Ocular graft versus host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) is predominantly an inflammatory and destructive ocular surface disease with increasing incidence. It not only leads to a reduced quality-of-life but can also impair vision and in severe cases lead to blindness. The occurrence of GVHD can lead to a severe, often refractory disorders of the ocular surface, which is associated with chronic inflammation. The occurrence of corneal involvement is a major problem. The establishment of comprehensive care structures and individually adapted stage-appropriate treatment in interdisciplinary collaboration with colleagues in hemato-oncology is therefore of particular importance.

INTRODUCTION:Chronic ocular graft-versus-host disease (oGVHD) is one of the most common complications after allogeneic hematopoietic stem cell transplantation (aHSCT). Recent studies indicate that desiccating stress by air-conditioning in transplantation wards increases the incidence of oGVHD. To test the hypothesis that experimental desiccating stress is a risk factor for oGVHD a mouse model of oGVHD was subjected to experimental desiccating stress. MATERIALS/METHODS:A previously established chemo-induced minor-mismatch mouse model of oGVHD was used. One group was challenged with desiccating stress for 18 days and compared to non-desiccated GVHD animals. Clinical phenotyping was performed weekly and ocular tissue and regional lymph nodes were collected on days 7 and 28 for flow-cytometry, tear film cytokine analysis, histology for corneal lymphatics and dendritic cell counts, and corneal gene expression. RESULTS:Desiccating stress leads to significant earlier and more severe systemic and oGVHD accompanied by higher numbers of activated corneal dendritic cells, higher expression of TNF in tear film and earlier corneal lymphangiogenesis. Gene expression analysis suggests that systemic GVHD severity may influence oGVHD. Different inflammatory pathways are upregulated at d28 following desiccating stress in contrast to non-desiccated GVHD. CONCLUSIONS:The data presented strengthens the hypothesis, that desiccating stress during aHSCT is a risk factor for oGVHD. Together with already published clinical data, there is increasing evidence that implicates protecting patients from desiccation during the engraftment of allogeneic hematopoietic stem cells. Furthermore, specific prophylactic therapies should be developed and tested to reduce the incidence and severity of oGVHD.

Purpose To assess morphological changes in the meibomian glands (MGs) pre- and post-hematopoietic stem cell transplantation (HSCT). Methods Participants yet to undergo HSCT were included in a pre-HSCT group. Meibography images of both lids were graded using Pult’s meiboscale and analyzed using a semi-automatic software program. Meibography variables in the pre-HSCT group were compared with those in a control group of healthy participants. The follow-up group, a subset of the pre-HSCT group, comprised participants followed up for at least 6 months post-HSCT. Ocular Surface Disease Index (OSDI), tear break-up time, corneal fluorescein staining, and Schirmer test were performed. The differences in meibography variables and ocular surface tests pre- and post-HSCT were analyzed. Results Pre-HSCT and control groups comprised 181 and 24 participants, respectively. The pre-HSCT group had a higher meiboscale in the lower lid (2 vs. 1, p = 0.011) than controls. The follow-up group comprised 20 patients followed up for 12.75 months post-HSCT. After HSCT, the meiboscale of the upper lid was higher (2 vs. 1, p = 0.011), the MG area was lower in both lids (upper lid = 16.14% vs. 21.49%, p = 0.001; lower lid = 11.92% vs. 17.59%, p = 0.011), and the OSDI increased (15.2 vs. 26.85, p = 0.018) in the second visit compared to the first visit. Conclusions Alterations in meibography were observed in patients pre- and post-HSCT. This may be attributed to the effect of treatments administered pre-HSCT, although an additive effect of conditioning regimen in the long-term cannot be discarded.

Sklerallinsen weisen im Unterschied zu klassischen kornealen Kontaktlinsen einen deutlich größeren Durchmesser auf und werden mit Flüssigkeit gefüllt auf das Auge aufgesetzt. Diese Besonderheiten ermöglichen einen Einsatz auch bei Augen, die wegen Erkrankungen oder Voroperationen nicht für eine Anpassung kornealer Kontaktlinsen geeignet sind. So kann einerseits auch in anatomisch außergewöhnlichen oder in der Benetzung eingeschränkten Augen ein optimaler Ausgleich von Fehlsichtigkeiten ermöglicht und andererseits insbesondere bei schweren Integritätsstörungen der Augenoberfläche eine Linderung der alltäglichen Beschwerden erreicht werden. Im vorliegenden Kapitel werden Beispiele für Erkrankungen erläutert, in denen eine Anpassung skleraler Kontaktlinsen sinnvoll und hilfreich sein kann.

