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Purpose Vasoproliferative tumours (VPT) are a rare but benign entity that can lead to severe visual acuity deterioration. There is no standard of care, and depending on the degree of clinical features, including tumour size and dissemination, visual acuity and subretinal fluid, treatment options include observation, cryotherapy and brachytherapy. Particularly in larger tumours, brachytherapy has advantages over other options, although higher radiation doses and the need for surgical application are disadvantages of this otherwise effective treatment option. CyberKnife radiosurgery might represent an alternative therapeutic option as no surgical intervention is needed and radiation doses are lower. Methods All patients diagnosed with vasoproliferative tumors who were treated with CyberKnife radiosurgery with a minimum follow-up time of 12 months were included in this case series. We recorded visual acuity, number of lesions, central retinal thickness with optical coherence tomography (OCT) and reflectivity using A-scan standardizes echography every three months. Results A total of four patients with a median age of 34 years (range: 24 - 51) who were observed over an average of 26.5 months (range: 17 - 49 months) matched our inclusion criteria. We appreciated stabilization or increase in visual acuity in all four patients and a regression in tumour thickness with subsequent increase in internal reflectivity as a marker of increasing fibrosis. Conclusion We observed good visual and functional outcome following CyberKnife therapy for VPT. We believe that further studies should be pursued to evaluate CyberKnife therapy for the treatment of VPT not treatable with cryo- or lasertherapy.

While proven to be an effective treatment for cystoid macular edema (CME) and diabetic macular edema, intravitreal steroid implants (IVSI) may cause undesirable side effects, including steroid-related glaucoma or migration into the anterior chamber in the case of iris–lens diaphragm disruption. Here we present a new surgical technique that allows for the easy implantation and subsequent fixation of the fluocinolone acetonide intravitreal implant without the risk of migration as a feasible and possibly reversible approach in the treatment of persistent CME in severely damaged eyes. In this single-center, prospective off-label, proof of principle, scleral fixation of the fluocinolone implant was performed in two eyes with disrupted anterior–posterior segment border and persistent CME. Both eyes were then followed monthly in accordance to a detailed protocol. The procedure was overall well tolerated without severe side effects. There was no migration of the implant in the anterior chamber in either eye. Scleral fixation of the fluocinolone implant proved to be a safe and feasible approach in eyes with persistent CME and disrupted anterior–posterior segment border. This new technique also allows for the possible removal of the implant and may therefore be suitable even for eyes at higher risk for side effects, such as glaucoma.

Background:Diabetes prevalence is constantly rising, involving the eyes with damage including development of diabetic macular oedema. Since 2012, intravitreal anti-vascular endothelial growth factor medication is available for diabetic macular oedema treatment. Endocrinological studies have shown that fewer women are affected by diabetes. However, when affected, they exhibit more severe diabetic complications than men. We have investigated gender-related differences in diabetic macular oedema and outcome in an ophthalmological tertiary referral hospital.Methods:We included 88 patients (54 males and 34 females) with 112 eyes (68 male and 44 female) having clinically significant diabetic macular oedema, treated with anti-vascular endothelial growth factor medication. A 1 year follow-up was performed in all patients (visual acuity and optical coherence tomography). Previous retinal surgery was an exclusion criterion, as were other retinal pathologies.Results:The mean visual acuity and mean central retinal thickness at baseline were 0.53 logMAR (male 0.49 and female 0.595) and 469 μm (male 452 μm and female: 494 μm), respectively. After 360 days, mean visual acuity changed by −0.07 (±0.36) logMAR (male −0.11 and female +0.01) and mean central retinal thickness changed by −119 μm (male −113 μm and female −127 μm). For visual acuity, a significant difference was noted at baseline ( p = 0.02) and at 1 year ( p Conclusion:Our study showed that female patients with diabetic macular oedema were diagnosed with and treated for diabetic macular oedema at a stage when visual acuity and optical coherence tomography were worse than those in their male counterparts. This gender difference could not be reduced, despite similar numbers of injections. Female diabetic patients should therefore be assessed early for ophthalmological pathologies.

This study identifies the endolysosomal two-pore channel TPC2 as a potential novel drug target for age-related macular degeneration (AMD). Inhibition of TPC2 reduces two key clinical hallmarks of the AMD, retinal inflammation and formation of leaky choroi., Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1β levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1β levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.

