[The Renaissance of "Forgotten Diseases" - A Renaissance of Ophthalmopathology?] / Die Renaissance "vergessener Erkrankungen" ­ eine Renaissance der Ophthalmopathologie?

Some "forgotten infectious diseases" are becoming increasingly common. Ophthalmic pathology is still important in their diagnosis.

Histological findings of corneal tissue after failed phototherapeutic keratectomy in macular corneal dystrophy - a case report.

BACKGROUND: Macular corneal dystrophy is a rare inherited disease of the cornea leading to deposits mainly in the stroma. Affected patients suffer from progressive loss of visual acuity which should be treated with penetrating keratoplasty. This is the first case report describing the clinical and histopathological findings of corneal tissue after failed phototherapeutic keratectomy (PTK) in a patient with macular corneal dystrophy. CASE PRESENTATION: A 32-year-old man presented with visual impairment, blurred vision and increasing glare sensitivity in both eyes in 2014. All symptoms had existed for several years and had recently increased sharply. A corneal dystrophy was diagnosed and penetrating keratoplasty was recommended but the patient was hesitant to undergo surgery. In 2018, in contrast to current guidelines, a PTK was performed in both eyes in Turkey for unknown reasons. In May 2019, he presented again in our clinic. Best corrected visual acuity was markedly reduced in both eyes. Slit-lamp examination revealed multiple dense, poorly circumscribed grey-white patchy changes in the stroma accompanied by corneal opacity in both eyes. In February 2020, the patient decided to have penetrating keratoplasty performed at the University Eye Hospital in Tübingen. The explanted cornea was stained for acid mucopolysaccharides (AMP) and periodic acid-Schiff staining (PAS). The histopathological examination revealed destruction of Bowman's layer and a subepithelial fibrosis band due to the PTK previously performed. The AMP staining demonstrated blue deposits typical of macular corneal dystrophy, mainly in the stroma but also in the endothelium. Interestingly, the acidic mucopolysaccharides were found increased in the PTK-induced subepithelial fibrosis band. The postoperative course after keratoplasty was favourable with a significant increase in visual acuity and a clear graft. CONCLUSIONS: This report presents the first case of a histologically evident exacerbation of macular corneal dystrophy after PTK and emphasizes the relevance of thorough pre-interventional diagnosis and patient selection to consider other therapeutic approaches, such as penetrating keratoplasty.

Outcomes after Descemet membrane endothelial keratoplasty over a period of 7 years at a tertiary referral center: endothelial cell density, central corneal thickness, and visual acuity.

PURPOSE: To better assess clinical trajectories of patients with or without ocular comorbidity after Descemet membrane endothelial keratoplasty. BACKGROUND: To report on the outcomes of eyes with differing starting conditions following surgery. DESIGN: Retrospective study at a University Eye Hospital. PARTICIPANTS: 361 eyes separated into group 1 (n=229; eyes with endothelial disease only) and group 2 (n=132; eyes with additional ocular comorbid conditions, such as herpetic eye disease 18/132 (13.6%), glaucoma 16/132 (12.1%), dry age-related macular degeneration 14/132 (10.6%), epiretinal membranes 10/132 (7.6%), and wet age-related macular degeneration 9/132 (6.8%)). METHODS: Consecutive eyes that underwent Descemet membrane endothelial keratoplasty over a follow-up period of up to 7 years at a tertiary referral center were reviewed. Main outcome measures were best-corrected visual acuity, postoperative complications, graft survival, central corneal thickness, and endothelial cell density. RESULTS: Postoperative best-corrected visual acuity at year 1 improved in both groups significantly (Wilcoxon signed rank test: group 1, p =.002; .63 to .23 logMAR; group 2, p <.001; 1.15 to .87 logMAR) with a group difference in favor of group 1 (p =.009, Mann-Whitney-Wilcoxon). A decrease of the endothelial cell density and central corneal thickness was noted at postoperative year 1 for both groups (paired t-tests (group 1, p <.001; group 2, p =.045) and paired t-tests (group 1, p <.001; group 2, p =.003). Complications were less common, and graft longevity was superior in group 1. CONCLUSION: Eyes with different starting conditions might experience a visual improvement and benefit from surgery. Descemet membrane endothelial keratoplasty is a valid treatment for endothelial disorders in manifold of eyes. Further long-term studies are required.

