Long-term results after surgical basal cell carcinoma excision in the eyelid region: revisited.

The aim of the study was to readdress basal cell carcinoma (BCC) in the periocular region to prove the efficacy of histologically controlled surgical treatment and to identify high-risk characteristics.Retrospective analysis of 451 microscopically controlled BCC excisions in the periocular region. Tumor location, tumor size, AJCC 7 classification, and histological results were recorded. The same procedure was followed for recurrences.A recurrence rate of 5.0% was observed after the first microscopically controlled excision. Recurrent BCCs show a shift from nodular to sclerosing BCC as the primary histological type as well as a change in primary location from lower eyelid to medial canthus. The frequency of BCC with deep extension increased from 7.3% to 24.7%, and 57.1% after the second and third operations, respectively. The recurrence rate increased to 9.5% and 42.9%, after the second and third operations, respectively.In conclusion, we are facing the same challenges in surgical BCC treatment as 30 years ago. The distribution of periocular BCC location, histologic subtype and recurrence rates mirror the literature und the general consensus. The recurrence rate increases with every operation needed. Sclerosing BCCs with deep extension at the medial canthus bear the greatest risk for recurrence. In such cases, centers of expertise should be consulted and additional treatment options should be considered.

Impact of Choroidal Melanoma Characteristics on Progression-Free Survival in Patients Undergoing Hypofractionated Stereotactic Photon Radiotherapy.

INTRODUCTION: In an effort to replace ultrasonography-based thickness measurements, we investigated whether choroidal melanoma characteristics are related to progression-free survival (PFS) in patients monitored after linear accelerator (LINAC)-based hypofractionated stereotactic photon radiotherapy. METHODS: In a retrospective dataset, we used a linear mixed model to assess the associations between PFS and tumor characteristics; in particular, thickness, largest basal diameter (LBD), base area and volume. RESULTS: Thickness and LBD are statistically significantly associated with PFS. In a subgroup of 16 patients undergoing enucleation due to melanoma recurrence or progression, there were statistically significant changes in mean thickness and LBD before surgery. Mean PFS was 42 ± 30 months. CONCLUSION: Ultrasonography-based thickness measurements may not be necessary for treated choroidal melanoma monitoring; instead, we propose sequential LBD assessments, which should preferably be performed using fundus photography in future.

Hypofractionated stereotactic photon radiotherapy of choroidal melanoma: 20-year experience.

BACKGROUND: To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016. MATERIAL AND METHODS: A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit. RESULTS: The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract (n = 127), neovascular glaucoma (n = 71) and corneal epithelium defects (n = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma (n = 41) or tumor recurrence (n = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years. CONCLUSION: Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects.

Axon numbers and landmarks of trigeminal donor nerves for corneal neurotization.

PURPOSE: Corneal anesthesia leads to chronic corneal injury. This anatomical study characterizes the donor nerve branches of the supratrochlear and supraorbital nerves used for corneal neurotization. METHODS: In 13 non-embalmed cadavers, the supratrochlear and supraorbital nerves were dissected and distances to anatomical landmarks measured. Cross-sections of supratrochlear and supraorbital donor nerves were harvested and histomorphometrically analyzed to assess the number of myelinated axons. RESULTS: The donor axon counts were 3146 ± 1069.9 for the supratrochlear and 1882 ± 903 for the supraorbital nerve distal to the supraorbital notch. The supratrochlear nerve was dissected on the medial upper eyelid 2 cm lateral to the facial midline and the branch of the supraorbital nerve 1 cm medial to the mid-pupillary line. CONCLUSION: The supraorbital and supratrochlear branches of the trigeminal nerve are potent donor nerves for corneal neurotization in the treatment of neuropathic keratopathy and can be reliably dissected using anatomical landmarks.

Early ultrasonographic tumor regression after linear accelerator stereotactic fractionated photon radiotherapy of choroidal melanoma as a predictor for metastatic spread.

