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.

[Global ophthalmology : Update]. / Globale Ophthalmologie : Aktueller Stand.

The aim of global ophthalmology is to maximize vision, ocular health and functional ability, thereby contributing to overall health and well-being, social inclusion and quality of life of every individual worldwide. Currently, an estimated 1.1 billion people live with visual impairment, 90% of which can be prevented or cured through largely cost-effective interventions. At the same time, 90% of people affected live in regions with insufficient eye health coverage. This challenge drove the World Health Organization (WHO) and a group of nongovernmental organizations to launch "VISION 2020: the Right to Sight", a global campaign which recently concluded after 20 years. The achievements, challenges and lessons learned were identified and incorporated into the current campaign "2030 IN SIGHT".

[Bacterial Conjunctivitis: Current Aspects of Diagnosis and Therapy]. / Bakterielle Konjunktivitis: Aktuelle Aspekte der Diagnostik und Therapie.

Bacterial conjunctivitis is a leading cause of infectious conjunctivitis in children and second most common cause in adults. Although often self-limiting, it can lead to complications like corneal scarring and systemic infections in high-risk groups including newborns and immunocompromised patients. Thus, prompt diagnosis and treatment are essential for these vulnerable populations. Common bacterial causes are Staphylococcus aureus and Streptococcus pneumoniae in adults and Haemophilus influenzae and Moraxella catarrhalis in children. Clinical features alone do not reliably identify the causative pathogen. Microbiological testing is necessary for persistent or severe cases. Topical antibiotics like azithromycin or fluorochinolones are usually prescribed. However, gonococcal and chlamydial conjunctivitis warrant systemic antibiotics due to their potential for severe complications. Increasing antibiotic resistance might even necessitate tailored therapy based on antibiotic susceptibility profiles. Screening and treating pregnant women is an effective prevention strategy by reducing perinatal transmission (especially of gonococcal and chlamydial infections). In summary, while often self-limiting, potential complications and rising antibiotic resistance underscore the importance of timely diagnosis and treatment of bacterial conjunctivitis. Preventive measures including maternal screening are crucial public health initiatives to curb the risks associated with this common eye infection.

Supine Positioning for Graft Attachment After Descemet Membrane Endothelial Keratoplasty: A Randomized Controlled Trial.

PURPOSE: The Supine Positioning for Descemet Membrane Endothelial Keratoplasty Attachment (SUPER-DMEK) trial assessed the efficacy of prolonged supine head positioning on graft attachment. DESIGN: Randomized controlled trial. METHODS: Participants with Fuchs' dystrophy were randomized to 5 days of supine head positioning (intervention) or to 1 day (control). Participants, surgeons, and investigators were masked until the day after surgery. Adherence to the allocated intervention was monitored using a head sensor. Main outcome measures were area and volume of graft detachment (coprimary end points) 2 weeks after surgery quantified using a validated neural network for image segmentation on anterior segment optical coherence tomography images, and repeat air injection (rebubbling), subjective visual function, and adverse events (secondary end points). RESULTS: A total of 86 participants received the allocated intervention (35 eyes intervention and 51 eyes control). In the intention-to-treat analysis, the mean area of graft detachment was 28.6% in the intervention arm and 27.5% in the control arm (adjusted between-arm difference, 1.3; 95% CI, -8.7 to 11.4; P = .80). Results for volume of detachment and as-treated analyses based on head position sensor data indicated no potentially clinically relevant effect of prolonged supine positioning on graft attachment. Results were not compatible with a relevant treatment effect on rebubbling or subjective visual function. Adverse events, most commonly back pain, were more common and more severe with the intervention. CONCLUSIONS: In this randomized controlled trial, graft attachment was not improved with prolonged supine head positioning. Prolonged supine positioning frequently caused back pain. Prolonged supine positioning after Descemet membrane endothelial keratoplasty for Fuchs' dystrophy may not be needed in routine practice.

