Keratoconus Progression Determined at the First Visit: A Deep Learning Approach With Fusion of Imaging and Numerical Clinical Data.

Purpose: Multiple clinical visits are necessary to determine progression of keratoconus before offering corneal cross-linking. The purpose of this study was to develop a neural network that can potentially predict progression during the initial visit using tomography images and other clinical risk factors. Methods: The neural network's development depended on data from 570 keratoconus eyes. During the initial visit, numerical risk factors and posterior elevation maps from Scheimpflug imaging were collected. Increase of steepest keratometry of 1 diopter during follow-up was used as the progression criterion. The data were partitioned into training, validation, and test sets. The first two were used for training, and the latter for performance statistics. The impact of individual risk factors and images was assessed using ablation studies and class activation maps. Results: The most accurate prediction of progression during the initial visit was obtained by using a combination of MobileNet and a multilayer perceptron with an accuracy of 0.83. Using numerical risk factors alone resulted in an accuracy of 0.82. The use of only images had an accuracy of 0.77. The most influential risk factors in the ablation study were age and posterior elevation. The greatest activation in the class activation maps was seen at the highest posterior elevation where there was significant deviation from the best fit sphere. Conclusions: The neural network has exhibited good performance in predicting potential future progression during the initial visit. Translational Relevance: The developed neural network could be of clinical significance for keratoconus patients by identifying individuals at risk of progression.

The role of multimodal imaging in characterization and monitoring of choroidal neovascularization secondary to angioid streaks.

BACKGROUND: To characterize and monitor choroidal neovascularisation (CNV) secondary to angioid streaks (AS) using multimodal imaging and to compare the results with conventional fluorescein angiography (FA). METHODS: A total of 11 eyes with CNV secondary to AS were included in this retrospective study. Multimodal morphological and functional assessment, including spectral-domain optical coherence tomography (SD-OCT), spectral-domain optical coherence tomography angiography (SD-OCTA), and fundus autofluorescence (FAF), were used to assess for evidence of CNV activity and compared with conventional FA. Morphological features of CNV were analyzed and treatment was continuously monitored using SD-OCT and SD-OCTA. RESULTS: Our results showed that SD-OCTA provided reliable results for the detection of secondary CNV in AS that were comparable to conventional FA. With SD-OCTA, a total of 13 CNVs were detected in 11 eyes and analyzed by means of outer retinal choriocapillaris depth (ORCC) segmentation and the corresponding B-scans. Twelve of the 13 CNVs were classified as active and therefore required treatment. For treatment monitoring during intravitreal therapy (IVT), SD-OCTA was found to be a valuable diagnostic tool over a mean follow-up of 76 weeks. CONCLUSIONS: Our study demonstrates that SD-OCTA can be routinely used to identify ill-defined CNV without dye-based angiography, especially in cases of CNV secondary to AS, where Bruch's membrane (BM) defects limit the diagnostic value of FA. Our results showed that non-invasive multimodal imaging facilitates sufficient CNV monitoring and treatment guidance. Further studies are warranted to provide more evidence in this rare retinal disease.

Conditions for modifying intraocular lenses as drug carriers for methotrexate using poly (lactic-co-glycolic acid).

INTRODUCTION: The intraocular lens (IOL) can be used as a slow-release drug carrier in cataract surgery to alleviate posterior capsular opacification (PCO). The following is a systematic development of an IOL using methotrexate and the solvent casting process with poly (lactic-co-glycolic acid) (PLGA) as a carrier polymer. METHODS: Different solvents for PLGA and methotrexate were tested for dissolution properties and possible damage to the IOL. The required biological concentration of methotrexate was determined in human capsular bags implanted with an IOL. To detect fibrosis, α-SMA, f-actin, and fibronectin were labelled by immunofluorescence staining. Cell proliferation and extracellular matrix contraction were observed in a lens epithelial cell line (FHL-124). Finally, the IOL was designed, and an ocular pharmacokinetic model was used to measure drug release. RESULTS: Solvent mixtures were found to allow coating of the IOL with drug and PLGA without damaging it. PCO in the capsular bag model was inhibited above 1 µM methotrexate (p = 0.02). Proliferation in FHL-124 was significantly reduced above a concentration of 10 nM (p = 0.04) and matrix contraction at 100 nM (p = 0.02). The release profile showed a steady state within therapeutic range. CONCLUSION: After determination of the required physicochemical manufacturing conditions, a drug releasing IOL was designed. A favourable release profile in an ocular pharmacokinetics model could be shown.

