Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25-73 letters) due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks -216.0/-202.6 µm, faricimab T&E -204.5/-197.1 µm, aflibercept every 8 weeks -196.3/-185.6 µm), and more patients achieved absence of DME (CST < 325 µm; YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 87%-92%/88%-93%, faricimab T&E 78%-86%/85%-88%, aflibercept every 8 weeks 77%-81%/80%-84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 59%-63%/56%-62%, faricimab T&E 43%-48%/45%-52%, aflibercept every 8 weeks 33%-38%/39%-45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Accuracy of Bruch's membrane opening minimum rim width and retinal nerve fiber layer thickness in glaucoma diagnosis depending on optic disc size.

BACKGROUND/AIM: The aim of this paper is to compare retinal nerve fiber layer thickness (RNFL) and Bruch's membrane opening-based minimum rim width (BMO-MRW) in terms of their performance in detecting early and moderate/advanced glaucoma using receiver operating characteristics (ROC) analysis and the classification using the 5th percentile as a cut-off. METHODS: One hundred eyes from 100 patients with early glaucoma (mean deviation (MD): < -5.0 dB) and 100 eyes from 100 patients with moderate/advanced glaucoma (MD: > -5.0 dB) were carefully matched to healthy controls based on optic disc size. Then, the dataset was divided, based on the 50th percentile of the measured Bruch's membrane opening area (BMO-A), into small (BMO-A < 1.95 mm2) and large optic discs (BMO-A > 1.95 mm2). Finally, the discriminative performance of BMO-MRW and RNFL between glaucoma and controls using ROC analysis and the manufacturer's classification based on the 5th percentile was analyzed. RESULTS: In discriminating between glaucoma and matched healthy controls, global BMO-MRW and global RNFL thickness had comparable areas under the ROC curve for eyes with early glaucoma and both small BMO-As (ROC ± confidence interval [CI] 0.91 [0.87 to 0.95] and 0.88 [0.83 to 0.93]) and large BMO-As (0.86 [0.82 to 0.92] and 0.84 [0.79 to 0.90]), as well as in moderate/advanced glaucoma with small BMO-As (0.99 [0.98 to 1.00] and 0.97 [0.95 to 1.00]) and large BMO-As (0.94 [0.91 to 0.98] and 0.97 [0.94 to 1.00]). Using the calculated 5th percentile as a threshold value, the sensitivities for the detection of early and moderate/advanced glaucoma were comparable for BMO-MRW and RNFL in eyes with small optic discs (early glaucoma: fifty-two percent and 61%; moderate/advanced glaucoma: ninety-one percent and 92%). In eyes with large optic discs, the sensitivity of BMO-MRW was inferior to that of RNFL for both early (38% versus 51%) and moderate/advanced (80% versus 91%) glaucoma. CONCLUSION: Based on an ROC analysis, the discriminative performance of BMO-MRW and RNFL between patients with early and moderate/advanced glaucoma and a healthy control group matched based on optic disc size is comparable in eyes with BMO-As smaller and larger 1.95 mm2. Using a classification based on the 5th percentile, as used in clinical practice, RNFL is shown to be superior to BMO-MRW regarding sensitivity in glaucoma detection with large optic discs. This study underscores the importance of RNFL imaging and measurement in the diagnostic evaluation of glaucoma, especially in cases of large optic discs.

Current Perspectives on Type 3 Macular Neovascularization due to Age-Related Macular Degeneration.

BACKGROUND: The aim of this review was to systematically summarize the current knowledge on type 3 macular neovascularization (MNV3) in age-related macular degeneration (AMD). SUMMARY: Recent histopathologic and multimodal imaging findings led to the consensus definition of the new term "type 3 macular neovascularization" in AMD. MNV3 originates in the deep vascular plexus as a neovascular process without connection with the retinal pigment epithelium in the initial stages. This type has numerous clinical and pathomorphologic features that separate it from the other two types of MNV in AMD. Besides, its frequency appears to be higher than previously thought. In optical coherence tomography (OCT), MNV3 can be classified into stages 1-3. Hyperreflective foci in the outer retina possibly represent a precursor lesion. In addition, MNV3 is characterized by a strong association with reticular pseudodrusen, a high rate of bilaterality, close associations with advanced age and arterial hypertension, decreased choroidal thickness, and decreased choriocapillaris flow signals. Data from latest anti-vascular endothelial growth factor studies in MNV3 suggest that the OCT biomarkers in intraretinal and subretinal fluids should be interpreted differently than in the other types. Additionally, data from MNV3 eyes should be analyzed separately, allowing optimal type-specific treatment strategies in the future. KEY MESSAGES: This review highlights the need for accurate characterization of neovascular AMD lesions and an MNV type-specific approach, particularly for MNV3.

Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1.

INTRODUCTION: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. METHODS: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. RESULTS: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0-70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2-0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. CONCLUSION: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV.

Retrospective Analysis of Bicanalicular Lacrimal Silicone Tube Intubation in Patients with Congenital Nasolacrimal Duct Obstruction: A Long-term Follow-up Study.

Congenital nasolacrimal duct obstruction (CNLDO) is the most common cause of epiphora in the first year of life. In addition to conservative therapy, there are several invasive methods available. The aim of this retrospective study was to conduct a long-term follow-up of bicanalicular lacrimal duct intubation as the primary intervention in a large cohort of patients with CNLDO. The electronic medical records of 487 patients with CNLDO who underwent bicanalicular tube intubation were reviewed. To determine the long-term outcomes, a telephone interview was conducted. A total of 328 eyes of 235 patients were included in the study. The median average follow-up period was 6.67 (5.58 - 8.67) years. At the time of the survey, 218 patients (92.8%) were symptom free. Mean patient satisfaction with surgical outcome was 10/10. To our knowledge, this study provides the longest follow-up of the largest patient cohort in the literature consisting of patients who underwent probing with bicanalicular lacrimal silicone tube intubation as a primary intervention for CNLDO. This study showed a high long-term postoperative success rate, with high postoperative satisfaction, few complications, and a low need for reintervention.

Originalbeiträge (Originals). Altered microvascular density in patients with anorexia nervosa ­ an optical coherence tomography angiography (OCTA) pilot study.

OBJECTIVES: To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. Methods:Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls. P-values ≤ 0.0125 were considered statistically significant. Results: VD in the superficialmacular en-face OCTA image was significantly lower in the study group compared to the control group. Neither the deepmacula nor the radial peripapillary capillary (RPC) in the whole-face image nor the RPC-peripapillary imaging appeared to be significantly different. Conclusion: Patients with AN showed reduced VD in the superficialmacular layers compared to healthy controls, which can be discussed as a consequence of the malnutrition. OCTA could be a useful non- invasive tool to detect reduced peripheral blood supply to show vascular changes that occur before ocular symptoms.

The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. RECENT FINDINGS: Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. SUMMARY: It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.

Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. RECENT FINDINGS: In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. SUMMARY: The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.

Retinal microvascular density analysis in patients with rheumatoid arthritis treated with hydroxychloroquine.

PURPOSE: Rheumatoid arthritis (RA) is the most common inflammatory joint disease, and hydroxychloroquine (HCQ) is an established treatment. The extent to which HCQ impacts ocular microvascular vessel density (VD) in patients with RA without evidence of HCQ retinopathy has not yet been conclusively clarified. The main aim of this study was to evaluate VD measured by optical coherence tomography angiography (OCTA) in patients with RA treated with HCQ. METHODS: The VD data of the 3 × 3 mm OCT angiogram (RTVue XR Avanti, Optovue Inc., Fremont, California, USA) as well as the retinal thickness (RT) data of patients with RA (n = 30) and healthy controls (n = 30) were extracted and analyzed. The study group was further divided into patients undergoing HCQ treatment for > 5 years (high-risk-group) and < 5 years (low-risk group). RESULTS: Patients with RA showed no evidence of VD reduction compared to the control group in all obtained regions (p > 0.05). Correlation analysis revealed no dependency between VD, RT, and HCQ therapy duration or cumulative HCQ dose (p > 0.05). High-risk patients showed a decreased VD in the superficial quadrant of the superficial capillary plexus compared to low-risk-patients (p = 0.022). Whole-en-face RT was reduced in the high-risk group compared to the control group (p = 0.019). CONCLUSION: Our study showed no evidence that HCQ diminishes VD in patients with RA without HCQ retinopathy measured by OCTA. However, RA patients with a long duration of therapy showed a significantly reduced RT. Our results suggest that quantitative VD analysis by OCTA may not be suitable for early detection of HCQ retinopathy and that the focus on detecting early HCQ retinopathy should be on intensive and sequential OCT diagnostics.

