Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium.

Pterygium pathogenesis is often attributed to a population of altered limbal stem cells, which initiate corneal invasion and drive the hyperproliferation and fibrosis associated with the disease. These cells are thought to undergo epithelial to mesenchymal transition (EMT) and to contribute to subepithelial stromal fibrosis. In this study, the presence of the novel limbal stem cell marker ABCB5 in clusters of basal epithelial pterygium cells co-expressing with P63α and P40 is reported. ABCB5-positive pterygium cells also express EMT-associated fibrosis markers including vimentin and α-SMA while their ß-catenin expression is reduced. By using a novel in vitro model of two-dose UV-induced EMT activation on limbal epithelial cells, we could observe the dysregulation of EMT-related proteins including an increase of vimentin and α-SMA as well as downregulation of ß-catenin in epithelial cells correlating to downregulation of ABCB5. The sequential irradiation of limbal fibroblasts also induced an increase in vimentin and α-SMA. Taken together, these data demonstrate for the first time the expression of ABCB5 in pterygium stem cell activity and EMT-related events while the involvement of limbal stem cells in pterygium pathogenesis is exhibited via sequential irradiation of limbal epithelial cells. The later in vitro approach can be used to further study the involvement of limbal epithelium UV-induced EMT in pterygium pathogenesis and help identify novel treatments against pterygium growth and recurrence.

[Diagnostics, clinical aspects and genetics of congenital corneal opacities]. / Diagnostik, Klinik und Genetik kongenitaler Hornhauttrübungen.

BACKGROUND: Congenital corneal opacities are comparatively rare diseases with high amblyogenic potential. PURPOSE: The present work provides an overview of the diagnostics, clinical aspects and genetics of congenital corneal opacities. METHODS: A literature search was carried out to compile an overview and illustration with own clinical case examples. RESULTS: Differentiated diagnostics are of high importance in the treatment of patients with congenital corneal opacities. A close cooperation between the medical departments involved and also the parents is absolutely essential. The structured classification of congenital corneal opacities provides the basis for a targeted treatment. DISCUSSION: The causes and the clinical symptoms of congenital corneal opacities are manifold. The correct diagnosis should be made early and in an interdisciplinary manner. Based on this, conservative and surgical treatment measures can be planned and an impending development of amblyopia can be specifically counteracted.

Graft survival of Descemet membrane endothelial keratoplasty (DMEK) in corneal endothelial decompensation after glaucoma surgery.

PURPOSE: This study aims to assess the results, rebubbling rate, and graft survival after Descemet membrane endothelial keratoplasty (DMEK) with regard to the number and type of previous glaucoma surgeries. METHODS: This is a clinical retrospective review of 1845 consecutive DMEK surgeries between 07/2011 and 08/2017 at the Department of Ophthalmology, University of Cologne. Sixty-six eyes were included: group 1 (eyes with previous glaucoma drainage devices (GDD); n = 27) and group 2 (eyes with previous trabeculectomy (TE); n = 39). Endothelial cell loss (ECL), central corneal thickness, graft failure, rebubbling rate, and best spectacle-corrected visual acuity (BSCVA) up to 3 years after DMEK were compared between subgroups of patients with different numbers of and the two most common types of glaucoma surgeries either GDD or TE or both. RESULTS: Re-DMEK rate due to secondary graft failure was 55.6% (15/27) in group 1 and 35.9% in group 2. The mean graft survival time in group 1 was 25 ± 11 months and 31.3 ± 8.6 months in group 2 (p = 0.009). ECL in surviving grafts in group 1 was 35% (n = 13) at 6 months, 36% at 12 months (n = 8), and 27% (n = 4) at 2 years postoperatively. In group 2, ECL in surviving grafts was 41% (n = 10) at 6 months, 36% (n = 9) at 12 months, and 38% (n = 8) at 2 years postoperatively. Rebubbling rate in group 1 was 18.5% (5/27) and 35.9% (14/39) in group 2 (p = 0.079). CONCLUSION: Eyes with previous GDD had no higher risk for an increased rebubbling rate but a higher risk for a re-DMEK due to secondary graft failure with a mean transplant survival time of about 2 years. Compared to eyes with preexisting glaucoma drainage device, eyes after trabeculectomy had less secondary graft failures and a longer mean graft survival rate.

[Preconditioning of vascularized high-risk eyes using fine-needle diathermy and cross-linking]. / Präkonditionierung von vaskularisierten Hochrisikoaugen mittels Feinnadeldiathermie und Crosslinking.

