[Feasibility of clinical examination scenarios under pandemic conditions]. / Möglichkeit von Prüfungsszenarien unter Pandemiebedingungen.

BACKGROUND: Due to the COVID-19 pandemic, contact restrictions occurred worldwide, which affected medical schools as well. It was not possible to hold classroom lectures. Teaching contents had to be converted to a digital curriculum within a very short time. Conditions for assessments posed an even greater challenge. For example, solutions had to be found for objective structured clinical examinations (OSCE), which were explicitly forbidden in some German states. The aim of this study was to evaluate the feasibility of an OSCE under pandemic conditions. MATERIALS AND METHODS: At the end of the 2020 summer semester, 170 students completed a combined otolaryngology and ophthalmology OSCE. Examinations were held in small groups over the course of 5 days and complied with strict hygiene regulations. The ophthalmology exam was conducted face to face, and the ENT OSCE virtually. Students were asked to rate the OSCE afterwards. RESULTS: Between 106 and 118 of the students answered the questions. Comparing the face-to-face OSCE with the virtual OSCE, about 49% preferred the face-to-face OSCE and 17% preferred the virtual OSCE; 34% found both variants equally good. Overall, the combination of an ENT and ophthalmology OSCE was rated as positive. CONCLUSION: It is possible to hold an OSCE even under pandemic conditions. For optimal preparation of the students, among other things, it is necessary to transform teaching contents to a digital curriculum. The combination of an ENT and ophthalmology OSCE was positively evaluated by the students, although the face-to-face OSCE was preferred. The overall high satisfaction of the students confirms the feasibility of a virtual examination with detailed and well-planned preparation.

[Early diagnosis of keratoconus]. / Frühdiagnose des Keratokonus.

Keratoconus is morphologically associated with increasing deformation, thinning and scarring of the cornea. This functionally leads to refractive changes and visual deterioration. In the early stages there are often no clear clinical signs in the slit-lamp examination; however, confirming the diagnosis as early as possible is important in order to provide patients with an appropriate treatment. For the early diagnosis of keratoconus, various diagnostic devices have been introduced in recent years and decades. These include keratometry with reflection-based or elevation-based systems and optical coherence tomography. High-frequency ultrasound microscopy and corneal biomechanics can also be used to establish the diagnosis of keratoconus by the measurement of other parameters. The necessity and the available possibilities for early diagnosis of keratoconus are presented in more detail in this article.

Toric IOL positioning with a no-touch head-up display axis alignment.

PURPOSE: To compare a new no-touch alignment technique for toric intraocular lenses (IOL) with the conventional technique that uses a manual pendulum. METHODS: In this retrospective case-control study, patients who underwent toric IOL implantation using two different alignment techniques (digital Callisto® system vs. manual-pendulum-based marking) were compared in a vector analysis using the Alpins method and an analysis of variance regarding corrected and uncorrected visual acuity and the deviation of the achieved IOL axis from the targeted axis. RESULTS: Sixty-one eyes were included into analysis. Thirty-six of these surgeries were performed via the Callisto® system and 25 eyes via pendulum-based corneal markings. Median IOL axis misalignment was 3° in both groups. Median uncorrected distance visual acuity was 0.097 logMAR versus 0.200. Median best-corrected visual acuity was 0.000 logMAR versus 0.097. All these data were below the range of statistical significance (p > 0.05). Vector analysis showed no significant difference for TIA [median of 3.14 diopters (D) vs. 2.73 D], SIA (median of 3.82 D vs. 3.79 D), DV (1.18 D vs. 1.08 D), and CI (1.23 vs. 1.29). Median angle of error was 1.96° versus - 0.44° (p > 0.05). CONCLUSIONS: We found no significant difference in the refractive results, the IOL positioning, and the best-corrected and uncorrected distance visual acuity between the two compared methods. Nevertheless, the Callisto® IOL alignment system delivers a standardized and easy-to-use technology. In particular, less-experienced surgeons might benefit from this marking technique.

[Scleral melting after cyclophotocoagulation]. / Skleraeinschmelzung nach Zyklophotokoagulation.

We report on a case of a scleral melting as a rare but severe complication of transscleral cyclophotocoagulation. The tissue defect was successfully repaired by tectonic keratoplasty.

[Pathogenesis and diagnostic evaluation of Fuchs' endothelial corneal dystrophy]. / Pathogenese, Diagnose und Klinik der Fuchs-Endotheldystrophie.

