Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts. / Atopische Keratokonjunktivitis: Pathophysiologie, Klinik und potenzielle neue Therapiekonzepte.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Peripheral Ulcerative Keratitis: Clinical Characteristics, Differential Diagnoses and Therapeutic Concepts. / Periphere ulzerative Keratitis: Klinik, Differenzialdiagnosen und Therapiekonzepte.

Peripheral ulcerative keratitis (PUK) is an inflammatory disease of the peripheral cornea, which may frequently be associated with several rare, but potentially life-threatening systemic diseases. The inflammatory pathogenesis of PUK results from humoral and cell-mediated inflammation. The diagnosis is usually based on the typical clinical findings and always requires detailed diagnostic testing to identify a potential systemic underlying disease. Treatment includes topical and systemic immunosuppressive and immunomodulatory therapeutic strategies and, in the event of impending or existing perforation, also various surgical interventions. PUK is a potentially blinding disease that initially affects the periphery, but, if left untreated, can lead to destruction of the entire cornea. Interdisciplinary diagnostic testing and therapy are crucial to preserve vision in the affected patients and reduce morbidity and mortality. The following article provides an overview of the pathophysiology, clinical findings, possible underlying systemic diseases, relevant differential diagnoses and therapeutic strategies.

Quality Control in the Corneal Bank with Artificial Intelligence: Comparison of a New Deep Learning-based Approach with Conventional Endothelial Cell Counting by the "Rhine-Tec Endothelial Analysis System". / Qualitätskontrolle in der Hornhautbank mit künstlicher Intelligenz: Vergleich eines neuen Deep-Learning-basierten Ansatzes mit der konventionellen Endothelzelldichtenbestimmung durch das "Rhine-Tec Endothelial Analysis System".

Endothelial cell density (ECD) is a crucial parameter for the release of corneal grafts for transplantation. The Lions Eye Bank of Baden-Württemberg uses the "Rhine-Tec Endothelial Analysis System" for ECD quantification, which is based on a fixed counting frame method considering only a small sample of 15 to 40 endothelial cells. The measurement result therefore depends on the frame placement and manual correction of the cells counted within the frame. To increase the sample size and create higher objectivity, we developed a new method based on "deep learning" that automatically detects all visible endothelial cells in the image. This study aims to compare this new method with the conventional Rhine-Tec system. 9375 archived phase-contrast microscopic images of consecutive grafts from the Lions Eye Bank were evaluated with the deep learning method and compared with the corresponding archived analyses of the Rhine-Tec system. Means, Bland-Altman and correlation analyses were compared. Comparable results were obtained for both methods. The mean difference between the Rhine-Tec system and the deep learning method was only - 23 cells/mm2 (95% confidence interval - 29 to - 17). There was a statistically significant positive correlation between the two methods, with a correlation coefficient of 0.748. What was striking in the Bland-Altman analysis were clustered deviations in the cell density range between 2000 and 2500 cells/mm2 - with higher values in the Rhine-Tec system. The comparable results for cell density measurement values underline the validity of the deep learning-based method. The deviations around the formal threshold for graft release of 2000 cells/mm2 are most likely explained by the higher objectivity of the deep learning method and the fact that measurement frames and manual corrections were specifically selected to reach the formal threshold of 2000 cells/mm2 when the full area endothelial quality was good. This full area assessment of the graft endothelium cannot currently be replaced by deep learning methods and remains the most important basis for graft release for keratoplasty.

Descemet Membrane Endothelial Keratoplasty in Eyes with an Artificial Iris.

The purpose of this study is to report the outcome of Descemet membrane endothelial keratoplasty (DMEK) in three eyes with a complex anterior segment and an artificial iris. A retrospective chart review of three cases was performed and clinically meaningful patient characteristics, clinical events, and therapeutic interventions were outlined. A literature search was performed and the clinical course of the three cases was discussed in the context of the published literature. DMEK in the presence of an artificial iris did not match the clinical results of DMEK in uncomplicated eyes. All three eyes experienced major complications, such as failure to achieve graft adherence, early graft failure, or an immune reaction. The indication for DMEK in complex anterior segments with an artificial iris should be made with the awareness of multiple possible complications and the potentially poor prognosis of the procedure.