The rising tide of rhegmatogenous retinal detachment in Germany: a nationwide analysis of the incidence, from 2005 to 2021.

PURPOSE: This nationwide study aims to delineate the incidence and trends of rhegmatogenous retinal detachment (rRD) in Germany across 17 years (2005-2021). METHODS: We conducted a retrospective cohort study using data from the German Federal Statistics Office and the Institute for the Hospital Remuneration System (InEK). The dataset includes approximately 19 million annual inpatient admissions annually. Retinal detachment was identified through ICD-10 code H33.0. Adjusted incidence rates were estimated after excluding reoperation cases. We used R Statistical Software to calculate estimates to 2021, and Tableau for visualisation. RESULTS: From 2005 to 2021, Germany reported 332,650 rRD cases, with males consistently more affected. Adjusted incidence rose from 15.6 per 100,000 in 2005 to 24.8 in 2021. Variable annual percentage changes in incidence were noted, averaging 4.0% for males and 2.6% for females. The annual mean age of affected individuals ranged from 60.2 to 62 years, with a median age between 62 and 63, suggesting increasing diagnoses at younger ages. Hospital stays declined from 6 to 3.3 days, and higher management rates were observed in Saarland and Rhineland-Palatine. CONCLUSION: The study confirms an increasing incidence of rRD in Germany from 2005 to 2021, particularly among males. These findings call for further research to investigate the underlying causes. Collaboration among healthcare professionals, researchers, and policymakers is essential for effective management and improved visual outcomes.

User Friendliness and Perioperative Guidance Benefits of a Cataract Surgery Education App: Randomized Controlled Trial.

BACKGROUND: Cataract surgeries are among the most performed surgeries worldwide. A thorough patient education is essential to inform patients about the perioperative process and postoperative target results concerning the intraocular lens and objectives for visual outcomes. However, addressing all relevant aspects and questions is time-consuming. Mobile apps can facilitate this process for both patients and physicians and thus be beneficial. However, the success of such an app depends on its user friendliness and acceptance by patients. OBJECTIVE: This study aimed to evaluate the user friendliness and acceptance of a cataract surgery education app on mobile devices among patients undergoing cataract surgery, the characteristics of patients who benefit the most from app use, and the influence of the app on patient satisfaction with treatment. METHODS: All patients who underwent cataract surgery at an ophthalmological practice from August 2020 to July 2021 were invited to participate in this randomized controlled trial. Out of 493 invited patients, 297 (60.2%) were enrolled in this study. Patients were randomized into 3 different groups. Half of the patients were offered to participate in Group 1 with use of the "Patient Journey" app. However, if they decided not to use the app, they were included in Group 2 (app denial). The other half of the patients were included in Group 3 (control) with no use of the app and with information provided conventionally. The app provided general information on the ophthalmological center, surgeons, cataract, and treatment options. Different questionnaires were used in all 3 groups to evaluate satisfaction with the perioperative process. Group 1 evaluated the app. Demographic characteristics, such as age, gender, and educational degree, were assessed. RESULTS: Group 1 included 77 patients (median age 69 years). Group 2 included 61 patients, and their median age was higher (median age 79 years). Group 3 included 159 patients (median age 74 years). There was no difference in satisfaction with the perioperative process and clinic between the 3 groups. Almost all app users appreciated the digital details provided for the organization and the information on the surgery. Age did not play a major role in appreciation of the app. Female patients tended to appreciate the information provided more than male patients. Patients who did not have a higher university degree experienced more benefits from the informational content of the app and were the most satisfied with the information. However, male patients and academics were in general more aware of technology and handled the app more easily. CONCLUSIONS: The app showed high user friendliness and acceptance, and could particularly benefit specific patient groups. App users demonstrated a noninferior high satisfaction with the treatment in the ophthalmological center in comparison with patients who were informed about the surgery only conventionally.

