Evaluation of the accuracy and readability of ChatGPT-4 and Google Gemini in providing information on retinal detachment: a multicenter expert comparative study.

BACKGROUND: Large language models (LLMs) such as ChatGPT-4 and Google Gemini show potential for patient health education, but concerns about their accuracy require careful evaluation. This study evaluates the readability and accuracy of ChatGPT-4 and Google Gemini in answering questions about retinal detachment. METHODS: Comparative study analyzing responses from ChatGPT-4 and Google Gemini to 13 retinal detachment questions, categorized by difficulty levels (D1, D2, D3). Masked responses were reviewed by ten vitreoretinal specialists and rated on correctness, errors, thematic accuracy, coherence, and overall quality grading. Analysis included Flesch Readability Ease Score, word and sentence counts. RESULTS: Both Artificial Intelligence tools required college-level understanding for all difficulty levels. Google Gemini was easier to understand (p = 0.03), while ChatGPT-4 provided more correct answers for the more difficult questions (p = 0.0005) with fewer serious errors. ChatGPT-4 scored highest on most challenging questions, showing superior thematic accuracy (p = 0.003). ChatGPT-4 outperformed Google Gemini in 8 of 13 questions, with higher overall quality grades in the easiest (p = 0.03) and hardest levels (p = 0.0002), showing a lower grade as question difficulty increased. CONCLUSIONS: ChatGPT-4 and Google Gemini effectively address queries about retinal detachment, offering mostly accurate answers with few critical errors, though patients require higher education for comprehension. The implementation of AI tools may contribute to improving medical care by providing accurate and relevant healthcare information quickly.

Prognostic value of clinical and radiomic parameters in patients with liver metastases from uveal melanoma.

Approximately every second patient with uveal melanoma develops distant metastases, with the liver as the predominant target organ. While the median survival after diagnosis of distant metastases is limited to a year, yet-to-be-defined subgroups of patients experience a more favorable outcome. Therefore, prognostic biomarkers could help identify distinct risk groups to guide patient counseling, therapeutic decision-making, and stratification of study populations. To this end, we retrospectively analyzed a cohort of 101 patients with newly diagnosed hepatic metastases from uveal melanoma by using Cox-Lasso regression machine learning, adapted to a high-dimensional input parameter space. We show that substantial binary risk stratification can be performed, based on (i) clinical and laboratory parameters, (ii) measures of quantitative overall hepatic tumor burden, and (iii) radiomic parameters. Yet, combining two or all three domains failed to improve prognostic separation of patients. Additionally, we identified highly relevant clinical parameters (including lactate dehydrogenase, thrombocyte counts, aspartate transaminase, and the metastasis-free interval) at first diagnosis of metastatic disease as predictors for time-to-treatment failure and overall survival. Taken together, the risk stratification models, built by our machine-learning algorithm, identified a comparable and independent prognostic value of clinical, radiological, and radiomic parameters in uveal melanoma patients with hepatic metastases.

The Chick Chorioallantoic Membrane as a Xenograft Model for the Quantitative Analysis of Uveal Melanoma Metastasis in Multiple Organs.

Uveal melanoma (UM) is the most common intraocular tumor in adults, and nearly 50% of patients develop metastatic disease with a high mortality rate. Therefore, the development of relevant preclinical in vivo models that accurately recapitulate the metastatic cascade is crucial. We exploited the chick embryo chorioallantoic membrane (CAM) xenograft model to quantify both experimental and spontaneous metastasis by qPCR analysis. Our study found that the transplanted UM cells spread predominantly and early in the liver, reflecting the primary site of metastasis in patients. Visible signs of pigmented metastasis were observed in the eyes, liver, and distal CAM. Lung metastases occurred rarely and brain metastases progressed more slowly. However, UM cell types of different origins and genetic profiles caused an individual spectrum of organ metastases. Metastasis to multiple organs, including the liver, was often associated with risk factors such as high proliferation rate, hyperpigmentation, and epithelioid cell type. The severity of liver metastasis was related to the hepatic metastatic origin and chromosome 8 abnormalities rather than monosomy 3 and BAP1 deficiency. The presented CAM xenograft model may prove useful to study the metastatic potential of patients or to test individualized therapeutic options for metastasis in different organs.

Electroporation with Calcium or Bleomycin: First Application in an In Vivo Uveal Melanoma Patient-Derived Xenograft Model.

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates.

Treatment Outcomes of Patients with Orbital Inflammatory Diseases: Should Steroids Still Be the First Choice?