FURTHER EVIDENCE AGAINST BILATERAL MANIFESTATION OF COATS DISEASE IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE MACULA.

PURPOSE: Recent studies have questioned the traditional view, which regards Coats disease as a strictly unilateral entity. Applying optical coherence tomography angiography, this prospective, monocentric study investigates quantitative capillary changes of the macula associated with Coats disease. METHODS: Twenty-four eyes (4 untreated, 8 pre-treated) of 12 patients with stage 2 Coats disease (age range: 9-61 years) and 15 eyes of healthy, age-matched controls from the University of Muenster Medical Center, Germany received macular optical coherence tomography angiography measurements of the superficial, deep, and choriocapillary capillary plexus. Flow density and parameters related to the foveal avascular zone were compared between Coats eyes and fellow eyes, and between fellow eyes and control eyes. Additional subanalyses investigated changes based on disease stage. RESULTS: Flow density did not differ between fellow eyes of Coats disease patients and control eyes in any of the parameters investigated. Comparison of Coats eyes to their respective fellow eyes revealed Coats disease to be associated with lower flow density in superficial, deep, and choriocapillary capillary plexus regions, irrespective of disease stage (all P < 0.03). There were no noticeable differences regarding the size or symmetry of the foveal avascular zone. CONCLUSION: In light of the recent discussion around the unilateral character of Coats disease, this trial provides evidence against a bilateral presentation of vascular changes in the macula.

Idiopathic Epiretinal Membranes - Pathophysiology, Classifications and OCT-Biomarkers. / Idiopathische epiretinale Membranen ­ Pathophysiologie, Klassifikationen und OCT-Biomarker.

Epiretinal membranes (ERMs) are a common finding in patients with increasing age. Diagnosis and treatment of ERMs have changed dramatically in recent years due to technological advances in ophthalmological care. In recent years, tomographic imaging has allowed for accurate visualization of ERMs and contributed to the growing understanding of the pathophysiology of this condition. The literature review conducted here summarizes recent innovations in diagnosis, classification, and treatment of idiopathic ERMs and specifically addresses novel optical coherence tomography (OCT) biomarkers that allow for the generation of prognoses regarding the clinical postoperative outcome.

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.

Optimizing intraocular lens power calculation using adjusted conventional keratometry for cataract surgery combined with Descemet membrane endothelial keratoplasty.

PURPOSE: To evaluate the utility of intraocular lens (IOL) power calculation using adjusted conventional keratometry (K) according to postoperative posterior to preoperative anterior corneal curvature radii (PPPA) ratio for eyes with Fuch's dystrophy undergoing cataract surgery combined with Descemet membrane endothelial keratoplasty (triple DMEK). METHODS: A fictitious refractive index (FRI) was determined (Pentacam HR®) based on the PPPA ratio in 50 eyes undergoing triple DMEK. Adjusted corneal power was calculated in every eye using adjusted K values: K values determined by the IOLMaster were converted to adjusted anterior corneal radius using the mean FRI. Posterior corneal radius was calculated using the mean PPPA ratio. Adjusted corneal power was determined based on the calculated corneal radii and thick lens formula. Refractive errors calculated using the Haigis, SRK/T, and HofferQ formulae based on the adjusted corneal power were compared with those based on conventional K measurements. RESULTS: Calculated PPPA ratio and FRI were 0.801 and 1.3271. Mean prediction error based on conventional K was in the hyperopic direction (Haigis: 0.84D; SRK/T: 0.74D; HofferQ: 0.74D) and significantly higher (P < 0.001) than that based on adjusted corneal power (0.18D, 0.22D, and 15D, respectively). When calculated according to adjusted corneal power, the percentage of eyes with a hyperopic shift > 0.5D fell significantly from 64 to 30% (Haigis), 62 to 36% (SRK/T), and 58 to 26% (HofferQ), respectively. CONCLUSION: IOL power calculation based on adjusted corneal power can be used to reduce the risk of a hyperopic shift after triple DMEK and provides a more accurate refractive outcome than IOL power calculation using conventional K.