BACKGROUND: Following new treatment options for Fuchs' endothelial corneal dystrophy, our understanding of optical and structural changes in the patient's cornea is also starting to improve. OBJECTIVE: To provide an update on clinical evaluation of Fuchs' dystrophy. MATERIAL AND METHODS: Standardized approaches to evaluate patients with Fuchs dystrophy in routine practice and research are discussed, accounting for the progressive and partially irreversible structural changes in all corneal layers. RESULTS: Early structural changes in the cornea can be detected before clinical edema becomes visible on slit-lamp exam. Optical limitations resulting from these structural changes can be quantified not only with high-contrast acuity but also with glare or contrast sensitivity tests. Characteristic vision-related limitations of patients with Fuchs dystrophy can, e.g., be assessed with V-FUCHS, a Fuchs dystrophy-specific "Visual Function and Corneal Health Status" instrument for patient-reported outcomes. CONCLUSION: Clinical grading of Fuchs dystrophy in an edematous and a non-edematous stage is outdated. Better therapy options and our improved understanding of progressive changes in the entire cornea require a standardized assessment of optical and structural changes and patient-reported limitations.

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia.

The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.

[Riboflavin UVA crosslinking in progressive keratoconus]. / Riboflavin-UVA-Crosslinking bei progredientem Keratokonus.

In patients with keratoconus, a progressive, ectatic disease of the cornea, the shape of the cornea is continuously changing leading to a reduction in visual acuity by progressive myopia and more and more (irregular) astigmatism. The symptomatic treatment consists of the prescription of glasses or special gas-permeable rigid contact lenses. Corneal tomography is generally used for diagnosis. After initial diagnosis of keratoconus, regular tomographic follow-ups should be performed. If clinically significant progression is found and confirmed by repeated measurements, riboflavin UVA collagen crosslinking should be offered to the patients. The aim of riboflavin UVA collagen crosslinking is to halt the progression of the disease to avoid further complications. The therapeutic principle is a combined effect of the photosensitizer riboflavin and UVA light. This stiffening effect of the corneal tissue halts the progression of keratoconus. The efficacy of this treatment has been demonstrated in various randomized, controlled trials.

[Pathophysiology of atopic blepharokeratoconjunctivitis]. / Pathophysiologie der atopischen Blepharokeratokonjunktivitis.

Atopic dermatitis (AD) is a systemic inflammatory disease, which is characterized by pronounced eczema and pruritus. In addition to the involvement of the entire integument, the periocular lid skin and the surface of the eye are frequently involved. Ocular involvement may occur solely without dermatitis of facial or body skin. Pathophysiologically, besides a dysregulated immune response, genetic changes can occur in various dermal structural proteins which will lead to a disturbed skin barrier. Furthermore, there is a regular colonization with bacterial pathogens and an increased susceptibility for viral skin infections. The lid margin reveals a loss of Meibomian glands whereas the conjunctiva shows reduced goblet cells. Consecutively, eye surface defects and recurrent conjunctival and corneal defects can be found. Increased mechanical manipulation in atopia-associated pruritus is seen as a cause of increased comorbidity with keratoconus. In addition, individual cases are reported of various malignomas of the eye surface, which are present in patients with AD. Understanding of the pathophysiological connections is essential for the correct diagnosis and therapy of this clinically very complex disease picture.

[Ocular involvement in atopic dermatitis : Clinical aspects and therapy]. / Augenbeteiligung bei atopischer Dermatitis : Klinik und Therapie.

Patients with atopic dermatitis frequently complain of ocular symptoms. The general dermatitis can directly affect the periocular skin and patients often present with chronic atopic blepharokeratoconjunctivitis. Early diagnosis of the characteristic ophthalmological alterations, such as blepharitis, allergic conjunctivitis, keratoconjunctivitis sicca, conjunctival scarring with formation of symblepharon and lid malpositioning, filiform keratitis, corneal plaques, (persistent) epithelial defects, corneal ulcers and keratoconus as well as appropriate stage-adapted treatment, including lid hygiene with preservative-free lubricants, topical and sometimes systemic anti-inflammatory therapy and surgical treatment are important for patients to prevent long-term damage of the ocular surface leading to severe visual impairment.

Nanoscale Tipping Bucket Effect in a Quantum Dot Transistor-Based Counter.

Electronic circuits composed of one or more elements with inherent memory, that is, memristors, memcapacitors, and meminductors, offer lower circuit complexity and enhanced functionality for certain computational tasks. Networks of these elements are proposed for novel computational paradigms that rely on information processing and storage on the same physical platform. We show a nanoscaled memdevice able to act as an electronic analogue of tipping buckets that allows reducing the dimensionality and complexity of a sensing problem by transforming it into a counting problem. The device offers a well adjustable, tunable, and reliable periodic reset that is controlled by the amounts of transferred quantum dot charges per gate voltage sweep. When subjected to periodic voltage sweeps, the quantum dot (bucket) may require up to several sweeps before a rapid full discharge occurs thus displaying period doubling, period tripling, and so on between self-governing reset operations.