The incidence of retinopathy of prematurity in neonates in Germany in 2019; a nationwide epidemiological cohort study.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness in preterm infants. The incidence of ROP varies widely across countries, with rates as high as 30% in some regions. This study investigated the incidence, risk factors, treatment, and mortality of ROP patients in Germany. Data were extracted from the German Federal Statistical Office (Destatis) diagnosis-related group (DRG) and Institute for the Remuneration System in Hospitals (InEK) databases. Patients with a secondary diagnosis of ROP (ICD-10 code H35.1) in the first 28 days of life were included. Data were extracted for patients admitted between January 1, 2019 and December 31, 2019. The diagnoses and procedures were determined using the German version of the International Classification of Diseases (ICD-10-GM) and the German procedure coding system (OPS). The codes 5-154.xx, 5-155.xx, 8-020.xx, 5-156.9, 6-003.(c&d), 6-007.(2&8) were utilised to denote different ocular treatments. Patient Clinical Complexity Levels were extracted and used to compare ROP with non-ROP patients. A total of 1326 patients with ROP were identified. The incidence of ROP is estimated to be 17.04 per 10,000 live births. The incidence was highest in infants with birth weights less than 500 g and decreased with increasing birth weight. The most common risk factors for ROP were low birth weight, male sex, and prematurity. Of the infants with ROP, 7.2% required ocular treatment. The most common treatment was intraocular injections, followed by photocoagulation. No surgical treatment was required for any of the infants during the study period. The mortality rate for infants with ROP was 60.33 per 10,000. This is higher than the overall neonatal death rate of 24.2 per 10,000. CONCLUSIONS: This study found that the incidence of ROP in Germany is similar to that in other developed countries. The study also found that the mortality rate for infants with ROP is higher than the overall neonatal death rate. These findings highlight the importance of early detection and treatment of ROP in preterm infants. WHAT IS KNOWN: • ROP is a severe eye condition often affecting preterm infants. • Previous data are limited in scope and generalizability. WHAT IS NEW: • Based on a national database, our study found ROP incidence to be 17.04 per 10,000 new births, higher in males (17.71) than in females (16.34). • 7.2% of ROP cases required ocular treatment, inversely correlated with birth weight. • High rates of multimorbidity such as neonatal jaundice (84.69%), respiratory distress syndrome (80.84%), and apnea (78.88%) were observed.

Ultrastructural Details of Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of this study was to describe differences in the vitreomacular interface (VMI) in idiopathic epiretinal membrane (ERM) foveoschisis compared to macular pseudohole (MPH) and lamellar macular hole (LMH). METHODS: We analysed surgically excised epiretinal material and internal limiting membrane (ILM) specimens obtained from 16 eyes of 16 patients with ERM foveoschisis (6 eyes), MPH (5 eyes), and LMH (5 eyes) during standard pars plana vitrectomy (PPV) with membrane peeling. The three entities were classified according to the newly introduced optical coherence tomography (OCT) terminology. Transmission electron microscopy (TEM) was used to describe the ultrastructural features. RESULTS: We found fibrocellular epiretinal tissues in all samples analysed. However, the cell and collagen composition of the VMI differed between groups. Eyes with ERM foveoschisis were characterized by a higher number of cells, multilayered membranes, and thick strands of vitreous collagen embedding the major cell types of myofibroblasts compared to MPH. Eyes with MPH also showed a predominance of myofibroblasts, but these were located directly on the ILM with no collagen between the cells and the ILM. Eyes with LMH showed a thick, multilayered epiretinal proliferation consisting mainly of non-tractional glial cells, corresponding to hypodense epiretinal proliferation on OCT. Eyes with ERM foveoschisis and MPH were more likely to have incomplete PVD compared to LMH in terms of posterior hyaloid status. DISCUSSION/CONCLUSION: Tractional ERMs in eyes with ERM foveoschisis and MPH differ in their ultrastructure. The main difference is in the amount and topographical distribution of vitreous collagen. However, the epiretinal cell types are predominantly myofibroblasts in both entities. This highlights the importance of distinguishing ERM foveoschisis from both MPH and LMH in terms of pathogenesis and surgical peeling procedures.