Objective: To clarify the therapy response in orbital inflammatory diseases (OID), we analyzed the treatment effects of steroid therapy, the use of disease-modifying antirheumatic drugs (DMARDS), and biologicals in our tertiary referral center cohort. Methods: We collected the clinical and demographic data of all patients treated for non-specific orbital inflammation (NSOI) (n = 111) and IgG4-ROD (n = 13), respectively at our center from 2008 to 2020 and analyzed them with descriptive statistics. NSOI were sub-grouped according to the location into either idiopathic dacryoadenitis (DAs) (n = 78) or typical idiopathic orbital myositis (n = 32). Results: Mean age at first clinical manifestation was significantly different between subgroups (IOI: 49.5 ± 18, IgG4-ROD: 63.2 ± 14, p = 0.0171). Among all examined OID, 63 patients (50%) achieved full remission (FR) with corticosteroids (NSOI 53%/IgG4-ROD 31%). In contrast, classic myositis showed a significantly higher response (76%). Disease-modifying drugs (DMARDS) for myositis accomplished only 33% FR (NSOI 57%) and 66% did not respond sufficiently (NSOI 43%). The biologic agent (Rituximab) was significantly more efficient: 19 of 23 patients (82%) achieved full remission and only 4 (17%) did not respond fully and needed orbital irradiation or orbital decompressive surgery.

Wolfram-silicone implants as effective radiation shielding for ocular brachytherapy: dosimetric features and in vivo animal study on biocompatibility.

OBJECTIVE: To evaluate wolfram as a photon and beta absorber in the management of uveal melanoma with radiotherapy, examining its potential ocular adverse effects and physiologic tolerance using an in vivo rabbit ocular model. METHODS: A method of manufacturing implants from mixtures of wolfram and silicone was developed. Their shielding effect on the radiation of sources used in ocular brachytherapy was investigated by dosimetric measurement in an eye phantom as well as numerical simulations. Different wolfram implantation techniques, such as extraocular fixation of a wolfram-silicone implant (n = 1), vitrectomy with silicone oil and intravitreal injection of a wolfram-silicone oil suspension (n = 2), and concurrent attachment of a wolfram implant onto the sclera (n = 2), were tested to investigate the long-term effects of wolfram. A vitrectomy with silicone oil without wolfram implantation was carried out in 2 rabbits (n = 2), constituting the control group. The eyes were enucleated after 3 months for histologic analysis. RESULTS: Wolfram-silicone mixtures have been dosimetrically proven to be very effective radiation absorbers for use in ocular brachytherapy. Severe complications, such as endophthalmitis, secondary glaucoma, cornea decompensation, and vessel occlusion, were not documented in the tested rabbit eyes after the application of wolfram. Histologic examination of the bulbi after enucleation showed epiretinal gliosis without further pathologic findings in all eyes after vitrectomy. CONCLUSIONS: The results of this study show that wolfram and wolfram-silicone implants constitute a promising candidate as potential radiation shielding substrates.

Evidence in Focus: The Sparse Landscape of Randomized Trials on Retinoblastoma Treatment.

Background: Retinoblastoma, although rare, is one of the most common intraocular malignancies worldwide. Its prognosis has improved significantly in the past few decades, thanks to modern treatments, like systemic, intra-arterial, and intravitreal chemotherapy. However, regarding survival, there are significant differences between high- and low-income countries, eye salvage is still a challenge worldwide, and treatment-related toxicity needs to be carefully and sufficiently managed. Summary: To appraise the strength of supporting evidence, we performed a systematic review of randomized controlled trials investigating any therapeutic protocol for retinoblastoma. Four trials with 174 participants (188 eyes) were eligible, all pertaining to different intravenous chemotherapy regimens. Vincristine, etoposide, and carboplatin (VEC) appear superior to a 5-drug combination for stage III retinoblastoma. Moreover, etoposide and carboplatin as neoadjuvant chemotherapy followed by thermochemotherapy seem to offer better local control than vincristine and carboplatin. However, increasing carboplatin dose in the VEC protocol failed to improve treatment efficacy. Key Messages: Retinoblastoma is a success story of modern medicine. However, only intravenous chemotherapy has been studied through randomized trials, while evidence for the most novel retinoblastoma treatments has mainly stemmed from observational studies. International collaborations for multicenter randomized trials could overcome difficulties and increase certainty and precision in the field.

