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Competing Interests: Glaxo Smith Kline (Teilnahme an Advisory Board, Referent). In Bezug auf diese Arbeit besteht kein Interessenkonflikt.

Purpose: Epigenetic alterations in uveal melanoma (UM) are still neither well characterized, nor understood. In this pilot study, we sought to provide a deeper insight into the possible role of epigenetic alterations in the pathogenesis of UM and their potential prognostic relevance. To this aim, we comprehensively profiled histone post-translational modifications (PTMs), which represent epigenetic features regulating chromatin accessibility and gene transcription, in UM formalin-fixed paraffin-embedded (FFPE) tissues, control tissues, UM cell lines, and healthy melanocytes., Methods: FFPE tissues of UM (n = 24), normal choroid (n = 4), human UM cell lines (n = 7), skin melanocytes (n = 6), and uveal melanocytes (n = 2) were analyzed through a quantitative liquid chromatography-mass spectrometry (LC-MS) approach., Results: Hierarchical clustering showed a clear separation with several histone PTMs that changed significantly in a tumor compared to normal samples, in both tissues and cell lines. In addition, several acetylations and H4K20me1 showed lower levels in BAP1 mutant tumors. Some of these changes were also observed when we compared GNA11 mutant tumors with GNAQ tumors. The epigenetic profiling of cell lines revealed that the UM cell lines MP65 and UPMM1 have a histone PTM pattern closer to the primary tissues than the other cell lines analyzed., Conclusions: Our results suggest the existence of different histone PTM patterns that may be important for diagnosis and prognosis in UM. However, further analyses are needed to confirm these findings in a larger cohort. The epigenetic characterization of a panel of UM cell lines suggested which cellular models are more suitable for epigenetic investigations.

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany., Methods: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used., Results: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%)., Conclusion: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term., Competing Interests: Martina Herwig-Carl: Forschungsförderung: EPIC-XS (Projektnr. 823839, gefördert durch das Horizon 2020 Programm der EU), Deutsche Forschungsgemeinschaft (HE5775/5-1); Beratung und Vortragstätigkeit: GlaxoSmithKline. Ich erkläre, dass die anderen Autoren während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne angeben./ Martina Herwig-Carl: Research grant: EPIC-XS (project no. 823839, funded by the Horizon 2020 programme of the EU), German Research Foundation (HE5775/5-1); lectures and consultancy work: GlaxoSmithKline. I declare that the other authors have not declared any economic or personal connections as defined above in the past 3 years., (Thieme. All rights reserved.)

Background: The clinical diagnosis as well as the treatment approach of periocular tumors in childhood and adolescence can be challenging. Knowledge of the most important differential diagnoses and their clinicopathological correlation is helpful for the treatment approach., Objective: The clinical and histological characteristics of various eyelid tumors in childhood and adolescence are presented taking the excision frequencies into consideration., Material and Methods: The frequencies and clinicopathologic correlation of the most important eyelid tumors (n = 485) are presented based on the data of the ophthalmopathology laboratory of the University Eye Hospital Bonn from 1998-2023., Results: The most frequent tumor in childhood and adolescence is chalazion (57.3%), followed by dermoid cysts (16.7%) and molluscum contagiosum (9.6%). Other lesions of childhood and adolescence include pilomatrixoma (2.1%), hemangioma and other vascular malformations (4.7%) and rare differential diagnoses, such as subcutaneous calcifying nodules and xanthogranuloma. Guidance on the approach in different age groups is presented in the form of a decision tree., Conclusion: Tumors in children and adolescents are mostly benign, yet there are important indications for excision. A histological examination of any excised tissue in childhood and adolescence is obligatory because unexpected findings are not uncommon and the spectrum of lesions also differs from that in adulthood. Knowledge of the histological picture can be very helpful in the preoperative clinical classification and for planning further procedures., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Corneal ectasia comprises keratoconus, keratoglobus, pellucid marginal degeneration, and iatrogenic keratectasia. In all forms of corneal ectasia, there is a thinning of the cornea, usually accompanied by steepening of the cornea, leading to irregular astigmatism. Here, we provide an overview of histopathologic alterations of the various corneal ectasias. Furthermore, histologic changes after surgical procedures that are performed in severe cases of corneal ectasia, such as corneal cross-linking and penetrating keratoplasty (pKPL), as well as refractive surgical procedures that may lead to postsurgical ectasia are presented. In addition to a literature review, histopathologic archival material was reviewed and examined to illustrate the specific histologic changes., Competing Interests: Im Zusammenhang mit diesem Projekt besteht kein Interessenskonflikt. Herwig-Carl: Forschungsförderung: EPIC-XS (Projektnr. 823839, gefördert durch das Horizon 2020 Programm der EU), Deutsche Forschungsgemeinschaft (HE5775/5-1); Beratung und Vortragstätigkeit: GlaxoSmithKline, (Thieme. All rights reserved.)