[Alterations in intraocular pressure and the CorVis parameters after LASIK]. / Änderung des Augeninnendrucks und der CorVis-Parameter nach LASIK.

INTRODUCTION: The reduction of corneal thickness following laser-assisted in-situ keratomileusis (LASIK) requires a correction of intraocular pressure (IOP) measurements. The corneal visualization Scheimpflug technology (CorVis ST, Oculus, Wetzlar, Germany) not only measures the IOP and central corneal thickness (CCT) but also determines 10 additional corneal parameters, such as the time to first and second applanation and velocity. Besides CCT we compared various corneal parameters before and after LASIK in order to detect possible correlations and to correct IOP measurements. METHODS: Measurements with CorVis ST were made before and after LASIK in 45 myopic patients (45 left eyes). We compared the IOP and CorVis ST parameters using a paired t­test before and after LASIK and corrected for possible correlations in a multifactorial linear model. Finally, we correlated the changes in IOP to changes in biomechanical parameters. RESULTS: We observed a direct correlation between the IOP measurements and the corneal thickness. The IOP was underestimated by 0.039 mm Hg per micrometer in reduction of corneal thickness. The multifactorial linear model showed a correlation of IOP change to A2 velocity and the radius of applanation. CONCLUSION: Surgical thinning of the central cornea via LASIK demonstrated a direct correlation between corneal thickness and IOP measurements using the CorVis ST technique. Postoperative changes of the A2 velocity and the applanation radius also had a statistically significant influence on post-LASIK IOP measurements. Our findings could be useful to obtain more precise post-LASIK IOP measurements.

[Surgical removal of Salzmann's nodules using intraoperative mitomycin C]. / Chirurgische Abtragung von Salzmann-Knoten unter Anwendung von intraoperativem Mitomycin C.

Salzmann's nodules comprise a heterogeneous group of greyish superficial corneal opacities. A substantial percentage is most likely caused by dystrophies. This could explain the recurrences after surgical removal. The Eye Center of the University Hospital Freiburg has been using mitomycin C intraoperatively during surgical removal of Salzmann's nodules since 2007 to prevent recurrences. We recently performed an uncontrolled prospective trial to evaluate this approach and also reviewed the literature. Worldwide, a total of 38 eyes have been treated with mitomycin C during surgery for Salzmann's nodules. No recurrences have been reported so far with follow-up exceeding at least 2 years in almost all eyes. No severe side effects have been observed to date. We therefore think that mitomycin C during surgery for Salzmann's nodules is advisable despite the lack of evidence from a randomized clinical trial. However, all patients must consent to the off label use of mitomycin C.

Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study.

PURPOSE: According to some pioneer surgeons, lamellar endothelial keratoplasty techniques (EK), including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), yield excellent clinical results. However, there is a lack of studies with high levels of evidence and results of large national keratoplasty registers are contradictory. Therefore, two large cohorts of DMEK and DSAEK procedures are compared to a cohort of penetrating keratoplasty (PK). METHODS: The study reports 868 keratoplasty procedures at a single centre (694 eyes with Fuchs endothelial dystrophy (FED) and 174 with bullous keratopathy (BK)). Patients underwent DMEK (450 eyes), DSAEK (89 eyes), or PK (329 eyes). Postoperative visual acuity, endothelial cell density (ECD), rate of regrafting, and rejections were recorded. RESULTS: Visual acuity recovers faster and to a greater extent in EK compared to PK. DMEK performs better than DSAEK. ECD drops faster initially for EK compared to PK. In EK the rate of regrafting is higher than in PK (7 % in DMEK, 20 % in DSAEK and 2 % in PK in FED). The rejection rate is lowest following DMEK (7 % after DMEK, 21 % after DSAEK and 18 % after PK in FED). CONCLUSIONS: In contrast to recent reports from national keratoplasty registers, the overall clinical outcome of EK in FED and BK is superior to PK. Including ocular comorbidities and learning curves, these data reflect a realistic setting for comparing the different keratoplasty techniques. Corneal surgeons may be encouraged to preferentially use DMEK in FED and BK.

Prolonged organ culture reduces the incidence of endothelial immune reactions.