Prognostic factors for surgical treatment of radiation-induced scleral necrosis after brachytherapy for uveal melanoma.

PURPOSE: Radiation-induced scleral necrosis (RISN) is a less frequent complication of brachytherapy for uveal melanoma, and may require surgical treatment in selected cases. We aimed to identify the prognostic factors for RISN treatment. METHODS: All patients with brachytherapy for uveal melanoma treated at our institution between 01/1999 and 12/2016 who developed RISN were followed until 02/2021. Various parameters were evaluated through univariable and multivariable Cox regression analysis. The surgical intervention due to RISN was the principal outcome event of this study. RESULTS: Of 115 patients in the final cohort, 51 individuals (44%) underwent RISN treatment (conjunctival revision [n = 2], patching [n = 46] or enucleation [n = 3]) at median 1.80 months after RISN occurrence. Significant RISN characteristics were summarized into a novel RISN severity scale - Grade I: largest diameter ≤ 5 mm and no progression; Grade II: largest diameter > 5 mm or any progression during the follow-up; Grade III: presence of uveal prolapse; and Grade IV: leakage through open eyewall perforation. In the multivariable analysis, the RISN severity scale (aHR = 2.37 per grade increase, p = 0.01) and the time between brachytherapy and RISN occurrence (<15 months, aHR = 6.33, p < 0.0001) were independently associated with the study endpoint. The RISN severity scale showed high diagnostic accuracy for prediction of RISN treatment (AUC = 0.869). CONCLUSIONS: In our series, about the half of RISN cases underwent surgical treatment. The presented novel severity scale for RISN might become a helpful tool for clinical management of individuals with RISN. We recommend external validation of the diagnostic accuracy of the presented scale.

Uncertainties in ocular proton planning and their impact on required margins.

PURPOSE: To review required margins in ocular proton therapy (OPT) based on an uncertainty estimation and to compare them with widely used values. Further, uncertainties when using registered funduscopy images in the 3D model is investigated. METHODS: An uncertainty budget in planning and delivery was defined to determine required aperture and range margins. Setup uncertainties were considered for a cohort of treated patients and tested in a worst-case estimation. Other uncertainties were based on a best-guess and knowledge of institutional specifics, e.g. range reproducibility. Margins for funduscopy registration were defined resulting from scaling, rotation and translation of the image. Image formation for a wide-field fundus camera was reviewed and compared to the projection employed in treatment planning systems. RESULTS: Values for aperture and range with margins of 2.5 mm as reported in literature could be determined. Aperture margins appear appropriate for setup uncertainties below 0.5 mm, but depend on lateral penumbra. Range margins depend on depth and associated density uncertainty in tissue. Registration of funduscopy images may require margins of >2 mm, increasing towards the equator. Difference in the projection may lead to discrepancies of several mm. CONCLUSIONS: The commonly used 2.5 mm aperture margin was validated as an appropriate choice, while range margins could be reduced for lower ranges. Margins may however not include uncertainties in contouring and possible microscopic spread. If a target base is contoured on registered funduscopy images care must be taken as they are subject to larger uncertainties. Multimodal imaging approach in OPT remains advisable.

Surgical Outcome After Treatment of Radiation-Induced Scleral Necrosis in Patients With Uveal Melanoma.

PURPOSE: Surgical repair might be required in patients with uveal melanoma (UM) that develop advanced forms of radiation-induced scleral necrosis (RISN). In this monocentric long-term observational study, we aimed at analyzing the treatment outcome after RISN surgery. METHODS: All consecutive cases with UM who underwent surgical intervention for RISN between 1999 and 2020 were included. Achievement of the tectonic stability and evaluation of incidence and the risk factors for a repetitive patch surgery (RPS) were the main endpoints. RESULTS: The final analysis included 57 patients (mean age: 58.7 years; 63.2% female patients), where 55 individuals underwent a patch grafting, and 2 cases were treated with conjunctival reconstructive surgery. The mean follow-up time after grafting was 38.5 months (0.03-221.1 months). Tectonic stability was achieved in 56 (98.3%) patients. Scleral graft (38/55, 69.1%) was the most frequent patching material, followed by Tutopatch (7/55, 12.7%), corneal graft (7/55, 12.7%), dura graft (2/55, 3.6%), and fascia lata (FL) graft (1/55, 1.8%). Eleven patients (20%) underwent RPS after the mean time of 12.9 months (0.3-50.3 months). In the final multivariate Cox regression analysis, the use of Tutopatch (5/7; 71.4%, adjusted hazard ratio = 4.66, P = 0.044) and RISN progression after patch grafting (9/11; 81.8%, adjusted hazard ratio = 9.67, P = 0.008) were independent risk factors for RPS. CONCLUSIONS: RISN surgery maintains long-term tectonic stability in most of the cases underwent surgical repair for RISN after brachytherapy for UM. Depending on graft material and, particularly, further RISN progression, an RPS might be necessary in certain cases.

