Comparability of input parameters in the German Retina.net ROP registry and the EU-ROP registry - An exemplary comparison between 2011 and 2021.

PURPOSE: The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries. METHODS: Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments. RESULTS: The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021. CONCLUSION: Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021.

Diagnosis and treatment of malignant eyelid tumors.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

Surgical excision of eyelid tumors and subsequent ophthalmoplastic reconstruction.

In recent years new modern therapeutic concepts have been developed in the treatment of malignant eyelid tumors; however, surgical restoration remains an important component of the therapeutic options addressed, which include microsurgical tumor excision into healthy tissue and subsequent coverage of the defects. An ophthalmic surgeon experienced in oculoplastic surgery is responsible for the recognition and evaluation of the existing alterations and planning a procedure together with the patient that meets the patient's expectations. The planning of surgery must always be individualized and fit the initial findings. Depending on the defect size and localization, different coverage strategies are available to the surgeon. To ensure successful reconstruction, every surgeon should master a wide range of reconstructive techniques.

[Surgical excision of eyelid tumors and subsequent ophthalmoplastic reconstruction]. / Chirurgische Exzision von Lidtumoren und anschließende ophthalmoplastische Rekonstruktionen.

In recent years new modern therapeutic concepts have been developed in the treatment of malignant eyelid tumors; however, surgical restoration remains an important component of the therapeutic options addressed, which include microsurgical tumor excision into healthy tissue and subsequent coverage of the defects. An ophthalmic surgeon experienced in oculoplastic surgery is responsible for the recognition and evaluation of the existing alterations and planning a procedure together with the patient that meets the patient's expectations. The planning of surgery must always be individualized and fit the initial findings. Depending on the defect size and localization, different coverage strategies are available to the surgeon. To ensure successful reconstruction, every surgeon should master a wide range of reconstructive techniques.

[Diagnosis and treatment of malignant eyelid tumors]. / Diagnose und Therapie der malignen Lidtumoren.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

[Diagnosis and treatment of benign eyelid tumors]. / Diagnose und Therapie der benignen Lidtumoren.

BACKGROUND: Benign tumors of the eyelids are frequent entities. They are often cause for cosmetic concern or can lead to irritation of the ocular surface. The differentiation from premalignant or malignant eyelid tumors is particularly important. In most cases this can be done clinically; however, in some cases histological evaluation is warranted. OBJECTIVE: The aim of this article is to characterize the most important benign tumors of the eyelid and to ascertain when a histological examination is necessary. Furthermore, fundamental treatment procedures are discussed. METHODS: This narrative review was prepared based on a selective literature search. The characteristics of some eyelid tumors are underlined with illustrations from clinical cases. RESULTS: Most benign eyelid tumors are treated because of cosmetic or functional concerns. Some of them, including actinic keratosis, keratoacanthoma, cutaneous horn, trichofolliculoma, resemble malignant lid tumors or precancerous lesions and are thus excised in oder to obtain a diagnosis. Dermoid cysts can cause complications and congenital melanocytic naevi can exhibit malignant transformation and may need treatment. Inflammatory tumors can be treated conservatively in most cases but might require surgery in certain cases. Systemic associations exist with some of the benign lid tumors and should not be overlooked as they can be crucial for overall patient morbidity. CONCLUSION: Benign tumors of the eyelids are frequent and can be found at any age depending on the diagnosis. This article describes the lesions most commonly encountered in the clinical routine and helps at making a plan for further management.

[Clinical procedures for intraocular lymphomas]. / Klinisches Vorgehen bei intraokulären Lymphomen.

BACKGROUND: The classification of intraocular lymphomas is based on their anatomical location. They are divided into uveal lymphomas with involvement of the choroid, ciliary body or iris and vitreoretinal lymphomas with isolated or combined involvement of the vitreous body and/or retina. Over the last decades it has become increasingly possible to work out the clinical and pathobiological features of the various subtypes, thereby reducing the diagnostic hurdles and creating improved treatment options. OBJECTIVE: A summary of the various types of intraocular lymphoma in terms of clinical features, diagnostics, treatment and prognosis is given as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the subject of intraocular lymphomas using PubMed and Google Scholar. RESULTS: Intraocular lymphomas affect different structures, so that the symptoms can also be very different. The diagnostic spectrum ranges from typical ocular examination methods to sample biopsies with subsequent cytological, histological and molecular pathological processing. The treatment pillars available are percutaneous irradiation and intravitreal drug administration as local treatment and systemic treatment or a combination of systemic and local treatment. The prognosis depends mainly on the subtype of the lymphoma and the extent of the infestation when the diagnosis is confirmed. Even though some effective treatment options are now available, it has not yet been possible to significantly reduce the mortality rate. CONCLUSION: Many different options are available for the diagnostics and treatment of intraocular lymphomas, which require close interdisciplinary cooperation. The further developments in the field of molecular pathology allow a faster and more accurate diagnosis and could open up new treatment options in the future.