PURPOSE We assessed differences in compliance and adherence (lateness of patients, visual acuity, reasons for abstaining) between patients with diabetic macular edema (DME) and patients with age-related macular degeneration (AMD), both under anti-vascular endothelial growth factor therapy. METHODS We included 136 patients with DME (36% women, 65 years, 22 visits, 13.9 injections, and 29.9 months of follow-up) and 109 patients with AMD (59% women, 76 years, 20 visits, 14.7 injections, and 22.3 months of follow-up) (minimum follow-up of 12 months and at least 5 injections). We assessed missed appointments (lateness >14 days) and therapy break-offs (lateness >100 days). All delayed patients were called and interviewed for abstaining reasons. RESULTS Forty-six percent of patients with DME and 22% of patients with AMD had at least one break-off. Thirty-five percent of patients with DME and 50% of patients with AMD were always on schedule. In patients with DME, there was significant correlation (P = 0.017) between the number of break-offs and change of visual acuity. In 60% DME and 38% AMD of break-off cases, visual acuity was worse than the before break-off. The most common reason for abstaining was comorbidities (33% AMD and 20% DME). CONCLUSION There are significant differences between patients with AMD and DME regarding compliance and adherence, which also affects outcome. Strategies to tie patients with DME to costly intravitreal therapy need to be developed to improve outcomes and efficacy.

BackgroundBrolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.MethodsPatients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (µm)), central subfield retinal thickness (CSRT (µm)) and macular volume (mm³).ResultsSixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years were included. Mean change of BCVA was 0.03±0.14 logMAR (p=0.115). Significant reductions were recorded for FCP with a mean (±SD) change of −66.81±72.63 µm, −66.76±60.71 µm for CSRT and −0.27±0.24 mm³ for macular volume (all pConclusionsThe results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.

BACKGROUND Hyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood. METHODS In 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy. RESULTS The highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P < 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71% versus 32%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P < 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P < 0.0001). CONCLUSION In extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP. TRIAL REGISTRATION ClinicalTrials.gov NCT02760472 (Donna Mega). FUNDING This study has been supported by the Swedish Medical Research Council (14940, 4732, 20144-01-3, and 21144-01-3), a Swedish government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 and 11601), the Skåne Council Foundation for Research and Development, the Linnéa and Josef Carlsson Foundation, the Knut and Alice Wallenberg Foundation, the NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, and P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), and Stiftelsen De Blindas Vänner., In extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased retinopathy of prematurity severity.

Iris melanoma is a rare form of uveal melanoma with potential metastic spread. Treatment options include surgical resection, enucleation or irradiation. We analysed visual outcome, complication appearance and management in eight patients with iris melanoma following robotic-assisted CyberKnife treatment. Consecutive patients from the Department of Ophthalmology at University of Munich were included in the study if they had an iris melanoma that was treated with CyberKnife and had a minimum follow-up of 12 months. We evaluated tumor thickness, largest diameter, visual acuity and complications. 8 patients were included in this report. The median age was 74 years (range: 53–86 years). The median follow-up was 23 months (range 12–48 months). Tumor thickness decreased from 2.1 to 1.4 mm on average. Four out of eight patients showed stable or increased visual acuity compared to visual acuity at first visit. We did not find a correlation of applied radiation volume or radiation dose on visual outcome. Radiation keratopathy was the most common complication in five patients. No recurrences were noted. Robotic-assisted radiosurgery following CyberKnife is a promising non-invasive, single session treatment option for iris melanoma with comparable results regarding recurrence rate or complications to brachytherapy and proton beam therapy. All included patients showed good visual outcome.

Purpose Clinical practice guidelines provide recommendations for the management of diseases. In orphan conditions such as uveal melanoma (UM), guideline developers are challenged to provide practical and useful guidance even in the absence of high-quality evidence. Here, we assessed the methodological quality and identified deficiencies of international guidelines on UM as a base for future guideline development. Methods A systematic search was carried out in guideline databases, Medline and Embase until 27th May 2019 for guidelines on UM published between 2004 and 2019. Five independent reviewers assessed the methodological quality of the identified guidelines using the instruments “Appraisal of Guidelines for Research and Evaluation II” (AGREE II) and AGREE-REX (Recommendation EXcellence). Descriptive analysis was performed and subgroup differences were explored with the Kruskal–Wallis (H) test. The relationship between the individual domains and items of the instruments were examined using Spearman’s correlation. Results Five guidelines published from 2014 to 2018 by consortia of the United States of America, Canada and the United Kingdom (UK) were included. The highest scores were obtained by the UK guideline fulfilling 48–86% of criteria in AGREE II and 30–60% for AGREE-REX. All guidelines showed deficiencies in the domains “editorial independence”, “applicability”, and “recommendation”. Subgroup differences were identified only for the domain “editorial independence”. Conclusion The UK guideline achieved the highest scores with both instruments and may serve as a basis for future guideline development in UM. The domains “editorial independence”, “recommendation”, and “applicability” were identified as methodological weaknesses and require particular attention and improvement in future guidelines.