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., (© 2022. The Author(s).)

Endophthalmitis is one of the most severe ophthalmic emergencies. Most patients experience a permanent decrease in visual acuity after the event, but the eye can be preserved in most cases. However, when the eye is enucleated after endophthalmitis, ophthalmopathologic investigation of the globe with respect to the clinical history can provide valuable information regarding the ultimately frustrating course of the disease that can be helpful for the treatment of future patients. Often, valuable aspects also emerge with regard to the therapeutic approach. For example, in therapy-resistant fungal endophthalmitis the necessity of penetrating keratoplasty with a large graft diameter and possibly even removal of the lens including the capsular bag should be stressed. In the following, five enucleated eyes with a different spectrum of endophthalmitis, as well as different potential pathways of exogenous and endogenous endophthalmitis, are illustrated clinically and ophthalmopathologically. In summary, endophthalmitis requires urgent intervention; however, various differential diagnoses must be excluded. Histopathologic examination of enucleated eyes is helpful for understanding the course of the disease and may also have forensic significance., Competing Interests: Herwig-Carl: Forschungsförderung: EPIC-XS (Projektnr. 823839, gefördert durch das Horizon 2020 Programm der EU), Deutsche Forschungsgemeinschaft (HE5775/5-1); Beratung und Vortragstätigkeit: GlaxoSmithKline., (Thieme. All rights reserved.)

The purpose of this study was to investigate Müller cells during the fetal development of the human eye. Müller cells in eyes of 39 human fetuses (11-38 weeks of gestation, WOG) and 6 infants (5 died of abusive head trauma, AHT, aged 1-9 months) were immunohistochemically stained and investigated for spatial and temporal immunoreaction of nestin, CD44, collagen IX and GFAP, which are stem cell markers or markers of intermediate filaments, respectively, in one of the hitherto largest cohorts of fetal eyes. Müller cells could be detected immunohistochemically as early as 12 WOG by immunohistochemical staining with nestin. Nestin was more strongly expressed in Müller cells of the peripheral retina and a centroperipheral gradient of immunoreaction over time was observed. CD44 was predominantly expressed in fetal eyes of the late second and early third trimester between (23 and 27 WOG) and significantly stronger in the infant eyes. Collagen IX labeling in the central retina was significantly stronger than in more peripheral sectors and increased with fetal age. GFAP staining in Müller cells was seen in the eye of a fetus of 38 WOG who died postnatally and in the infant eyes with and without history of AHT. Additionally, GFAP staining was present in the astrocytes of fetal and infant eyes. All examined markers were expressed by Müller cells at different developmental stages highlighting the plasticity of Müller cells during the development of the human eye. GFAP should be cautiously used as a marker for AHT as it was also expressed in fetal astrocytes and Müller cells in eyes without history of AHT., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. The Author(s).)