[Alterations of the anterior segment of the eye caused by exposure to UV radiation]. / UV-strahlenexpositionsbedingte Veränderungen am vorderen Augenabschnitt.

BACKGROUND: By identifying diseases of the anterior segment of the eye associated with exposure to UV light, recommendations for action can be derived. AIM: After reading this review, the reader should be familiar with UV light-associated diseases of the anterior segment of the eye. METHOD: Using a selective literature search, UV light-associated diseases of the anterior segment of the eye were identified and protective mechanisms are described. RESULTS: The UV light-associated lesions of the anterior segment of the eye include basal cell and squamous cell carcinomas, malignant melanoma of the eyelids and conjunctiva, pterygium, keratoconjunctivitis photoelectrica and climatic droplet keratopathy as well as cortical cataract. CONCLUSION: Eyeglasses for filtering UV light, sunglasses and special safety glasses, such as welding helmets and wearing headgear protect against UV light exposure to the anterior segment of the eye and the associated diseases.

[Chorioretinal atrophy in pediatric cerebral folate deficiency-a preventable disease?] / Chorioretinale Atrophie bei kindlichem zerebralem Folatmangel ­ eine vermeidbare Erkrankung?

Cerebral folate deficiency (CFD) results in neurological alterations and a massive degeneration of the choroid/retina if left untreated, which limit the visual field and visual acuity. This article reports the case of a female patient with CFD, who developed autistic personal characteristics prior to reaching school age and first started to speak at the age of 3 years. At the age of 6 years she was presented because of unclear reduced visual acuity in the right eye. At that time mild bilateral peripheral chorioretinal atrophy was present, which subsequently became more pronounced. Additionally, a centrally emphasized chorioretinal atrophy further developed. Visual acuity of both eyes progressively deteriorated until stagnating at 0.1 at the age of 14 years. The causal assignment of the findings of the patient was not possible for many years. Choroideremia was excluded by molecular genetic testing (CHM gene with no mutations) and gyrate atrophy was ruled out by a normal ornithine level. The existence of a mitochondrial disease was almost completely excluded by exome sequencing. After the onset of further nonocular symptoms, e.g. neuromuscular disorders, electroencephalograph (EEG) alterations and autistic disorder, intensified laboratory diagnostics were performed in the treating pediatric hospital. Finally, an extremely low level of the folic acid metabolite 5­methyltetrahydrofolate was detected in the cerebrospinal fluid (CSF) leading to the diagnosis of CFD. High-dose substitution treatment with folic acid was subsequently initiated. After excluding the presence of a pathogenic mutation of the FOLR1 gene for the cerebral folate receptor 1, a high titer blocking autoantibody against cerebral folate receptor 1 was detected as the cause.

[Molecular genetic investigations as the basis for targeted treatment of basal cell carcinoma of the eye]. / Molekulargenetische Untersuchungen als Basis zielgerichteter Therapien beim Basalzellkarzinom am Auge.

BACKGROUND: Basal cell carcinomas are generally the most common malignant human cancers. They grow destructively and invasively into surrounding tissue. OBJECTIVE: The rising incidence of basal cell carcinomas in an aging society demands new, less destructive treatment approaches especially for advanced and difficult to resect basal cell carcinomas at surgically demanding locations, such as those growing or metastasizing on the eyelid. MATERIAL AND METHODS: New key technologies, such as next generation sequencing (NGS) enable high-throughput genetic analyses of tumors. In this way new knowledge on the molecular genetic pathogenesis of basal cell carcinomas is gained, which enables the development of new targeted treatment of the affected signal pathway. RESULTS: In line with the multistep photocarcinogenesis theory, basal cell carcinomas possess a high load of UV-induced gene mutations (75%). Independent of the genesis 85% of basal cell carcinomas harbor activating mutations of the hedgehog signaling pathway. Accordingly, two hedgehog inhibitors for the treatment of difficult to resect or metastasized basal cell carcinomas have been licensed (vismodegib and sonidegib); however, only 60% of patients respond to this treatment. This is due to the high mutational load with 85% of the tumors harboring additional mutations in other signaling pathways. CONCLUSION: Molecular genetic analyses will enable the identification of further targeted therapies for advanced basal cell carcinomas. Due to the high mutational load checkpoint inhibitors (e. g. cemiplimab) are also effective in the treatment of basal cell carcinomas. Nicotinamide and UV protection can reduce the mutational load and hence decrease the risk for tumor development.

[Surgical resection with ophthalmoplastic reconstruction : Gold standard in periocular basal cell carcinoma]. / Chirurgische Resektion mit ophthalmoplastischer Rekonstruktion : Goldstandard beim periokulären Basalzellkarzinom.