Ciliary body melanoma have the worst prognosis among all uveal melanoma (UM). In this report we share our experience with CyberKnife and show that the outcome is not considerably worse than with UM located elsewhere.

Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal diseases. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulin-deficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography. PF-05231023 administration protected against diabetes-induced disorganization of photoreceptor segments seen in retinal cross section with immunohistochemistry and attenuated the reduction in the thickness of photoreceptor segments measured by optical coherence tomography. PF-05231023, independent of its downstream metabolic modulator adiponectin, reduced inflammatory marker interleukin-1β (IL-1β) mRNA levels. PF-05231023 activated the AKT-nuclear factor erythroid 2–related factor 2 pathway and reduced IL-1β expression in stressed photoreceptors. PF-05231023 administration did not change retinal expression of vascular endothelial growth factor A, suggesting a novel therapeutic approach for the prevention of early diabetic retinopathy by protecting photoreceptor function in diabetes.

The neural cells and factors determining normal vascular growth are not well defined even though vision‐threatening neovessel growth, a major cause of blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is driven by delayed normal vascular growth. We here examined whether hyperglycemia and low adiponectin (APN) levels delayed normal retinal vascularization, driven primarily by dysregulated photoreceptor metabolism. In premature infants, low APN levels correlated with hyperglycemia and delayed retinal vascular formation. Experimentally in a neonatal mouse model of postnatal hyperglycemia modeling early ROP, hyperglycemia caused photoreceptor dysfunction and delayed neurovascular maturation associated with changes in the APN pathway; recombinant mouse APN or APN receptor agonist AdipoRon treatment normalized vascular growth. APN deficiency decreased retinal mitochondrial metabolic enzyme levels particularly in photoreceptors, suppressed retinal vascular development, and decreased photoreceptor platelet‐derived growth factor (Pdgfb). APN pathway activation reversed these effects. Blockade of mitochondrial respiration abolished AdipoRon‐induced Pdgfb increase in photoreceptors. Photoreceptor knockdown of Pdgfb delayed retinal vascular formation. Stimulation of the APN pathway might prevent hyperglycemia‐associated retinal abnormalities and suppress phase I ROP in premature infants.

Neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, threaten the visual health of children and adults. Current treatment options, including anti–vascular endothelial growth factor therapy and laser retinal photocoagulation, have limitations and are associated with adverse effects; therefore, the identification of additional therapies is highly desirable. Both clinical and experimental studies show that dietary ω-3 (n–3) long-chain polyunsaturated fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis. The ω-3 LC-PUFA metabolites from 2 groups of enzymes, cyclooxygenases and lipoxygenases, inhibit [and the ω-6 (n–6) LC-PUFA metabolites promote] inflammation and angiogenesis. However, both of the ω-3 and the ω-6 lipid products of cytochrome P450 oxidase 2C promote neovascularization in both the retina and choroid, which suggests that inhibition of this pathway might be beneficial. This review summarizes our current understanding of the roles of ω-3 and ω-6 LC-PUFAs and their enzymatic metabolites in neovascular eye diseases.

Pathological neovessels growing into the normally avascular photoreceptors cause vision loss in many eye diseases. Sun et al. find that a master inflammatory regulator, c-Fos, in photoreceptor controls retinal blood vessel growth into the photoreceptors through the inflammatory signal–induced STAT3/VEGFA pathway., Pathological neovessels growing into the normally avascular photoreceptors cause vision loss in many eye diseases, such as age-related macular degeneration and macular telangiectasia. Ocular neovascularization is strongly associated with inflammation, but the source of inflammatory signals and the mechanisms by which these signals regulate the disruption of avascular privilege in photoreceptors are unknown. In this study, we found that c-Fos, a master inflammatory regulator, was increased in photoreceptors in a model of pathological blood vessels invading photoreceptors: the very low-density lipoprotein receptor–deficient (Vldlr−/−) mouse. Increased c-Fos induced inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor (TNF), leading to activation of signal transducer and activator of transcription 3 (STAT3) and increased TNFα–induced protein 3 (TNFAIP3) in Vldlr−/− photoreceptors. IL-6 activated the STAT3/vascular endothelial growth factor A (VEGFA) pathway directly, and elevated TNFAIP3 suppressed SOCS3 (suppressor of cytokine signaling 3)–activated STAT3/VEGFA indirectly. Inhibition of c-Fos using photoreceptor-specific AAV (adeno-associated virus)-hRK (human rhodopsin kinase)–sh_c-fos or a chemical inhibitor substantially reduced the pathological neovascularization and rescued visual function in Vldlr−/− mice. These findings suggested that the photoreceptor c-Fos controls blood vessel growth into the normally avascular photoreceptor layer through the inflammatory signal–induced STAT3/VEGFA pathway.

