[Short Review of the History of Radiotherapy for Intraocular Tumours]. / Kurzer historischer Rückblick der Strahlentherapie intraokularer Tumoren.

For many decades, radiotherapy with its different modalities has proved to be the gold standard in the treatment of benign and malignant intraocular tumours. The various complicated therapeutic developments in this field cover a period of over 100 years and the present year deserves special mention because of the 100th anniversary of the first mention of a successful brachytherapy for a uveal melanoma by R. Deutschmann in Hamburg in 1915.

Measurements regarding a combined therapy concept for ophthalmic tumors consisting of brachytherapy and x-rays.

Objective.We present a novel concept to treat ophthalmic tumors which combines brachytherapy and low-energy x-ray therapy. Brachytherapy with106Ru applicators is inadequate for intraocular tumors with a height of 7 mm or more. This results from a steep dose gradient, and it is unfeasible to deliver the required dose at the tumor apex without exceeding the maximum tolerable sclera dose of usually 1000 Gy to 1500 Gy. Other modalities, such as irradiation with charged particles, may be individually contraindicated. A dose boost at the apex provided by a superficial x-ray therapy unit, performed simultaneously with the brachytherapy, results in a more homogeneous dose profile than brachytherapy alone. This avoids damage to organs at risk. The applicator may also serve as a beam stop for x-rays passing through the target volume, which reduces healthy tissue dosage. This study aims to investigate the suitability of the applicator to serve as a beam stop for the x-rays.Approach.A phantom with three detector types comprising a soft x-ray ionization chamber, radiochromic films, and a self-made scintillation detector was constructed to perform dosimetry. Measurements were performed using a conventional x-ray unit for superficial therapy to investigate the uncertainties of the phantom and the ability of the applicator to absorb x-rays. The manufacturer provided a dummy plaque to obtain x-ray dose profiles without noise from106Ru decays.Results.The phantom is generally feasible to obtain dose profiles with three different detector types. The interaction of x-rays with the silver of the applicator leads to an increased dose rate in front of the applicator. The dose rate of the x-rays is reduced by up to 90% behind a106Ru applicator. Therefore, a106Ru applicator can be used as a beam stop in combined x-ray and brachytherapy treatment.

[ChatGPT and the German board examination for ophthalmology: an evaluation]. / ChatGPT und die deutsche Facharztprüfung für Augenheilkunde: eine Evaluierung.

PURPOSE: In recent years artificial intelligence (AI), as a new segment of computer science, has also become increasingly more important in medicine. The aim of this project was to investigate whether the current version of ChatGPT (ChatGPT 4.0) is able to answer open questions that could be asked in the context of a German board examination in ophthalmology. METHODS: After excluding image-based questions, 10 questions from 15 different chapters/topics were selected from the textbook 1000 questions in ophthalmology (1000 Fragen Augenheilkunde 2nd edition, 2014). ChatGPT was instructed by means of a so-called prompt to assume the role of a board certified ophthalmologist and to concentrate on the essentials when answering. A human expert with considerable expertise in the respective topic, evaluated the answers regarding their correctness, relevance and internal coherence. Additionally, the overall performance was rated by school grades and assessed whether the answers would have been sufficient to pass the ophthalmology board examination. RESULTS: The ChatGPT would have passed the board examination in 12 out of 15 topics. The overall performance, however, was limited with only 53.3% completely correct answers. While the correctness of the results in the different topics was highly variable (uveitis and lens/cataract 100%; optics and refraction 20%), the answers always had a high thematic fit (70%) and internal coherence (71%). CONCLUSION: The fact that ChatGPT 4.0 would have passed the specialist examination in 12 out of 15 topics is remarkable considering the fact that this AI was not specifically trained for medical questions; however, there is a considerable performance variability between the topics, with some serious shortcomings that currently rule out its safe use in clinical practice.

Prognostic relevance of circulating tumor cells in metastatic uveal melanoma.

OBJECTIVE: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance. METHODS: Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics. RESULTS: CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis. CONCLUSION: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.