Tumor- and Radiation-Related Complications after Ruthenium-106 Brachytherapy in Small to Medium Uveal Melanomas (Part 1).

PURPOSE: The purpose of this study was to analyze tumor-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma, with respect to local tumor control, insufficient radiation response, enucleation, and metastasis rate. PATIENTS/METHODS AND MATERIALS: This retrospective study included 608 patients treated consecutively with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The occurrence of radiation-induced results was analyzed by estimating the risk by applying the Kaplan-Meier method, i.e., the "time to event" analysis. The Cox model test was used for the univariate and multivariate risk factor analyses. The median follow-up was 51 months after primary treatment. RESULTS: Tumor recurrence was found in 21 patients (3.5%) and repeated treatment due to insufficient effect after the initial ruthenium-106 brachytherapy was performed in 40 patients (6.6%). The 5-year cumulative risk of recurrence was 4.0% and that of insufficient effect was 7.3%. Thirteen patients (2.1%) underwent a secondary enucleation; 8 because of a local recurrence and 5 because of severe post-brachytherapy complications. The cumulative enucleation risk was 2.3% after 5 years and 2.9% after 10 years, corresponding to eye preservation of 97.7 and 97.1%, respectively. In forty-two patients (7.2%), metastatic disease was diagnosed during the follow-up. The metastatic rate as calculated by the Kaplan-Meier method was 9.0, and 13.1% at 5 and 10 years, respectively. CONCLUSION: Our study demonstrated that ruthenium-106 brachytherapy is an excellent treatment option for achieving local tumor control and eye preservation in well-selected patients. The metastatic rate is in agreement with that of previous studies analyzing small to medium size uveal melanomas.

Treatment-Related Complications and Functional Results after Ruthenium-106 Brachytherapy in Small to Medium Size Uveal Melanomas (Part 2).

PURPOSE: To analyze the treatment-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma in terms of radiation-induced optic neuropathy, maculopathy and retinopathy, radiation-related vitreous hemorrhage, and retinal detachment, as well as secondary glaucoma and radiogenic cataract. In addition, the course of visual acuity was analyzed. PATIENTS/METHODS AND MATERIALS: This retrospective study included 608 patients treated with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The follow-up time was 11 years. The occurrence of the radiation-induced complications was analyzed using the Kaplan-Meier method. Cox regression was used for univariate and multivariate risk factor analyses. Hazard ratios were calculated for each variable. RESULTS: Regarding the complications, 34% (N = 207) of the patients had no reported side effects or complications during follow-up. Radiation optic neuropathy was observed in 18.8% (N = 114) of the patients, with a median time to onset of 16 months (range: 3 - 78 months). Radiation maculopathy occurred in 8.2% (N = 50) after a median time of 17 months (range: 3 - 67 months). Radiation retinopathy was observed in 20.1% (N = 122), with a median time to onset of 21 months (range: 6 - 67 months). Secondary glaucoma developed in 9.7% of the patients (N = 53) and radiogenic cataract in 46.8% (N = 227). Vitreous hemorrhage (11.8%, N = 72) and scleral necrosis (2.1%, N = 13) occurred relatively rarely. CONCLUSION: The observed radiogenic complication rate is comparable with that reported in previous studies.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model.

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.

How Age Affects Graves' Orbitopathy-A Tertiary Center Study.

