Influence of Ranibizumab versus laser photocoagulation on radiation retinopathy (RadiRet) - a prospective randomized controlled trial.

PURPOSE: To demonstrate superiority of intravitreal ranibizumab 0.5 mg compared to focal and peripheral laser treatment in patients with radiation retinopathy for choroidal melanoma. METHODS: Inclusion criteria were as follows: patients with radiation retinopathy and visual acuity impairment due to radiation maculopathy accessible for laser therapy, age ≥ 18 years, and BCVA less than 20/32. The main objective was to study the change in best-corrected visual acuity (BCVA) over 6 months from ranibizumab 0.5 mg (experimental) compared to focal laser of the macula and panretinal laser treatment of the ischemic retina (control) in patients with radiation retinopathy in choroidal melanoma. The secondary objectives of the radiation retinopathy study were to compare functional and anatomical results between ranibizumab and laser group over 12 months and to measure the frequency of vitreous hemorrhage and rubeosis iridis. RESULTS: The intention-to-treat analysis included 31 patients assigned to ranibizumab (n = 15) or laser treatment (n = 16). In terms of BCVA at month 6, ranibizumab was superior to laser treatment, with an advantage of 0.14 logMAR, 95% CI 0.01 to 0.25, p = 0.030. The positive effect of ranibizumab disappeared after treatment was discontinued. Similar results without statistically significant difference were found with respect to macular thickness. In both groups, no change was observed at month 6 in the size of ischemia in the macula or periphery compared to baseline. There was 1 case of vitreous hemorrhage in the laser group and no case of rubeosis iridis over time. CONCLUSIONS: This study showed a statistically significant improvement in visual acuity and clear superiority of ranibizumab compared to laser treatment up to 26 weeks, but this effect disappeared at week 52 after completion of intravitreal treatment. Ranibizumab and PRP are considered equivalent in terms of the non-appearance of proliferative radiation retinopathy during the study. TRIAL REGISTRATION: EudraCT Number: 2011-004463-69.

Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve.

PURPOSE: To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic neuropathy, radiation-induced retinopathy, iris neovascularization, secondary glaucoma, enucleation, and local tumor control after proton beam therapy (PBT) of choroidal melanoma. METHOD: Retrospective analysis of 1129 patients, who received primary PBT for the treatment of choroidal melanoma with a dose of 60 cobalt gray equivalents (CGE) between 1998 and 2013 at the Helmholtz-Zentrum Berlin, Germany. Kaplan-Meier curves and logrank test have been used for time-to-event analyses. Adjustment for potential confounders was done using multiple Cox regression models with forward and backward selection. RESULTS: We found a significant correlation between the irradiated length of the optic nerve and the dose to the optic disc (correlation coefficient, 0.93). Multivariate Cox regression revealed the dose to the optic disc as an independent predictive risk factor for the development of radiation-induced optic neuropathy (p < 0.001, HR 1.023, 95 CI 1.016-1.029), iris neovascularization (p < 0.001, HR 1.013, 95% CI 1.008-1.019), secondary glaucoma (p < 0.001, HR 1.017, 95% CI: 1.011-1.023) and enucleation (p < 0.001, HR 1.037, 95% CI 1.020-1.053). The irradiated length of the optic nerve was not a statistically independent predictive risk factor in multivariate analysis. CONCLUSION: Our data implicate the predominance of the dose to the optic disc over the irradiated length of the optic nerve regarding radiation-induced optic neuropathy, iris neovascularization, secondary glaucoma, and enucleation.

[Pharmacotherapy of Non-neovascular AMD]. / Medikamentöse Therapieansätze für die nicht neovaskuläre AMD.

BACKGROUND: Non-neovascular age-related macular degeneration (AMD) is not yet treatable. This article summarises current clinical research approaches. The reasons for the current lack of success are analysed. METHODS: Literature and databank search. RESULTS: The number of therapeutic approaches and mechanisms is limited. Only reduction in lipofuscin containing deposits is specific for AMD. Further approaches include modulation of inflammation and neuroprotection. Confirmatory studies have failed to demonstrate efficacy in AMD, i.e. slowing or stopping AMD progression. DISCUSSION: To increase the probability of success for future developments, the pharmacological target space needs to be broadened. This may be achieved by application of molecular network analyses. As visual acuity is commonly not primarily affected by non-neovascular AMD, research on patient perspective is required to define reasonable target profiles for future therapies.