BACKGROUND AND PURPOSE: During extended follow-up (of up to 15 years), approximately fifty percent of patients with choroidal melanoma will develop metastatic disease and eventually die. Thus, continuing research on prognostic factors, early detection and treatment is necessary. Height regression rates both after plaque brachytherapy and proton beam irradiation have been shown to have prognostic value. The purpose of this study was to analyze the influence of early tumor regression rate after treatment of choroidal melanoma with LINAC stereotactic fractionated radiotherapy (SFRT) as an independent risk factor for metastasis. MATERIAL AND METHODS: 256 patients with choroidal melanoma treated with LINAC SFRT were included. Follow-up included standardized echography yielding apical height, smallest and largest basal linear diameter, tumor volume and mean reflectivity. The influence of baseline measurements and of a longitudinal, normalized area under the curve coefficient (NAC) of the latter marker on metastasis risk was assessed. RESULTS: NAC for tumor thickness at months 3, 6, and 12 had a statistically significant (p < 0.001) non-linear effect on risk of metastasis. Additionally, ultrasonographic baseline tumor dimensions, but not internal reflectivity were found to be statistically significant risk factors for metastasis. CONCLUSIONS: Our results demonstrate a non-linear influence of regression rate of choroidal melanoma as independent risk factor of metastatic disease after LINAC SFRT. These prove the clinical experience that, in comparison to rather slow regressions, very quick and very slow early tumor responses to LINAC SFRT are associated with a significantly higher metastasis risk.

Retina dose as a predictor for visual acuity loss in 106Ru eye plaque brachytherapy of uveal melanomas.

BACKGROUND AND PURPOSE: To evaluate the retina dose as a risk factor associated with loss of visual acuity (VA) in 106Ru plaque brachytherapy. MATERIAL/METHODS: 45 patients receiving 106Ru plaques brachytherapy (median follow-up 29.5 months) were included in this study. An in-house developed treatment planning system with Monte Carlo based dose calculation was used to perform treatment planning and dose calculation. Risk factors associated with loss of VA were evaluated using the Cox proportional hazards models, Kaplan-Meier estimates and Pearson correlation coefficients. RESULTS: A significant correlation was found between VA loss and mean (r = 0.49, p = 0.001) and near maximum (r = 0.47, p = 0.001) retina dose D2% and tumor basal diameter (r = 0.50, p < 0.001). The Kaplan-Meier and Cox proportional hazards model yielded a significantly higher risk for VA loss (>0.3Snellen) for patients receiving a maximum dose of >500 Gy (p = 0.002). A Cox multivariate analysis including the macula dose (p = 0.237) and basal diameter (p = 0.791) showed that a high maximum retinal dose is the best risk factor (p = 0.013) for VA loss. CONCLUSION: The study showed that retina dose (D2% and Dmean) is a suitable predictor for VA loss.

Treatment plan optimization and robustness of 106Ru eye plaque brachytherapy using a novel software tool.

BACKGROUND AND PURPOSE: To analyze treatment plan robustness and plan optimization strategies of 106Ru eye plaque brachytherapy using a novel software tool. MATERIALS AND METHODS: A treatment planning software was developed that allows to calculate dose-volume metrics. Plaque misplacements were simulated and evaluated with respect to the effect on tumor coverage and dose changes in critical structures. Two treatment plan optimization approaches were analyzed: (a) reducing plaque size and (b) shifting the plaque away from organs-at-risk (OAR). RESULTS: Maximum tumor sizes were identified which can be covered by the prescribed dose for different robustness levels (0-2mm). For an apex height of 5mm a 1mm uncertainty yielded changes in D2% to the lens of up to ±13Gy in anterior and ±20Gy to the optic nerve in posterior tumors. By reducing the plaque size Dmean and D2% to lens, optic nerve and macula were decreased by >60% for most simulated cases. Similarly, by shifting the plaque away from the lens dose reductions of 15%/mm in anterior and even 30%/mm in central tumors were achieved. CONCLUSION: Critical structures in the treatment of uveal melanomas with 106Ru plaques can benefit from the proposed, computational treatment plan optimization.

ROLE OF ADDITIONAL DEXAMETHASONE FOR THE MANAGEMENT OF PERSISTENT OR RECURRENT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION UNDER RANIBIZUMAB TREATMENT.