PURPOSE: Graves' orbitopathy (GO) is an autoimmune disorder leading to inflammation, adipogenesis, and fibrosis. The severity of GO can vary widely among individuals, making it challenging to predict the natural course of the disease accurately, which is important for tailoring the treatment approach to the individual patient. The aim of this study was to compare the clinical characteristics, course, treatment, and prognosis of GO patients under 50 years with older patients. METHODS: We reviewed the medical records of a random sample of 1000 patients in our GO database Essen (GODE) comprising 4260 patients at our tertiary referral center. Patients were divided into two groups: Group 1 (≤50 years) and Group 2 (>50 years). Only patients with a complete data set were included in the further statistical analysis. RESULTS: The results showed that younger patients (n = 484) presented significantly more often with mild GO (53% vs. 33%, p < 0.0001), while older patients (n = 448) were more likely to experience moderate-to-severe disease (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility, and clinical activity scores (5.9 vs. 2.3 PD/310° vs. 330° both p < 0.0001, CAS: 2.1 vs. 1.7, p = 0.001). Proptosis and occurrence of dysthyroid optic neuropathy (DON) showed no significant difference between groups (both 3%). Multiple logistic regression revealed that the need for a second step of eye muscle surgery was most strongly associated with prior decompression (OR = 0.12, 95% CI: 0.1-0.2, p < 0.0001) followed by orbital irradiation and age. The model showed good fitness regarding the area under the curve (AUC = 0.83). DISCUSSION: In conclusion, younger GO patients present with milder clinical features such as a lower rate of restrictive motility disorders and less pronounced inflammatory signs. Therefore, older patients tend to need more steroids, irradiation, and lid and eye muscle surgery. Still, the risk of DON and the necessity of secondary eye muscle surgery are not or only slightly associated with age, respectively.

Leadership in ophthalmology by humanity and competence.

Leadership in healthcare institutions has a direct impact on the practice of the medical and nursing professions. The respective leadership style that is cultivated in a medical institution therefore has a direct impact on the personnel and thus a direct impact on the treatment of patients, in both senses of the word. Leadership in healthcare should therefore inspire, motivate, and guide healthcare workers to use their individual and collective skills as well as the available resources in the best possible way for the benefit of patients. This is the task and obligation of all those working in the healthcare system. The German Society of Ophthalmology (DOG) has established a leadership academy for ophthalmologists to meet the requirements of the modern healthcare market for leadership qualifications.

Leadership in ophthalmology training : Opportunities and risks of medical specialist education.

Medical specialist training requires constant improvement and adaptation of the contents to the current situation. Nowadays, young physicians have the opportunity to select among the most renowned institutions and can choose the one most qualified for their training. Hospitals on the other hand still have the desire to recruit highly qualified physicians for their resident programs, which requires a good, well-rounded and reliable offer by the department under good leadership. Thus, among other issues a modern and multilingual homepage is already an important instrument for successfully addressing applicants and winning them over for the department. In addition to a well-planned and structured training plan (e.g., the "Homburg Curriculum") and a so-called "resident guide", many other additional offers are nowadays part of a successful training, such as structured internal and external specialist training courses, well thought out research concepts available to all interested parties, wet labs for practical exercises on pig's eyes and as the latest most innovative addition, a virtual reality simulator. Due to a structured curriculum with regular continuous education during the daily early morning meetings and an exchange program with another university eye hospital, not only the residents can benefit but ultimately also the department itself. In addition, future specialists are involved in the respective organization (so-called "service teams") from the very beginning. This conveys a great deal of knowledge and expertise but also organizational skills and thus improves the quality of training. In any case, standardized residency training with a view beyond the horizon, which is transparently organized and reliably carried out, improves the quality of training in order to become a certified ophthalmologist and increases the satisfaction of the residents. A department which is committed and can offer a wide range of services will benefit from motivated and satisfied employees in a good interpersonal climate, which in the end benefits not only the team but also the patients.

[Importance of fluorescein angiography for differentiating between early papilledema and papillitis]. / Stellenwert der Fluoreszenzangiographie zur Differenzierung zwischen einer frühen Stauungspapille und einer Papillitis.

BACKGROUND: Optic disc swelling poses a diagnostic challenge due to its multiple underlying pathological causes. This study aimed to investigate the use of fluorescein angiography (FLA) in combination with optical coherence tomography (OCT) as a diagnostic tool for differentiating between papilledema and papillitis in cases of optic disc swelling. MATERIAL AND METHODS: A total of 12 patients were included in the study in whom both FLA and OCT of the optic disc were performed to evaluate the optic disc swelling in cases of papilledema (7 patients, 14 eyes) and papillitis (5 patients, 7 eyes). The fluorescence behavior of the optic disc during late phase FLA was examined in relation to papillary thickness measured by OCT. RESULTS AND DISCUSSION: In the papilledema group OCT revealed a mean papillary thickness of 873 µm. In 6 patients FLA detected a ring-shaped papillary hyperfluorescence with papillary thicknesses ranging from 611 µm to 972 µm. Another patient with chronic and marked papilledema exhibited bilateral panpapillary leakage in FLA and papillary thicknesses of 1287 µm (right eye) and 1526 µm (left eye). In the papillitis group FLA showed panpapillary leakage in all cases. The mean papillary thickness was 865 µm (range 632-1195 µm). CONCLUSION: In acute optic disc swelling and a papillary prominence less than 1000 µm in OCT, a difference in FLA was noticeable between papilledema and papillitis. While acute and mild papilledema exhibited a ring-shaped hyperfluorescence, papillitis showed a panpapillary leakage in late phase FLA in the examined cases. This difference could not be seen in the case of papilledema with chronic and severe swelling.