Quantification of radiation retinopathy after beam proton irradiation in centrally located choroidal melanoma.

PURPOSE: To localize and quantify ischemic changes induced by proton beam irradiation of central choroidal melanoma and to identify baseline predictors correlated with the extent of ischemic changes. METHODS: Retrospective chart review of patients with central choroidal melanoma treated by proton beam irradiation and conducted widefield fluorescein angiography (≥ 20 months after radiation therapy). Quantification and location of ischemic areas and correlation to baseline predictors. Multiple linear regression model was performed for analyses. RESULTS: Twenty-five eyes from 25 patients were included in final analysis. Mean largest basal tumor area was 56.6 ± 40.0 mm2 and mean maximal tumor prominence 2.5 ± 1.4 mm. Mean total radiated area was 339.1 ± 68.3 mm2. All patients showed ischemic changes. Mean ischemic area was 387.6 ± 123.3 mm2 and mean ischemic index (ischemic area/total visible area) was 0.53 ± 0.23. Twenty-two patients (88%) presented ischemic changes outside of the irradiation field, which comprised of 23% of total ischemic area. Mean angular distance between lateral border of irradiation field and ischemic area outside of the radiated area was 44.8 ± 36.5°. Multivariable analysis revealed a positive correlation of total ischemic area with total radiated area (p = 0.02) and initial sonographic tumor prominence (p = 0.02). CONCLUSIONS: Ischemic changes induced by proton beam irradiation of central choroidal melanoma were localized and quantified. Ischemic changes exceed the tumor area distinctly and are found also outside of the irradiation field in the majority of patients. Size of irradiation area and tumor prominence are positively correlated with extent of ischemic area.

Salvage proton beam therapy for recurrent iris melanoma: outcome and side effects.

PURPOSE: This study aims to analyze the effect of salvage proton beam therapy for the treatment of recurrent iris melanoma. METHOD: In this clinical case series, we retrospectively analyzed the data of eight patients who underwent proton beam therapy of the whole anterior segment as salvage therapy between 2000 and 2016 for recurrent iris melanoma after resection, ruthenium brachytherapy, or sector proton beam therapy. Two patients received salvage proton beam therapy for repeated tumor relapse. All patients were observed and prepared for proton beam therapy at the Charité and irradiated at the Helmholtz-Zentrum Berlin where they received 50 cobalt Gray equivalents (CGE) in four daily fractions. We investigated survival rates and ocular outcome. RESULTS: Median follow-up after salvage proton beam therapy was 39 months. No local recurrence was detected during follow-up. One patient died from hepatic metastases 5.5 years after salvage therapy. Secondary glaucoma occurred in seven out of eight patients during follow-up. Two patients had chronic corneal erosion and two other patients presented with corneal decompensation, necessitating Descemet membrane endothelial keratoplasty (DMEK), and perforating keratoplasty. Median visual acuity was 0.2 logMAR before salvage proton beam therapy and 0.7 logMAR at the end of follow-up. CONCLUSION: Whole anterior segment salvage proton beam therapy has effectively controlled recurrent iris melanoma in our patients, but has been associated with a high incidence of radiation-induced corneal impairment and secondary glaucoma requiring extensive secondary treatment.

Neoadjuvant proton beam irradiation vs. adjuvant ruthenium brachytherapy in transscleral resection of uveal melanoma.