Purpose To assess quality of life (QoL) status via the National Comprehensive Cancer Network (NCCN ) distress thermometer as a psychooncological screening tool in uveal melanoma patients. Methods One hundred and six consecutive patients suffering from uveal melanoma completed the distress thermometer between 04/2018 and 12/2018. Practical, emotional, family concerned, spiritual, physical and overall distress levels, distribution of distress and subgroup analyses defining groups of potential high distress levels in need of intervention were assessed. Descriptive statistics, cross‐tabulations, chi‐square and Fisher's exact test as well as correlation coefficients (Spearman's rho) and receiver operating characteristic (ROC ) were used for analysis. Results Patients with higher T‐category had significantly more emotional problems and spiritual concerns (p = 0.046 and p = 0.023, respectively). Female patients accounted for higher rates of physical issues (p = 0.034). Lower best corrected visual acuity (BCVA ) was correlated with higher distress levels (p = 0.037). Patients resulting in loss of BCVA of ≥3 lines reported higher distress levels (p = 0.029). A distress threshold of 5 on the basis of ROC analysis showed a corresponding sensitivity of 100% and specificity of 76%. Conclusion The NCCN distress thermometer could be integrated well into our clinical routine and proved to be a rapid, yet sensible screening tool for emotional and physical distress in patients with uveal melanoma. Special attention should be paid to patients with higher T‐category and patients resulting in lower levels of BCVA . As in patients with different tumour entities, the established distress threshold of ≥5 proposing intervention proved to be adequate for uveal melanoma patients.

Ischemic retinal diseases can be caused by various pathologies, which often lead to formation of preretinal neovascularization. A very common and well-established model to study normal as well as pathological angiogenic mechanisms in retina is the oxygen-induced retinopathy model in mice. This model is based on oxygen exposure of mouse pups during retinal vascular development, leading to a depletion of retinal capillaries. Upon return to room air, the lack of retinal vasculature results in hypoxia, which in turn induces vascular repair and preretinal neovascularization. In this review, we will focus on the scientific options, practical implementation, and quantification of the OIR model and its potential pitfalls.

PurposeComparison of scanning laser ophthalmoscopy (SLO) based ‘en face’ imaging techniques of patients with epiretinal membranes (ERM) and evaluation of the accuracy of preoperative diagnostic imaging.MethodsA consecutive, prospective series of 53 study eyes of 46 patients with clinically diagnosed and in optical coherence tomography (OCT) confirmed symptomatic ERMs were included in this study. Spectral domain (SD-) OCT volume scans (20°×20° with 49 horizontal sections, ART 15) including SLO en face and fundus autofluorescence (FAF) images of the macula were obtained with HRA2 (Heidelberg Retina Angiograph-Optical Coherence Tomography, Heidelberg Engineering, Heidelberg, Germany). In addition, wide-field SLO color and FAF images (Optomap 200Tx, Optos PLC, Dunfermline, UK) were performed also covering the macular area. En face images of both devices were graded for each included study eye based on SD-OCT cross sectional scans.ResultsGrading of SD-OCT (HRA2) based SLO en face green–blue enhanced multi-color, green reflectance, blue reflectance and standard multi-color visualization revealed a better detectability of ERM than SD-OCT-based en face infrared or FAF images or wide-field SLO (Optomap) based pseudo-color, red laser separation, green laser separation, or FAF images. Both FAF visualizations, HRA2 and Optomap based, achieved low mean scores. SD-OCT based en face thickness map visualization revealed good visualization but poor demarcation of epiretinal membranes.ConclusionsIn summary, en face regular or enhanced multicolor SLO images acquired with HRA2 allow a better visualization of epiretinal membranes for preoperative evaluation compared to SD-OCT based en face thickness map or pseudo-color images acquired with Optomap while infrared or FAF images are least suitable to depict epiretinal membranes.

