[Bottlenecks in the availability of ophthalmological medications : Initiative of the Working Group on Ethics in Ophthalmology of the DOG and the University Eye Clinic Bonn]. / Engpässe bei der Verfügbarkeit von ophthalmologischen Medikamenten : Initiative der Arbeitsgemeinschaft Ethik in der Augenheilkunde der DOG und der Universitäts-Augenklinik Bonn.

BACKGROUND: Bottlenecks in drug supply in the field of ophthalmological are continuously increasing in Germany. So far, these have hardly been communicated and discussed. We see the transparent presentation of the problem as a first step in compiling concepts to counteract this development. AIM OF THE WORK: Presentation of the supply shortages in ophthalmological drugs. MATERIAL AND METHODS: A listing and discussion of the shortages in drug supply to the best of our knowledge are presented. RESULTS: We distinguish between the problems in (1) supply shortages, (2) discontinuation of production, (3) lack of availability in Germany and (4) manufacture of drugs in specialized pharmacies often lacking approval for the ophthalmological indications. DISCUSSION: The reasons for drug supply shortages in ophthalmology are complex and therefore no easy solutions can be expected; however, industrial and regulatory authorities at the national and European levels are called upon to analyze the underlying problems and to find appropriate solutions.

Clinico-pathological correlation of lacrimal caruncle tumors: a retrospective analysis over 22 years at the University Eye Hospital Bonn.

PURPOSE: The lacrimal caruncle is composed of numerous structures including different glands as well as hair follicles. Accordingly, the spectrum of benign and malignant lesions is broad, and the clinical diagnosis is often challenging. Here we systematically analyzed excised caruncular tumors over the past 22 years with special emphasis on the clinico-pathological correlation to provide a guidance for clinicians. METHODS: Retrospective evaluation with clinico-pathologic correlation of surgically removed caruncular tumors between 1998 and 2020 at a tertiary referral center. RESULTS: Eighty-two caruncular tumors were identified in the respective period. The patients were between 11 and 85 years of age (mean, 46.8 years; median, 49 years). Nevi (n = 35), cystic lesions (n = 14), oncocytoma (n = 9), papilloma (n = 8), sebaceous gland hyperplasia (n = 8), and reactive lymphoid hyperplasia (n = 4) were observed most frequently. Besides, we are the first reporting herniated orbital fat accompanied by a pyogenic granuloma. 2.4% (n = 2) were malignant tumors (sebaceous gland carcinoma, conjunctival intraepithelial neoplasia with pyogenic granuloma). CONCLUSION: Caruncular tumors show a broad spectrum of mostly benign tumors. They can occur in patients of any age. However, 8/9 oncocytomas and both malignant lesions were detected in patients older than 60 years. Although the clinical diagnosis was confirmed in only 68.3% by the histopathological analysis, the two malignant lesions were identified as such already clinically. Caruncular lesions with a history of growth or other signs of malignancy should be excised followed by detailed histopathological examination to allow a final diagnosis and exclude rare malignant tumors with lethal potential.

[Differential diagnoses of dry eye syndrome and blepharitis]. / Differenzialdiagnosen der Benetzungsstörung.

Dry eye syndrome and blepharitis are diseases that affect many patients from different age groups. There is not only a great variability in the manifestation between patients but they also show a mixture of associated symptoms. Thus, very different ocular and systemic diseases have to be included in the differential diagnosis of a primary dry eye disorder. This article provides a structured overview of these differential diagnoses and their characteristic appearance as well as the pitfalls and therapeutic options.

Genetic and epigenetic insights into uveal melanoma.

Uveal melanoma (UM) is the most frequent primary intraocular tumor in Caucasian adults and is potentially fatal if metastases develop. While several prognostic genetic changes have been identified in UM, epigenetic influences are now getting closer attention. Recent technological advances have allowed to exam the human genome to a greater extent and have improved our understanding of several diseases including malignant tumors. In this context, there has been tremendous progress in the field of UM pathogenesis. Herein, we review the literature with emphasis on genetic alterations, epigenetic modifications and signaling pathways as well as possible biomarkers in UM. In addition, different research models for UM are discussed. New insights and major challenges are outlined in order to evaluate the current status for this potentially devastating disease.

[Epithelial ingrowth after evisceration]. / Epithelinvasion nach Eviszeration.

A 67-year old patient presented with persistent wound dehiscence after evisceration. The scleral shell and the implant were removed. The histopathological and immunohistochemical examination of the tumor revealed epithelial ingrowth and infection of the implant. Even if the intervention is known since the 16th century, technics and materials are still undergoing improvements and discussions. Incarceration or tension on the suture should be avoided in order to prevent secondary complications.