BACKGROUND: Uveal melanoma is the most common primary ocular malignancy in adults in the USA and Europe. The optimal treatment of large uveal melanoma is still under debate. Radiation therapy has its limitation due its eye-threatening secondary complications and is therefore often combined with surgical excision of the tumor. METHODS: In a retrospective interventional review, we evaluated in total 242 patients with uveal melanoma that underwent transscleral tumor resection with a predefined protocol, either with adjuvant ruthenium brachytherapy (Ru-106 group, n 136,), or with neoadjuvant proton beam therapy (PBT group, n 106). Kaplan-Meier estimates with log-rank test were used to show survival curves and a multivariable Cox regression model was used to calculate adjusted rate ratios. RESULTS: Local tumor recurrence rates after 3 and 5 years were 4% (95% CI 1.2-17.8%) and 9.1% (95% CI 2.9-27.3%), respectively, in the PBT group and 24.6% (95% CI 15.8-37.1%) and 27.5 (95% CI 17.8-41.1%), respectively, in the Ru-106 group. This leads to an overall recurrence rate almost 4 times higher in the Ru-106 group compared to the PBT group. After adjusting for the a priori confounders and the tumor distance to optic disc and ciliary body infiltration, the adjusted risk of tumor recurrence was 8 times (RR 7.69 (2.22-26.06), p < 0.001) higher in the Ru-106 group as compared to the PBT group. Three- and 5-year metastatic rates were 23.2% (95% CI 5.6-37.1%) and 31.8% (95% CI 20.7-46.8%), respectively, in the PBT group and 13.2% (95% CI 6.8-24.9%) and 30.3% (95% CI 18.3-47.5%), respectively, in the Ru-106 group. There was no statistically significant difference in the overall metastasis rate between the two groups even after adjusting for possible confounders. CONCLUSION: Transscleral resection of large uveal melanomas combined with neoadjuvant proton beam therapy leads to a lower local tumor recurrence rate compared to transscleral tumor resection with adjuvant ruthenium brachytherapy. There was no statistically significant difference in the occurrence of rubeosis iridis, neovascular glaucoma, and in the need for enucleation later on.

[Peripheral Ischemia in Diabetic Retinopathy and Retinal Vein Occlusion: New Insights with Ultra-Wide-Angle Fundus Imaging and Wide-Angle Fluorescein Angiography]. / Periphere Ischämie bei diabetischer Retinopathie und retinalen Venenthrombosen: neue Einblicke durch die Ultraweitwinkelfundusfotografie und Weitwinkelangiografie.

BACKGROUND: In several diseases such as diabetic retinopathy and retinal vein occlusion, relevant pathophysiological changes take place in the retinal periphery. These changes may determine the prognosis and outcomes of therapy. Recent ultra-wide-angle camera systems promise improved and simplified visualisation of the outer periphery of the retina. This could potentially lead to novel clinical applications of these methods, with potential impact on therapy decisions. MATERIAL AND METHODS: Literature and database research on ultra-wide imaging for diabetic retinopathy and retinal vein occlusion. RESULTS: With ultra-wide-angle angiography, it is possible to visualise up to 3.2-fold more retinal surface than conventional 7SF images (7SF: 7 standard field). Initial studies imply that diabetic changes can be found outside of the boundaries of the 7SF images. Patients with central vein occlusion have more extended and severe macular oedema and poorer visual acuity if ischemia of the periphery is more pronounced (measured by the ischemic index [ISI]). The amount of ischemia influences the size of the macular oedema, its resolution under therapy and the number of anti-VEGF injections needed to treat it. DISCUSSION: Ultra-wide-angle camera systems allow visualisation of the peripheral retina outside the boundaries of standard methods. Initial studies have detected potentially relevant changes in the outer periphery, which would have been missed by 7SF. Nevertheless, there have been no systematic studies on the relevance of these changes with regards to prognosis and therapeutic decisions.

[Peripheral Exudative Haemorrhagic Chorioretinopathy: Course of Disease and Diagnosis - Including Wide-field Imaging of Associated Diseases Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy, Therapy]. / Peripher exsudative hämorrhagische Chorioretinopathie: Krankheitsverlauf, Diagnosestellung inklusive Weitwinkelbildgebung der assoziierten Erkrankungen altersabhängige Makuladegeneration und polypoidale Choriovaskulopathie, Therapie.