Background: Keratoconus is classified as a corneal ectasia and is a multifactorial disease. In those affected, mostly adolescent patients visual deterioration occurs due to the development of irregular astigmatism. Treatment by corneal cross-linking (CXL) has been indicated in progressive disease for several years., Objective: To present the pathophysiology and histological changes in keratoconus as well as wound healing processes after CXL and their potential complications., Material and Methods: Histological changes in keratoconus as well as wound healing processes after CXL and their potential complications are presented based on histological examination of corneal specimens with keratoconus with and without a condition after CXL. Relevant literature and own data are analyzed and discussed., Results: Besides inflammatory processes, atopic and genetic dispositions play a role in the development of keratoconus. The histological characteristics of keratoconus include changes in the epithelium, Bowman's layer and stroma. Wound healing processes after CXL include healing of the surface epithelium and transient loss of keratocytes and nerve fibers., Conclusion: Keratoconus shows characteristic histopathological changes, such as epithelial irregularities, stromal thinning and breaks of Bowman's layer, whereas the endothelium and Descemet's membrane remain unchanged (apart from cases of corneal hydrops). After CXL wound healing processes can be followed primarily in vivo by confocal microscopy. Complications after CXL are rare. Persistent loss of keratocytes can be clinically manifested as a visually relevant scar., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The human choroid derives from the mesectoderm, except the melanocytes originating from the neuroectoderm. To date, it is unclear whether all choroidal melanocytes share the same origin or might have different origins. The purpose of this study was to screen immunohistochemically for mesenchymal elements in the adult healthy human choroid, in the malignant melanoma of the choroid, as well as in the developing human fetal choroid., Methods: Human choroids were obtained from cornea donors and prepared as flat whole mounts for paraffin- and cryoembedding. Globes enucleated for choroidal melanoma and eyes from human fetuses between 11 and 20 weeks of gestation were also embedded in paraffin. Sections were processed for immunohistochemistry of the mesenchymal marker vimentin, the melanocyte marker Melan-A, and the macrophage marker CD68, followed by light-, fluorescence-, and confocal laser scanning-microscopy., Results: The normal choroid contained 499 ± 139 vimentin, 384 ± 78 Melan-A, and 129 ± 57 CD68 immunoreactive cells/mm 2 . The vimentin immunopositive cell density was significantly higher than the density of Melan-A and CD68 immunopositive cells (p < 0.001, respectively). By confocal microscopy, 24 ± 8% of all choroidal melanocytes displayed vimentin immunoreactivity. In choroidal melanomas, numerous melanoma cells of the epithelioid and spindle cell type revealed immunopositivity for both vimentin and Melan-A. The intratumoral density of vimentin immunoreactive cells was 1758 ± 106 cells/mm 2 , significantly higher than the density of Melan-A and CD68 immunopositive cells (p < 0.001, respectively). Comparing to healthy choroidal tissue, the choroidal melanomas revealed significantly higher densities of vimentin, Melan-A, and CD68 immunoreactive cells (p < 0.001, respectively). In the developing human fetal choroid, numerous vimentin and Melan-A immunopositive cells were detected not before the 16th week of gestation, with some of them showing colocalization of vimentin and Melan-A., Conclusions: The adult healthy human choroid is endowed with a significant number of vimentin immunopositive mesenchymal structures, including a subpopulation of vimentin immunoreactive choroidal melanocytes. These vimentin immunopositive melanocytic cells are also present in choroidal melanomas as well as in the developing human fetal choroid. Therefore, different embryologic origins can be considered for choroidal melanocytes., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: PPARγ (peroxisome proliferator-activated receptor gamma) is involved in the pathology of numerous diseases, including UM and other types of cancer. Emerging evidence suggests that an interaction between PPARγ and DNMTs (DNA methyltransferase) plays a role in cancer that is yet to be defined., Methods: The configuration of the repeating elements was performed with CAP3 and MAFFT, and the structural modelling was conducted with HDOCK. An evolutionary action scores algorithm was used to identify oncogenic variants. A systematic bioinformatic appraisal of PPARγ and DNMT1 was performed across 29 tumor types and UM available in The Cancer Genome Atlas (TCGA)., Results: PPAR-responsive elements (PPREs) enriched with Alu repeats are associated with different genomic regions, particularly the promotor region of DNMT1. PPARγ-DNMT1 co-expression is significantly associated with several cancers. C-terminals of PPARγ and DNMT1 appear to be the potential protein-protein interaction sites where disease-specific mutations may directly impair the respective protein functions. Furthermore, PPARγ expression could be identified as an additional prognostic marker for UM., Conclusions: We hypothesize that the function of PPARγ requires an additional contribution of Alu repeats which may directly influence the DNMT1 network. Regarding UM, PPARγ appears to be an additional discriminatory prognostic marker, in particular in disomy 3 tumors.