SALUS-a non-inferiority trial to compare self-tonometry in glaucoma patients with regular inpatient intraocular pressure controls: study design and set-up.

PURPOSE: The SALUS study aims to improve the healthcare situation for glaucoma patients in Germany. In order to detect diurnal intraocular pressure (IOP) fluctuations, inpatient monitoring of IOP in an eye hospital for a minimum of 24 h is the current standard. SALUS assesses the benefits of a new form of outpatient care, where IOP can be measured by the patients themselves at home using a self-tonometer. This approach should promote the patient's health competence and empowerment within the healthcare system while reducing treatment costs. METHODS: The SALUS study is a randomized controlled, open non-inferiority trial, alongside an economic analysis, determining whether outpatient monitoring of IOP with self-tonometry is at least as effective as current standard care and would reduce treatment costs. Participants (n = 1980) will be recruited by local ophthalmologists in the area of Westphalia-Lippe, Germany, and randomized to receive 7-day outpatient or 24-h inpatient monitoring. Participants in both study arms will also receive 24-h blood pressure monitoring. Furthermore, patient data from both study groups will be collected in an electronic case file (ECF), accessible to practitioners, hospitals, and the study participants. The primary endpoint is the percentage of patients with IOP peaks, defined as levels 30% above the patient-specific target pressure. Data will also be collected during initial and final examinations, and at 3, 6, and 9 months after the initial examination. RESULTS: The study implementation and trial management are represented below. CONCLUSION: SALUS is a pioneering prospective clinical trial focused on the care of glaucoma patients in Germany. If SALUS is successful, it could improve the healthcare situation and health literacy of the patients through the introduction of various telemedical components. Furthermore, the approach would almost certainly reduce the treatment costs of glaucoma care. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04698876, registration date: 11/25/2020. DRKS-ID: DRKS00023676, registration date: 11/26/2020.

High User Acceptance of a Retina e-Learning App in Times of Increasing Digitalization of Medical Training for Ophthalmologists.

INTRODUCTION: The aim was to identify changes in continuing education and training in ophthalmology in the context of the COVID-19 pandemic and advancing digitalization and to analyse the acceptance of e-learning tools among German ophthalmologists using a novel Retina Case App as an example. METHODS: The participants' training behaviour before and during the COVID-19 pandemic was surveyed. Furthermore, the acceptance and usability of the Retina Case App were evaluated using the System Usability Scale (SUS). A possible influence of the app on everyday clinical practice was assessed. RESULTS: A total of 145 ophthalmologists participated in the survey. The frequency of continuing medical education did not decrease for 62.8% of ophthalmologists during the pandemic. A significant increase in at least monthly use of online courses or lectures has been observed (90.3% vs. 28.2%, p < 0.001). No significant difference was identified in terms of frequency of use of print and digital journals or printed textbooks. The majority of participants stated that online training platforms are well suited to replace the absence of face-to-face events (73.8%). The mean SUS score was 87.7 (SD 11.9), which categorizes the app's usability as excellent. The majority agreed that the newly developed app enables faster learning (82.1%) and leads to increased motivation (71.7%). Most ophthalmologists (80.7%) felt that regular use of the app would improve confidence in the treatment of retinal diseases. CONCLUSIONS: The COVID-19 pandemic has led to a significant change in training behaviour in ophthalmology towards e-learning and online courses, which has not been accompanied by a general decline in training activity. The exemplarily investigated application showed a high user acceptance among ophthalmologists.

Overexpression of Neuregulin-1 Type III Has Impact on Visual Function in Mice.