PEHCR (peripheral exudative haemorrhagic chorioretinopathy) is a disease manifested clinically, particularly by subretinal bleeding, retinal exudates, retinal pigment epithelium detachments (RPE detachments), exudative retinal detachment and sub-RPE bleeding. The PEHCR lesion is often characterized by its polypoidal pattern, which is very similar to PCV (polypoidal choroidal vasculopathy) polyps. Diagnosis is best made with a wide-field ICGA (indocyanine green angiography). In approximately half of patients, macular changes in the form of drusen, up to exudative AMD (age-related macular degeneration), are detected in the affected eye or partner eye. Since there is very little literature directly available on PEHCR, this work also discusses the peripheral changes described in the context of AMD that were investigated with wide-field imaging.

[Ultra-Wide Field Retinal Imaging and Angiography in the Differential Diagnosis and Therapeutic Decisions in Vascular Diseases of the Peripheral Retina]. / Ultraweitwinkel-Fundusfotografie und -angiografie in der Differenzialdiagnose und zur Therapieplanung bei peripheren vaskulären Netzhauterkrankungen.

Investigation of vascular diseases of the peripheral retina requires imaging procedures that allow a comprehensive view of the periphery, as well as reproducible pictures. In particular, ultra-wide field fluorescence angiography facilitates diagnosis, therapeutic decisions and follow-up examinations. While vasculopathies such as Coats disease and familiar exudative vitreoretinopathy are diagnosed within the first and second decade of life, patients' compliance during fundus imaging is typically reduced within this age range. Compared to the repeated imaging procedures for composite formation, ultra-wide field imaging has significantly reduced recording time. Nevertheless, current imaging systems are not able to map the entire retina in scaled proportions. Therefore, the imaging frame must be guided by patients' gaze onto the affected retinal area. Moreover, the medical photographer must be aware of the clinical setting and the region of interest. Hence, previous detailed funduscopy by trained ophthalmologists will remain indispensable.

[Multimodal Imaging of the Choroidal Melanoma, with Differential Diagnosis, Therapy (Radiation Planning) and Follow-up]. / Multimodale Bildgebung des Aderhautmelanoms mit seinen Differenzialdiagnosen, Therapie (Bestrahlungsplanung) und Verlaufskontrolle.

Imaging of intraocular tumors is multimodal, multi-purpose, and in continuous development. Therefore, imaging is indispensable for the detection, diagnosis, therapy and monitoring of intraocular tumours. A broad spectrum of imaging procedures is available for diagnostic testing and follow-up. This includes colour image acquisition, infrared imaging, autofluorescence imaging, fluorescence and indocyanine green angiography, optical coherence tomography (OCT) and sonography (US). In this article, the various investigations and their benefits are described using individual examples for the differential diagnosis of choroidal melanoma and retinal vascular tumours located in the fundus periphery.

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

PURPOSE: 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. METHODS: MR safety assessment included deflection angle measurements (DAMs), electromagnetic field (EMF) simulations for specific absorption rate (SAR) estimation, and temperature simulations for examining radiofrequency heating using a bow-tie dipole antenna for transmission. MR compatibility was assessed by susceptibility artifacts in agarose, ex vivo pig eyes, and in an ex vivo tumor eye using gradient echo and fast spin-echo imaging. RESULTS: DAM (α < 1 °) demonstrated no risk attributed to magnetically induced OTM deflection. EMF simulations showed that an OTM can be approximated by a disk, demonstrated the need for averaging masses of mave = 0.01 g to accommodate the OTM, and provided SAR0.01g,maximum = 2.64 W/kg (Pin = 1W) in OTM presence. A transfer function was derived, enabling SAR0.01g estimation for individual patient scenarios without the OTM being integrated. Thermal simulations revealed minor OTM-related temperature increase (δT < 15 mK). Susceptibility artifact size (<8 mm) and location suggest no restrictions for MRI of the nervus opticus. CONCLUSION: OTMs are not a per se contraindication for MRI. Magn Reson Med 78:1533-1546, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Neovascular glaucoma after proton beam therapy of choroidal melanoma: incidence and risk factors.