Background: For an understanding of the pathology of retinal diseases, direct comparisons of high-resolution in vivo retinal imaging and ex vivo histological preparations are desirable., Material and Methods: Multimodal in vivo and ex vivo imaging of a human donor eye with secondary alterations showing atrophic retina due to central retinal arterial occlusion. The subsequent correlation with the histological examination was carried out on identical tissue localizations., Results: Appropriate custom-built retinal imaging devices facilitate in vivo and ex vivo correlations and the examination of human eye tissue and acquisition of retinal images, e.g. SD-OCT. The precise alignment of the tissue enables a histological analysis on identical sites., Conclusion: The direct correlation of clinical in vivo imaging with ex vivo imaging including histopathology can further enhance our understanding in the pathogenesis of retinal diseases; however, the proposed method is currently limited due to restricted availability of human donor tissue., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Abstract: Compared with penetrating keratoplasty (PK), Descemet membrane endothelial keratoplasty (DMEK) is characterized as lower risk for complications such as immunological graft reaction and faster and better postoperative visual recovery. In patients with endothelial graft failure after PK, DMEK can be used to regenerate PK graft transparency. The surgical technique for DMEK in this specific situation is still under debate, particularly regarding stripping of Descemet membrane (DM) from the failed PK and diameter of the DMEK graft. Here we report a case of a 75-year-old female patient with a failed graft 16 years after PK for Fuchs endothelial dystrophy, who underwent uneventful DMEK surgery. Stripping of DM in this particular case was performed outside the failed PK and demonstrated a biomechanically stable junction between the PK donor and the host DM. Histopathologic analysis of the excised DM showed continuous extracellular matrix connecting the host and donor DM, indicating primary intention wound healing after PK at this tissue level. This case demonstrates that after PK, a biomechanically stable and histologically continuous DM can enable Descemetorhexis outside the failed graft and transplantation of a DMEK graft larger than the previous PK. This may provide more endothelial cells for transplantation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors A.S., C.M., and K.U.L. have no conflicts of interest to declare. M.C.H.-C. received a research grant from the German Research Foundation (DFG, HE 5775/5-1) and EPIC-XS (www.epic-xs.eu). F.G.H. received research grants from Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, CenterVue, Ellex, Roche/Genentech, Geuder, Kanghong, NightstaRx, Novartis, Optos, and Zeiss; and is a consultant for Acucela, Allergan, Apellis, Bayer, Boehringer-Ingelheim, Roche/Genentech, Geuder, Graybug Vision, Lin BioScience, Kanghong, Novartis, Pixium Vision, Oxurion, Stealth BioTherapeutics, and Zeiss.