[Intraocular manifestations of systemic neoplasms]. / Intraokulare Manifestationen bei systemischen Tumorerkrankungen.

There are multiple possible intraocular manifestations in patients with systemic neoplasms. At first line there are uveal, retinal and vitreous metastases from carcinomas, melanomas and lymphomas. In patients with von Hippel Lindau syndrome or familiar adenomatous polyposis coli (FAP), Gardner or Turcot syndromes, fundus examinations can help in the primary diagnosis and thereby facilitate the early detection of systemic neoplasms such as cerebral and spinal haemangioblastoma, kidney or bowel cancer. Furthermore there are rare ocular paraneoplastic syndromes such as the cancer- or melanoma-associated retinopathies (CAR/MAR), the paraneoplastic optic neuropathy (PON) and the bilateral diffuse melanocytic proliferation (BDUMP) that develop secondary to systemic malignancies and can be the primary manifestation.

[Retinoblastoma]. / Retinoblastom.

Retinoblastomas represent 6% of all malignant tumors in children under 5 years old, which untreated lead to blindness in the affected eye and death due to metastases. The main symptoms are leukocoria and strabismus, which if possible, always necessitate a clarification within 1 week for exclusion of a retinoblastoma. The most frequent differential diagnoses are Coats' disease and persistent fetal vasculature (PFV) as well as other intraocular tumors, in particular astrocytomas. Systemic chemotherapy, if necessary in combination with laser hyperthermia, local chemotherapy and brachytherapy are the most important methods for eye-preserving treatment. Advanced cases mostly necessitate enucleation.

[Surgical treatment modalities in uveal melanomas]. / Chirurgische Behandlungsmöglichkeiten beim Aderhautmelanom.

The treatment of large uveal melanomas poses a therapeutic challenge, due to the expected treatment-related side-effects. After sole radiotherapy the majority of patients are faced with radiogenic complications secondary to the large amount of tumour necrosis. Alternative treatment modalities addressing this issue are transscleral resection in arterial hypotension in anteriorly located tumours and endoresection via pars plana vitrectomy in posteriorly located tumours. A surgical resection treatment was applied in 292 patients with large uveal melanomas. In 150 patients the tumour was treated by transscleral resection and postoperative adjuvant (106)ruthenium brachytherapy and 142 patients were treated by primary proton beam irradiation and secondary endoresection. The mean follow-up time was 3.8 and 2.5 years, respectively. Local tumour control was achieved in 76 % and 98 %, respectively. The 5-year metastatic rates were 28 % and 21 % and eye retention was achieved in 82 % and 97 %, respectively. Surgical resection of uveal melanomas with adjuvant radiotherapy is the treatment of choice in cases of large tumours, avoiding enucleation in the vast majority of cases in the long term, without increasing the incidence of tumour-related risks.

[Therapy for peripapillary located and large choroidal haemangioma with PDT 'paint-brush technique']. / Behandlung peripapillärer und grosser Aderhauthämangiome mittels PDT-"Paint-Brush-Technik"

BACKGROUND: Today photodynamic therapy (PDT) with Verteporfin is the standard treatment option for symptomatic choroidal haemangiomas. Nevertheless, peripapillary or large haemangiomas pose a therapeutic dilemma, since severe adverse events have been demonstrated in cases where the optic disc was included in the treatment spot. In addition due to the size and the shape of the laser spot, peripapillary and large haemangiomas can only be undertreated or overtreated (with overlapping multiple spots). With the presented new "paint-brush technique" it is possible to treat peripapillary and large choroidal haemangiomas completely without danger for the optic disc and without overtreatment. MATERIAL AND METHODS: With the new technique the application of the laser spot is performed in a "paint-brush fashion" by moving he spot with constant speed excentrically around the lesion's centre over the entire tumour surface. This allows under visual control a complete and confluent PDT of the whole tumour surface without overlapping and/or missing areas or treating the optic disc. In total, 13 eyes of 13 patients (6 with peripapillary and 7 with large choroidal haemangiomas) have been treated. The mean follow-up time was 25.6, respectively, 14.5 months. RESULTS: The PDT with the "paint-brush technique" allows an effective treatment of the leakage in both groups. The mean increase of visual acuity was 1, respectively, 1.4 ETDRS lines 3 months after therapy, which could be maintained over the whole follow-up period. At the last examination visual acuity was unchanged or better in 12 / 13 (92 %) of eyes. After 3 months the tumour height was significantly (p = 0.031 and 0.018) reduced to 1.7 mm (52 %), respectively, 1.3 mm (30 %), which was stable during the whole follow-up. No significant side effects could be detected. CONCLUSION: The use of the PDT "paint-brush technique" allows complete treatment of choroidal haemangiomas under visual control. Sensitive structures like the optic disc could be excluded from treatment without double- or undertreatment. The functional and anatomic results are good. The technique is a safe and effective amendment in the treatment of symptomatic choroidal haemangiomas.