PURPOSE: To analyze the risk factors for the development of neovascular glaucoma (NVG) of patients with choroidal melanoma after proton beam therapy (PBT). METHOD: Clinical case series, retrospective study. We evaluated 629 consecutive patients receiving proton beam therapy for the treatment of a choroidal melanoma at the oncology service at Charité, Berlin and Helmholtz-Zentrum, Berlin between 05/1998 and 11/2008 regarding the development and risk factors of NVG. Patients with tumor resection, salvage proton beam therapy for recurrent disease and known glaucoma of other origin were excluded from the cohort. RESULTS: Of the 629 patients matching the inclusion criteria, 20.8% developed neovascularization of the iris after a mean time of 2.0 years (range 0.45 to 8.4 years) after PBT. Forty-seven percent of the patients with a neovascularization of the iris developed NVG after a mean time of 2.0 years after PBT, ranging from 5 months to 11.6 years. Univariate analysis revealed tumor height [p < 0.001, hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.36-5.35 for tumors >6 mm ≤9 mm and 11.32 (4.03-31.73) for tumors >9 mm], distance of the tumor to the optic disc (p < 0.001, HR: 0.43, 95% CI: 0.24-0.77 for >0 mm ≤3 mm and HR: 0.13, 95% CI: 0.04-0.37 for >3 mm), dose to the ciliary body (p < 0.001, HR: 9.21, 95% CI: 5.08-16.71 (21-40 cobalt gray equivalents (CGE), HR 27.23, 95% CI: 6.33-116.97 (41-60 CGE)), dose to the optic disc (p < 0.001, HR: 3.53, 95% CI: 1.11-11.27 (21-40CGE), HR: 5.37, 95% CI: 2.72-10.63 (41-60CGE)), the irradiated length of the optic nerve (p < 0.001, HR: 4.48, 95% CI: 2.47-8.13) and diabetes mellitus (p < 0.05, HR: 2.53, 95% CI: 1.4-4.5) were found to be risk factors for the development of NVG. Multivariate regression analysis identified the dose to the ciliary body [p < 0.001, HR: 4.39, 95% CI: 2.28-8.44 (21-40 CGE), HR: 11.04, 95% CI: 1.97-61.69 (41-60 CGE)], the irradiated length of the optic nerve (p < 0.001, HR: 3.88, 95% CI: 2.11-7.16), the existence of diabetes mellitus (p < 0.01, HR: 1.28, 95% CI: 1.24-4.21) and tumor height [p < 0.05, HR: 2.28, 95% CI: 1.17-4.83 (>6 mm ≤9 mm), HR: 3.74, 95% CI: 1.05-13.23, (>9 mm)] to be independent risk factors for the development of NVG. CONCLUSIONS: In the present analysis we found tumor height, dose to the ciliary body, irradiated length of the optic nerve and diabetes mellitus to be risk factors for the development of NVG. Whenever possible, critical structures of the anterior and posterior segment should be spared by beam shaping or changing of the beam entry angle.

Predictive risk factors for radiation retinopathy and optic neuropathy after proton beam therapy for uveal melanoma.

PURPOSE: This study was performed in order to evaluate the incidence of radiation retinopathy and optic neuropathy occurring after proton beam therapy for uveal melanoma. METHODS: Included in this study were all patients who had been treated with primary proton beam therapy for uveal melanoma at the oncology service between May 1998 and June 2014 with a minimum follow-up of 12 months. Excluded were all patients who underwent re-irradiation, or vitrectomy due to exudative retinal detachment or for tumor-resection. RESULTS: During this period, 1127 patients matched the inclusion criteria, of whom 768 (68.1 %) and 463 (41.0 %) developed radiation retinopathy and optic neuropathy after a median time of 18.9 months (2.0-99.84 months) and 19.8 months (0.2-170.4 months), respectively. Mean follow-up was 53.4 months (12-170.4 months). Included were 558 men (49.5 %) and 569 women (50.5 %). Mean age was 61 years (16-89 years). Visual acuity slightly decreased from initial levels of 0.3 logMAR-0.4 logMAR in patients without developing any radiation-induced complication but severely decreased to 1.0 logMAR or 1.5 logMAR in the case of developing radiation retinopathy only or optic neuropathy, respectively. Independent risk factors for radiation retinopathy were a centrally (<2.5 mm from sensitive structures) located tumor or a thick tumor located more than 2.5 mm from sensitive structures, while those for radiation optic neuropathy comprised a short distance and applied dose to the optic disk. CONCLUSION: The risk for radiation retinopathy is higher in central uveal melanoma. Mid-/peripheral tumors are at high risk for radiation retinopathy and maculopathy if presenting with increased thickness.