P43-A106†Eyebank stripped vs. Surgeon stripped tissue for DMEK.

During the recent years Descemet membrane endothelial keratoplsty (DMEK) has replaced penetrating keratoplasty and more or less Descemet stripping automated endothelial keraoplasty (DSAEK) as the goldstandard for the treatment of endothlial corneal diseases. Following DMEK the clinical recovery is faster and patients reach higher visual acuities with a lower risk for graft rejection. However, the technique of preparing the graft for DMEK is more demanding and less standardised than the perparation of a DSAEK graft. Therefore, the preparation may take longer and risk of a preparation failure seems higher. For this reason surgeons look for prestripped tissue for DMEK to avoid the potential inconveniences with the graft preparation. However, prestripped tissue might not always be advantageous as the graft might loose endothelial cells during storage and transportation and the surgeon is not aware of the specific properties of the graft. Advantages and disadvantages of eyebank stripped and surgeon stripped tissue will be discussed.

Indications, techniques, and graft survival of mini and corneo-scleral tectonic keratoplasties: A retrospective single-center case series.

PURPOSE: Tectonic keratoplasties (TK) are used to treat corneal and scleral perforations and to prevent the loss of the eye. In this study, we retrospectively analyzed indications, surgical procedures, and outcomes of eccentric mini and corneo-scleral tectonic keratoplasties with respect to anatomical survival and clear graft survival rates to identify risk factors for graft failure. METHODS: This retrospective study includes 33 eccentric mini (graft diameter <6 mm) and/or corneo-scleral TK of 32 consecutive patients of a total of 41 TK carried out between 2005 and 2020 in the Eye Center, University of Freiburg, Germany, making up 0.7% of all keratoplasties performed during this period (n = 5557). Patient and graft specific data were extracted from medical files. Anatomical survival-defined as achieving integrity of the globe without further surgical interventions-and clear graft survival-defined as persisting graft clarity-were estimated using the Kaplan-Meier method. We also fitted Cox proportional hazard models to account for factors influencing anatomical and clear graft survival. RESULTS: Median duration of anatomical success was 72.5 months (95% confidence interval (CI) 18.1-infinite (inf.)) and median duration of clear graft survival was 29.6 months (95% CI 12.5-Inf.). The 1-year survival rate for anatomical survival was 67.6% (95% CI 52.2% - 87.6%) and for clear graft survival 66.4% (95% CI 50.5%- 87.1%). No enucleation was necessary during this time-period. Non-inflammatory primary causes (n = 14) presented a trend towards better anatomical survival rates (median remained above 0.75 during follow-up) compared to inflammatory primary causes (n = 19, median 18.1 months (95% CI 2.8 - inf.)) and longer clear graft survival (median 29.6 months (95% CI 12.5 - inf.) versus 13.1 months (95% CI 3.2 - inf.)). Corneo-scleral grafts (n = 18) compared to corneal grafts (n = 15) showed a trend towards better anatomical survival (more than 50% of eyes did not fail during follow-up period (95% CI 21.9-Inf. months) versus 18.1 months (95% CI 2.4-Inf.)) and clear graft survival (median 29.6 months (95% CI 12.6-Inf.) versus 6.2 months (95% CI 2.8-Inf.)). Old age (n = 11, 75.2 - 90.1 years) compared to young age (n = 11, 6.2 - 60.2 years) was the only hazard ratio (hazard ratio 0.04 (95% CI 0.002-0.8)) that reached the level of significance (p = 0.03). CONCLUSION: Eccentric TK is helpful in the successful treatment of a variety of severe eye diseases. Patients at young age, with pre-existing inflammatory conditions or corneal TK are at higher risk for anatomical failure as well as clear graft failure and therefore need to be monitored closely.

Characterization of the Immediate and Delayed Biomechanical Response to UV-A Crosslinking of Human Corneas.