Intrastromal Keratolimbal Epithelial Cysts: Congenital and Postsurgical. / Intrastromale keratolimbale Epithelzysten: kongenital und postoperativ.

Two very rare cases of intrastromal keratolimbal epithelial cysts are reported. Firstly, an enlarging congenital cyst in a 9-year-old boy, and secondly, a recurrent postsurgical cyst in an 18-year-old female patient. Both cases presented with a limbal cyst, continuing into the corneal stroma as a whitish mass up to the optical axis. The indication for surgery was stabilization of visual acuity in case one and improvement of cosmetic aspects in case two. In the first case, a small part of the cyst was opened at the limbus and the whitish material in the cyst was flushed out. In the second case, anterior lamellar keratectomy over the whole cyst was performed with subsequent application of mitomycin C. Immunohistochemical analysis revealed cytokeratin 19-positive epithelial cells in both cysts. Therefore, an implantation of conjunctival epithelium into the sclera seems to be responsible for the respective keratolimbal cyst. Postsurgically, satisfying cosmetic and functional results were obtained in both cases, with follow-ups of 4 and 9 months. Keratolimbal cysts have rarely been described in the literature. In most cases, a conjunctival epithelial implantation occurs following surgery or trauma and very rarely congenitally. After simple aspiration of the cyst's content, a rapid recurrence is often observed, so that partial or - if possible - complete removal of the anterior cyst wall is recommended, as shown in our cases.

[The 2021 Activity Report of the Tissue Transplantation and Biotechnology Section of the German Ophthalmological Society]. / Aktivitäten der Sektion Gewebetransplantation und Biotechnologie der Deutschen Ophthalmologischen Gesellschaft: Leistungsbericht 2021.

The Section on Tissue Transplantation and Biotechnology of the German Ophthalmologic Society presented its 11th annual report for the year 2021. The number of corneal samples has still risen in comparison to former years. Nevertheless, there is still a need for import of transplants from abroad. Therefore, the transplant bottleneck has not yet been eliminated.

[Keratoconus: biomechanics ex vivo]. / Keratokonus: Biomechanik ex vivo.

BACKGROUND: Keratoconus is associated with an impairment in corneal biomechanics. Using nanoindentation, spatially resolved measurement of biomechanical properties can be performed on corneal tissue. The aim of this study is to assess the biomechanical properties of corneas with keratoconus in comparison to healthy controls. METHODS: 17 corneas with keratoconus and 10 healthy corneas unsuitable for transplantation were included in the study. After explantation, corneas were kept in culture medium containing 15% dextran for at least 24 h. Nanoindentation was then performed to a depth of 25 µm at a force increase of 300 µN/min. RESULTS: A total of 2328 individual indentations were performed for this study. In the keratoconus group; the mean modulus of elasticity was 23.2 kPa (± 15.0 kPa) for a total of 1802 indentations. In the control group, the mean modulus of elasticity was 48.7 kPa (± 20.5 kPa) with a total of 526 indentations. The Wilcoxon test showed that the differences were statistically significant. CONCLUSION: Using nanoindentation, a significantly lower elastic modulus was found in corneas with keratoconus compared to corneas without keratoconus. Further studies are needed to gain a better understanding of how keratoconus affects corneal biomechanics.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

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.

Cataract Surgeries in Patients with Fuchs Endothelial Dystrophy. / Kataraktoperation beim Vorliegen einer Fuchs-Endotheldystrophie.