Schizophrenia is associated with several brain deficits, including abnormalities in visual processes. Neuregulin-1 (Nrg1) is a family of trophic factors containing an epidermal growth factor (EGF)-like domain. It is thought to play a role in neural development and has been linked to neuropsychiatric disorders. Abnormal Nrg1 expression has been observed in schizophrenia in clinical studies. Moreover, in schizophrenia, there is more and more evidence found about pathological changes of the retina regarding structural, neurochemical and physiological parameters. However, mechanisms of these changes are not well known. To investigate this, we analysed the function of the visual system using electroretinography (ERG) and the measurement of visual evoked potentials (VEP) in transgenic mice overexpressing Nrg1 type III of three different ages (12 weeks, 24 weeks and 55 weeks). ERG amplitudes tended to be higher in transgenic mice than in control mice in 12-week old mice, whereas the amplitudes were almost similar in older mice. VEP amplitudes were larger in transgenic mice at all ages, with significant differences at 12 and 55 weeks (p values between 0.003 and 0.036). Latencies in ERG and VEP measurements did not differ considerably between control mice and transgenic mice at any age. Our data show for the first time that overexpression of Nrg1 type III changed visual function in transgenic mice. Overall, this investigation of visual function in transgenic mice may be helpful to understand corresponding changes that occur in schizophrenia, as they may find use as biomarkers for psychiatric disorders as well as a potential tool for diagnosis in psychiatry.

Treating Severe Pediatric Keratoconjunctivitis with Topical Cyclosporine A. / Behandlung der chronischen Keratokonjunktivitis im Kindesalter mit topischem Ciclosporin A.

The incidence of chronic keratoconjunctivitis, which potentially causes long-term loss of visual acuity due to corneal opacity, is considerably less common in children than in adults. It is therefore in danger of being overlooked. In children the appropriate treatment is therefore often introduced too late, or to an insufficient extent. In this article we would like to raise awareness about the diagnosis of chronic keratoconjunctivitis in children, and to present an effective treatment plan for severe stages of the disease. There are two forms of chronic keratoconjunctivitis that occur most frequently in children: hyperergic blepharokeratoconjunctivitis (hBKC) and vernal keratoconjunctivitis (VKC). With hBKC, the patient often has a history of recurring hordeolum and also presents with blepharitis; it is characterized by the marked presence of corneal neovascularization in the lower circumference of the cornea. VKC is typically characterized by changes under the upper eyelid, with marked changes to the superior limbus. If there is a risk of complications involving the cornea, or in the presence of such complications, a consistent long-term topical immunosuppressive and anti-inflammatory treatment is required. Both of these properties are combined in the active ingredient cyclosporine A. Other advantages of topical CSA treatment are its steroid-sparing effect and the long-term reduction of exacerbations. Parents need to be informed about the chronic nature of these two diseases and their tendency to recur; because of these characteristics, treatment, in most cases, should be envisaged for at least one year in order to effectively disrupt the complex immunologic processes. This safeguards the child's visual development and prevents amblyopia caused by scarring and astigmatism. We hope that the data presented will lower the barriers related to prescribing CSA for topical eye application in children.

Differential effects of high-intensity interval training (HIIT) on choriocapillaris perfusion in healthy adults and patients with type 1 diabetes mellitus (T1DM).

PURPOSE: To investigate the effects of a four-week high-intensity interval training (HIIT) on choriocapillaris (CC) perfusion in young healthy adults and type 1 diabetes mellitus (T1DM) patients. METHODS: Data of two HIIT studies with baseline to follow-up comparison were retrospectively analysed. Twenty healthy participants and twenty T1DM patients without clinical signs of diabetic retinopathy were included. All participants had performed a four-week all-out HIIT protocol with a total of 8 training sessions. Changes in physical fitness were assessed using power output at the individual aerobic lactate threshold (IANT). Optical coherence tomography angiography (OCTA) imaging was performed at baseline and follow-up. CC images were analysed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution. RESULTS: At baseline, CC OCTA revealed a lower and more heterogeneous intensity signal in T1DM eyes (mean intensity signal and standard deviation of signal intensity, p < 0.001). Percent of CC FD area was greater in T1DM eyes (p < 0.001). While T1DM patients showed greater improvement of exercise capacity at IANT than healthy controls (group×time p = 0.0403), CC FD area and standard deviation of intensity increased in healthy controls but not in T1DM patients (group×time p ≤ 0.029). Moreover, linear regression slopes of FD region distribution differed significantly at baseline and follow-up (p = 0.0002) in healthy individuals but not in T1DM patients. CONCLUSIONS: Effects of regular physical exercise performed as HIIT on CC perfusion were only seen in healthy participants, not in T1DM patients suggesting impaired CC adaptation in T1DM.