BACKGROUND: The risk of allograft rejection following high-risk keratoplasty increases with the area of corneal neovascularization. Pharmaceutical and physical regression of corneal neovascularization before keratoplasty may offer the potential to reduce the risk of graft rejection after high-risk keratoplasty. OBJECTIVE: This article provides a review of the literature on the preconditioning of vascularized high-risk eyes using fine-needle diathermy and corneal cross-linking (preoperative preconditioning by lymphangioregression). METHODS: A literature search was carried out in PubMed and a summary of own data is presented. RESULTS: Animal experimental studies showed that both fine-needle diathermy and corneal cross-linking lead to a regression of corneal neovascularization and prolong graft survival after high-risk keratoplasty. Furthermore, studies from our institute provide first evidence that both procedures also lead to a reduction of corneal neovascularization in the clinical practice and thus potentially reduce the risk of allograft rejection after subsequent high-risk keratoplasty. DISCUSSION: Fine-needle diathermy and corneal cross-linking provide effective therapeutic approaches for angioregressive treatment and seem to prolong graft survival following high-risk keratoplasty. Larger prospective and controlled clinical trials are needed to further investigate these promising therapeutic approaches.

[Descemet membrane endothelial keratoplasty (DMEK) for graft failure after penetrating keratoplasty and in vascularized high-risk eyes]. / "Descemet membrane endothelial keratoplasty" (DMEK) bei Transplantatversagen nach perforierender Keratoplastik und in vaskularisierten Hochrisikoaugen.

BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) is considered the gold standard for the treatment of corneal endothelial dysfunction and generally leads to good postoperative results. Recently, studies have also analyzed the outcome of DMEK in so-called high-risk eyes. MATERIAL AND METHODS: The relevant literature and own data on DMEK for graft failure after penetrating keratoplasty and in vascularized high-risk eyes are presented and discussed. RESULTS: A DMEK for the treatment of transplant failure after penetrating keratoplasty can be considered for eyes without stromal scars and without high astigmatism. A retrospective analysis of 52 patients with failed penetrating grafts showed that DMEK leads to a significant increase in visual acuity, albeit to a lesser extent than after primary DMEK. Rejection and transplant failure rates seem to be similar those seen after penetrating re-keratoplasty and are thus higher than after primary DMEK. A DMEK might also be a feasible option for eyes with corneal neovascularization and stromal edema without stromal scars. A retrospective analysis of 24 eyes with at least 2 vascularized corneal quadrants demonstrated that DMEK leads to a significant improvement in visual acuity and regression of corneal neovascularization. The rejection rate in this cohort was 4.2% and is therefore slightly higher than after low-risk DMEK in eyes without corneal neovascularization but still much better compared to penetrating keratoplasty. CONCLUSION: Indications for DMEK are expanding and it can be a therapeutic option for transplant failure after penetrating keratoplasty with acceptable outcomes. Furthermore, DMEK seems to be a good option for the treatment of endothelial dysfunction in vascularized high-risk eyes without stromal scars.

[Treatment of vascularized high-risk eyes with a Boston keratoprosthesis]. / Versorgung von vaskularisierten Hochrisikoaugen mittels Boston-Keratoprothese.

BACKGROUND: In severely compromised and vascularized high-risk eyes, the Boston keratoprosthesis procedure is often the last treatment option. The transparency of the optics is not impaired by endothelial immune reactions. METHODS: This review article discusses relevant literature as well as our own data and experiences with the Boston keratoprosthesis in high-risk eyes. The relevant complications as well as the postoperative management are discussed. RESULTS: In more than 60% of the high-risk eyes a long-term increase in visual acuity can be achieved. Keratoprosthesis retention rates show a variable span with reported mean 5­year retention rates of 75%. The most common postoperative complications include the formation of a retroprosthetic membrane and keratolysis in up to 50% each. More than 70% of the eyes already suffer from (secondary) glaucoma preoperatively, so that glaucoma surgery is performed simultaneously in at least 20% of cases and in the postoperative course further antiglaucomatous surgery is necessary in up to 31%. Vitreoretinal complications include, in particular, sterile vitritis and infectious endophthalmitis but persistent hypotonia is also described in one third of patients. CONCLUSION: The Boston keratoprosthesis is an alternative to conventional corneal replacement if the prognosis for allogeneic transplants is poor. Postoperative complications are common; therefore, postoperative management plays an important role. For vascularized high-risk eyes, however, it is often the only remaining option for visual rehabilitation.