Patients with Fuchs endothelial dystrophy often develop visual symptoms between 50 - 60 years of age, which is the same time that the first symptoms of a developing cataract start to appear. On the other hand, in patients with a clinically significant cataract, corneal guttata may be detected by chance during a routine clinical workup. In both situations, the surgeon has to decide whether DMEK or cataract surgery should be performed alone or in combination. In the case of advanced Fuchs dystrophy with or without a clinically significant cataract, a combined surgery known as the triple procedure seems favorable as the clinical course after this procedure is the same as following sequential surgery. Furthermore, the affected patients will only have to undergo one surgery and will reach the final visual acuity much faster. Posterior lamellar keratoplasty alone can only be an option in the case of young patients with advanced Fuchs dystrophy, intact accommodation, and no signs of cataract. In the case of a clinically significant cataract combined with corneal guttata, clinical features including central corneal thickness and endothelial cell density, among others, can help to decide which surgical procedure seems to be the best. In case of cataract surgery alone, the surgeon needs to protect the corneal endothelium as well as possible. The softshell technique can help to reduce the loss of endothelial cells during cataract surgery, whereas femtosecond laser assisted cataract surgery is still controversial. The following review will discuss the most important preoperative, perioperative, and postoperative factors that need be considered in order to achieve the best result for our patients.

Scrolling of the Donor Cornea in Dependence of Temperature and Osmolarity for Descemet Membrane Endothelial Keratoplasty. / Rollung der Spenderhornhaut in Abhängigkeit von Temperatur und Osmolarität für die Descemet Membrane endothelial Keratoplasty.

BACKGROUND: After preparation of a graft for Descemet membrane endothelial keratoplasty (DMEK), the diameter of the graft's scroll varies significantly. In particular, narrow scrolls may complicate DMEK surgery. In this study we investigated how temperature, osmolarity, and deswelling of the donor tissue influence scrolling diameter. MATERIAL AND METHODS: In this study we examined donor corneas that could not be used for transplantation. The diameter of the DMEK donor scrolls was measured after graft preparation by reflected light microscopy under different conditions: (1) The diameter of the roll was measured in Ringer's solution at temperatures of 5 °C, 24 °C and 35 °C. (2) To study the effect of different culture conditions we used 6% dextran-containing medium for 10 min, 20 min, 16 h and 24 h, and hyper- and hypoosmolar fluids (5% NaCl or aqua dest) for 5 min each. RESULTS: The median donors age was 62 years. The median endothelial cell density of the donor corneas was 1679 cells/mm2. The median diameter of the DMEK scroll was 1.35 mm in Ringer's solution at 24 °C (IQR, 1.04 - 1.89). In Ringer's solution at different temperatures, the scrolling diameter changed between 0.02 mm and 0.29 mm. The change in osmolarity resulted in a difference of 0.02 mm to 0.46 mm. Deswelling with dextran resulted in a change of scrolling diameter between 0.02 mm and 0.09 mm. SUMMARY: In this experimental case series, the diameter of the DMEK scroll did not change due to changes of temperature, osmolarity or deswelling. Influencing the graft's scroll to standardize and simplify the DMEK surgery remains an interesting goal for future studies.

[The 2018 Activity Report of the Tissue Transplantation and Biotechnology Section of the German Ophthalmological Society]. / Aktivitäten der Sektion Gewebetransplantation und Biotechnologie der Deutschen Ophthalmologischen Gesellschaft: Leistungsbericht 2018.

The Section on Tissue Transplantation and Biotechnology presented its 9th annual report. On the one hand, the number of cornea samples has risen to 10,840, of which 7168 have been transplanted. On the other hand, 1340 transplants have still been imported from abroad and more than 3300 patients were waiting for a transplant at the end of the year. The transplant bottleneck has not yet been eliminated.

[Keratoplasty in Germany: Systematic Analysis of the Quality Reports of German Hospitals between 2006 and 2017]. / Die Keratoplastik in Deutschland: systematische Auswertung der Krankenhausqualitätsberichte der Jahre 2006 bis 2017.

