Quality of life and treatment-related burden during ocular proton therapy: a prospective trial of 131 patients with uveal melanoma.

BACKGROUND: Proton beam therapy is a well-established treatment option for patients with uveal melanoma (UM). The treatment procedure, in general, includes placing radiopaque clips to ensure exact eye-positioning during radiotherapy, followed by the delivery of proton irradiation. The short-term burden associated with proton therapy in patients with UM has rarely been addressed. In this prospective study, we investigated the physiological and psychological aspects of proton therapy that might affect the well-being of patients during the different stages of treatment. METHODS: During the treatment procedure, we conducted longitudinal assessments of the Quality of life (QOL), organ-specific symptoms, and psychological aspects in patients with UM with three questionnaires (EORTC QLQ-C30, EORTC QLQ-OPT30, and GAD-7). Patients completed questionnaires before clip surgery (T0), before proton therapy (T1), after completing treatment (T2), and three months after treatment completion (T3). We also collected data on tumor characteristics and socio-demographics to identify potential risk factors associated with high treatment burdens. RESULTS: We prospectively included 131 consecutive patients. Questionnaire data showed a significant, temporary decline in global QOL and an increase in eye-related symptoms, as a result of the clip surgery (T0-T1). After treatment completion (T2), global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy. The global QOL returned to baseline levels three months after treatment (T3). We identified baseline anxiety as an independent risk factor for experiencing an acute treatment-related burden. Furthermore, we found interactions between GAD7 and patient sex showing that anxiety had a more pronounced effect on QOL outcome in female patients. CONCLUSION: The short-term treatment-related burden of ocular proton therapy appeared to be largely associated with the preceding clip surgery, rather than the irradiation procedure. We found that anxiety was strongly associated with experiencing QOL issues during the treatment procedure. Our findings could contribute to the development of future strategies for improving the treatment process and psycho-oncologic patient care.

The Genetics of Uveal Melanoma: Overview and Clinical Relevance. / Genetik der Aderhautmelanome: Übersicht und klinische Relevanz.

Over the last ten years, much has been learnt about the genetic characteristics and genetic evolution of uveal melanoma. It has been shown that uveal melanoma differs fundamentally from non-uveal melanoma and is an independent genetic subtype. Compared to other tumours, uveal melanoma has a low mutational burden. There are recurring chromosomal aberrations with losses of 1p, 6q, 8p and 16q, gains of 6p and 8q, and the presence of monosomy 3. GNAQ, GNA11, PLCB4, CYSLTR2, MAPKAPK5, as well as mutations in BAP1, SF3B1, SRSF2 and EIF1AX, the latter being linked to a higher risk of metastasis, have been identified as significantly mutated genes. In rare cases, a BAP1 germline mutation may also be present. In addition to higher risk of uveal melanoma, this variant is also linked with other tumours. In this case, additional work-up, genetic counselling and screening of family members should be offered. While the knowledge about the genetic characteristics of uveal melanoma is already routinely used for diagnostic and prognostic purposes, targeted genotype-dependent therapy of uveal melanoma is currently still missing.

Breakdown of the blood-eye barrier in choroidal melanoma after proton beam radiotherapy.

PURPOSE: Irradiation of choroidal melanoma is a safe and globe preserving procedure. Chronic inflammatory processes and ischemia are the main reasons for secondary enucleation in the long run. The aim of this study was to determine whether intraocular inflammation and especially inflammatory response after proton beam therapy (PBT) is related to primary tumor characteristics such as height, tumor volume, and initial flare values. METHODS: Twenty-six patients treated for uveal melanoma using PBT were included. All patients were examined for signs of inflammation using laser flare photometry (LFP). Each examination included assessment of the melanoma and fellow eye (which acted as the control) and imaging of the melanoma. RESULTS: Significant differences of flare values between melanoma eyes and control group were found both at baseline (median 17.65 ph/ms (min 4, max 37.10), 7.45 ph/ms (min 0.80, max 16.40), respectively) and during follow-up (median 21.45 ph/ms (min 4.5, max 70.90); 6.05 ph/ms (min 2.40, max 16.40), respectively) (p < 0.001, Wilcoxon test). Flare values in melanoma eyes increased significantly after PBT (p = 0.005, Wilcoxon test) and after a follow-up of 94 days (median, 7-420 days). Flare values of the control group did not change (p = 0.946, Wilcoxon test). The increase of flare values correlated significantly with maximum tumor height and volume (Spearman-Rho 0.633, p = 0.001 and 0.519, p = 0.007, respectively). CONCLUSION: LFP has proven to show significantly higher flare values in melanoma eyes as compared with the control group and provides data on the course of the inflammatory response after treatment. It may ease treatment planning both at baseline and during follow-up.

[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.

[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.

Descemet Membrane Endothelial Keratoplasty as a Secondary Approach After Failure of Penetrating Keratoplasty.