Trabeculectomy in patients with uveal melanoma after proton beam therapy.

BACKGROUND: Retrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma. METHODS: In this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010. RESULTS: The median IOP decreased significantly from 35 mmHg ± 8.8 before TE to 16 mmHg ± 8.2 (=52.3 %) six months after TE (Wilcoxon-Mann-Whitney-U Test, p<0.01). None of the patients needed any glaucoma medication six months after trabeculectomy. Two patients developed local recurrence during follow-up, which were independent of the trabeculectomy. One patient had to be enucleated due to intractable pain and suspected remaining tumor activity. One patient died due to metastasis. CONCLUSIONS: Trabeculectomy is an option in intractable glaucoma in patients with uveal melanoma after proton beam therapy in single cases. Secondary interventions are common. Inoculation metastases are possible. Secure local tumor control must be a prerequisite for filtrating operations.

Anti-VEGF therapy in symptomatic peripheral exudative hemorrhagic chorioretinopathy (PEHCR) involving the macula.

INTRODUCTION: The purpose of this study was to describe the anatomical and functional outcome of vascular endothelial growth factor inhibitor (anti-VEGF) treatment in symptomatic peripheral exudative hemorrhagic chorioretinopathy (PEHCR) involving the macula. METHODS: Clinical records from patients seen between 2012 and 2013 at a single academic center were reviewed to identify PEHCR patients receiving anti-VEGF therapy due to disease-associated changes involving the macula. Affected eyes were either treated with consecutive intravitreal injections of anti-VEGF or vitrectomy combined with anti-VEGF followed by pro re nata injections. RESULTS: The mean age of the patients was 76 years (range 70-89 years). In all nine eyes, visual acuity was reduced due to central subretinal fluid. On average, three anti-VEGF injections (range 2-5 injections) were required initially to achieve complete resolution of macular subretinal fluid. In three eyes, subretinal fluid reappeared after an average of 10 months (range 5-16 months), and an average of 2.5 anti-VEGF injections (range 2-3 injections) were necessary to attain complete resolution of macular subretinal fluid a second time. Median visual acuity at the visit before the first injection was 1.0 logMAR (range 2.1-0.4 logMAR) and increased to 0.8 logMAR (range 2-0.1 logMAR) at the last visit. CONCLUSION: Results of this study show that for cases in which PEHCR becomes symptomatic due to macular involvement, anti-VEGF treatment may have drying potential. Although vision was improved in some patients, it remained limited in cases with long-term macular involvement, precluding any definitive functional conclusion. However, we believe that the use of anti-VEGF agents should be recommended in PEHCR that threatens the macula. Due to its often self-limiting course, peripheral lesions should be closely observed. Larger studies are needed in order to provide clear evidence of the efficacy of anti-VEGF therapy in PEHCR.

Cataract development in patients treated with proton beam therapy for uveal melanoma.