PURPOSE: Keratoconus leads to visual deterioration due to irregular astigmatism and corneal thinning. Riboflavin-based corneal UV-A crosslinking (CXL) induces novel intramolecular and intermolecular links resulting in corneal tissue stiffening, thereby halting disease progression. The purpose of this study was to analyze the immediate and delayed biomechanical responses of human donor corneas to CXL. METHODS: CXL was performed according to the Dresden protocol to corneas not suitable for transplantation. Biomechanical properties were subsequently monitored by measuring the Young modulus using nanoindentation. The immediate tissue response was determined after 0, 1, 15, and 30 minutes of irradiation. Delayed biomechanical effects were investigated with follow-up measurements immediately and 1, 3, and 7 days after CXL. RESULTS: Young's modulus indicated a linear trend in direct response to increasing irradiation times (mean values: total 61.31 kPa [SD 25.53], 0 minutes 48.82 kPa [SD 19.73], 1 minute 53.44 kPa [SD 25.95], 15 minutes 63.56 kPa [SD 20.99], and 30 minutes 76.76 kPa [SD 24.92]). The linear mixed model for the elastic response of corneal tissue was 49.82 kPa + (0.91 kPa/min × time [minutes]); P < 0.001. The follow-up measurements showed no significant delayed changes in the Young modulus (mean values: total 55,28 kPa [SD 15.95], immediately after CXL 56,83 kPa [SD 18.74], day 1 50.28 kPa [SD 14.15], day 3 57.08 kPa [SD 14.98], and day 7 56.83 kPa [SD 15.07]). CONCLUSIONS: This study suggests a linear increase of corneal Young modulus as a function of CXL timing. No significant short-term delayed biomechanical changes posttreatment were observed.

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.

[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.

[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.

Developing and validating a questionnaire to assess the symptoms of blepharitis accompanied by dry eye disease.

PURPOSE: To propose additional items for established dry eye disease (DED) instruments that cover blepharitis-specific signs and symptoms and to determine the association between the clinical findings and subjective complaints. METHODS: Thirty-one patients with blepharitis and DED were prospectively included in the pretest period for selecting suitable questions. In the main phase of the study, the selected questions were then tested on 68 patients with blepharitis and DED and 20 controls without blepharitis or DED. Pearson's coefficient of correlation was calculated between the blepharitis-specific questions, tear break-up time (TBUT), the Schirmer test score, and the ocular surface disease index (OSDI) score; and the similarity between the blepharitis-specific questions, OSDI questions, and objective parameters for DED was assessed via hierarchical clustering. Furthermore, the discriminatory power of the blepharitis-specific questions was investigated with the receiver operating characteristic (ROC) curve. RESULTS: The additional question about heavy eyelids revealed a significant correlation with the OSDI score (r = 0.45, p < 0.001) and Schirmer score (r = - 0.32, p = 0.006). Cluster analysis demonstrated the similarity between the question about heavy eyelids and TBUT. In addition, the OSDI questionnaire had the highest discriminatory power in ROC analysis, and the OSDI score significantly correlated with the specific questions about eyelids sticking together (r = 0.47, p < 0.0001) and watery or teary eyes (r = 0.34, p = 0.003). CONCLUSIONS: The blepharitis-specific additional questions were closely associated with objective parameters for DED. The question about heavy eyelids might be well suited for recording the symptoms of hyposecretory and hyperevaporative dry eye with blepharitis.

Cataract Surgery-Indications, Techniques, and Intraocular Lens Selection.