Albrecht von Graefe in the present, the past, and the future.

Albrecht von Graefe (1828-1870) is the founder of this archive (1854) and the founder of modern ophthalmology. In 2020, the anniversary of his death will be observed for the 150th time. The "German Ophthalmological Society" (DOG), also a Graefe foundation (1857), has therefore proclaimed a "Graefe year." In Berlin, his hometown, several Graefe-monuments exist. Ophthalmology owes Albrecht von Graefe numerous first discoveries such as excavation of the optic disc in glaucoma (1855), iridectomy in glaucoma (1857), or central artery occlusion (1859). But his after-effects are not only based on his clinical and scientific merits but also on his extraordinary, fascinating personality, which can be characterized by his spirit of internationality, friendship, self-criticism, love of truth, and modesty. Graefe became a myth not only because of his early death but also because he had apart from great successes, to accept human misfortunes at the same time. Albrecht von Graefe can be regarded as the conscience of ophthalmology in Germany.

[What is a Cataract, and When Should its Removal be Indicated? An Opinion]. / Was ist eine Katarakt, und wann sollte ihre Operation indiziert werden? Eine Meinung.

Not every cataract needs phacoemulsification. One problem is the terminological differentiation between "physiological loss of transparency due to ageing" and "cataract". In case of a "real cataract" the autonomous patient must be informed "in any direction". The time of phacoemulsification is determined by the patient and not by the ophthalmologist.

Novel mouse model for primary uveal melanoma: a pilot study.

BACKGROUND: To establish a mouse model with the aim of studying the tumour biology and metastasis formation of uveal melanoma. METHODS: Two human primary uveal melanoma cell lines (UMT2 and UMT42) were injected into the choroid of BALB/c nude mouse eyes. Intraocular tumour growth and metastasis formation in the liver and lungs were assessed after 13 to 22 weeks. Formalin-fixed, paraffin-embedded material was processed via haematoxylin and eosin staining for histological examination and periodic acid Schiff staining to search for extravascular matrix patterns. Immunohistochemistry for Melan A, CD34 and Ki67 was performed to assess the expression of a melanocytic lineage marker, angiogenesis and proliferative activity. RESULTS: All eyes injected with UMT2 cells, but only 25% of eyes treated with UMT42, developed intraocular tumour growth. The morphology of intraocular melanomas resembled that of primary tumours and showed signs of malignancy, including retinal invasion, optic nerve invasion and scleral penetration with extraocular tumour growth. UMT2 tumours formed extravascular matrix patterns exclusively. Most of the tumour cells expressed Melan A. Intratumoural angiogenesis was detected in both tumour entities. Proliferative activity was verified in all but one tumour. However, no metastases appeared in the liver or lungs. CONCLUSIONS: The mouse model presented with the UMT2 cell line allows for investigations of tumour biology of the primary UM because of the high degree of similarity between the tumours generated in the mouse eyes and the corresponding primary human UM. Unfortunately, the model is not suitable for investigations of metastasis formation.

CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas.

BACKGROUND: Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis. METHODS: The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression). RESULTS: CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident. CONCLUSIONS: These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.

Analysis of caveolin-1 and phosphoinositol-3 kinase expression in primary uveal melanomas.