Eye changes in space : New insights into clinical aspects, pathogenesis, and prevention.

BACKGROUND: More than ever research into changes in the eye caused by long-term space flight is becoming the focus of the international and national space agencies National Aeronautics and Space Administration (NASA), European Space Agency (ESA) and German Aerospace Center (DLR). In addition to space radiation-induced cataract formation considerable eye changes, summarized under space flight-associated neuro-ocular syndrome (SANS), can occur. OBJECTIVE: This article gives an overview of the current state of research and future directions in the field of research concerned with ocular alterations in SANS and presents the relevance for terrestrial ophthalmological research. MATERIAL AND METHODS: An analysis of existing publications on SANS in PubMed and reports on the risk of SANS published by the NASA of the USA was carried out. RESULTS: The reasons for the development of the eye changes in space have not been clarified. Factors such as the increase in intracranial pressure, fluid shifts, hypercapnia and genetic factors are the subject of intensive research efforts. A terrestrial model for the induction of papilledema could be established (bed rest studies with -6° head-down tilt as a space analogue). Countermeasures for the development of eye changes, such as intermittent artificial gravity, are the subject of current research studies. CONCLUSION: Research into SANS as part of bed rest studies will provide further important insights in the future for space research and also for terrestrial research. Clinical research projects can be derived from space research.

[Dependency of intraocular pressure on body posture in glaucoma patients : New approaches to pathogenesis and treatment]. / Lageabhängigkeit des Augeninnendruckes bei Glaukompatienten : Neue Ansätze zur Pathogenese und Therapie.

BACKROUND: Human intraocular pressure (IOP) depends on the position of the head in relation to the body in space. Physiologically, the IOP increases in a lying position compared to an upright posture. Microgravity in space also appears to cause an increase in intraocular pressure, accompanied by other ophthalmological changes, which are summarized under the term spaceflight associated neuro-ocular syndrome (SANS). Bed rest studies are being carried out to investigate the effects of weightlessness on the human body. So here there is an intersection between research into SANS and glaucoma. Increased intraocular pressure remains the most important risk factor for glaucoma development and progression that can be influenced by treatment. The influence of position-dependent IOP fluctuations on glaucoma is still not sufficiently understood. MATERIALS AND METHODS: A literature search was carried in PubMed on the subject of IOP fluctuations related to posture. Analysis and evaluation of the published study results and a summary of available clinical data. RESULTS: The increase in IOP when changing from a seated to a lying body position is greater in glaucoma patients with an increase of up to 8.6 mm Hg compared to healthy subjects with an increase up to 5 mm Hg. In small pilot studies the increase in lying IOP in some glaucoma patients and healthy volunteers could be attenuated by elevation of the head by 30%. A lower compartmental pressure in the subarachnoid space has been associated with glaucoma and may represent a risk factor for glaucoma development. Not only the level of IOP but also IOP fluctuations were associated with an increased risk of disease progression. CONCLUSION: The clinical significance of IOP peaks during sleep on glaucoma is still not sufficiently understood. New methods for continuous IOP measurement offer promising opportunities for further research into the importance of IOP fluctuations related to changes of body and head posture.

[Eye changes in space : New insights into clinical aspects, pathogenesis and prevention]. / Augenveränderungen im All : Aktuelles zu Klinik, Pathogenese und Prävention.

BACKGROUND: More than ever research into changes in the eye caused by long-term space flight is becoming the focus of the international and national space agencies National Aeronautics and Space Administration (NASA), European Space Agency (ESA) and German Aerospace Center (DLR). In addition to space radiation-induced cataract formation considerable eye changes, summarized under space flight-associated neuro-ocular syndrome (SANS), can occur. OBJECTIVE: This article gives an overview of the current state of research and future directions in the field of research concerned with ocular alterations in SANS and presents the relevance for terrestrial ophthalmological research. MATERIAL AND METHODS: An analysis of existing publications on SANS in PubMed and reports on the risk of SANS published by the NASA of the USA was carried out. RESULTS: The reasons for the development of the eye changes in space have not been clarified. Factors such as the increase in intracranial pressure, fluid shifts, hypercapnia and genetic factors are the subject of intensive research efforts. A terrestrial model for the induction of papilledema could be established (bed rest studies with -6° head-down tilt as a space analogue). Countermeasures for the development of eye changes, such as intermittent artificial gravity, are the subject of current research studies. CONCLUSION: Research into SANS as part of bed rest studies will provide further important insights in the future for space research and also for terrestrial research. Clinical research projects can be derived from space research.