After cataract surgery, residual lens epithelial cells migrate and proliferate within the capsular bag resulting in posterior capsule opacification (PCO). The up-regulation of TGF-β2, EGF and FGF-2 has been identified as a key factor in PCO pathogenesis leading to actin fiber assembly and alterations in the migration pattern. In this in vitro study, the influence of Erlotinib as a selective EGFR inhibitor is investigated on the cellular features indicated, which might promote a future clinical application.Expression of EGF, FGF-2 and TGF-β2 was measured using RT-PCR and ELISA in human lens epithelial cells (HLEC). Computational data of an in vitro time lapse microscopy assay were used for statistical analysis of single cell migration with a particular focus on cell-cell interaction; cell velocity distribution; and displacement before, during and after mitosis. The effect of Erlotinib on the actin-cytoskeleton was evaluated using Alexa Fluor 488 Phalloidin and epifluorescence microscopy.EGF and TGF-β2 mRNA expression and protein levels are reduced by Erlotinib, while FGF-2 expression remained stable. Overall fluidity of cell-cell interaction is less in the presence of Erlotinib compared to the control and the velocity distribution across all cells becomes less uniform within the cell cluster. After mitosis, HLEC move significantly faster without EGFR inhibition, which can be completely blocked by Erlotinib. Furthermore, Erlotinib diminishes the amount of actin stress fibers and the stress fiber diameter.As a novel effect of Erlotinib on HLEC, we describe the down-regulation of EGF and TGF-β2 expression, both are crucial factors for PCO development. Cellular movement displays complex alterations under EGFR inhibition, which is partly explained by actin fiber depletion. These findings further underline the role of Erlotinib in pharmacologic PCO prophylaxis.

The pathogenesis of central serous chorioretinopathy (CSC) is still not fully understood. The involvement of corticosteroids is undisputed, although their exact role has not been clarified; other parts of the underlying mechanism of CSC have been mainly elucidated by imaging techniques such as fluorescein and indocyanine green angiography. Even though most cases of CSC are self-limiting, severe as well as recurrent courses exist, and for these patients only a limited number of treatment options are available: laser photocoagulation, with a risk of scotoma and choroidal neovascularization, and photodynamic therapy. In this review article, we give an overview of its epidemiology, the current understanding of its pathogenesis as well as systemic and ocular risk factors. We illuminate modern diagnostic tools as well as current treatment options in the context of CSC, particularly in the light of a better understanding of corticosteroids and their receptors involved in its pathogenesis.

The development of an intraocular lens (IOL) as a drug delivery device has been the purpose of numerous preclinical studies and might become a future technology in cataract surgery. There are three techniques of pharmacological IOL modification: surface modification (coating), optic modification (soaking) or haptic modification with a slow-release-system. The therapeutic goals are endophthalmitis, postoperative inflammation and posterior capsule opacification.

Fragestellung: Multikinase-Inhibitoren (MKI) greifen an verschiedenen Stellen der Neovaskularisationskaskade wirkungsvoll an. Erste klinische und experimentelle Daten deuten darauf hin, dass MKIs einen vielversprechenden, neuartigen Ansatz in der Therapie der neovaskularen altersbedingten Makuladegeneration (AMD) darstellen, bisher ist jedoch wenig uber die Biokompatibilitat von MKIs in Bezug auf humane okulare Zellen bekannt. Diese In-vitro-Studie untersucht und vergleicht die Biokompatibilitat der MKIs Axitinib, Pazopanib und Sorafenib an okularen Zellen des vorderen und hinteren Augenabschnitts, sowie an organkultivierten Spenderhornhauten. Methodik: Primare humane Astrozyten aus dem Sehnervenkopf (ONHA), Trabekelmaschenwerkzellen (TMC) und retinale Pigmentepithelzellen (RPE), sowie humane korneale Endothel- und Linsenepithelzellen (CEC und LEC) wurden mit unterschiedlichen Konzentrationen von Axitinib, Pazopanib und Sorafenib (0,1–100 µg/mL) behandelt. Zur Simulation von oxidativem Stress wurden die Zellen zusatzlich mit 400 µM Wasserstoffperoxid koinkubiert. Die Induktion von Zelltod (Live-Dead-Assay), sowie die zellulare Vitalitat wurden mittels Live-Dead- und Tetrazolium-Farb-Reduktions-Assay (MTT) untersucht. Auserdem wurde der Einfluss der 3 Testsubstanzen auf das humane Hornhautendothel an seropositiven Spenderhornhauten in Organkultur mittels Phasenkontrastmikroskopie evaluiert. Ergebnisse: Bis zu einer Konzentration von 7,5 µg/mL zeigten sich bei keiner der untersuchten Substanzen und an keinem der untersuchten Zelltypen toxische Effekte. Auch nach 10 Tagen Inkubation der organkultivierten Spenderhornhaute mit 7,5 µg/mL Axitinib, Pazopanib oder Sorafenib ergab sich kein Hinweis auf endotheliale Toxizitat. Schlussfolgerung: Alle 3 untersuchten Substanzen, Axitinib, Pazopanib und Sorafenib, zeigten an den untersuchten okularen Zellen eine gute Biokompatibilitat. Auch unter den Bedingungen von oxidativem Stress kam es bis zu einer Konzentration von 7,5 µg/mL zu keinerlei toxischen Effekten. Erst bei hoheren Konzentrationen kam es zu einer dosisabhangigen Abnahme der zellularen Vitalitat und zur Induktion von Zelltod. Diese Effekte waren bei Pazopanib, gefolgt von Sorafenib, starker ausgepragt als bei Axitinib.

Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery, leading to a loss of sight if untreated. Erlotinib might be of therapeutic interest as an effective target agent (selective EGF-tyrosin-kinase-1 inhibitor). In this in-vitro study, erlotinib was evaluated for ocular biocompatibility and its effect on cell proliferation, migration, 3D matrix contraction and spreading of human lens epithelial cells. To exclude toxic concentrations, erlotinib was assessed for its biocompatibility on five different human ocular cell types in vitro by the tetrazolium dye-reduction assay (MTT) and the Live–Dead assay. To determine its effect on human lens epithelial cell (HLE-B3) proliferation, the MTT test was performed after incubation with different concentrations of erlotinib. Chemotactic migration was analyzed with the Boyden chamber assay and chemokinetic migration was assessed by time lapse microscopy. Contraction was measured by a 3D collagen type 1 matrix contraction assay, and cell spreading was determined by measuring the cell diameter on a fibronectin coated surface. The maximum non-toxic concentration of erlotinib was determined to be 100 μM in cell culture. Erlotinib potently inhibits human lens epithelial cell proliferation, with an IC50 of about 10 μM (8.8 μM ± 0.9 μM SD; r 2 = 0.94). Chemotactic migration (p = 0.004) and chemokinetic migration (p = 0.001) were reduced significantly in a concentration-based manner. Erlotinib prevented human lens epithelial cells from matrix contraction (p = 0.001) and cell-spreading (p = 0.001). Erlotinib might become of clinical relevance for PCO prophylaxis in the future since it displayed good biocompatibility on ocular cells and mitigated human lens epithelial cell proliferation, migration, contraction, and spreading in vitro. Further studies are warranted to evaluate its potential for clinical application.

Hintergrund: Evaluierung des Fixationsverhaltens und der Fixationsstabilitat als mogliche Verlaufsparameter, zusatzlich zur Sehscharfe- und Netzhautdickenentwicklung, bei Patienten mit diabetischem Makulaodem (DMO) unter intravitrealer Ranibizumab-Therapie. Patienten und Methoden: Es wurden 30 Patienten (39 Augen) mit Fovea involvierendem DMO untersucht. Morphologische (zentrale Netzhautdicke gemessen mit der optischen Koharenztomografie, OCT) und funktionelle (Visus, Mikroperimetrie Fixationsverhalten und Fixationsstabilitat) Parameter wurden vor Therapiebeginn und nach dreimaliger monatlicher intravitrealer Ranibizumab-Therapie ausgewertet. Ergebnisse: Unter Ranibizumab-Therapie stieg der durchschnittliche bestkorrigierte Ausgangsvisus signifikant (p

Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization. FGF21 inhibited tumor necrosis α (TNF-α) expression but did not alter Vegfa expression in neovascular eyes. These data suggest that FGF21 may be a therapeutic target for pathologic vessel growth in patients with neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration.

Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma. This study evaluates anti-angiogenic properties of axitinib in an in-vitro model of choroidal neovascularizations in nAMD. Human endothelial cells (HUVEC) and human pericytes (hPC-PL) were treated with axitinib doses ranging from 1.0 ng/ml to 10 μg/ml. Cellular viability and proliferation were assessed with a modified MTT assay. VEGF- and PDGF-stimulated migration was observed in modified Boyden chambers. Formation of capillary structures was evaluated on Cultrex basement membrane. Proliferation was significantly inhibited in both cell lines in a dose-dependent manner. VEGF and PDGF significantly induced, whereas simultaneous axitinib normalized cellular migration in HUVEC and pericytes. On growth-factor-reduced Cultrex, VEGF induced the formation of capillary structures, while axitinib significantly reverted this effect. Axitinib reduced the amount of vessel associated tissue on full growth factor Cultrex. All effects on both cell lines were observed in non-toxic concentrations of axitinib. Axitinib inhibits angiogenesis in endothelial cells and pericytes via VEGFR and PDGFR modulation in vitro. Further studies are needed to elucidate whether axitinib may also improve therapy of CNV in AMD in vivo by interference with pericyte stabilization of pathological vessels.