[Current diagnostics and therapy recommendations for ocular basal cell carcinoma]. / Aktuelle Diagnostik und Therapieempfehlungen beim Basalzellkarzinom am Auge.

The treatment options for basal cell carcinoma (BCC) have recently been augmented with the introduction of novel chemotherapeutic drugs. New S2 guidelines on the disease have also been published. The aim of this article is to present a comprehensive state of the art description of the features of ocular BCC and an overview of the various therapeutic options. Particular emphasis is placed on the clinical signs, the diagnostic tools to identify periocular BCC and interpretation of the different histopathological subtypes. Tumor staging, TNM classification, interdisciplinary tumor conference reviews as well as psycho-oncological services play an important role in patients with pronounced periocular BCC. Surgical removal with a histological R0 resection is an important component of therapy options in this disease and includes the microsurgical excision into healthy tissue and the subsequent covering of the defect. A special focus of this article is the treatment of locally extensive and metastasized BCC.

[Nodular eyelid margin and lip tumors without MEN2b syndrome in a 29 year old man]. / Lidkanten- und Lippentumoren ohne MEN2b-Syndrom bei einem 29-jährigen Mann.

Neuromas of the eyelid margin and lower lip were diagnosed in a 29-year-old man. As the combination of these lesions is indicative of multiple endocrine neoplasia type 2b (MEN2b) syndrome, the presence of a medullary thyroid carcinoma or a pheochromocytoma were excluded by a systematic work-up. A mutation in the RET proto-oncogene was not found by genetic testing. In summary, the patient presented with neuromas on the eyelid margin and lower lip without an association to a syndrome; however, patients with such neuromas should be screened for MEN2b syndrome due to the high mortality.

[Mucinous sweat gland carcinoma of the eyelid]. / Muzinöses Schweißdrüsenkarzinom des Augenlids.

A 52-year-old patient presented with a painless nodular tumor of the upper left eyelid, which was first noticed 6 months prior to the initial presentation. The histopathological and immunohistochemical examination of the excised tumor revealed a mucinous sweat gland carcinoma. This very rare neoplasm (1/150,000 skin lesions) is located within the ocular adnexa in 40 % of cases. If completely excised the prognosis is usually good; however, due to the histological similarity to metastases of an adenocarcinoma, a hitherto unknown primary tumor at another site should be excluded.

[Salmon-pink colored conjunctival tumor with amyloid deposits]. / Lachsfarbener Bindehauttumor mit Amyloidablagerung.

An 82-year-old male patient presented with a salmon-pink colored conjunctival tumor of the left eye. A circumscribed, dense and whitish portion was detected by clinical examination. The histophological and immunhistochemical examination of the biopsy tissue revealed a CD20+ marginal zone lymphoma of the conjunctiva with amyloid deposits. Extranodal marginal zone lymphoma at this site is the most common lymphoma of the ocular adnexa and accounts for 5-10% of malignant diseases. An association with amyloid production is very rare and according to the current state of knowledge has no known impact on the outcome.

[Subcutaneous tumour in an adolescent]. / Subkutaner Tumor bei einem Jugendlichen.

A 13-year-old adolescent presented with an enlarging subcutaneous mass beneath the right eyebrow. Clinically suspicious for dermoid cyst or pilomatrixoma, it was decided to remove the tumour completely. Based on histopathological examination the diagnosis of intravascular papillary endothelial hyperplasia (IPEH) was made. Histopathological features are discussed with regard to the possible pathogenesis.

[Conjunctival myxoma: two cases. Histopathological examination and clinical course]. / Konjunktivales Myxom - zwei Kasuistiken. Histopathologische Aufarbeitung und klinische Korrelation.

Conjunctival myxoma is a rare and benign tumour without tendency for recurrence. Here, we present the histological features and the clinical course of two cases. Removal of each tumour was followed by histopathological examination including immunohistochemistry as well as electron microscopy. Besides the expected findings characteristic of conjunctival myxoma some features reflecting the possible aetiology of this entity are shown.

Deletions of BRCA1/2 and p53 R248W gain-of-function mutation suggest impaired homologous recombination repair in fragile histidine triad-negative sebaceous gland carcinomas.