[Family screening in patients with retinal angiomatosis]. / Familienuntersuchungen bei Patienten mit Angiomatosis retinae.

BACKGROUND: The aim of this study was to characterise the results of a screening for von Hippel-Lindau disease (VHL), angiomatosis retinae (AR) and further VHL lesions in at-risk relatives of ophthalmological VHL index patients. METHODS: A retrospective analysis of 20 VHL index patients identified by the presence of angiomatosis retinae and a mutation of the VHL gene was carried out. A molecular genetic test for a VHL mutation and funduscopy was offered to all available at-risk relative. In the case of a positive test result, repeated screening for AR and further VHL lesions were suggested. RESULTS: Fifty-one out of 86 first- and second-degree relatives were screened, and 73 % showed a VHL mutation. At first presentation, asymptomatic AR was present in 55 %, at the end of the study in 72 % of gene carriers. In contrast to the index patients, angiomas were small and could be treated without functional loss. During the study 4 eyes of index patients developed blindness, whereas in the affected relatives no such event occurred. Affected relatives developed further VHL lesions to the same number and extent as the index patients. CONCLUSIONS: This study demonstrates the necessity of a screening of at-risk relatives of patients with AR and VHL. Molecular genetic screening allows an early identification of affected relatives. Early and regular screening enables the detection of small retinal angiomas and their treatment without functional loss.

[Treatment modalities for conjunctival melanoma]. / Therapeutische Optionen in der Behandlung des malignen Melanoms der Bindehaut.

BACKGROUND: Because of high local recurrence rates after excision of conjunctival melanoma adjuvant local chemotherapy employing mitomycin C (MMC) or irradiation is recommended. Brachytherapy is possible with ruthenium-106-plaques ((106)Ru) or with the strontium-90-plaques ((90)Sr). PATIENTS AND METHODS: Fifty-six patients received an excision and adjuvant radiotherapy of conjunctival melanoma between 1992 and 2007. The mean follow-up was 42 months (12 - 151 months). Mean age was 62 (28- 86) years. As an adjuvant radiotherapy 15 patients received X-ray irradiation, 12 patients received (106)Ru-brachytherapy, 4 patients received proton beam therapy and 16 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. Four patients received proton beam irradiation and in 13 patients an exenteratio was performed. RESULTS: Twelve patients (21 %) developed tumour recurrences in or adjacent to the irradiated area. Thirteen patients (22 %) showed a recurrence distant from the primary site. Ten patients (18 %) developed systemic metastasis during follow-up. Seven patients (46 %) had no recurrence during the follow-up. Three patients (20 %) had a recurrence in the treated or adjacent areas. Eight patients (53 %) developed new tumours in non-treated areas. CONCLUSIONS: Adjuvant radiotherapy allows an acceptable local tumour control rate after excision of conjunctival melanoma. No obvious differences regarding tumour control or systemic metastasis could be seen between the different modes of radiotherapy used.

[Multimodal diagnostic of CSNB1 with NYX gene mutation]. / Stufendiagnostik einer CSNB1 mit NYX-Genmutation.

This article presents the case of a young male patient with complete congenital stationary night blindness (CSNB1). The informative value of the general medical history and clinical findings for the diagnosis was impaired due to language barriers and low compliance. Full-field electroretinography and optical coherence tomography help to define particular hereditary retinal dystrophies. Molecular genetic analysis by next generation sequencing as a part of multimodal diagnostics finally uncovered a rare, causal missense mutation in the nyctalopin (NYX) gene.