BACKGROUND: Keratoplasty is considered the most frequently performed type of transplantation in humans. Traditionally, penetrating keratoplasty has been the most common procedure. However, over the last 15 years, the importance of posterior lamellar keratoplasty has increased for the treatment of Fuchs endothelial dystrophy and bullous keratopathy. In Germany, based on national surveys, it was suggested that there was a trend towards lamellar keratoplasty. OBJECTIVE: The main objective of this study was to determine whether the proportion of lamellar keratoplasties carried out in Germany between 2006 and 2017 had increased. Furthermore, the number of keratoplasties carried out as HLA-matched (HLA: human leukocyte antigen) keratoplasties should be calculated. MATERIALS AND METHODS: The numbers of all keratoplasties carried out as lamellar/penetrating and HLA-matched keratoplasties was extracted from the hospital quality reports published between 2006 and 2017. Descriptive statistical analysis was carried out in R (www.r-project.org). RESULTS: Between 2006 and 2017, 43,021 keratoplasties were carried out in Germany. The number of keratoplasties increased from 2,849 (2006) to 8,231 (2017). The number of penetrating keratoplasties remained stable. The proportion of lamellar keratoplasties increased from 6.5% (2006) to 61.4% (2017). The proportion of HLA-matched keratoplasties was below 20% and declined between 2010 and 2017 (2010: 19.7%; 2017: 9.8%). DISCUSSION: In Germany, posterior lamellar keratoplasty has become increasingly important. Since 2014, the number of lamellar keratoplasties has exceeded the number of penetrating keratoplasties. However, the number of penetrating keratoplasties remained stable between 2006 and 2017 and still plays an important role in the management of patients with predominantly stromal or corneal defects affecting all layers. The decreasing number of HLA-matched keratoplasties is most likely due to the lack of clear evidence of a significant reduction in the rejection rates in cases of normal risk keratoplasty.

Survey of Rejection Prophylaxis Following Suture Removal in Penetrating Keratoplasty in Germany. / Umfrage zur Abstoßungsprophylaxe bei Fadenentfernung nach perforierender Keratoplastik in Deutschland.

BACKGROUND: Penetrating keratoplasty (PK) gets more and more reserved to cases of increasing complexity. In such cases, ocular comorbidities may limit graft survival following PK. A major cause for graft failure is endothelial graft rejection. Suture removal is a known risk factor for graft rejection. Nevertheless, there is no evidence-based regimen for rejection prophylaxis following suture removal. Therefore, a survey of rejection prophylaxis was conducted at 7 German keratoplasty centres. OBJECTIVE: The aim of the study was documentation of the variability of medicinal aftercare following suture removal in Germany. METHODS: Seven German keratoplasty centres with the highest numbers for PK were selected. The centres were sent a survey consisting of half-open questions. The centres performed a mean of 140 PK in 2018. The return rate was 100%. The findings were tabulated. RESULTS: All centres perform a double-running cross-stitch suture for standard PK, as well as a treatment for rejection prophylaxis with topical steroids after suture removal. There are differences in intensity (1 - 5 times daily) and tapering (2 - 20 weeks) of the topical steroids following suture removal. Two centres additionally use systemic steroids for a few days. DISCUSSION: Rejection prophylaxis following PK is currently poorly standardised and not evidence-based. All included centres perform medical aftercare following suture removal. It is assumed that different treatment strategies show different cost-benefit ratios. In the face of the diversity, a systematic analysis is required to develop an optimised regimen for all patients.

The Development and Status of Eye Banking with Special Focus on the Commitment of LIONS Clubs. / Entwicklung und Stand des Hornhautbankings unter besonderer Berücksichtigung des Engagements von LIONS Clubs.