Retinal Toxicity after Initial Administration of Nivolumab and Ipilimumab.

Background: To present a rare case of a bilateral immune checkpoint inhibitor- (ICI-) induced photoreceptor injury with a bacillary layer detachment (BALAD) and a dissection of the photoreceptor inner and outer segment, accompanied by ICI-induced Vogt-Koyanagi-Harada- (VKH-) like uveitis after initial administration of nivolumab and ipilimumab. Case Presentation. A 52-year-old female with metastatic malignant cutaneous melanoma experiencing bilateral progressive visual acuity reduction, after treatment initiation with 1 mg/kg nivolumab and 3 mg/kg ipilimumab two weeks prior symptom onset. An extensive laboratory workup, including uveitis workup, onconeuronal and retinal antibodies, ruled out a paraneoplastic autoimmune disorder and a granulomatous disease. Furthermore, a B-scan was performed to exclude a posterior scleritis. Ensuing temporary treatment discontinuation of nivolumab and complete discontinuation of ipilimumab, treatment with high-dose systemic steroids was initiated, which resulted in alleviation of her symptoms and stability of ocular findings. Conclusions: ICIs can induce significant ocular side effects. As ocular inflammation can be well controlled using systemic steroids, treatment with ICIs can be continued whenever possible, in particular, if there is a good treatment response of the systemic malignancy.

The Use of Corneoscleral Grafts to Maintain Tectonic Stability in Severe Keratolysis.

Severe corneal ulcerations, causing major keratolysis with large perforation of the cornea or extending to the limbal region, are an ophthalmic emergency. In these cases, a larger corneoscleral graft can be transplanted to restore tectonic integrity, alleviate pain, save vision, and prevent loss of the eye. Chart review of 34 patients with a corneoscleral graft ≥9.5 mm was conducted. Primary endpoints of the study were tectonic stability defined as no need for another keratoplasty or enucleation. In addition, visual acuity, postoperative complications, and secondary procedures were analyzed. In total, 12 patients (35%) were female. The mean age at transplantation was 65 ± 19 years. The underlying disease was a perforated infectious corneal ulcer in 30 cases (88%). Mean follow up was 675 ± 789 days. Tectonic stability at the end of the follow-up was maintained with a probability of 56% in a Kaplan-Meier analysis. Another penetrating keratoplasty was necessary in six cases (17%) and enucleation in five cases (15%). A corneoscleral transplant remains a viable treatment option to prevent enucleation in severe keratolysis. In our study, this was possible in about half of the cases. Postoperative complications, secondary surgeries, and markedly reduced visual acuity put the advantages into perspective.

Successful treatment of multidrug-resistant Pseudomonas aeruginosa keratitis with meropenem eye drops - a case report.

BACKGROUND: This case report describes the course and therapeutic management of a fast-spreading bacterial keratitis caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). CASE PRESENTATION: A 27-year-old male contact lens wearer presented with a multi-resistant, fast spreading P. aeruginosa keratitis. After initial resistance to various antibiotic therapies, testing revealed a MDR P. aeruginosa. The keratitis was treated successfully with specially prepared 50 mg/ml off-label meropenem eye drops for 18 days as well as systemic meropenem for seven days with rapid improvement of the corneal infiltrate. CONCLUSION: This case report demonstrates the combination of topical and systemic meropenem as a useful treatment option for corneal ulcers caused by MDR P. aeruginosa.

Influence of endotamponade on anterior chamber depth and refractive outcome after combined phacovitrectomy: case-control study.

