Retrospective analysis of OCT parameters after intravitreal anti-VEGF inhibitors in neovascular AMD patients in a real-world setting.

PURPOSE: The aim of the present study was to evaluate changes of best corrected visual acuity (BCVA), retinal nerve fiber layer thickness (RNFL), total macular volume (TMV), intraocular pressure (IOP) and central retinal thickness (CRT) after intravitreal injection of ranibizumab, bevacizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD) in a clinical real world setting. METHODS: In a retrospective clinical study design, 120 patients (80 women and 40 men) were analyzed after being diagnosed with nAMD within 8 years (2010-2018). Every patient received at least 6 anti-VEGF injections in a Pro-Re-Nata or Treat-and-Extend regimen. OCT parameters (RNFL, TMV, CRT) and visual acuity (BCVA) were assessed at first diagnosis, at treatment day and during the course. RESULTS: Intraretinal fluid was reduced significantly in a magnitude of 88-64 µm (CRT) and 0.75-0.55 mm3 (TMV). Apart from a significant reduction immediately after the therapy start (post-3 injections) with ranibizumab (- 1.4 µm, p = 0.03), RNFL thickness remained constant. A slight improvement in visual acuity of 0.06 logMAR could initially be observed. If further injections were required, only stabilization was achieved compared to baseline visual acuity. CONCLUSION: The changes of OCT parameters CRT, TMV, and RNFL as well as the stabilization of functional results (BCVA) as illustrated in this study comparing effects of different anti-VEGF-agents provide evidence for the transferability of former results to a clinical real-world setting.

KIF15 plays a role in promoting the tumorigenicity of melanoma.

Kinesins are a superfamily of motor proteins and are often dysregulated in many cancers. KIF15, which belongs to the kinesin-12 family, has been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. However, the role of KIF15 in melanoma, remains unknown. In this study, the expression levels of KIF15 in melanoma cells lines and tissues were determined via real-time PCR, immunohistochemical staining and western blot. The effect of KIF15 on tumorigenesis was evaluated by using MTT and colony information. The function of KIF15 on cell survival was detected through flow cytometry assay. Microarray assay and bioinformatics analysis were used to find the potential target of KIF15. We show that KIF15 was significantly upregulated in melanoma cells and tissues. The suppression of KIF15 in tumors significantly reduced tumor growth and increased apoptosis in A375 and OCM1 cells. Findings based on the subcutaneous xenograft model were further consistent with the in vitro results that KIF15 knockdown inhibited melanoma tumor growth in vivo. Microarray assay and bioinformatics indicated that BIRC5, CDK4 and WNT5A were three potential targets of KIF15. Taken together, our results suggest that KIF15 plays a positive role in the tumorigenicity of melanoma and it may serve as a novel diagnostic and therapeutic target for melanoma, especially uveal melanoma.

[Importance of interdisciplinary collaboration for optimal treatment of orbital tumors]. / Bedeutung der interdisziplinären Zusammenarbeit für eine optimale Behandlung orbitaler Tumoren.

Optimal treatment of tumors with orbital invasion may exceed the competences of an individual medical specialty and require interdisciplinary cooperation. The aim of this article is to present an interdisciplinary treatment concept based on the examples of intraorbital hemangioma and squamous cell carcinoma of the paranasal sinuses infiltrating the orbit. In addition to a detailed medical history and a complete ophthalmological examination, a detailed imaging technique with standardized echography and tomography methods such as orbital thin-slice CT and/or in many cases MRI is essential for the primary classification of an intraorbital pathology. Depending on the type of pathology, a purely surgical procedure involving various disciplines such as ophthalmology, otorhinolaryngology, maxillofacial surgery, neurosurgery, and pathology, or an interdisciplinary treatment regimen including (neo)adjuvant radiotherapy or chemotherapy is necessary. Orbital tumors have a wide range of potential pathologies, requiring complex surgical procedures and multimodal therapies. In case of infiltration of the paranasal sinuses or intracranial structures, an interdisciplinary team including neuroradiologists, oral-maxillofacial surgeons, otorhinolaryngologists, neurosurgeons, radiation therapists, ophthalmologists, pathologists, oncologists, and psycho-oncologists is essential for successful treatment.

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

[Transcanalicular Laser Dacryocystorhinostomy: One-Year-Experience in the Treatment of Acquired Nasolacrimal Duct Obstructions]. / Transkanalikuläre Laserdakryozystorhinostomie--1-Jahres-Erfahrung in der Behandlung infrasakkaler Tränenwegsstenosen.