OBJECTIVES: To investigate visual outcome and postoperative complications in patients undergoing Descemet membrane endothelial keratoplasty with graft failure after penetrating keratoplasty. MATERIALS AND METHODS: A retrospective analysis was performed with 5 patients who underwent Descemet membrane endothelial keratoplasty after failed penetrating keratoplasty. Intraoperative and postoperative complications were recorded. Visual acuity, rehabilitation phase, refraction stability, central corneal thickness, endothelial cell count, possible immunologic reactions, and optical coherence tomography of the anterior eye segment were evaluated. A subjective questionnaire was used to evaluate patient satisfaction. RESULTS: There were no intraoperative complications. All patients had graft detachment, which made air injection necessary. In all cases, visual acuity significantly increased (medium visual acuity [logarithm of the minimum angle of resolution]: 0.68 ± 0.31 logarithm of the minimum angle of resolution after 4 weeks and 0.35 ± 0.37 after 6 months; P = .043), refraction was stable, corneal thickness was reduced (average, 514 ± 11 µm), and endothelial cell count was reduced (average, 1398 ± 510 cells/mm(2)) after 6 months, which corresponds with a medium loss 40%. In the questionnaire, visual outcome, estimated time for recovery, and rehabilitation and patient satisfaction were better after Descemet membrane endothelial keratoplasty than penetrating keratoplasty. No postoperative elevation of pressure, development of pupillary block, or graft rejection, and no peripheral anterior synechiae or other abnormalities were observed with optical coherence tomography during the first 6 postoperative months. CONCLUSIONS: Descemet membrane endothelial keratoplasty is a suitable technique for the treatment of graft failure after penetrating keratoplasty and helped our patients rapidly achieve good visual acuity, with reduction of postoperative complications, but the visual outcome might be limited.

DMEK in phakic eyes: targeted therapy or highway to cataract surgery?

PURPOSE: To investigate outcome and postoperative complications in patients undergoing isolated DMEK in phakic eyes compared to patients undergoing DMEK combined with cataract surgery (triple procedure). METHODS: A retrospective analysis of 13 eyes undergoing DMEK in phakic eyes and 54 eyes undergoing triple procedure. Intraoperative and postoperative complications were recorded, visual acuity, refraction outcome, central corneal thickness, endothelial cell count and optical coherence tomography (OCT) of the anterior eye segment were evaluated 6 months postoperatively. RESULTS: Graft detachment occurred in two eyes (18 %) undergoing phakic DMEK surgery and 23 eyes (50 %) undergoing triple procedure. Two eyes of the phakic group needed subsequent cataract surgery. In all cases, visual acuity significantly increased with a medium visual acuity of 0.13 ± 0.12 (phakic group, p = 0.005) and 0.15 ± 0.11 (triple group, p < 0.001) logMAR. Visual acuity of at least 0.1 logMAR was found in 55 % (phakic group) and 52 % (triple procedure group) of eyes. In the group after triple procedure, there were 62.8 % of eyes within 1 D of emmetropia. Corneal thickness was reduced to 515.3 ± 36.9 µm (phakic group, p = 0.012) and 516.5 ± 40.4 µm (triple group, p < 0.001). Endothelial cell count was reduced to 1529.7 ± 695.6/mm(2) (phakic group, p = 0.008) and 1,676.8 ± 355.2/mm(2) (triple group, p < 0.001). CONCLUSIONS: DMEK in phakic eyes provides very good visual acuity with lower postoperative complications compared to eyes undergoing triple procedure. As the accommodative power can be preserved, this method is especially interesting for young patients.

The Development of Orange Pigment Overlying Choroidal Metastasis.

AIMS: The aim of this study was to correlate the ophthalmoscopic and histopathological findings of orange pigment overlying a choroidal metastasis. METHODS: This is a single case report with clinical follow-up and histopathological examination. RESULTS: Histopathology revealed a choroidal metastasis with subretinal CD68-positive macrophages showing autofluorescent deposits in fluorescence microscopy. CONCLUSION: The development of orange pigment is not pathognomonic for choroidal melanoma but may be seen in other lesions such as carcinoma metastasis.

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.

Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells.

Uveal melanoma (UM) is both the most common and fatal intraocular cancer among adults worldwide. As with all types of neoplasia, changes in Ca(2+) channel regulation can contribute to the onset and progression of this pathological condition. Transient receptor potential channels (TRPs) and cannabinoid receptor type 1 (CB1) are two different types of Ca(2+) permeation pathways that can be dysregulated during neoplasia. We determined in malignant human UM and healthy uvea and four different UM cell lines whether there is gene and functional expression of TRP subtypes and CB1 since they could serve as drug targets to either prevent or inhibit initiation and progression of UM. RT-PCR, Ca(2+) transients, immunohistochemistry and planar patch-clamp analysis probed for their gene expression and functional activity, respectively. In UM cells, TRPV1 and TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced Ca(2+) transients as well as changes in ion current behavior characteristic of TRPV1 and TRPM8 expression. Such effects were blocked with either La(3+), capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN 55,212-2, induced Ca(2+) transients, which were suppressed by La(3+) and CPZ whereas CAP-induced Ca(2+) transients could also be suppressed by CB1 activation. Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these tissues may provide novel drug targets for treatment of this aggressive neoplastic disease.