PURPOSE: To compare the changes in the anterior chamber depth (ACD) and in the refractive outcomes after combined phacovitrectomy with respect to the endotamponade (balanced salt solution, air, sulfur hexafluoride [SF 6 , gas]). SETTING: Department of Ophthalmology, University Hospital Ulm, Ulm, Germany. DESIGN: Retrospective, longitudinal case-control study. METHODS: 160 eyes of 160 patients were included in the study. 120 eyes underwent phacoemulsification with in-the-bag implantation combined with vitrectomy and were divided into 3 groups according to tamponade (balanced salt solution, air, gas). 40 control eyes with cataract surgery only were included. Further inclusion criteria were uneventful surgery, no postoperative complications and absence of corneal pathology. Endpoints were ACD as measured by swept-source optical coherence tomography-based biometry (IOLMaster 700) preoperatively, 1 to 2 days and 6 weeks postoperatively and refractive prediction error (PE) using the Barrett and Haigis formulas. RESULTS: Within the first 2 days after surgery the ACD was shallower in the eyes left with gas or air tamponade, when compared with balanced salt solution or cataract surgery alone ( P < .001). This effect diminished 6 weeks later, and all eyes reached comparable ACD ( P = .396). The refractive PE was slightly, but statistically significantly higher in the gas group when compared with cataract surgery alone ( P = .012 for Barrett, P = .006 for Haigis). CONCLUSIONS: The resulting ACD after combined phacovitrectomy was independent of the tamponade used, but a gas-tamponade was associated with a higher refractive PE.

PORES OF THE INTERNAL LIMITING MEMBRANE: A Common Finding in Vitreomaculopathies.

PURPOSE: To describe presence and distribution of pores of the inner limiting membrane (ILM) in eyes with vitreomaculopathies. METHODS: Inner limiting membrane specimens were harvested from 117 eyes of 117 patients during vitrectomy with membrane peeling from eyes with vitreomacular traction syndrome, idiopathic and secondary epiretinal gliosis, and idiopathic full-thickness macular hole. All specimens were processed as flat-mounts for immunocytochemistry and examined by phase-contrast, interference, and fluorescence microscopy. Demographic and clinical data were correlated. RESULTS: Inner limiting membrane pores were found in all vitreomaculopathies. They were identified in 47 (40.2%) of 117 eyes being most evident with antilaminin. In eyes with full-thickness macular hole >400 µ m, pores were seen in more than half of all eyes. They occur as numerous and uniformly distributed defects of the flat-mounted ILM with a mean diameter of 9.5 ± 2.4 µ m. Edges of ILM pores are round with an irregular contour and no specific cellular pattern. Pores were distinguished from retinal vessel thinning and iatrogenic artefacts. CONCLUSION: Contrary to previous reports, ILM pores are a common finding in vitreomaculopathies easily visible with antilaminin staining. Further studies are needed to clarify whether their presence correlates with differences in disease progression or imaging before and after vitrectomy with ILM peeling.

Are Retinal Detachments Becoming More Frequent? Data from 2 University Eye Clinics and Literature Review. / Werden Netzhautablösungen häufiger? Daten von 2 Universitätsaugenkliniken und Literaturübersicht.

There have been marked increases in the numbers of patients with retinal detachments at individual centres in recent years and this is supported by the subjective impression of many experts. We therefore surveyed the literature on changes in the incidence of retinal detachments worldwide. This revealed quite significant methodological differences between the studies, so that it was difficult to achieve a conclusive comparison of the development of the incidence of retinal detachment. Despite these limitations, all data from recent studies suggest an increase in the number of retinal detachments. The incidence of retinal detachment in the western world currently seems to be more than 20 cases per 100,000 person-years, which is significantly higher than described in earlier decades. It can be assumed that an increase in the number of individuals with myopia, a demographic increase in patients of the typical age group for retinal detachment and an increasing number of cataract surgeries, especially in younger patients, are responsible for the rising incidence of retinal detachment.

NOVEL TECHNIQUE FOR INTRAOCULAR FOREIGN BODY REMOVAL: Magnetized Disposable Microforceps. A Systematic Approach and First Clinical Result.