The gold standard for the treatment of periocular basal cell carcinoma is surgical resection followed by ophthalmoplastic reconstruction. The highest priority in most cases is the complete histopathologically controlled tumor excision. The histopathological preparation can be carried out in two stages by rapid overnight embedding or intraoperatively by a rapid frozen section procedure. A variety of reconstruction methods enable a customized and in most cases also a cosmetically and functionally attractive defect coverage. Postoperatively, a regularly performed tumor aftercare is essential.

[The German keratomycosis registry : Initial results of a multicenter survey]. / Das Deutsche Pilz-Keratitis-Register : Erste Ergebnisse einer multizentrischen Erhebung.

BACKGROUND AND PURPOSE: Mycotic keratitis is a serious but relatively rare disease. No targeted data collection in Germany existed until the foundation of the German Pilz-Keratitis Register in 2015. PATIENTS AND METHODS: The inclusion of retrospective and prospective patients was carried out. INCLUSION CRITERIA: diagnosis confirmed by the polymerase chain reaction (PCR), culture, histology or confocal microscopy (IVCM). Collected parameters: date of symptom onset, date and method of diagnosis, risk factors, visual acuity and findings at admission and at follow-up, conservative and surgical treatment. RESULTS: By January 2018, a total of 102 eyes from the years 2000-2017 were reported from 16 centers (64.3% female, mean age 52 years, range 18-95 years). The initial diagnosis was made correctly in only 20.6% of cases. The mean time to correct diagnosis was 31.7 ±â€¯46.9 (0-296) days. The diagnosis was confirmed in cultures in 74.5%, histologically in 30.4%, by PCR in 38.2% and IVCM in 27.4%. Fungal species identified were: 36.7% Fusarium spp., 35.8% Candida spp., 6.4% Aspergillus spp. and 21.1% other. The most important risk factor was the use of contact lenses. The most commonly used antifungal agent was voriconazole (64.7%) followed by amphotericin B (37.2%). Penetrating keratoplasty was performed in 65.7% of the cases and 8.8% of the affected eyes had to be enucleated. The visual acuity of the entire study population increased from the initial 0.16 ±â€¯0.25 (0.001-1.0) decimal to 0.28 ±â€¯0.34 (0-1.0) decimal. CONCLUSION: The correct diagnosis of fungal keratitis is often significantly delayed. The treatment can be very difficult and keratoplasty is often necessary. In order to gain a better understanding of this disease, to recognize previously unknown risk factors and, if necessary, a change in the spectrum of pathogens and to identify approaches to treatment optimization, the fungal keratitis registry will be continued.

[Clinico-echographic diagnostics of iris tumors]. / Klinisch-echographische Diagnostik bei Iristumoren.

BACKGROUND: The differentiation of iridic space-occupying lesions represents a regularly reoccurring diagnostic challenge. OBJECTIVE: This article presents an overview of the epidemiological data and describes the diagnostic procedure for iris tumors. MATERIAL AND METHODS: The article provides a review of the literature from PubMed and own clinical results. RESULTS: Melanocytic lesions comprise the vast majority of all iris tumors and include nevi and melanomas. Slit lamp biomicroscopy with standardized photography reveals two-dimensional planar tumor growth over time, which is the only recognized clinical surrogate finding for a malignant event. Ultrasound biomicroscopy (UBM) is additionally obligatory because it is the only method which enables documentation of the extent of tumor penetration, ciliary body involvement and internal structure of iris tumors. CONCLUSION: Serial slit lamp and UBM examinations with reproducible pupillary diameters are indispensable for the differentiation of cystic, solid and tumor-simulating lesions and for the detection of malignant transformation in iris tumors.

[New molecular pathological strategies for malignant iris tumors]. / Neue molekularpathologische Ansätze bei malignen Iristumoren.

BACKGROUND: Molecular pathological research offers new chances for the diagnostic and therapeutic management of malignant iris tumors. Besides immunohistological and polymerase chain reaction analyses further techniques, such as multiplex ligation-dependent probe amplification, microsatellite analyses and next-generation sequencing are able to detect various mutations in the tumor genome. OBJECTIVE: An up to date review of new molecular pathological strategies for malignant iris tumors was carried out. METHODS: This article provides a review of the recent literature based on a PubMed search and clinical experience with iris tumors. RESULTS: The diagnostic characteristics and targeted treatment options are presented, exemplified by iris melanoma and iris carcinoma metastases. In iris melanomas, mutations in the GNA11 and GNAQ genes (in approximately 85% of the cases) seem to be important. Furthermore, the monosomy-3 status should be investigated in these tumors. In iris lymphomas, molecular pathological analyses are essential for an exact diagnosis. Detection of mutations in MYD88, BRAF, KLF2, ID3, TCF3, STAT3, RHo, TET2, IDH2, CXCR4, CD79B and DNMT3A are helpful. In particular, the detection of the CD20 antigen is of therapeutic relevance because this lymphoma subgroup responds well to rituximab, a CD20 antibody treatment. In iris carcinoma metastases, investigations for mutations are helpful because then a targeted treatment seems to be possible. CONCLUSION: Molecular pathological analyses will become essential in the future management of iris tumors because they play a key role towards a personalized treatment approach.