BACKGROUND: External dacryocystorhinostomy (DCR) is at present the gold standard for the surgical treatment of acquired nasolacrimal duct obstructions, but tremendous progress has been made in recent years in improving minimally invasive techniques, sparing not only the skin, but also the medial lid structures, which contribute to the physiological palpebral-canalicular pump mechanism. The purpose of this study is to report our 1-year experience with the surgical technique, complications and results of transcanalicular laser assisted DCR. PATIENTS AND METHODS: 48 consecutive transcanalicular laser-assisted DCRs combined with bicanalicular silicone intubation were performed for acquired nasolacrimal duct obstruction, and evaluated for intra- and postoperative complications, as well as subjective and objective success rates. RESULTS: Transcanalicular laser-assisted DCR combined with bicanalicular silicone intubation was surgically feasible in 45 cases (94 %). In 3 patients (6 %) it was impossible to position the aiming beam correctly at the anteroinferior rim of the middle turbinate using the superior canalicular approach, due to superior orbital rim prominence. Therefore 2 patients received no silicone intubation, despite a patent osteotomy at the back of the middle turbinate, and 1 patient underwent intraoperative conversion to external DCR due to anatomical narrowness of the nasal cavity. Perioperatively, 1 patient developed canalicular infection, 1 patient exhibited thermal injury to the canaliculus, and 4 patients exhibited premature prolapse of the silicone tube. At 6-months follow-up, functional success--defined as resolution of preoperative symptoms--was achieved in 35 of 45 surgically successful transcanalicular laser-assisted DCRs (78 %). Of the 10 postoperative failures (22 %), all patients reported epiphora, 6 patients were unable to irrigate the lacrimal drainage system, and 6 patients required surgical revision using external DCR. CONCLUSIONS: Transcanalicular laser assisted DCR is a promising minimally invasive approach for the surgical treatment of acquired nasolacrimal duct obstruction, in order to fill the gap between recanalising first step procedures and external DCR.

[Tumors of the lacrimal drainage system]. / Tumoren der ableitenden Tränenwege.

BACKGROUND: The prevalence of tumors affecting the lacrimal drainage system is low, thus generating a risk of late diagnosis and treatment in clinical routine. However, these tumors can be potentially life-threatening, which emphasizes the relevance of early diagnosis and treatment. OBJECTIVE: This review focuses on the symptoms, incidence, management, and prognosis of the different tumor entities affecting the lacrimal drainage system. METHODS: The study provides a PubMed-based literature review and presents own clinical results. RESULTS: Alongside detailed medical history taking and comprehensive clinical examination, precise inspection during external dacryocystography is important for diagnosis of tumors affecting the lacrimal drainage system. There is a wide spectrum of tumor entities located in the lacrimal drainage system. The tumors are classified into three groups: primary epithelial, primary nonepithelial, and inflammatory lesions. The most common primary epithelial tumors include papilloma, squamous cell carcinoma, and transitional cell carcinoma. The most common nonepithelial tumors include fibrous histiocytoma, malignant lymphoma, and malignant melanoma; while the most common inflammatory lesions comprise sarcoidosis, Wegener granulomatosis, and pyogenic granuloma. Treatment depends on the entity and stage of the tumor. In the case of malignancy, a multimodal and interdisciplinary approach is usually indicated. CONCLUSION: Differential diagnostic signs in favor of a malignancy include a long medical history, predisposing conditions in the patient's history, a mass above the medial canthal ligament, teleangiectasis above the mass, and serosanguinous secretion.

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.

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.

Evaluation of colour vision impairment during acute hypobaric hypoxia in aviation medicine: a randomized controlled trial.

The digitization of aircraft cockpits places high demands on the colour vision of pilots. The present study investigates colour vision changes upon acute exposure to hypobaric hypoxia. The digital Waggoner Computerized Color Vision Test and the Waggoner D-15 were performed by 54 healthy volunteers in a decompression chamber. Respective altitude levels were sea level, 10,000 or 15,000 ft for exposure periods of 15 and 60 min, respectively. As for 60 min of exposure a significant decrease in colour perception was found between subjects at 15,000 ft as compared to the control group as well as between subjects at 15,000 ft as compared to subjects at 10,000 ft. No significant difference was found in the comparison within the 15,000 ft groups across time points pre-, peri-, and post-exposure. Thus, pilots appear to experience only minor colour vision impairment up to an exposure altitude of 15,000 ft over 60 min of exposure.

[Therapeutic management of a kissing nevus of the eyelid]. / Therapeutisches Management eines "kissing nevus" des Augenlids.

Congenital divided melanocytic nevi of the upper and lower eyelid are rare pigmented changes of the eyelids. These processes are also known as "kissing nevi," "panda nevi," and "split ocular nevi," and were first described by Fuchs in 1919. About 120 cases have been described in the literature so far. Congenital melanocytic nevi are either present at birth (small nevi are already found in about 1% of neonates) or manifest predominantly during the first decade of life. These rare melanocytic changes of the eyelids should be controlled regularly, as malignant transformation can occur. The actual incidence of malignant transformation is highly variable in the literature, ranging from 2 to 40% depending on the duration of follow-up, with an average of 14% for the whole lifetime. Moreover, nevi of the eyelids may be considered cosmetically disturbing and cause functional problems. Therapeutic removal (dermabrasion, cryotherapy, laser therapy, and surgical excision with ophthalmoplastic reconstruction) is rarely medically indicated due to the low risk of malignant transformation. Removal can be performed in cases of secondary amblyopia in ptosis, compression of the lacrimal point, epiphora, or cosmetic desire. Treatment becomes necessary not only in case of suspicious manifestation or impairment of eyelid function, but it also helps to avoid possible bullying at school among children and is recommended at age 4 to 6 (before school age).