PURPOSE: To assess the efficacy of a combination therapy of intravitreal ranibizumab together with a dexamethasone implant in comparison with ranibizumab monotherapy in neovascular age-related macular degeneration. METHODS: Forty eyes of recurrent or persistent neovascular age-related macular degeneration were included in this prospective study. Patients were randomly assigned to two groups. Based on a pro re nata treatment regimen, the first group received intravitreal ranibizumab monotherapy (IVM). The second group received a combination of intravitreal dexamethasone implant and ranibizumab (intravitreal combination [IVC]) at baseline and was retreated with ranibizumab as needed. A second dexamethasone implant was allowed for retreatment after at least 6 months. Retreatment criteria included evidence of subretinal fluid, cystoid macular edema or new hemorrhage, and/or a visual acuity decrease of 5 Early Treatment Diabetic Retinopathy Study letters. RESULTS: During 12 months, a mean of 7.95/5.5 (IVM/IVC; P = 0.042) retreatments were given. The median time until first retreatment differed significantly between the groups (P = 0.004). Functional variables could be maintained in both groups with no differences between them. Visual acuity changed from 62 letters at baseline to 67 at Month 12 in the IVM and remained stable at 68 letters in the IVC group (P = 0.68); macular sensitivity changed from 6.95 dB to 7.01 dB in IVM and from 7.24 dB to 7.12 dB in IVC (P = 0.4). Central retinal thickness decreased, however, with no difference between the groups (P = 0.38). In the IVM/IVC group, 11/12 (55/60%) patients were phakic at the time of study entry. One (9%) patient from the IVM and 4 (33%) from the IVC group were referred to cataract surgery after study completion (P = 0.4). CONCLUSION: This pilot study indicates combined therapy to delay retreatment in patients with persistent/recurrent neovascular age-related macular degeneration and an overall reduction in required ranibizumab retreatments compared with ranibizumab monotherapy with consistent functional outcomes.

Multimodal Imaging of Cotton Wool Spots in Branch Retinal Vein Occlusion.

PURPOSE: To describe and follow cotton wool spots (CWS) in branch retinal vein occlusion (BRVO) using multimodal imaging. METHODS: In this prospective cohort study including 24 patients with new-onset BRVO, CWS were described and analyzed in color fundus photography (CF), spectral domain optical coherence tomography (SD-OCT), infrared (IR) and fluorescein angiography (FA) every 3 months for 3 years. The CWS area on SD-OCT and CF was evaluated using OCT-Tool-Kit software: CWS were marked in each single OCT B-scan and the software calculated the area by interpolation. RESULTS: 29 central CWS lesions were found. 100% of these CWS were visible on SD-OCT, 100% on FA and 86.2% on IR imaging, but only 65.5% on CF imaging. CWS were visible for 12.4 ± 7.5 months on SD-OCT, for 4.4 ± 3 months and 4.3 ± 3.4 months on CF and on IR, respectively, and for 17.5 ± 7.1 months on FA. The evaluated CWS area on SD-OCT was larger than on CF (0.26 ± 0.17 mm(2) vs. 0.13 ± 0.1 mm(2), p < 0.0001). The CWS area on SD-OCT and surrounding pathology such as intraretinal cysts, avascular zones and intraretinal hemorrhage were predictive for how long CWS remained visible (r(2) = 0.497, p < 0.002). CONCLUSIONS: The lifetime and presentation of CWS in BRVO seem comparable to other diseases. SD-OCT shows a higher sensitivity for detecting CWS compared to CF. The duration of visibility of CWS varies among different image modalities and depends on the surrounding pathology and the CWS size.

Detection and Differentiation of Intraretinal Hemorrhage in Spectral Domain Optical Coherence Tomography.