[Advanced periocular basal cell carcinoma-a therapeutic challenge]. / Das fortgeschrittene periokuläre Basalzellkarzinom ­ eine therapeutische Herausforderung.

BACKGROUND: Basal cell carcinomas are the most common periocular malignant tumor. In advanced periocular basal cell carcinoma, vismodegib is a new treatment option which might potentially avoid surgical eye removal. CASE REPORT: We treated a 76-year-old patient unwilling to consent to surgery with vismodegib for advanced periocular basal cell carcinoma on the left forehead that had already undergone several previous treatments. After initial partial remission, the tumor regrew under ongoing therapy, so that radical surgical excision including orbital exenteration was performed. Unfortunately, the patient died thereafter due to septic multi-organ failure. CONCLUSION: Basal cell carcinoma and its new treatment options are gaining importance for ophthalmology due to rising incidence and prevalence rates. Vismodegib is a new encouraging option. However, for advanced tumors, it must be resolved whether complete histological remission may be achieved to avoid surgical intervention, or whether the area of resection can be significantly reduced. Current multicenter studies investigate these aspects further (ClinicalTrails.gov identifier: NCT03035188).

[New treatment options for iridociliary tumors]. / Neue therapeutische Möglichkeiten bei iridoziliären Tumoren.

BACKGROUND: Benign iridal tumors rarely necessitate a therapeutic intervention. In contrast, malignant tumors of the iris can threaten the patient's life and eyesight and require early treatment to prevent the development of metastases. OBJECTIVE: Presentation of current treatment options for iridal tumors with special emphasis on iridal melanoma. METHODS: This article gives an overview of the current literature based on a PubMed search as well as own clinical experience. RESULTS: Treatment options for iridal and ciliary body melanomas comprise radiotherapeutic and surgical (eyeball-sparing and non-sparing) approaches. The eyeball-sparing surgical procedure of choice is block excision. While local tumor control rates and metastasis rates of block excision and radiotherapy are comparable, there are distinct differences especially between the spectra of complications. New treatment procedures include immunomodulatory approaches and targeted therapies. Using checkpoint inhibitors, no convincing enhancement of overall survival could be demonstrated for metastatic iridal melanoma, as is the case for cutaneous melanoma. In contrast, tumor vaccination with the help of tumor RNA-laden patient-derived dendritic cells seems to be a promising option for a subgroup of high-risk patients. Targeted therapies aiming to suppress the MAPK and PI3K/Akt pathways could not achieve any improvement in patient survival. CONCLUSION: For the primary treatment of iridal melanoma a surgical, eyeball-sparing approach and also when appropriate, radiotherapy can be recommended. In the future, eligible high-risk patients could profit from a tumor vaccination. To date, there is no effective systemic treatment for metastatic iridal melanoma.

[Early onset of fingolimod-associated macular edema]. / Frühzeitiges Auftreten eines Fingolimod-assoziierten Makulaödems.

BACKGROUND: Fingolimod, a disease-modifying sphingosine 1­phosphate receptor modulator, which was approved in Germany in 2011, decreases the relapse rate and reduces neuroinflammation in patients with relapsing-remitting multiple sclerosis. Macular edema is a well-known ocular side effect of fingolimod therapy. Specific intervals for ophthalmologic check-ups after starting fingolimod and definite treatment schedules for fingolimod-associated macular edema are, however, still lacking. CASE REPORT: We present a case of early fingolimod-associated macular edema in a 45-year-old female patient with relapsing-remitting multiple sclerosis. The patient complained about visual impairment 1 month after the start of fingolimod and visited an eye specialist. Funduscopic examination and imaging diagnostics revealed macular edema in both eyes. The treatment with fingolimod was immediately stopped. For therapy of macular edema topical application of nepafenac and oral acetazolamide were given. During the 6 months of treatment the macular edema completely disappeared and visual function recovered completely. DISCUSSION: At the time of diagnosis, it is fundamentally important to discuss the continuation of fingolimod administration with the attending neurologist and if necessary to discontinue the drug. Regular ophthalmologic check-ups at 4­week intervals over a period of 3 months are meaningful after beginning fingolimod treatment. As before, it is still a key aspect to determine predictive opthalmologic and neurological factors before beginning treatment to evaluate which patients are at risk of fingolimod-associated macular edema.