BACKGROUND: To evaluate the regulation of blood supply in primary uveal melanomas through caveolin-1 (Cav-1)/phosphoinositol-3 kinase (PI3K). METHODS: The expression of Cav-1 and PI3K was analysed in 51 paraffin sections of metastatic (n = 30) and non-metastastic uveal melanomas (n = 21). Two trained observers quantified Cav-1 and PI3K immunofluorescensce expression by determining intensity of staining and percentage of positive cells. The expression was correlated with known prognostic factors. Besides angiogenesis by means of endoglin expression, the normal vasculature (von Willebrand Factor expression) was evaluated semi-quantitatively. Vasculogenic mimicry (VM) was analysed by CD31/PAS staining. RESULTS: All examined specimens expressed Cav-1 with a mean of 90.34% Cav-1 positive cells (range, 3.23-100%). Metastatic disease was associated with a higher Cav-1 expression. The correlation of Cav-1 with well-established prognostic factors showed a significant association between Cav-1 expression and largest tumour diameter (P = 0.022), tumour node metastasis classification (P = 0.008) and invasion of optic nerve head (P = 0.048). PI3K was expressed by all uveal melanomas with a mean of 87.28% cells showing PI3K expression. A higher level of PI3K was significantly associated with larger height (P = 0.042) and progressed tumour node metastasis stage (P = 0.016). The percentage of PI3K and Cav-1 positive cells were significantly associated (P = 0.034). For PI3K and Cav-1 expression a non-significant association with VM was shown (P = 0.064 and P = 0.072, respectively). No correlation of PI3K or Cav-1 with angiogenesis or mature vasculature was seen (P > 0.05). CONCLUSIONS: Cav-1 expression may be especially up-regulated in larger uveal melanomas. As it was correlated with PI3K expression and VM in this series of uveal melanoma, Cav-1 might induce the formation of VM via the PI3K-signalling cascade.

Serotonin (5-HT7) receptor-stimulated activation of cAMP-PKA pathway in bovine corneal epithelial and endothelial cells.

BACKGROUND: 5-Hydroxytryptamine (5-HT; serotonin) is a major neurotransmitter, and its receptors are found throughout the whole body. The 5-HT7 receptor subtype was detected in human corneal epithelial and endothelial cells and found to be functionally active in a corneal epithelial cell line. The aim of the present study was to demonstrate that native bovine corneal epithelial and endothelial cells express a functional 5-HT7 receptor positively coupled to adenylyl cyclase and protein kinase A (PKA) formation. METHODS: 5-HT7 receptors were studied using polyclonal antibodies. cAMP concentration after 5-HT7 receptor stimulation with 5-carboxamidotryptamine (5-CT, a 5-HT7 agonist) was tested by enzyme immunoassay, PKA activity was estimated by kinase consumption of ATP. RESULTS: Immunocytochemistry and immunofluorescence revealed the presence of 5-HT7 receptors in corneal epithelial and endothelial cells. Stimulation of corneal 5-HT7 receptors with 5-CT revealed a dose-dependent increase in intracellular cAMP concentration in corneal epithelium (0.01-0.34 pmol/ml) and endothelium (0.01-0.19 pmol/ml) between 10(-10) and 10(-7) mg/ml 5-CT (p = 0.001) with maximal stimulation from 10(-7) to 10(-3) mg/ml 5-CT (0.30 ± 0.03 and 0.18 ± 0.01 pmol/ml, respectively). Incubation with 10(-6) mg/ml SB269970 (a selective 5-HT7 antagonist) blocked 5-CT-induced cAMP increase in corneal epithelial (0.03 pmol/ml) and endothelial cells (0.02 pmol/ml; p = 0.001). Stimulation of corneal 5-HT7 receptors with 5-CT revealed a dose-dependent increase in PKA activity between 10(-10) and 10(-8) mg/ml 5-CT in corneal epithelium and endothelium (<1 to >99%; p = 0.013 and p = 0.017, respectively) with maximal stimulation from 10(-8) to 10(-4) mg/ml (>99%) 5-CT. CONCLUSIONS: Our data demonstrate that native corneal epithelial and endothelial cells express a functional 5-HT7 receptor positively coupled to adenylyl cyclase and PKA formation. However, at the present time, the physiological role of 5-HT receptors and the cAMP-PKA pathway in the cornea remains a matter of speculation.

[Ocular changes as a diagnostic tool for malaria]. / Okuläre Veränderungen als Hilfsmittel in der Malariadiagnostik.