PURPOSE The number of antigen-presenting cells decreases during organ culture of corneoscleral discs. This might result in a decrease of immune reactions with increasing duration of organ culture. To investigate this hypothesis, we performed a retrospective analysis of all penetrating keratoplasties that were consecutively performed over the last 5 years.PATIENTS AND METHODS All cases of penetrating keratoplasties (n=1006) were divided into two groups, with the division made at the median of the storage time (21 days). These two groups were compared by a Cox proportional hazards survival model regarding the incidence of endothelial immune reactions, clear graft survival, and chronic endothelial cell loss following penetrating keratoplasty considering patient's age, donor's age, and risk situation as co-variates.RESULTS We observed statistically significantly fewer endothelial immune reactions (20.1% (95% confidence interval 15.5-24.5%) after 2 years) in the group with a storage time of more than 21 days compared with the group with a storage time of <21 days (26.5% (95% confidence interval 21.6-31.2%) after 2 years). However, the duration of organ culture did not have a statistically significant effect on clear graft survival or chronic endothelial cell loss.CONCLUSION Our results demonstrate that an increased duration of organ culture leads to a lower incidence of endothelial immune reactions following penetrating keratoplasty. However, we do not recommend increased storage times in general as overall graft survival did not improve. The reason for this apparent paradox may be that the endothelial cell count decreases during storage time.

[Intraocular Lens Opacification Following Posterior Lamellar Keratoplasty]. / Kunstlinsentrübungen nach hinterer lamellärer Keratoplastik.

BACKGROUND: The opacification of an artificial intraocular lens is a rare but serious complication following cataract surgery as an exchange of the intraocular lens can become necessary. At our eye center we observed single cases of IOL opacifications following complicated posterior lamellar keratoplasty (Descemet stripping automated endothelial keratoplasty = DSAEK or Descemet membrane endothelial keratoplasty = DMEK). Therefore, we performed a retrospective analysis of all our digital charts regarding the incidence of this serious complication with respect to posterior lamellar keratoplasty, penetrating keratoplasty or sole cataract extraction. METHODS: We searched our digital patient database from 2003 to 2015 using the following headings: intraocular lens, artificial lens or IOL and opacification or calcification and selected only those patients who had undergone either DSAEK, DMEK, penetrating keratoplasty or sole cataract surgery (n = 19,565). RESULTS: In total we found five IOL opacifications out of 153 DSAEK and two out of 450 DMEK cases, respectively. Five of these seven cases had a complicated clinical course with repeated rebubbling or additional intraocular surgery (i.e., repeat DSAEK or DMEK or secondary penetrating keratoplasty). There were no documented IOL opacifications following penetrating keratoplasty or sole cataract extraction. In two cases intraocular lens exchange became necessary. All opacifications showed similar clinical appearance in form of small granular deposits on the surface of the intraocular lens. Almost all implanted lenses were made from hydrophilic acrylate. DISCUSSION: In total we found seven cases of intraocular lens opacification that have only been observed following DSAEK or DMEK. According to reports from the literature these opacifications are superficial calicifications of the hydrophilic lenses. As five of the seven cases had a complicated clinical course, the repeated air contact of the lens could be one major factor in inducing the calcification. Besides the air contact a breakdown of the blood-aqueous barrier could also play a role in the induction of calcium phosphate crystallisation on the intraocular lens. The risk of this serious complication in mainly hydrophilic intraocular lenses with respect to posterior lamellar keratoplasty should be kept in mind for the selection of the type of intraocular lens in patients with endothelial diseases or in patients undergoing combined cataract extraction and DSAEK/DMEK.

Endothelial Caveolin-1 regulates the radiation response of epithelial prostate tumors.

The membrane protein caveolin-1 (Cav1) recently emerged as a novel oncogene involved in prostate cancer progression with opposed regulation in epithelial tumor cells and the tumor stroma. Here we examined the role of stromal Cav1 for growth and radiation response of MPR31-4 prostate cancer xenograft tumors using Cav1-deficient C57Bl/6 mice. Syngeneic MPR31-4 tumors grew faster when implanted into Cav1-deficient mice. Increased tumor growth on Cav1-deficient mice was linked to decreased integration of smooth muscle cells into the wall of newly formed blood vessels and thus with a less stabilized vessel phenotype compared with tumors from Cav1 wild-type animals. However, tumor growth delay of MPR31-4 tumors grown on Cav1 knockout mice to a single high-dose irradiation with 20 Gray was more pronounced compared with tumors grown on wild-type mice. Increased radiation-induced tumor growth delay in Cav1-deficient mice was associated with an increased endothelial cell apoptosis. In vitro studies using cultured endothelial cells (ECs) confirmed that the loss of Cav1 expression increases sensitivity of ECs to radiation-induced apoptosis and reduces their clonogenic survival after irradiation. Immunohistochemical analysis of human tissue specimen further revealed that although Cav1 expression is mostly reduced in the tumor stroma of advanced and metastatic prostate cancer, the vascular compartment still expresses high levels of Cav1. In conclusion, the radiation response of MPR31-4 prostate tumors is critically regulated by Cav1 expression in the tumor vasculature. Thus, Cav1 might be a promising therapeutic target for combinatorial therapies to counteract radiation resistance of prostate cancer at the level of the tumor vasculature.