Allogeneic limbo-deep anterior lamellar keratoplasty (Limbo-DALK)-A novel surgical technique in corneal stromal disease and limbal stem cell deficiency.

Purpose: To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD).

Methods: Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease.

Combined Osteopontin Blockade and Type 2 Classical Dendritic Cell Vaccination as Effective Synergetic Therapy for Conjunctival Melanoma.

Angiogenesis and immune protection are essential at the onset of tumorigenesis. Angiogenesis serves to nourish the tumor, and prevention of immune defenses, for example, by dendritic cells (DCs), allows tumor growth. In this study, we investigated whether there are factors with dual functions that are both angiogenic and immunomodulatory and represent a therapeutic target.

Excimer Laser Phototherapeutic Keratectomy for Anterior Corneal Opacification After Descemet Membrane Endothelial Keratoplasty.

Purpose: The aim of this study was to assess the long-term outcome of excimer laser phototherapeutic keratectomy (PTK) for treating remaining anterior corneal opacities after Descemet membrane endothelial keratoplasty (DMEK).

Methods: This cohort study analyzed 67 eyes of 66 patients undergoing PTK in addition to and after DMEK between 2012 and 2021 at the Department of Ophthalmology, University of Cologne. Patients who were treated by PTK after previous DMEK on the same eye were included.

[Surgical treatment options for congenital/infantile corneal opacities and anterior segment dysgenesis].

Background: Due to the risk of amblyopia congenital and infantile corneal opacities have a narrow therapeutic window, frequently with a complex surgical treatment.

Objective: The present study gives an overview of the current treatment options for congenital and infantile corneal opacities.

Methods: The results of a literature search are presented and own clinical data and examples are shown.

New Therapeutic Approaches for Conjunctival Melanoma-What We Know So Far and Where Therapy Is Potentially Heading: Focus on Lymphatic Vessels and Dendritic Cells.

Conjunctival melanoma (CM) accounts for 5% of all ocular melanomas and arises from malignantly transformed melanocytes in the conjunctival epithelium. Current therapies using surgical excision in combination with chemo- or cryotherapy still have high rates for recurrences and metastatic disease. Lately, novel signal transduction-targeted and immune checkpoint inhibitors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) receptor inhibitors, BRAF- or MEK-inhibitors for systemic treatment of melanoma have improved the outcome even for unresectable cutaneous melanoma, improving patient survival dramatically.

New Technologies in Clinical Trials in Corneal Diseases and Limbal Stem Cell Deficiency: Review from the European Vision Institute Special Interest Focus Group Meeting.

To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation.

Long-term outcome of descemet membrane endothelial keratoplasty (DMEK) following failed penetrating keratoplasty (PK).

Purpose: To assess the long-term outcome of Descemet membrane endothelial keratoplasty (DMEK) following failed penetrating keratoplasty (PK).

Methods: Retrospective review of 1840 consecutive DMEK surgeries from the prospective Cologne DMEK database performed between 07/2011 and 08/2017 at the Department of Ophthalmology, University of Cologne.

Results: Fifty-two eyes received a DMEK surgery after failed PK.

Detection of Pro- and Antiangiogenic Factors in the Human Sclera.

Purpose: Avascular tissues can be used to identify antilymph- or antihemangiogenic factors. The human sclera-the outer covering layer of the eye, lacks lymphatic vessels and contains only a superficial network of blood vessels and was used here to identify endogenous antiangiogenic factors.

Methods: Expression levels of a panel of 96 known pro- and antiangiogenic factors were analyzed in 12 scleral or conjunctival control samples from normal human donors using real-time PCR.

Characterization of Antigen-Presenting Macrophages and Dendritic Cells in the Healthy Human Sclera.

Purpose: The sclera is mainly made of collagen and fibroblasts. The aim of this study was to analyze whether immune cells are present in the healthy human sclera.

Methods: Ten human anterior episcleral or stromal tissue samples from globe donors were immunohistochemically examined using confocal microscopy.

Using a Laminating Technique to Perform Confocal Microscopy of the Human Sclera.

The sclera is a dense connective tissue that covers and protects the eye. It mainly consists of dense collagen bundles (types I, III, IV, V, VI, and VII). Due to its autofluorescence, opaqueness, and thickness, it has not been found suitable for confocal microscopy.

A Novel Model of Metastatic Conjunctival Melanoma in Immune-Competent Mice.

Purpose: Conjunctival melanoma (CM) is an ocular surface tumor that can lead to fatal metastases. Patients developing, tumor-associated lymphangiogenesis have a significantly increased risk of metastatic disease, because tumor spread primarily occurs via lymphatic vessels to the draining lymph node. Here, we describe a novel immune-competent mouse model of CM that displays tumor-associated lymphangiogenesis with development of metastatic tumors.