The retina is part of the central nervous system and both the retina as well as the brain can suffer from severe damage after very preterm birth. Retinopathy of prematurity is one of the major causes of blindness in these children and brain neuronal impairments including cognitive defects, cerebral palsy and intraventricular hemorrhage (IVH) are also complications of very preterm birth. Insulin-like growth factor 1 (IGF-1) acts to promote proliferation, maturation, growth and survival of neural cells. Low levels of circulating IGF-1 are associated with ROP and defects in the IGF-1 gene are associated with CNS disorders including learning deficits and brain growth restriction. Treatment of preterm infants with recombinant IGF-1 may potentially prevent ROP and CNS disorders. This review compares the role of IGF-1 in ROP and CNS disorders. A recent phase 2 study showed a positive effect of IGF-1 on the severity of IVH but no effect on ROP. A phase 3 trial is planned.

Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). While ω-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both ω-3 and ω-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C ω-3 LCPUFA (and ω-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPARα-/-mice and augmented ω-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic ω-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPARα. Fenofibrate augmented the overall protective effects of ω-3 LCPUFAs on neovascular eye diseases., Graphical Abstract Image 1, Highlights • Fenofibrate inhibits retinal and choroidal neovascularization by inhibiting CYP2C activity as well as by activating PPARα. • Fenofibrate augments the protective effects of ω-3 LCPUFAs on pathological ocular angiogenesis. • Inhibition of CYP2C is a potential therapeutic approach for treatment of proliferative retinopathy and neovascular AMD. Findings from clinical trials indicate that fenofibrate reduces the progression of proliferative diabetic retinopathy, but the mechanism of this effect is currently unknown. Dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) is generally associated with a suppression of proliferative retinopathy and age-related macular degeneration acting through LCPUFA cyclooxygenase and lipoxygenase metabolites. However, cytochrome P450 epoxygenase (CYP)2C ω-3 and ω-6 LCPUFA metabolites promote retinopathy. Fenofibrate is a potent inhibitor of CYP2C. Our findings suggested that fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition. Combination therapy of dietary ω-3 LCPUFA supplementation with fenofibrate may be a promising approach to prevent incidence or progression of neovascular eye diseases.

Hintergrund Es erfolgte eine Evaluation der Zielgenauigkeit von navigierter Lasertherapie mit dem NAVILAS®-System bei diabetischem Makulaodem (DMO).

Purpose The prospective, comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema has shown advantage of a combination therapy compared to ranibizumab monotherapy at year 1 with significantly reduced injections. The purpose of this retrospective study was to determine the long-term visual gains and need of injections in a 3 year-follow-up period. Methods Retrospective analysis of patients of the original study in the long-term follow-up from month 12 to 36. BCVA measurements following the original 1 year study were taken using logMAR charts. Injections were provided with standard of care using PRN, based on change in BCVA and CRT using SD-OCT scans. Main outcome measures were change in BCVA and mean number of injections from 12 to 36 months. Results BCVA was stable in both groups from 12 through 36 months, showing a change of 0.16 +/- 0.1 log MAR. Following the initial reduction in required injections at month 12, combination therapy patients continued to require 1.3 times fewer injections over the next 24 months (2.91 +/- 2.3 vs 3.85 +/- 3.7 injections for monotherapy). Conclusions Combination of navigated laser and ranibizumab achieved BCVA gains equivalent to anti-VEGF monotherapy. These results could be maintained through month 36. Required injections were 2.0 injections lower in year 1 and further 1.3 times fewer in year 2 and 3 in the combination group compared to monotherapy. Adding navigated laser photocoagulation to intravitreal anti-VEGF therapy may still represent a superior therapeutic approach to DME patients.