[Tamoxifen retinopathy: a case series of clinical and functional data]. / Tamoxifen-Retinopathie: Eine Fallserie von klinischen und funktionelle Daten.

BACKGROUND: Tamoxifen is used in the treatment of selected patients with breast carcinoma. Rarely, it has been shown to cause ocular toxic effects including crystalline retinopathy. METHODS: Retrospective analysis of clinical and functional (visual acuity, visual field, colour vision) data of a case series of eight female patients under tamoxifen therapy with electrophysiological examination. RESULTS: Seven of eight patients complained of visual disturbances. In one case, examination showed crystalline deposits in the cornea and macular area. Three patients revealed changes in full-field and multifocal electroretinogram, and two had a pathological multifocal electroretinogram only. In six cases we applied a desaturated panel D-15 colour vision test; five of these showed some disorders. CONCLUSIONS: Most tamoxifen patients who complained of visual disturbances showed electrophysiological changes, particularly in the multifocal electroretinogram and often without a certain morphological correlate. We recommend electrophysiological examination for patients with unclear visual deterioration who are receiving tamoxifen therapy.

[Recurrence rate following adjuvant strontium-90 brachytherapy after excision of conjunctival melanoma]. / Rezidivhäufigkeit nach Exzision von Bindehautmelanomen und adjuvanter Strontium-90-Kontaktbestrahlung.

BACKGROUND: Because of the high local recurrence rates after excision of conjunctival melanomas, adjuvant local chemotherapy or irradiation is recommended. Strontium-90 brachytherapy is one radiotherapeutic option due to its low penetration depth. METHODS: 15 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. The treatment was fractionated into 9 irradiation sessions with 6 Gy each. The mean follow-up was 35 months (12-60 months). RESULTS: Seven patients (46%) had no recurrence during the follow-up. Three patients (20%) had a recurrence in the treated or adjacent area. Eight patients (53%) developed new tumours in non-treated areas. CONCLUSIONS: Strontium-90 brachytherapy is a useful adjuvant in the treatment of conjunctival melanomas. Regular ophthalmoscopic controls are necessary because of the high rate of new tumours in non-irradiated areas, especially in cases with primary acquired melanosis.

[Rhegmatogenous retinal detachment : Epidemiology and risk factors]. / Rhegmatogene Netzhautablösung : Epidemiologie und Risikofaktoren.

The incidence of rhegmatogenous retinal detachment in the European population is approximately 10 cases per 100,000 inhabitants per year and reaches a peak in the 6th and 7th decades of life, mostly in atemporal association with posterior vitreous body detachment. Known risk factors include myopia and higher axial length of the eye, male gender, previous trauma and vitreoretinal degeneration or dystrophy. In recent years, an increase in the risk of rhegmatogenous retinal detachment following cataract surgery was also found, especially after capsule rupture and vitreous body loss. In contrast to clear lens extraction (CLE), the refractive intervention of laser in situ keratomileusis (LASIK) does not seem to increase the risk of rhegmatogenous retinal detachment. Retinal detachment stabilizes during physical protection and posturing but progresses through bodily activity and during interruptions in patients with macula-on retinal detachment.

[Juxtapapillary capillary retinal angioma with epiretinal membrane of the macula in familial Von-Hippel-Lindau-Syndrome]. / Juxtapapilläres kapilläres retinales Angiom mit epiretinaler Membran der Makula bei familiärem Von-Hippel-Lindau-Syndrom.

A case of juxtapapillary capillary retinal angioma associated with a vascularized epiretinal membrane of the macula in a 6-year-old girl is presented. Von-Hippel-Lindau-Syndrome was revealed by molecular genetic methods, and further family members were identified as gene carriers. The retinal angioma embedded in an epiretinal membrane was removed completely with the membrane by pars plana vitrectomy with a good functional result. Histopathology confirmed the diagnosis of capillary angioma.