BACKGROUND: Sebaceous gland carcinomas represent rare malignancies of the skin and some 60% of them demonstrate high-grade microsatellite instability on the background of a defective mismatch repair system. However, a significant fraction of periocular sebaceous gland carcinomas exhibits microsatellite stability associated with a frequent loss of the candidate tumour suppressor fragile histidine triad (FHIT). OBJECTIVES: We hypothesized that in those sebaceous gland carcinomas with microsatellite stability and loss of FHIT, effector molecules participating in homologous recombination repair (HRR), such as BRCA1/2, could be somatically inactivated. METHODS: A pilot series of 10 paraffin-embedded sebaceous gland carcinoma specimens with a defined FHIT status was studied for loss of heterozygosity (LOH) events in the genes BRCA1, BRCA2, FHIT and WWOX. We sequenced the coding exons 5-8 of the p53 gene. RESULTS: Sebaceous gland carcinomas with FHIT negativity displayed LOH and biallelic deletions of the BRCA1 gene in five of 10 (50%) of the sebaceous gland carcinoma specimens analysed. Tumour-specific genomic losses close to BRCA2 were also uncovered. A homozygous p53 R248W gain-of-function mutation as the result of a CGG to TGG transition was identified in one of seven sebaceous gland carcinomas. It has been demonstrated previously that p53 R248W mutants inactivate ATM-directed HRR. This particular sebaceous gland carcinoma presented with concomitant genomic deletions at the BRCA1 and BRCA2 loci, and also at the constitutively fragile sites FRA3B/FHIT and FRA16D/WWOX. CONCLUSIONS: Our study demonstrates for the first time that microsatellite-stable FHIT-negative sebaceous gland carcinomas accumulate mutations that target central components of the HRR network. This observation will prompt investigations in synthetic lethality of BRCA-deficient sebaceous gland carcinomas by therapeutic poly(ADP-ribose) polymerase inhibitors.

Keratoepithelin in secondary corneal amyloidosis.

BACKGROUND: Amyloid is found in several corneal dystrophies, including distinct lattice corneal dystrophies (LCD) and Avellino corneal dystrophy. Recently, point mutations in the transforming growth factor-beta-induced gene (TGFBI) encoding for keratoepithelin (KE) have been demonstrated in these corneal disease entities. We intended to investigate if KE was also a component of the rarely seen secondary corneal amyloid deposits. METHODS: Immunohistochemical staining with a polyclonal antibody against KE was performed on formalin-fixed paraffin-embedded tissue of five corneal buttons with secondary amyloid obtained after keratoplasty. Secondary amyloidosis was due to Fuchs endothelial dystrophy (FED) with bullous keratopathy and/or recurrent erosions in all cases. The diagnosis had been established by light microscopy using Congo red staining. Two cases of LCD type I served as positive controls and three corneas with FED and one with keratoconus without amyloid served as negative controls. RESULTS: All corneas with secondary amyloidosis as well as LCD type I revealed positive staining in the respective amyloid deposits. KE was localized in the subepithelial pannus and in the anterior stroma in the corneas with secondary amyloidosis. In the specimens with LCD type I it was distributed in the amyloid deposits located in the anterior and mid-stroma. Staining for KE showed a granular appearance in all cases. The intensity of staining was variable among the specimens. CONCLUSIONS: KE is found not only in primary amyloid deposits of hereditary corneal dystrophies, but also in secondary amyloidosis of the cornea of diverse ethiologies.

Effect of ultraviolet radiation on melanogenesis in four different types of cultured bovine ocular pigmented cells.

BACKGROUND: Ultraviolet radiation is thought to play a causative role in various ocular diseases such as macular degeneration, cataract, and possibly melanomas. Since most of the energy is absorbed by pigmented cells, the aim of this study was to examine and compare the reactions of different ocular melanocytic cells to ultraviolet light in vitro. MATERIALS AND METHODS: Bovine iris melanocytes, choroidal melanocytes, iris pigment epithelial cells, and retinal pigment epithelial cells were isolated and cultured. Semiconfluent cultures were exposed to ultraviolet radiation (280-380 nm). Cell number and melanin content were measured 10 days after radiation. Selected samples were examined by transmission electron microscopy. RESULTS: Following irradiation with ultraviolet light for 30 s, 60 s, and 120 s, the number of cells in culture decreased markedly. In contrast, total melanin content in the cultures of iris melanocytes, choroidal melanocytes, and iris pigment epithelial cells did not decrease despite the reduced number of cells. This finding suggested an increase in melanin per cell. However, the increase in average melanin content observed was not due to melanogenesis, because treatment with the melanogenesis inhibitor alpha-methyl-p-tyrosine did not reduce the melanin content of the cultures and electron-microscopic examination showed no morphological evidence of increased melanogenesis. CONCLUSION: In vitro, there was no convincing evidence of ultraviolet radiation-induced melanogenesis in ocular pigmented cells. Thus, it seems that ultraviolet radiation is a selection factor: more densely pigmented cells survive the treatment better than less pigmented cells.