A modified protocol for isolation of retinal microglia from the pig.

Microglia are the resident immune cells in the retina. To investigate their properties and behaviour, a reliable and yielding procedure to culture them is necessary. We here describe a way of isolation of microglial cells from the porcine retina, as pig eyes are similar to human eyes in size, structure and vasculature, including similarities in proteins and pathways. Retina was isolated from fresh pig eyes, dissociated by a mixture of collagenase, hyaluronidase and DNAse, and passed through a cell strainer. After triple centrifugation with decreasing velocity and re-suspension, cells were seeded into poly-d-lysine coated culture flasks and cultured using DMEM and macrophage-colony stimulating factor (M-CSF). Number of cells increased gradually during the first 10-14 days, till they could be split and used for experiments. Identity of isolated cells as microglia was assessed by immunostaining against the microglia/macrophage markers Iba1, CD11b, CD68, CD45 and TMEM119. Phagocytic function of microglia could be demonstrated by phagocytosis of fluorescence beads and their response to lipopolysaccharide (LPS). As a conclusion, we developed a protocol for isolation and cultivation of pig retinal microglial cells that are suitable for research in the laboratory.

Assessing the validity of corneal power estimation using conventional keratometry for intraocular lens power calculation in eyes with Fuch's dystrophy undergoing Descemet membrane endothelial keratoplasty.

PURPOSE: The present retrospective study was designed to test the hypothesis that the postoperative posterior to preoperative anterior corneal curvature radii (PPPA) ratio in eyes with Fuch's dystrophy undergoing Descemet membrane endothelial keratoplasty (DMEK) is significantly different to the posterior to anterior corneal curvature radii (PA) ratio in virgin eyes and therefore renders conventional keratometry (K) and the corneal power derived by it invalid for intraocular lens (IOL) power calculation. METHODS: Measurement of corneal parameters was performed using Scheimpflug imaging (Pentacam HR, Oculus, Germany). In 125 eyes with Fuch's dystrophy undergoing DMEK, a fictitious keratometer index was calculated based on the PPPA ratio. The preoperative and postoperative keratometer indices and PA ratios were also determined. Results were compared to those obtained in a control group consisting of 125 eyes without corneal pathologies. Calculated mean ratios and keratometer indices were then used to convert the anterior corneal radius in each eye before DMEK to postoperative posterior and total corneal power. To assess the most appropriate ratio and keratometer index, predicted and measured powers were compared using Bland-Altman plots. RESULTS: The PPPA ratio determined in eyes with Fuch's dystrophy undergoing DMEK was significantly different (P < 0.001) to the PA ratio in eyes without corneal pathologies. Using the mean PA ratio (0.822) and keratometer index (1.3283), calculated with the control group data to convert the anterior corneal radius before DMEK to power, leads to a significant (P < 0.001) underestimation of postoperative posterior negative corneal power (mean difference (∆ = - 0.14D ± 0.30) and overestimation of total corneal power (∆ = - 0.45D ± 1.08). The lowest prediction errors were found using the geometric mean PPPA ratio (0.806) and corresponding keratometer index (1.3273) to predict the postoperative posterior (∆ = - 0.01 ± 0.30) and total corneal powers (∆ = - 0.32D ± 1.08). CONCLUSIONS: Corneal power estimation using conventional K for IOL power calculation is invalid in eyes with Fuch's dystrophy undergoing DMEK. To avoid an overestimation of corneal power and minimize the risk of a postoperative hyperopic shift, conventional K for IOL power calculation should be adjusted in eyes with Fuch's dystrophy undergoing cataract surgery combined with DMEK. The fictitious PPPA ratio and keratometer index may guide further IOL power calculation methods to achieve this.