Ocular graft-versus-host disease (GvHD) is predominantly an inflammatory ocular surface disorder after allogeneic hematopoietic stem cell transplantation (HSCT) with increasing incidence. It is not only associated with reduced quality of life because of dry eye syndromes but can also impair visual acuity and lead to blindness due to corneal complications. The GvHD is mostly associated with severe moisturizing disorder of the ocular surface, which is often resistant to therapy and accompanied by chronic inflammation. Corneal complications are an important problem in these patients. An individually adapted multimodal stage-related and interdisciplinary therapy in cooperation with hematologists and oncologists is therefore important for the treatment of patients with ocular GvHD.

ZusammenfassungHornhautnerven und dendritische Zellen werden zunehmend bei der Diagnostik von Erkrankungen der Augenoberfläche als klinische Parameter mittels intravitaler Konfokalmikroskopie dargestellt. In dieser Übersichtsarbeit werden unterschiedliche Verfahren der Bildauswertung dargestellt. Die Verwendung von Deep-Learning-Algorithmen, die eine automatisierte Mustererkennung ermöglichen, wird anhand eigener Entwicklungen detailliert erläutert und mit anderen etablierten Verfahren verglichen.

Corneal nerves and dendritic cells are increasingly being visualised to serve as clinical parameters in the diagnosis of ocular surface diseases using intravital confocal microscopy. In this review, different methods of image analysis are presented. The use of deep learning algorithms, which enable automated pattern recognition, is explained in detail using our own developments and compared with other established methods.

Dry eye disease (DED) is a rapidly growing ocular surface disease with a significant socioeconomic impact that affects the patients' visual function and, thus, their quality of life. It is distinguished by a loss of tear film homeostasis, leading to tear film instability, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities, with all of these playing etiological roles in the propagation of the vicious DED circle. While current treatments primarily focus on reducing tear film instability and hyperosmolarity, increasingly more attention is being placed on tackling the underlying inflammation that propagates and potentiates these factors. As such, preclinical models are crucial to further elucidate the DED pathophysiology and develop novel therapeutic strategies. This review outlines the role of inflammation in DED, highlighting related signs and diagnostic tools before focusing on relevant preclinical animal models and potential therapeutic strategies to tackle DED-associated inflammation.

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions.Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye.

Corneal wound, associated with pain, impaired vision, and even blindness, is the most common ocular injury. In this study, we investigated the effect of a novel ferroptosis inhibitor, UAMC-3203 (10 nM–50 µM), in corneal epithelial wound healing in vitro in human corneal epithelial (HCE) cells and ex vivo using alkali-induced corneal wounded mice eye model. We evaluated in vivo acute tolerability of the compound by visual inspection, optical coherence tomography (OCT), and stereomicroscope imaging in rats after its application (100 µM drug solution in phosphate buffer pH 7.4) twice a day for 5 days. In addition, we studied the partitioning of UAMC-3203 in corneal epithelium and corneal stroma using excised porcine cornea. Our study demonstrated that UAMC-3203 had a positive corneal epithelial wound healing effect at the optimal concentration of 10 nM (IC50 value for ferroptosis) in vitro and at 10 µM in the ex vivo study. UAMC-3203 solution (100 µM) was well tolerated after topical administration with no signs of toxicity and inflammation in rats. Ex-vivo distribution study revealed significantly higher concentration (~12–38-fold) and partition coefficient (Kp) (~52 times) in corneal epithelium than corneal stroma. The UAMC-3203 solution (100 µM) was stable for up to 30 days at 4 °C, 37 °C, and room temperature. Overall, UAMC-3203 provides a new prospect for safe and effective therapy for corneal wounds.

Vernarbungen der Bindehaut sind insgesamt selten und werden oft übersehen. Die differenzialdiagnostische Abgrenzung des vernarbenden Schleimhautpemphigoids von anderen Ursachen ist wichtig für die weitere Therapieplanung. Zu anderen Erkrankungen, die zu einer konjunktivalen Vernarbung führen, gehören die okuläre Rosazea, die okuläre Graft-versus-Host Erkrankung, die atopische Keratokonjunktivitis, Infektionen, Traumata und weitere zum Teil sehr seltene Entitäten. Den meisten dieser Differenzialdiagnosen ist gemein, dass die Vernarbung im Gegensatz zum Schleimhautpemphigoid auch unbehandelt häufig zum Stillstand kommt.

Overall, conjunctival scarring is rare and often overlooked during routine examination. However, the differential diagnostic distinction of cicatricial mucous membrane pemphigoid from other causes is crucial for further treatment planning. Other entities that lead to conjunctival scarring, are ocular rosacea, ocular graft-versus-host disease, atopic keratoconjunctivitis, infections, trauma and further sometimes very rare diseases. Most of these differential diagnoses have in common that conjunctival scarring does not progress indefinitely if untreated, in contrast to mucous membrane pemphigoid.