between proton beam therapy and surgery was 4.5 months (range 0.1-9.2). Reattachment was achieved in 95% of the patients after one vitrectomy. One patient was lost to follow-up because enucleation was performed after 45.9 months due to a secondary glaucoma. Mean visual acuity decreased from 1.1 to 1.8 logMAR before vitrectomy and after 4 years, respectively. No patient showed local tumor recurrence. Metastatic disease was present in 1 patient after 15.2 months, and this patient died after 19.2 months. Conclusion: Vitrectomy is indicated after therapeutic proton beam irradiation in patients who present with persisting exudative retinal detachment involving the macula and high local or systemic risk factors for hemorrhagic complications, thus excluding endoresection.

Minimalinvasive Therapie der exsudativen Amotio nach Radiatio durch Vitrektomie und Endotamponade mit Laserung der Tumoroberfläche

Einleitung: Aderhautmelanome gehen oft mit einer visusbedrohenden, exsudativen Begleitablatio einher. Eine Endoresektion des Tumorgewebes ist bei zentralen Tumoren mit einer unabdingbaren Visusminderung, bei Ziliarkorpertumoren mit einer erhohten Blutungsgefahr verbunden. Diese Studie untersucht, ob die alleinige Vitrektomie mit Endodrainage und Silkonoltamponade in Kombination mit einer intraoperativen Laserung der Tumoroberflache zu einer dauerhaften Netzhautanlage fuhren kann. Methodik: Es wurden 26 Patienten mit choroidalen Melanomen (n=24 mit AHMM, n=2 mit AHZKMM) untersucht, die im Zeitraum von 2003–2011 nach Protonentherapie (N=24) oder Ruthenium (n=2) bei persistierender, exsudativer Ablatio eine PpV mit Silikonoltamponade erhalten haben. Untersucht wurden Tumorkontrolle, Visus, Netzhautanlage und Komplikationen. Ergebnisse: Follow-Up Zeit betrug im Median 17,1 Monate (4,2–95,1) Monate. Die Tumorprominenz betrug im Median 6,1mm bei einem maximalen Durchmesser von 14,4mm vor Bestrahlung. Im Follow-Up lag die Prominenz bei 3,4mm (p<0,004). Die Zeit zwischen Protonen/Ruthenium und PpV lag bei durchschnittlich 4,2 Monaten, nach durchschnittlich 7,5 Monaten wurde das Ol wieder entfernt. Die Netzhaut lag bei 11 (n=13) Patienten nach primarer Olentfernung dauerhaft an, bei den 2 Patienten nach Re-PpV und Gas auch dauerhafte Netzhautanlage. Im Follow-Up nach 17,1 Monaten ist bei 13 Patienten noch die Oltamponade vorhanden, alle Patienten mit Netzhautanlage. Der initiale Visus lag bei 0,3 nach DIN, im Follow-Up nach 17,1 Monaten bei 0,1. Eine lokale Tumorkontrolle wurde bei allen Patienten erreicht. Es wurde eine Enukleation wegen eines nicht beherrschbaren Sekundarglaukoms durchgefuhrt, weitere schwere Komplikationen traten nicht auf. Diskussion: Das „minimal invasive“ Vorgehen fuhrte bei diesem Patientenkollektiv zu einem anatomisch zufriedenstellenden Ergebnis mit guter Tumorkontrolle. Weitere Untersuchungen sollen helfen, die Patientengruppe, bei der dieses Vorgehen erfolgversprechend ist, einzugrenzen