Comparing the Hem- and Lymphangiogenic Profile of Conjunctival and Uveal Melanoma Cell Lines.

Purpose: Malignant melanomas of the ocular surface (conjunctival melanoma [CM]) and within the eye (uveal melanoma [UM]) show different types of metastatic behavior. While CM has a propensity to spread first to regional lymph nodes, UM metastasizes almost exclusively via the hematogenic route to the liver. We investigated whether these different metastatic patterns might be attributable to differential hem- and lymphangiogenic characteristics of CM and UM cells.

Topography of Lymphatic Markers in Human Iris and Ciliary Body.

Purpose: Reports of lymphatics in the anterior human uvea are contradictory. This might be caused due to a certain topography, which has not been considered yet. Therefore, here we systematically analyze iris and adjacent ciliary body with immunohistochemistry by combining various lymphatic markers.

Antilymphangiogenic therapy to promote transplant survival and to reduce cancer metastasis: what can we learn from the eye?

The lymphatic vasculature is - amongst other tasks - essentially involved in inflammation, (auto)immunity, graft rejection and cancer metastasis. The eye is mainly devoid of lymphatic vessels except for its adnexa, the conjunctiva and the limbus. However, several pathologic conditions can result in the secondary ingrowth of lymphatic vessels into physiologically alymphatic parts of the eye such as the cornea or the inner eye.

Consensus statement on the immunohistochemical detection of ocular lymphatic vessels.

There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research.

Impact of the prolymphangiogenic crosstalk in the tumor microenvironment on lymphatic cancer metastasis.

Lymphangiogenesis is a very early step in lymphatic metastasis. It is regulated and promoted not only by the tumor cells themselves, but also by cells of the tumor microenvironment, including cancer associated fibroblasts, mesenchymal stem cells, dendritic cells, or macrophages. Even the extracellular matrix as well as cytokines and growth factors are involved in the process of lymphangiogenesis and metastasis.

Expression of the lymphatic marker podoplanin (D2-40) in human fetal eyes.

During human ocular development, expression of proteins varies in different maturation stages. This study aims to characterize structures in human fetal eyes stained by the lymphatic marker podoplanin (D2-40) with emphasis on the stage of maturation and the presence of intraocular lymphatic structures. Formalin-fixed paraffin-embedded eyes from 40 human fetuses between 10 and 38 weeks of gestation (WoG) were investigated.

Absence of lymphatic vessels in the developing human sclera.

The adult sclera is free of lymphatic vessels, but contains a net of blood vessels. Whether and when this selectively lymphangiogenic privilege is achieved during embryologic development is not known yet. Therefore, we investigated the developing human sclera for blood- and lymphatic vessels in 34 abortions/stillborns (12-38 weeks of gestation).

A novel pro-angiogenic function for interferon-γ-secreting natural killer cells.

Purpose: To explore the function of natural killer (NK) cells in inflammatory angiogenesis in mice.

Methods: To study ocular angiogenic responses we used the cornea BFGF micropellet and the laser-induced choroidal neovascularization (CNV) mouse models (C57BL/6). To deplete NK cells in these models, we injected an anti-NK1.

Autocrine impact of VEGF-A on uveal melanoma cells.

Purpose: Tumor-derived VEGF-A, apart from expediting sufficient vascularization, subsequent tumor growth, and metastatic spread, can act on malignant cells themselves provided that VEGF receptors 1 or 2 (VEGF-R1, -R2) are co-expressed. The study goal was to investigate whether such autocrine VEGF-A signaling exists in uveal melanoma (UM).

Methods: Primary (MEL-270, OM-431) and metastatic (OMM-2.

Enrichment of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)-positive macrophages around blood vessels in the normal human sclera.

Purpose: To investigate whether the normal adult human sclera contains lymphatic vessels and to study their relation to immune cells and blood vessel anatomy.

Methods: Scleral tissue probes from 35 adult human donor bulbi were analyzed by immunohistochemistry and confocal microscopy for blood vessels (CD31+), lymphatic vessels (lymphatic vessel endothelial hyaluronan receptor 1 [LYVE1]+, podoplanin+), and macrophages (CD68+) at 12 locations (anterior, equatorial, and posterior at 3, 6, 9, and 12 o'clock positions of the eye) in all three scleral layers (episclera, stroma, and lamina fusca). Approval for scientific examination was obtained.

NK cell depletion delays corneal allograft rejection in baby rats.

Purpose: Penetrating keratoplasty has a very poor outcome compared with adults if performed in the first years of life. Rejection in these young patients occurs even in the absence of known immunological risk factors. Recently, a baby rat model was introduced and an essential contribution of natural killer (NK) cells during allograft rejection was suggested.