"OSMO-UT-DSAEK" using THIN-C medium.

BACKGROUND: When performing ultra-thin Descemet's stripping automated endothelial keratoplasty (UT-DSAEK), the quality of the stromal interface and stromal thickness seem to be critical for visual outcome. The aim of this study was to investigate whether additional osmotic deswelling prior to UT-DSAEK improves the quality of the cut surface and leads to a more reliable and deeper cut in UT-DSAEK ("OSMO-UT-DSAEK"). METHODS: Seventeen human donor corneas not usable for transplantation were used in this experiment. After standard deswelling with culture Medium II, ten corneas were randomly assigned to be additionally deswollen within THIN-C medium. The other remaining seven corneas were put back into culture Medium II. All corneas were placed in an artificial anterior chamber system (Moria); a double path cutting procedure using a microkeratome (Moria) was then performed. Corneal thickness was measured by ultrasound biomicroscopy and in paraffin-embedded slides, followed by histological grading of the cut surface. RESULTS: Stromal interface smoothness significantly improved after preconditioning in THIN-C medium (Pearson P = 0.019). The correlation of the corneal thickness obtained by UBM (mean 706 ± SD 208 µm) and histology (mean 530 ± SD 159 µm) was not significant (Pearson r = 0.11, P > 0.05, mean difference 247, 95 % CI [+50;+304]). We found no significant correlation between the microkeratome setting and the actual thickness of the lenticule measured in histological analysis in both media as well as for the first and second cut (first cut: Pearson r = 0.9, P = 0.1, 95 % CI [-10;+96], second cut: Pearson r = 0.9, P = 0.4, 95 % CI [-10;+22]). CONCLUSION: Preconditioning of corneas with THIN-C medium significantly improved the quality of the graft interface in UT-DSAEK, but did not significantly improve the cut precision of the microkeratome.

[Immune reactions after DMEK, DSAEK and DALK]. / Immunreaktionen nach DMEK, DSAEK und DALK.

PURPOSE: The aim of this study is to describe incidence, diagnosis and therapy for endothelial immune reactions after modern lamellar corneal transplantat surgery (DMEK, DSAEK, DALK). METHODS: A PubMed-based literature review and our own clinical and experimental data are evaluated. RESULTS: There is no longer an endothelial immune reaction after DALK for keratoconus. DMEK significantly reduces the risk for endothelial immune reactions after surgery for Fuchs dystrophy. CONCLUSIONS: Modern lamellar corneal transplant techniques such as DALK and DMEK have nearly abolished the risk for endothelial immune reactions in the avascular recipient bed.

[Anti(lymph)angiogenic preconditioning prior to keratoplasty]. / Antiangiogene Präkonditionierung vor Keratoplastik.

PURPOSE: The aim of this study is to describe novel therapeutic concepts to promote graft survival in high-risk keratoplasty by targeting (lymph)angiogenesis in the transplant context. METHODS: A PubMed literature search and our own clinical and experimental data are evaluated. RESULTS: There are three options for anti(lymph)angiogenic preconditioning: a) primary prevention of neovascularisation during the disease process, b) secondary prevention by regressing established blood vessels prior to transplantation and (c) tertiary prevention through inhibition of post-keratoplasty neovascularisation. CONCLUSION: Modern topical anti(lymph)angiogenic therapies seem to be able to reduce the risk of graft rejection especially in high-risk keratoplasty.

[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.

[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.

[Split-cornea transplantation - a novel concept to reduce corneal donor shortage]. / Split-Cornea-Transplantation - ein neues Konzept gegen Spendermangel.

BACKGROUND: Penetrating keratoplasty is at present the gold standard for corneal transplantation, but tremendous progress has been made in recent years in improving lamellar keratoplasty techniques, such as deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK). The purpose of this report is to describe split-cornea transplantation by combining DALK and DMEK as a novel concept to reduce donor shortage. METHODS: The study consists of a PUBMED literature review and our own clinical results. RESULTS: Splitting of a single donor cornea into an anterior part (including epithelium, its basement membrane, Bowman layer, and stroma) for use in a DALK procedure in a patient with anterior-stromal disease (e. g., keratoconus) and into a posterior part (endothelium-Descemet membrane layer) for use in a DMEK procedure in a patient with endothelial disease (e. g., Fuchs endothelial dystrophy) can reduce the need for corneal donor tissue by around 50 %. A short-term 6-months follow-up has revealed good visual and refractive outcomes with low complication rates and acceptable endothelial cell loss. CONCLUSION: Split-cornea transplantation by combining DALK and DMEK surgeries is a promising concept to reduce donor shortage in corneal transplantation surgery in the future.

[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.