PURPOSE: To evaluate the incidence, risk factors, and dosages of proton beam therapy associated with cataract development, and long-term visual outcomes after treatment of uveal melanoma. METHODS: All patients receiving primary proton beam therapy for uveal melanoma between 1998 and 2008 with no signs of cataract before irradiation were included. A minimum follow-up of 12 months was determined. Exclusion criteria included all applied adjuvant therapies such as intravitreal injections, laser photocoagulation, tumor resections, or re-irradiation. For subgroup analysis, we included all patients who underwent brachytherapy between 1998 and 2008 for uveal melanoma, considering the above mentioned inclusion and exclusion criteria. RESULTS: Two hundred and fifty-eight patients matched our inclusion criteria. Median follow-up was 72.6 months (12.0-167.4 months). Of these 258 patients, 71 patients (66.3 %) presented with cataract after 31.3 months (0.7-142.4 months), of whom 35 (20.4 %) required surgery after 24.2 (0.7-111.1 months) to ensure funduscopic tumor control. Kaplan-Meier estimates calculated a risk for cataract of 74.3 % after 5 years. There was no increase in metastasis or local recurrence in these patients. Patient's age was the sole independent statistically significant risk factor for cataract development. The probability of cataract occurrence significantly increased with doses to lens exceeding 15-20 CGE. Neither the appearance of cataract nor cataract surgery influenced long-term visual outcome. CONCLUSION: Cataract formation is the most frequent complication after irradiation. There is no benefit vis-a-vis brachytherapy with regard to cataract development. Data indicate a dose-effect threshold of 0.5 CGE for cataractogenesis, with significantly increasing risk above a dose of 15 CGE. Furthermore, cataract surgery can be performed without an increased risk for metastasis.

Sclerochoroidal calcification: clinical features, outcomes, and relationship with hypercalcemia and parathyroid adenoma in 179 eyes.

PURPOSE: To describe the clinical features and long-term ophthalmic and systemic findings in patients with sclerochoroidal calcification (SCC). METHODS: Retrospective non-interventional clinical chart review of 179 eyes of 118 patients with SCC to evaluate for the relationship of SCC with systemic calcium metabolic abnormalities. RESULTS: The mean patient age at diagnosis was 69 years. There were 47 (40%) men and 71 (60%) women of Caucasian (n = 116, 98%) and Hispanic (n = 2, 2%) heritage. The condition was unilateral in 57 patients (48%) and bilateral in 61 (52%), with a mean of 1.6 lesions per eye (range, 1-7 lesions per eye). The referring diagnosis was choroidal nevus (n = 23, 20%), melanoma (n = 15, 13%), lymphoma (n = 12, 10%), metastasis (n = 6, 5%), osteoma (n = 4, 3%), SCC (n = 6, 5%), and no diagnosis (n = 51, 43%). Of 277 SCC lesions, the most common location was superotemporal quadrant (n = 191, 69%). The largest lesion per eye demonstrated mean basal diameter of 3.6 mm and thickness of 1.8 mm, with yellow or white color (n = 150 lesions, 84%) and located superiorly (n = 105, 61%) at the retinal vascular arcade or near the equator (n = 161, 94%). The lesion demonstrated overlying focal choroidal atrophy (n = 63, 35%) and retinal pigment epithelium atrophy (n = 88, 49%). There was no case of subretinal fluid, hemorrhage, or choroidal neovascular membrane. At mean 4 years follow up, there was no lesion enlargement, decalcification, or related subretinal fluid/hemorrhage, choroidal neovascularization, or vision loss. Ocular treatment was not necessary in any case. Systemic outcomes revealed hyperparathyroidism (n = 9/33, 27%) with parathyroid adenoma (n = 5/33, 15%), Bartter syndrome (n = 1/53, 2%), or Gitelman syndrome (n = 6/53, 11%). CONCLUSIONS: Sclerochoroidal calcification is a stable deposition of calcium in the sclera that, unlike choroidal osteoma, has minimal risk for vision loss. All patients with SCC should be evaluated for underlying systemic calcium disorders, especially parathyroid and renal metabolic conditions.

Vascular findings in primarily affected and fellow eyes of middle-aged patients with Coats' disease using multimodal imaging.