PURPOSE: To verify whether disposable microforceps can be magnetized to atraumatically attract and then grasp intraocular foreign bodies. An effective magnetization protocol was developed. The clinical relevance was tested, and a first practical application was performed. METHODS: The magnetic flux density (MFD) of a bar magnet and an electromagnet was measured. Steel screws were used to determine the magnetization protocol. Disposable microforceps was magnetized, MFD generated at the tip was measured, and the weight that can be lifted was tested. Foreign body removal with such forceps was performed. RESULTS: The electromagnet MFD was much higher than the bar magnet. The most effective magnetization protocol was to pass the screw from the end along the shaft and back over the electromagnet. Magnetized microforceps had a 7.12 mT change in MFD at the tip. Steel balls up to 87 mg could be lifted in buffered saline solution. In clinical use, the intraocular foreign body could be attracted and grasped safely. CONCLUSION: Disposable microforceps can be easily and inexpensively magnetized. The achievable MFD is clinically relevant to attract typical intraocular foreign bodies. An electromagnet is best suited for this purpose. With such prepared forceps, foreign bodies can be attracted atraumatically and grasped securely.

Reutilization of disposable rebound tonometer probes: Risk or return?

Purpose: An advantage of rebound tonometry (RT) is its ease of use so that it can also be operated by health care technicians. However, the cost of the disposable measuring probes is high and their reuse carries the risk of infection. Therefore, this study aims to objectify the potential risk of bacterial transmission by RT. Methods: Our experimental setting consisted of two experiments. The first aimed to quantify the number of bacteria on a tonometer probe after immersion in a bacterial suspension in vitro. The experiment was carried out with two different bacteria and compared with results from a Goldmann tonometer probe. The second experiment tested whether bacteria could be transmitted by simulating reuse of a nondisinfected rebound tonometer probe. Results: First experiment: After immersion of the rebound tonometer probe, we measured a bacterial count of 2.43 × 106 Escherichia coli (EC) and 1.12 × 106 Pseudomonas fluorescens. In total, 1.09 × 107 bacteria for EC and 2.61 × 106 for Pseudomonas fluorescens (PF) were measured on the Goldmann tonometer probe. Second experiment: A bacterial transmission could be detected in 36% of cases in which reuse of nondisinfected tonometer probes was simulated. Conclusion: These results show that despite the small surface of the rebound tonometer probe, there is a clear risk of bacterial transmission. Thorough disinfection according to general standards should be mandatory if the tonometer probes are to be reused.

The role of the calcofluor white staining in the diagnosis of Acanthamoeba keratitis.

PURPOSE: Acanthamoeba keratitis is often misdiagnosed at disease onset. This study presents data to confirm the diagnosis using calcofluor white (CFW) staining. METHODS: Forty three patients were retrospectively included who presented to the Department of Ophthalmology at the University Hospital Ulm with keratitis between 2000 and 2022. Condition positive cases were diagnosed based on the typical clinical presentation of Acanthamoeba keratitis with a positive polymerase chain reaction (PCR). Condition negative were patients with ulcers due to other causing pathogens with a negative Acanthamoeba PCR result. The condition was compared with the CFW test results. RESULTS: After symptom onset, time until presentation was 17 ± 12 days and until diagnosis 27 ± 13 days in the 15 condition positive patients. Among the 35 patients with additional CFW test, 7 patients were condition positive and 28 negative. 5 of the 7 patients were true positive, 2 were false negative. In the 28 condition negative patients, 1 was false positive. Sensitivity of CFW was 71% and specificity 96%. The positive PCR results were available 3.4 ± 2.3 days after corneal scraping, the positive CFW test results on the same day in each case. CONCLUSION: Our data demonstrate that diagnosis of Acanthamoeba keratitis remains difficult and therapy is initiated late. A positive CFW test confirms the diagnosis as there are almost no false positive results and it was available faster than PCR. In case of a negative CFW test, Acanthamoeba keratitis cannot be ruled out because of a high false negative rate.

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

Pharmacological Therapy of Proliferative Vitreoretinopathy: Systematic In Vitro Comparison of 36 Pharmacological Agents.