BACKGROUND: Ever since the first successful keratoplasty in 1905, there has been a need to store corneas for transplantation. R. Townley Paton founded the first eye bank in New York in 1944. With Helen Keller's call in 1925 for LIONS to "constitute themselves Knights of the Blind in the crusade against darkness", LIONS Clubs International has become involved in the establishment of eye banks worldwide. This paper presents the development of eye banking in general and with special attention to the support offered by LIONS Clubs. METHODS: Selective literature search through PubMed, Google Scholar and Google in close cooperation with the LIONS Eye Banks already established in Germany, LIONS Clubs International (USA) and the Julius Hirschberg Society (Austria). Analysis focused on the founding processes of 6 German eye banks and their current services. RESULTS: Filatov was the first to keep donor eyes in a cool, moist container for a few days. In 1973, Summerlin et al described the technique of organ culture for donor corneas, and McCarey & Kaufman described a liquid storage medium in 1974. LIONS Clubs International and their organisational structure first supported an eye bank in the US in 1952, outside America in Hong Kong in 1962 and in Germany in 1969. Funding is provided across all levels of LIONS as network support and material resources. In general, staff funding is not provided. Of the 88 eye banks operating worldwide today, 44 are called LIONS Eye Banks. 6 of the current 26 eye banks in Germany are operating under LIONS sponsorship and run by departments of ophthalmology at university medical centres. Although the number of transplants has increased in recent years due to new surgical techniques, the number of patients waiting for donor tissue is also growing as a result of the broadening indication. CONCLUSIONS: Even today, the availability of donor corneas limits patient care. Eye banks help to meet the need for donor corneas. However, the techniques and technical equipment of eye banks must undergo continuous improvement. The local, national and international network of LIONS Clubs can assist in establishing these in order to facilitate legal requirements and structural developments. This support frequently lasts for many years, often triggers additional public commitment and is thus also a supporting element for the future development of eye banking in Germany.

Gelatinous Drop-Like Corneal Dystrophy - 2 Clinical Cases. / Gelatinöse Hornhautdystrophie ­ 2 Verlaufsdarstellungen.

Gelatinous drop-like corneal dystrophy is a very rare autosomal recessive disease classified as an epithelial and subepithelial corneal dystrophy. Patients typically present under the age of 20 with drop-like corneal lesions showing high corneal fluorescein uptake. Their disease course is typically protracted and prone to frequent relapses. The condition is caused by a dysfunction of the epithelial barrier, leading to protein deposits most likely originating from tear fluid. Histology typically shows subepithelial amyloid deposits with corresponding defects of Bowman's layer and epithelial atrophy. Where topical lubricating and anti-inflammatory therapy proves insufficient, penetrating allogenic limbokeratoplasty can be considered in a curative approach. In this report, we present disease courses of 2 unrelated patients. Current findings on pathogenesis are discussed.

[Therapeutic Options in Endothelial Decompensation Following Glaucoma Surgery]. / Therapieoptionen bei Endotheldekompensation nach Glaukomchirurgie.

During the last few years, Descemet membrane endothelial keratoplasty (DMEK) has become first line surgical treatment for patients with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy. However, in eyes with previous trabeculectomy or implantation of a glaucoma drainage device, this surgical technique, where the diseased Descemet's membrane and endothelium are replaced by a lamella of donor Descemet's membrane and endothelium, may have some limitations. These include complications during surgery such as difficult unfolding of the graft in the presence of a glaucoma tube with a risk of an increased endothelial cell loss and problems after surgery like the loss of the air/gas tamponade in the anterior chamber through the opening of the trabeculectomy or the tube, with an increased risk of graft dislocation. The following review contains information on endothelial cell loss following different glaucoma operations, discusses the advantages and disadvantages of various keratoplasty techniques and gives some technical advice for improving the surgical technique.

[Corneal Biomechanics and Measurement of Intraocular Pressure Measurement in Pathological Corneas]. / Biomechanik und Augeninnendruck bei Hornhauterkrankungen.

Measuring the intraocular pressure in eyes with corneal diseases or after corneal interventions often results in false values due to abnormal corneal biomechanics. Many different approaches are used to compensate for these abnormal corneal biomechanic properties, with varying measuring methods. There are differences when these alternative measuring methods are compared to the gold standard, applanation tonometry according to Goldmann. These differences vary between the methods and with different corneal changes. There is no clear recommendation on a precise method that is suitable for every pathological cornea. Therefore it is important to know the different variations and to include them in the analysis of every patient's intraocular pressure analysis.