[Explantation of two historical posterior chamber phakic intraocular lenses 31 years after implantation]. / Explantation zweier historischer phaker Hinterkammerlinsen 31 Jahre nach Implantation.

This article reports the case of a 56-year-old male patient who had undergone implantation of posterior chamber phakic intraocular lenses in 1987 in Russia. The patient presented to this clinic 31 years after the initial surgery with anterior cortical cataracts and initial stages of corneal decompensation in both eyes. Strategic planning and execution of surgical treatment and the further clinical course are portrayed in this report.

[Unmet research and developmental needs in ophthalmology : A consensus-based road map of the European Vision Institute for 2019-2025]. / Forschungs- und Entwicklungsbedarf in der Augenheilkunde ("Unmet needs") : Ein konsensbasierter Fahrplan des European Vision Institute (EVI) für die Jahre 2019 bis 2025.

PURPOSE: To define unmet needs in ophthalmology which can realistically be addressed in the next years (2019-2025) and to describe potential avenues for research to address these challenges. METHODS: Outcomes of a consensus process within the European Vision Institute (EVI, Brussels) are outlined. Disease areas which are discussed comprise glaucoma, retinal dystrophies, diabetic retinopathy, dry eye disease, corneal diseases, cataract and refractive surgery. RESULTS: Unmet needs in the mentioned disease areas are discussed and realistically achievable research projects outlined. CONCLUSION: Considerable progress can be made in the field of ophthalmology and patient-relevant outcomes in the near future.

Phase-specific functions of macrophages determine injury-mediated corneal hem- and lymphangiogenesis.

Macrophages are critical mediators of injury-associated corneal hemangiogenesis (HA) and lymphangiogenesis (LA). Yet, molecular regulators of the hem- and lymphangiogenic potential of corneal wound macrophages are poorly understood. Using two different mouse models of acute (perforating corneal incision injury) and chronic (corneal suture placement model) corneal injury, here we identified distinct functions of early- versus late-phase corneal wound macrophages in corneal HA and LA. Whereas early-phase wound macrophages are essential for initiation and progression of injury-mediated corneal HA and LA, late-phase wound macrophages control maintenance of established corneal lymphatic vessels, but not blood vessels. Furthermore, our findings reveal that the hem- and lymphangiogenic potential of corneal wound macrophages is controlled by the type of the corneal damage. Whereas perforating corneal incision injury induced primarily wound macrophages with lymphangiogenic potential, corneal suture placement provoked wound macrophages with both hem- and lymphangiogenic potential. Our findings highlight a previously unrecognized injury-context dependent role of early- versus late-phase corneal wound macrophages with potential clinical impact on therapy development for sight-threatening corneal neovascular diseases.

[Descemet membrane endothelial keratoplasty in complex eyes]. / "Descemet membrane endothelial keratoplasty" in komplexen Augen.

BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) has become the standard surgical treatment for Fuchs' endothelial corneal dystrophy (FECD) in Germany. In addition to classical FECD, there are endothelial disorders amenable to DMEK associated with complex changes in the anterior segment of the eye, such as anterior synechia of the iris, larger iris defects, after glaucoma surgery, after vitrectomy and after trauma. OBJECTIVE: This article provides an overview of the possibilities to treat patients with complex anterior segment situations in the presence of corneal endothelial decompensation with DMEK. MATERIAL AND METHODS: Description of problems and current surgical techniques when performing DMEK in complex situations. RESULTS: Reconstruction of the iris or the iris/lens diaphragm often needs to be performed either simultaneously or in a previous operation to treat patients with complex anterior segment alterations with DMEK. Both very shallow and very deep anterior chambers pose a major problem. A DMEK graft from older donors (above 70 years) is prone to less rolling and should be preferred in patients with a deep anterior chamber (e.g. after vitrectomy). The graft size should also be adapted to the available space, e. g. a smaller graft diameter should be selected for eyes with anterior synechia. CONCLUSION: There are only a few evaluations of DMEK under complex conditions; however, it appears that the rate of secondary graft failure, endothelial cell loss and the rebubbling rate are increased in this very heterogeneous group of diseases. Further studies are needed to identify risk factors for a negative progression after DMEK in "complex" eyes.