Purpose: Proliferative vitreoretinopathy (PVR) is currently treated surgically. Reliable pharmaceutical options would be desirable, and numerous drugs have been proposed. This in vitro study is intended to systematically compare and determine the most promising candidates for the treatment of PVR. Methods: A structured literature review was conducted in the "PubMed" database to identify previously published agents proposed for medical treatment of PVR -36 substances that met the inclusion criteria. Toxicity and antiproliferative effects were evaluated on primary human retinal pigment epithelial (hRPE) using colorimetric viability assays. The seven substances with the widest therapeutic range between toxicity and no longer detectable antiproliferative effect were then validated with a bromodeoxyuridine assay and a scratch wound healing assay using primary cells derived from surgically excised human PVR membranes (hPVR). Results: Among 36 substances, 12 showed no effect on hRPE at all. Seventeen substances had a significant (P < 0.05) toxic effect of which nine did not have an antiproliferative effect. Fifteen substances significantly reduced hRPE proliferation (P < 0.05). The seven most promising drugs with the highest difference between toxicity and antiproliferative effects on hRPE were dasatinib, methotrexate, resveratrol, retinoic acid, simvastatin, tacrolimus, and tranilast. Whereof resveratrol, simvastatin, and tranilast additionally showed antiproliferative and dasatinib, resveratrol, and tranilast antimigratory effects on hPVR (P < 0.05). Conclusion: This study presents a systematic comparison of drugs that have been proposed for PVR treatment in a human disease model. Dasatinib, resveratrol, simvastatin, and tranilast seem to be promising and are well-characterized in human use.

Epiretinal Amniotic Membrane in Complicated Retinal Detachment: a Clinical and In Vitro Safety Assessment.

INTRODUCTION: Amniotic membrane (AM) is a popular treatment for external ocular diseases. First intraocular implantations in other diseases reported promising results. Here, we review three cases of intravitreal epiretinal human AM (iehAM) transplantation as an adjunct treatment for complicated retinal detachment and analyze clinical safety. Possible cellular rejection reactions against the explanted iehAM were evaluated and its influence was assessed on three retinal cell lines in vitro. METHODS: Three patients with complicated retinal detachment and implanted iehAM during pars plana vitrectomy are retrospectively presented. After removal of the iehAM at subsequent surgery, tissue-specific cellular responses were studied by light microscopy and immunohistochemical staining. We investigated the influence of AM in vitro on retinal pigment epithelial cells (ARPE-19), Müller cells (Mio-M1), and differentiated retinal neuroblasts (661W) . An anti-histone DNA ELISA for cell apoptosis, a BrdU ELISA for cell proliferation, a WST-1 assay for cell viability, and a live/dead assay for cell death were performed. RESULTS: Despite the severity of the retinal detachment, stable clinical outcomes were obtained in all three cases. Immunostaining of the explanted iehAM showed no evidence of cellular immunological rejection. In vitro, there was no statistical significant change in cell death or cell viability nor were proliferative effects detected on ARPE-19, Müller cells, and retinal neuroblasts exposed to AM. CONCLUSION: iehAM was a viable adjuvant with many potential benefits for treatment of complicated retinal detachment. Our investigations could not detect any signs of rejection reactions or toxicity. Further studies are needed to evaluate this potential in more detail.

Recurrence of perforation and overall patient survival after penetrating keratoplasty versus amniotic membrane transplantation in corneal perforation.

PURPOSE: The following is a comparative analysis on the treatment outcomes of corneal perforations using amniotic membrane transplantation (AMT) or penetrating keratoplasty (PK). METHODS: This monocentric retrospective study was performed at the Department of Ophthalmology, University Hospital Ulm, Germany. A total of 78 eyes of 78 patients were included. Thirty-nine eyes received an AMT, and 39 patients were treated with a PK. Primary outcome was recurrence of perforation. Secondary outcomes were patient mortality and visual acuity. RESULTS: No statistically significant difference was observed with regard to a recurrence of perforation between the two groups (26% in AMT vs 23% in PK, p > 0.99). The time of recurrences was within the first two years and did not differ statistically (p = 0.97). In addition, a proportional hazards model with cox regression regarding recurrent perforation showed no significant differences (p = 0.5). After AMT, 41% and after KP, 28% of the patients died during follow-up (p = 0.2), respectively. The Charlson Comorbidity Index (p < 0.0001) and the age at the time of surgery (p = 0.0002) were statistically significantly higher in those who were deceased. A mean follow-up of 485 ± 517 days was recorded. CONCLUSION: Both surgical methods show good results and no statistically significant difference regarding recurrent perforation rate. About a third of the patients died during the follow-up period. The decision regarding the appropriate method should therefore be based on a combination of all factors.