BACKGROUND: According to the WHO Malaria Report 2019 a total of 229 million people fall ill with malaria each year and two thirds of deaths involve children under 5 years of age. AIM: To review the fundus changes in the context of malaria and the importance of ophthalmoscopy in the diagnosis. MATERIAL AND METHODS: Summary of changes in cerebral malaria visible on fundus examination, possible underlying pathomechanisms and the value of ophthalmoscopy in practice. RESULTS: Retinal findings in malaria include white or gray staining of the retina (retinal whitening), color change of retinal vessels (orange or white staining), hemorrhages often with a white center, such as Roth's spot and papilledema. DISCUSSION: The retinal changes in malaria are specific and may help to differentiate malaria from other causes of coma and fever. Smartphone-based fundus photography and artificial intelligence could support malaria diagnostics particularly in resource-poor regions.

[Advertising or information in ophthalmology? : Scientific evaluation of a YouTube sample]. / Werbung oder Information in der Ophthalmologie? : Wissenschaftliche Bewertung einer YouTube-Stichprobe.

BACKGROUND: Despite the liberalization of the Therapeutic Products Advertising Act, advertising that praises, misleads or compares is still contrary to the German professional conduct. In view of the increasing commitment of financial investors and the economization in ophthalmology, this study was initiated to examine and check which (advertising) statements are affected in openly accessible videos on the YouTube platform. METHODS: Using the search terms "ophthalmologist" and "eye center" as well as predefined criteria (German origin, audio track with spoken text, duration >1 min), videos were identified and transcribed into an anonymized text version. Using a self-developed predefined questionnaire, the individual statements were then subjected to a critical review by three experts and clarity, relevance and completeness of the information were also assessed. At the same time, laypersons were asked how convincingly, comprehensibly and completely they assessed the information and whether they would want to be treated by the physicians. RESULTS: Out of 68 videos 30 met the defined inclusion criteria. Of the videos 46% focused on procedures for refractive surgery. From the experts' point of view, at least 11.8% of the individual statements were completely wrong or only slightly correct. Over 80% of the videos presented information incompletely. Perioperative and postoperative complications were only mentioned by three films. Laypersons evaluated the texts very inconsistently and could not identify the videos that contained problematic statements as assessed by the ophthalmologists. Conflicts with the legal requirements for advertising, e.g. the use of lurid superlatives were found. A balanced presentation, such as alternatives to treatment procedures was rare. There was a great need to improve the comprehensibility for laymen. CONCLUSION: Only a very small number of freely accessible videos provide scientifically founded and correct information. Until now, many ophthalmologists do not sufficiently consider the legal and moral requirements for advertising statements. Therefore, there may be negative effects on the professional image in the public eye and opportunities for health promotion remain unused.

Can SARS-CoV-2 infect the eye? An overview of the receptor status in ocular tissue.

Is the new coronavirus SARS-CoV­2 able to infect ocular tissue and thus poses a risk of infection through the tissue in addition to the risk of contact? This is the question that has occupied ophthalmologists since the beginning of the outbreak. In order to infect a certain type of tissue specific receptors for each virus and sometimes also coreceptors or other proteins must be present. The aim of this review was to summarize and reflect the current state of research with the help of the currently available literature as of 28 May 2020. At the time of the research, angiotensin-converting enzyme 2 (ACE2) was clearly identified as the receptor and transmembrane serine protease 2 (TMPRSS2) as the necessary protease to enable the infection of human cells with SARS-CoV­2. In the eye both ACE2 and TMPRSS2 are expressed, although sometimes very weakly and with varying degrees in different tissues. It is noteworthy that very different results were obtained with different methods. Several reasons can account for this effect: Firstly, the method of detection or preservation of the tissue, secondly, the possibly different expression of the tested tissue samples and thirdly, a possibly rapid loss of receptor expression post-mortem. Therefore, an infection of the eye seems possible, which has already been reported in various publications. The amount of virus or receptor expression necessary to cause an infection is not known. According to current state of knowledge the eye is not considered to be a high-risk tissue due to the low ACE2 and TMPRSS2 expression. Nevertheless, appropriate protective measures are necessary for both medical personnel and patients. In cases of corneal transplantation an infection of the donor tissue with SARS-CoV­2 must be excluded.