BACKGROUND: Opacification of the lens of the eye (cataract) is usually due to aging. It is a painless, progressive condition that affects contrast and color perception and alters refraction, leading to visual loss that may be total. In cataract surgery, the turbid lens is replaced by an artificial lens. An estimated 600 000 to 800 000 such procedures are performed in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including meta-analyses, Cochrane reviews, and randomized controlled clinical trials (RCTs). RESULTS: Cataract is the most common reversible cause of blindness around the world (approximately 95 million people). The surgical replacement of a turbid lens with an artificial lens is usually carried out under local anesthesia. The standard technique for fragmentation of the nucleus of the lens is ultrasonic phacoemulsification. RCTs have not shown the superiority of the femtosecond laser over phacoemulsification for this purpose so far. The spectrum of artificial intraocular lenses, aside from the conventional type with a single focus, include lenses with multiple foci, extended-depth-of-focus (EDOF) lenses, and astigmatism-correcting lenses. CONCLUSION: In Germany, cataract surgery is usually performed on an outpatient basis under local anesthesia. Artificial lenses with various additional functions are available nowadays; the choice of lens depends on the needs of the individual patient. Patients must be adequately informed about the advantages and disadvantages of the different lens systems.

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.

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.

Clinical Course of Different Types of Immune Reactions following Keratoplasty.

BACKGROUND: Immune-mediated corneal graft rejection (IR) is a leading cause of corneal graft failure. The endothelium, stroma, epithelium, or a combination can be affected. Little is known about the long-term outcomes of different types of IR. METHODS: We reviewed the medical records of all keratoplasties that had been performed at our eye centre between 2003 and 2016 (n = 3934) for any kind of IR that occurred between the surgery and 2019. All patients with a definite diagnosis of IR and sufficient clinical data were included in the analysis. IRs were grouped according to the affected part of the graft (endothelial, stromal, epithelial, and mixed). We analysed the dynamics of recovery and the clinical outcomes. RESULTS: We identified a total of 319 patients with IR. Twenty-seven of those were lost to follow-up and were excluded from further analysis. Of the IRs, 89% affected the endothelium. Endothelial IR resulted more frequently in a considerable loss of endothelial cell density than other forms of IR. Stromal IR showed a lower relapse rate and a better visual recovery than other types of IR and resulted less often in a failure of the graft. CONCLUSIONS: We herein report comprehensive data about the prognosis regarding functional recovery after different types of IR following keratoplasty. Our data underline that timely recognition and correct classification of IR are important because they determine the clinical course and prognosis.

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.

Long-Term Outcomes of Excimer Laser-Assisted Penetrating Keratoplasty Using a Commercially Available Laser System - A Retrospective Case Series.

BACKGROUND: Favorable functional outcomes have been reported after excimer laser-assisted penetrating keratoplasty (EXL PKP). But this technique has not been widely adopted, and there are reports on EXL PKP from only a very limited number of institutions. Some of these results refer to operations carried out with laser systems that are not commercially available. In this retrospective case series, we report the long-term outcome of EXL PKP using the Schwind Amaris 500E laser system. MATERIAL AND METHODS: This retrospective consecutive case series included 30 eyes of 29 patients who had undergone EXL PKP between 2010 and 2013. Primary outcome measures were topographic astigmatism and visual acuity. Secondary outcome measures were the rates of graft rejection and graft failure, and the rate of grafts with an endothelial cell density below 500 cells/mm2. Survival analyses were carried out for the following endpoints: visual acuity, rate of graft rejection, and rate of grafts with endothelial cell densities higher than 500 cells/mm2. RESULTS: The median interquartile range (IQR) duration of follow-up was 45 (36) months. The indications for PKP were keratoconus (n = 21), corneal scarring (n = 6), Fuchs endothelial dystrophy (n = 1), and corneal dystrophy other than Fuchs endothelial dystrophy (n = 2). The median (IQR) topographic astigmatism at the end of the follow-up period was 5.3 (2.9) D. Forty-five months after surgery, 73% of all eyes had a visual acuity better than 0.3 LogMAR. The rate of graft rejection after 45 months of follow-up was 32%. All eyes maintained endothelial cell densities higher than 500 cells/mm2. There was no graft failure. CONCLUSIONS: EXL PKP is a safe and effective surgical procedure. No general conclusions can be drawn on the refractive outcome of EXL PKP. Potential advantages, such as a higher degree of graft-host congruity, that could possibly improve the refractive outcome should be weighed against the higher costs of EXL PKP.