PURPOSE: The purpose of this study was to classify and detect intraretinal hemorrhage (IRH) in spectral domain optical coherence tomography (SD-OCT). METHODS: Initially the presentation of IRH in BRVO-patients in SD-OCT was described by one reader comparing color-fundus (CF) and SD-OCT using dedicated software. Based on these established characteristics, the presence and the severity of IRH in SD-OCT and CF were assessed by two other masked readers and the inter-device and the inter-observer agreement were evaluated. Further the area of IRH was compared. RESULTS: About 895 single B-scans of 24 eyes were analyzed. About 61% of SD-OCT scans and 46% of the CF-images were graded for the presence of IRH (concordance: 73%, inter-device agreement: k = 0.5). However, subdivided into previously established severity levels of dense (CF: 21.3% versus SD-OCT: 34.7%, k = 0.2), flame-like (CF: 15.5% versus SD-OCT: 45.5%, k = 0.3), and dot-like (CF: 32% versus SD-OCT: 24.4%, k = 0.2) IRH, the inter-device agreement was weak. The inter-observer agreement was strong with k = 0.9 for SD-OCT and k = 0.8 for CF. The mean area of IRH detected on SD-OCT was significantly greater than on CF (SD-OCT: 11.5 ± 4.3 mm(2) versus CF: 8.1 ± 5.5 mm(2), p = 0.008). CONCLUSIONS: IRH seems to be detectable on SD-OCT; however, the previously established severity grading agreed weakly with that assessed by CF.

Dose-response of critical structures in the posterior eye segment to hypofractioned stereotactic photon radiotherapy of choroidal melanoma.

PURPOSE: To identify modifying factors and dose-/volume-response relationships for the retina and optic nerve related to highly conformal hypofractionated radiotherapy. PATIENTS AND METHODS: Seventy-three patients undergoing hypofractionated stereotactic photon radiotherapy of choroidal melanoma were included in this retrospective study. The volumes of the optic nerve receiving doses of more than 7.5 or 12 Gy, respectively, were defined. Optic nerve circumference included in the 30%, 40%, 50%, or 80% isodose (ON%) and retina included in 30% or 40% were determined as quantal effects. Univariate and multivariate analyses were performed for clinical variables as well as probit analysis to define EDx (doses where a positive response is expected in x% of the cases). RESULTS: Median follow-up was 90.0 (interquartile range 69.0-98.0) months. Fifty-two (71%) and 49 (67%) patients developed radiation retinopathy and optic neuropathy (any grade). Age, length of follow-up and diabetes were significant parameters regarding retinopathy. Optic neuropathy was significantly influenced by age, length of follow-up, and ON30. The probability of optic neuropathy (any grade and grade ≥ 2) significantly increases with the dose (p ranges from 0.0126 to 0.0211). CONCLUSION: Treatment planning should aim at minimizing encompassing isodoses particularly in the low dose region, without compromising PTV coverage.

Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy--clinical results after six years of experience.

PURPOSE: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. MATERIALS AND METHODS: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2-49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. RESULTS: Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10-13.70), 9.80 mm (IQR 7.80-11.70), 4.53 mm (IQR 3.33-6.43) and 253.8mm(3) (IQR 127.5-477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p<0.001). The most common toxicities (any grade) were radiation retinopathy (n=39), optic neuropathy (n=32), radiogenic cataract (n=21), neovascular glaucoma (n=15) and dry eye syndrome (n=10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. CONCLUSION: Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile.

Response of retinal sensitivity to ranibizumab treatment of macular edema after acute branch retinal vein occlusion.

PURPOSE: To evaluate microperimetry changes in patients with acute macular edema secondary to branch retinal vein occlusion during a follow-up period of 12 months with intravitreal ranibizumab treatment (Lucentis; Novartis). METHODS: Patients with macular edema secondary to branch retinal vein occlusion received an intravitreous injection of 0.5 mg of ranibizumab (0.05 mL). Best-corrected visual acuity, Spectralis OCT (Heidelberg Engineering), and color fundus photography were performed at monthly intervals over a follow-up period of 1 year. Macular function was documented by microperimetry (Nidek, MP-1) at baseline, 3, and 12 months. RESULTS: Data of 20 patients without lack of microperimetry results were included to the statistical analyses. The size of the area of absolute scotoma was reduced from 16% at baseline to 11.7% at Month 3 and remained stable in the entire study duration (P > 0.05). Mean differential light threshold improved significantly under therapy from 9.47 dB at baseline to 12.53 dB at 12 months (P < 0.001). Best-corrected visual acuity correlated significantly with central millimeter thickness and mean retinal sensitivity at baseline and at 12-month follow-up visits. CONCLUSION: In addition to anatomical restoration and increased visual acuity, intravitreal ranibizumab also improved the central macular function in patients with acute macular edema after branch retinal vein occlusion.