Purpose: We sought to compare the sensitivity, specificity, accuracy, and interobserver agreement of the two most commonly used classification systems for conjunctival melanocytic intraepithelial lesions with the new World Health Organization (WHO) classification., Design: Retrospective case series and evaluation of classification systems., Methods: We reviewed the pathology and medical records of all patients who underwent a primary biopsy procedure for conjunctival primary acquired melanosis (PAM) at Wills Eye Hospital between 1974 and 2002 who had ≥36 months of follow-up. Data collected included age, sex, clinical findings, recurrence, and progression to melanoma. Twelve ophthalmic pathologists analyzed scanned hematoxylin and eosin-stained virtual microscopic slides using 3 classification systems: PAM, conjunctival melanocytic intraepithelial neoplasia, and the WHO 4th edition classification of conjunctival melanocytic intraepithelial lesions. Observer agreement, sensitivity, specificity, and diagnostic accuracy of each classification system were assessed., Results: There were 64 patients who underwent 83 primary excisions with cryotherapy for conjunctival PAM who had adequate tissue for histopathologic evaluation. The interobserver agreement in distinction between the low- and high-grade lesions was 76% for PAM, 67% for conjunctival melanocytic intraepithelial neoplasia, and 81% for WHO classification system. Low-grade lesions provided the greatest interpretative challenge with all 3 classification systems. The 3 classification systems had comparable accuracy of 81%-83% in their ability to identify lesions with potential for recurrence., Conclusions: This study highlights the comparable strengths and limitations of the 3 classification systems for conjunctival melanocytic intraepithelial lesions and suggests that the simplified WHO classification scheme is appropriate for evaluation of these lesions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Epigenetic regulation is an important layer of transcriptional control with the particularity to affect the broad spectrum of genome. Over the years, largely due to the substantial number of recurrent mutations, there have been hundreds of novel driver genes characterized in various cancers. Additionally, the relative contribution of two dysregulated epigenomic entities (DNA methylation and histone modifications) that gradually drive the cancer phenotype remains in the research focus. However, a complex scenario arises when the disease phenotype does not harbor any relevant mutation or an abnormal transcription level. Although the cancer landscape involves the contribution of multiple genetic and non-genetic factors, herein, we discuss specifically the mutation spectrum of epigenetically-related enzymes in cancer. In addition, we address the coexistence of these two epigenetic entities in malignant human diseases, especially cancer. We suggest that the study of epigenetically-related somatic mutations in the early cellular differentiation stage of embryonic development might help to understand their later-staged footprints in the cancer genome. Furthermore, understanding the co-occurrence and/or inverse association of different disease types and redefining the general definition of "healthy" controls could provide insights into the genome reorganization.

Background: For an understanding of the pathology of retinal diseases, direct comparisons of high-resolution in vivo retinal imaging and ex vivo histological preparations are desirable., Material and Methods: Multimodal in vivo and ex vivo imaging of a human donor eye with secondary alterations showing atrophic retina due to central retinal arterial occlusion. The subsequent correlation with the histological examination was carried out on identical tissue localizations., Results: Appropriate custom-built retinal imaging devices facilitate in vivo and ex vivo correlations and the examination of human eye tissue and acquisition of retinal images, e.g. SD-OCT. The precise alignment of the tissue enables a histological analysis on identical sites., Conclusion: The direct correlation of clinical in vivo imaging with ex vivo imaging including histopathology can further enhance our understanding in the pathogenesis of retinal diseases; however, the proposed method is currently limited due to restricted availability of human donor tissue.

Background: A variety of findings can be obtained from enucleated eyes, which provide the ophthalmologist with information with respect to the effectiveness, improvement options and of course also the possible complications of surgical interventions. Representative for many important findings, relevant clinical and ophthalmopathological findings are presented and discussed on the basis of three enucleated eyeballs., Methods: Clinical histopathological correlation of three enucleated eyeballs., Results: Enucleated eyeballs typically exhibit advanced changes in different tissues making it sometimes difficult to draw direct conclusions about the original surgical interventions. Nevertheless, many findings on the pathophysiology of different diseases, on wound healing and also on the surgical procedures can be deduced, as shown here in three different cases of epithelial invasion, historical retinal surgery and an endogenous fungal endophthalmitis., Conclusion: Each enucleated eye should be histopathologically examined and under consideration of the clinical history in order to understand the course of the disease and to use the knowledge gained for the treatment of future patients.

Ophthalmic pathology has a long tradition in Germany. And, like in general pathology, there is continuous progress due to new technologies and the improvement of molecular biology techniques. Ophthalmic pathology cannot be disregarded, particularly in the context of basic research but also as a medium for understanding pathophysiologic interrelationships and evaluating innovative surgical techniques. By means of various examples, the "four columns" of ophthalmic pathology shall be illustrated: diagnostics, clinicopathologic correlation, evaluation of new surgical and medical techniques and finally research. Ophthalmic pathology is not a discipline of the past but is rather one of the future. It develops and improves together with medical and ophthalmological progress and serves, at the same time, as a critical evaluation tool. Clinicopathologic correlations are of paramount importance for a lasting quality in ophthalmology, and we should not risk depriving ourselves of this instrument by carelessly saving at the wrong end and closing our laboratories. Ophthalmic pathology was, is and will further be the gold standard in many aspects of ophthalmology., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)