Preoperative Detection of Local Tumor Extent in Patients with Advanced Retinoblastoma: Predictive Value of MRI and Clinical Findings. / Präoperativer Nachweis der lokalen Tumorausdehnung bei Patienten mit fortgeschrittenem Retinoblastom: prädiktiver Wert MR-tomografischer und klinischer Befunde.

OBJECTIVE: Before planned enucleation, local tumor extension in advanced retinoblastoma is routinely assessed preoperatively using high-resolution magnetic resonance imaging (MRI). The aim of our study was to analyse the predictive value of MRI and clinical characteristics for predicting tumor extent, as confirmed by histopathology postoperatively. PATIENTS AND METHODS: All consecutive patients were included who underwent primary enucleation for advanced retinoblastoma after high-resolution MRI examination in our hospital between January 2011 and December 2021. The primary study endpoint was the evaluation of the predictability of histopathological risk factors on preoperative MRI examination. The sensitivity and specificity of the MRI examination with respect to clinically relevant optic nerve infiltration and choroidal infiltration were determined. RESULTS: The mean age of the 209 included patients was 1.6 years (range 1 month to 4.7 years). MRI indicated optic nerve infiltration in 46 (22%) patients, extensive choroidal infiltration in 78 (40.2%) patients, and scleral infiltration in one patient (2.6%). Histopathological examination demonstrated postlaminar optic infiltration in 25 (12%) patients and extensive choroidal infiltration in 17 (8.1%) cases. Scleral infiltration was evident in 8 (3.8%) patients. In the final multivariate analysis, MRI findings of tumor infiltration and a preoperative intraocular pressure ≥ 20 mmHg were independently associated with histopathological evidence of clinically relevant optic nerve (p = 0.033/p = 0.011) and choroidal infiltration (p = 0.005/p = 0.029). The diagnostic accuracy of the prediction models based on the multivariate analysis for the identification of the clinically relevant optic nerve (AUC = 0.755) and choroidal infiltration (AUC = 0.798) was greater than that of purely MRI-based prediction (respectively 0.659 and 0.742). The sensitivity and specificity of MRI examination for determining histopathological risk factors in our cohort were 64% and 65% for clinically relevant optic infiltration and 87% and 64% for clinically relevant choroidal infiltration. CONCLUSION: The local tumor extent of retinoblastoma with infiltration of the optic nerve and choroid can be well estimated based on radiological and clinical characteristics before treatment initiation. The combination of clinical and radiological risk factors supports the possibility of early treatment stratification in retinoblastoma patients.

Release of Cell-Free Tumor DNA in the Plasma of Uveal Melanoma Patients Under Radiotherapy.

Purpose: Uveal melanoma (UM) is a tumor of the eye that metastasizes in approximately half of cases. Prognostic testing requires accessibility to tumor tissue, which is usually not available with eye-preserving therapies. Noninvasive approaches to prognostic testing that provide valuable information for patient care are therefore needed. The aim of this study was to evaluate the use of circulating cell-free plasma DNA analysis in UM patients undergoing brachytherapy. Methods: The study recruited 26 uveal melanoma patients referred to the department between February and October 2020. Blood samples were collected at various time points before, during, and after treatment, and deep amplicon sequencing was used to identify oncogenic variant alleles of the GNAQ and GNA11 genes, which serve as indicators for the presence of circulating tumor DNA (ctDNA). Results: The results showed that all patients were ctDNA negative before brachytherapy. In 31% of patients, ctDNA was detected during therapy. The variant allele fraction of GNAQ or GNA11 alleles in ctDNA positive samples ranged from 0.24% to 2% and correlates with the largest basal diameter and thickness of the tumor. Conclusions: The findings suggest that brachytherapy increases the presence of tumor DNA in the plasma of UM patients. Thus ctDNA analysis may offer a noninvasive approach for prognostic testing. However, efforts are still required to lower the limit of detection for tumor-specific genetic alterations.