Macular edema following cataract surgery in eyes with previous 23-gauge vitrectomy and peeling of the internal limiting membrane.

PURPOSE: To investigate intraretinal changes after successful cataract surgery in patients with previous pars plana vitrectomy (PPV) and indocyanine green-assisted peeling of epiretinal membrane and internal limiting membrane (ILM). DESIGN: Prospective nonrandomized controlled clinical study. METHODS: Twenty eyes of 20 patients with cataract with previous 23-gauge PPV and ILM peeling (PPV group) and 15 consecutive eyes with senile cataract with a healthy macula (control group) were included. Best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography (OCT), infrared fundus imaging, and biomicroscopy were performed at baseline and at week 1, month 1, and month 3 after cataract surgery. OCT raster scans were further analyzed regarding the central millimeter thickness (CMMT), area of retinal thickening size on the topographic map, and changes in retinal structural morphology. RESULTS: The baseline mean visual acuity in the PPV group was 0.3 ± 0.18 Snellen lines, which improved significantly to 0.85 ± 0.18 (P < .05) 3 months after cataract surgery. CMMT was 393 (± 44) µm at baseline and increased to 408 (± 47) µm at month 3 (P < .05). One patient was not seen at the final visit, so data of 19 patients was used. In the PPV group, 8 of 19 patients (42%) developed an increase in CMMT more than 35 µm 1 month after cataract surgery; 5 of these 8 patients (26%) developed macular edema with cyst formation. Three months after surgery, the area of retinal thickening was significantly larger in most patients compared with baseline values. No cystoid macular edema was observed in the control group. CONCLUSIONS: This study provides evidence that patients with previous PPV and membrane and ILM peeling often develop macular edema after successful cataract surgery.

Quantitative proteomics of aqueous and vitreous fluid from patients with idiopathic epiretinal membranes.

The purpose of the study was to perform a detailed, quantitative protein analysis of the aqueous (AF) and vitreous fluids (VF) from human eyes with idiopathic epiretinal membranes (iERM). The complementary approaches of quantitative liquid chromatography mass spectrometry (LCMS) and multiplex protein assays were utilised to reveal the protein composition in ocular fluids of this retinal disorder. In a prospective clinical trial, AF and VF was collected during surgery from twenty four eyes corresponding to twenty four patients with iERM. VF and AF from eight patients were labelled with the 4-plex iTRAQ reagent and analysed by LCMS. Each iTRAQ 4-plex experiment consisted of the AH and VH from two patients. A total of 323 proteins were identified in the AF and VF from eyes with iERM. Grouping the proteins according to involvement in biological processes, showed that the majority were involved in the classical and alternative pathway of complement activation (n = 27), proteolysis (n = 26) and cell adhesion (n = 28). iTRAQ relative quantitation revealed minimal variation in the protein content between both ocular compartments with only 3.96% of the identified proteins significantly, differentially-expressed. Eight proteins were expressed at a higher level in the VF compared to the AF; and 4 proteins were expressed at a lower level in the VF compared to the AF. For the multiplex bead assays, 29 growth factors and cytokines were assessed in the AF and VF from 16 additional patients with iERM. The protein profile was shown to be similar between VF and AF for the majority of factors except PDGF-AA. This factor was expressed at a higher level in the VF compared to the AF. The data presented in this study revealed that the majority of the proteins identified by LCMS and multiplex bead assays were present in both ocular compartments in similar quantities. This study is a first step, 'discovery phase' towards revealing and quantitating the protein content in the aqueous and vitreous fluid in human eyes with iERM.

Retreatment with anti-vascular endothelial growth factor therapy based on changes in visual acuity after initial stabilization of neovascular age-related macular degeneration: 3-year follow-up results.