AIMS: To investigate the retinal vascular structure and capillary anomalies of affected and fellow eyes of patients with unilateral Coats' disease using multimodal imaging. METHODS: Clinical investigation of both eyes of each patient with diagnosed Coats' disease using ultra-widefield (UWF) fundus imaging, including UWF fluorescein angiography (UWFFA), spectral domain optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). RESULTS: We analysed 38 eyes of 19 patients with unilateral Coats' disease and found that all fellow eyes (19/19; 100%) revealed vascular alterations, detected by UWFFA, predominantly located in the temporal periphery. Thereby, 89% of the fellow eyes (17/19) presented capillary bed abnormalities, that did not exceed the capillary level; 58% (11/19) presented tortuous abnormalities and 26% (5/19) presented microaneurysmatic abnormalities, exceeding the capillary level. If primarily affected eyes presented central Coats' specific vascular abnormalities, fellow eyes revealed tortuous vascular abnormalities twice as often (78% (7/9) vs 40% (4/10); P=0.096). In primarily affected eyes, a tendency towards larger foveal avascular zones was revealed, compared to fellow eyes (0.28±0.16 mm2 vs 0.20±0.10 mm2; P=0.123). CONCLUSION: The use of modern multimodal imaging allows the detection of even subtle vascular changes in fellow eyes of patients with Coats' disease. Coats' disease appears to be a bilateral ocular disease with a predominant manifestation in one eye of the affected patients.

[Success of psychotherapy referral of a psychosomatic consultation service among neurologic inpatients]. / Erfolg von Psychotherapieempfehlungen bei psychosomatischen Konsiliarpatienten einer neurologischen Station.

OBJECTIVES: This study investigates the success of recommendations for psychotherapy given in a psychosomatic consultation service to neurological inpatients. METHODS: In 2005, a subset of 401 (55.7 %) former neurologic inpatients from the initial sample of 720 who underwent psychosomatic consultation between 1999 and 2004 completed follow-up questionnaires to telephone interviews. RESULTS: 279 (69.6 %) participants stated that they had received a recommendation for in- or outpatient psychotherapy during the psychosomatic consultation. Of these, 152 (54.5 %) followed this recommendation. No differences in age, gender, familial status, initial symptoms, and diagnoses were detected between those who underwent psychotherapy and those who did not. Patients who underwent psychotherapy reported significant improvement of symptoms, less impairment, and less disability. CONCLUSIONS: A psychosomatic consultation may be a useful adjunct to neurological diagnostics in order to determine the correct diagnosis and therapy for patients with pseudo-neurological symptoms or evidence of psychological problems.

Radiation-Induced Optic Neuropathy: Observation versus Intravitreal Treatment: Can Visual Acuity Be Maintained by Intravitreal Treatment?

PURPOSE: To compare intravitreal therapy with the natural course of radiation optic neuropathy after primary proton beam therapy for choroidal melanoma with respect to long-term visual acuity and development of optic atrophy. DESIGN: Retrospective comparative case series. METHODS: Inclusion criteria: patients treated with primary proton beam therapy for choroidal melanoma with a minimum follow-up of 24 months after the occurrence of radiation optic neuropathy and optic disc imaging during follow-up. EXCLUSION CRITERIA: pathologic condition of the optic disc before irradiation and intravitreal therapy to treat cystoid macular edema not originating from the optic disc. RESULTS: Of 93 patients, 48 were observed only after radiation optic neuropathy, and 45 were treated with intravitreal therapy (triamcinolone, bevacizumab, and/or dexamethasone). Median follow-up was 55 months (29-187 months); median interval between onset of radiation optic neuropathy and the last patient visit was 34 months (24-125 months). Of 48 observed patients, 41 (85.4%) developed an optic atrophy after a median of 14 months (3-86 months) after radiation optic neuropathy; and of 45 intravitreally treated patients, 34 (75.5%) presented with an optic atrophy after a median of 12.5 months (1-55 months) following optic neuropathy, indicating no statistically significant differences between the groups. Comparing the change in visual acuity from occurrence of optic neuropathy to final visual acuity, no statistically significant differences were found between either group (P = 0.579). CONCLUSIONS: Patients treated with intravitreal therapy for radiation optic neuropathy showed no statistically significant differences related to visual acuity or optic atrophy development from patients who underwent only observation.