PURPOSE: To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab in neovascular related macular degeneration (nAMD) in a standard clinical setting involving 3 initial injections and a pro re nata regimen as recommended in the PRONTO study. METHODS: In this interventional clinical study, 181 eyes of 160 consecutive patients with active neovascular related macular degeneration meeting recommended criteria for inclusion and protocol criteria for anti-vascular endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed separately from eyes that had undergone previous photodynamic therapy plus intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on clinical outcome following the official European label regimen. After 1 year of continuous service at an academic referral center, follow-up was performed in private practices in collaboration with the referral center. Main outcome parameters were best-corrected visual acuity and central retinal thickness. RESULTS: After 3 years, best-corrected visual acuity decreased in the overall population (0.23 ± 0.16 to 0.16 ± 0.21. P = 0.002) and in both groups compared with baseline (0.24 ± 0.21 to 0.17 ± 0.21, Group 1, P = 0.03; 0.22 ± 0.19 to 0.16 ± 0.21, Group 2, P > 0.05), whereas central retinal thickness increased in the overall population (291 ± 92 to 319 ± 110 µm, P = 0.01) and in both groups (291 ± 96 to 325 ± 117 µm, Group 1, P > 0.05; 290 ± 83 to 308 ± 96 µm, Group 2, P > 0.05) because of chronic cystic degeneration changes of the macula. Mean treatment rate was 5.1 ± 3.9 (Group 1) versus 3.7 ± 2.7 (Group 2, P = 0.01). Five cases of severe intraocular inflammation after intravitreal bevacizumab were documented. DISCUSSION: While the functional and morphological benefits persisted for the first year after intravitreal bevacizumab treatment, after this time both functional and morphologic results were disappointing during long-term follow-up with visual acuity loss as the main retreatment criterion. After stabilization of the disease, a monthly follow-up of optical coherence tomography and re-treatment based on morphologic, clinical, and vision outcomes may increase the efficacy in patients with neovascular related macular degeneration under anti-vascular endothelial growth factor treatment.

Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma.

PURPOSE: To identify and quantify angiogenic and inflammatory cytokines in aqueous and vitreous humor in eyes with untreated uveal melanoma and to analyze clinicopathologic correlations. METHODS: Intraocular fluid samples of patients (uveal melanoma aqueous n = 21, vitreous n = 34) and controls (cataract aqueous n = 41, vitreomacular traction aqueous n = 35, vitreous n = 36) were taken intraoperatively and analyzed using Luminex xMAP suspension array technology. Beadlyte kits were used for detection of 28 different cytokines. RESULTS: Flt-3 ligand, interleukin (IL) 1α, IL-6, IL-8, interferon-γ inducible protein (IP)-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α, platelet-derived growth factor AA, and vascular endothelial growth factor were significantly elevated in aqueous and vitreous of melanoma eyes when compared with controls. Eotaxin was significantly elevated in aqueous, and IL-7 and RANTES were significantly elevated in vitreous samples of melanoma eyes. Interferon-γ inducible protein 10, macrophage inflammatory protein 1α (aqueous and vitreous), Flt-3 ligand, IL-6, IL-8, and MCP-1 (vitreous) correlated with tumor dimensions. Further correlations were found between infiltration of Bruch membrane and Flt-3 ligand, MCP-1 (aqueous and vitreous), IL-8, interferon-γ inducible protein 10, macrophage inflammatory protein 1α, and platelet-derived growth factor AA (vitreous). Analyzing 16 paired aqueous and vitreous melanoma samples, Flt-3 ligand, IL-7, interferon-γ inducible protein 10, MCP-1, and platelet-derived growth factor AA were significantly elevated in vitreous, and IL-1α and vascular endothelial growth factor in aqueous samples. CONCLUSION: A range of significantly elevated angiogenic, inflammatory, and chemotactic cytokines in eyes with uveal melanoma supports the link between inflammation and tumorigenesis.

Radiogenic side effects after hypofractionated stereotactic photon radiotherapy of choroidal melanoma in 212 patients treated between 1997 and 2007.

PURPOSE: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. PATIENTS AND METHODS: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. RESULTS: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. CONCLUSION: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.