Purpose: Indocyanine green (ICG) is a commonly used vital dye for macular surgery. Recent reports implicate that its use might be associated with less favourable results regarding postoperative visual outcome and damage of retinal cells, and atrophic degeneration of the retinal pigment epithelium (RPE) has been described. This study investigates the effects of ICG on light-induced senescence of RPE cells. Methods: Primary human RPE cells were either pre-incubated with ICG in concentrations of 0.005% and 0.05% or not and then exposed to white light. After 10 min of irradiation viability, induction of intracellular reactive oxygen species (ROS) and senescence-associated β-galactosidase activity (SA β-Gal) were determined. Expression and secretion of matrix metalloproteinases (MMPs) 1 and 3 and their mRNA were determined by RT-PCR and ELISA. Results: Light exposure decreased RPE cell viability by 46%. Treatment with 0.005% and 0.05% ICG alone decreased RPE cell viability by 7% and 21%. In addition, expression of ROS, SA β-Gal, and MMP-1 and 3 was significantly increased. When 0.005% and 0.05% ICG treatments were combined with light exposure, viability decreased by 69% and 82% compared to the untreated control. Effects on the expression of ROS, SA β-Gal, and MMP-1 and 3 were, depending on the ICG dose, significantly increased when cells were pre-incubated with ICG and then illuminated. Conclusion: In this study, pretreatment with ICG significantly increased light-induced oxidative stress and senescence. This might indicate a potential, supplementary mechanism that could explain RPE alterations and reduced functional results after ICG-assisted internal limiting membrane peeling.

Der Nachstar ist die haufigste Komplikation nach erfolgreicher Kataraktchirurgie. 10 Jahre nach Operation benotigen bis zu 42% der Patienten mit Acryllinsen und scharfer Kante eine Nd:YAG-Kapsulotomie. Akkomodative und multifokale Intraokularlinsen weisen zum Teil sogar noch hohere Nachstarraten auf. Eine pharmakologische Prophylaxe mit Alkylphosphocholinen (APC) konnte eine effektive Alternative darstellen. Als In-vitro-Modell diente die humane Linsenepithelzelllinie HLE-B3. Nach Inkubation mit APC in unterschiedlichen Konzentrationen (0,01; 0,1 und 1 mM) in Gegenwart von 5% Serum erfolgten der Trypanblau-Ausschlusstest und der Live/Dead-Test. Die Proliferation der Zellen wurde mit dem Tetrazoliumreduktionsassay bestimmt. Die Untersuchung der Anhaftung der Zellen wurde mittels mit Fibronektin und erstmals auch mit Laminin beschichteten Platten durchgefuhrt. APC konnen die Proliferation von humanen Linsenepithelzellen in Gegenwart von nur 5% Serum dosisabhangig hemmen. Die Proliferation wurde zu mehr als 60% durch APC-Konzentrationen von 0,1 µM inhibiert, ebenso wie auch die Anhaftung der Linsenepithelzellen um mindestens 50% in Gegenwart von 0,1 µM APC. APC hemmen die Proliferation und Anhaftung von humanen Linsenepithelzellen in-vitro. Die Substanz ist topisch applizierbar und eine intraoperative Anwendung zur pharmakologischen Nachstarprophylaxe mit APC grundsatzlich moglich.

PURPOSE: The purpose of this study was to investigate the biocompatibility of aniline and methyl blue in a well-established cell culture model and assess the staining properties of these dyes at the level of the internal limiting membrane (ILM) in human donor eyes. METHODS: Dye-related toxicity was evaluated by a colorimetric test (MTT) measuring the inhibition of retinal pigment epithelium (ARPE-19 and primary human retinal pigment epithelium) cell proliferation. Cell viability was also quantified based on a two-color fluorescence assay (Life-Dead Assay). Aniline blue and methyl blue at a concentration of 0.2% was applied over the macula during vitrectomy in human donor eyes to evaluate the staining properties at the level of the ILM. RESULTS: Both dyes and dye concentrations of 0.1% and 0.2% showed no toxic effect on ARPE-19 and primary human retinal pigment epithelium cell proliferation for exposure times of 1 and 10 minutes, respectively. Cell viability was also not affected at all. Both dyes provided a good contrast at the level of the ILM and allowed for a controlled removal of the ILM during surgery. No penetration into deeper retinal layers was noted. CONCLUSION: Our results indicate that aniline blue and methyl blue might be applicable for intraocular surgery, providing a very good biocompatibility and required selective staining characteristics at the level of the ILM.

BackgroundMoxifloxacin (Vigamox®), a 4th-generation fluoroquinolone, covers most isolates causing endophthalmitis. It is safe and effective for systemic and topical use; however, only very limited data are available on prophylactic intracameral administration to prevent endophthalmitis. This study investigated the safety of Vigamox® for intracameral application in a cell-culture model.MethodsThe endothelial toxicity of moxifloxacin (Vigamox®) was evaluated in cultured human corneas. Primary human retinal pigment epithelium cells (RPEs), trabecular meshwork cells (TMCs), lens epithelium cells (LECs), and corneal endothelial cells (CECs) were treated with concentrations of Vigamox. Toxic effects were evaluated after 24 h (MTT assay and live-dead assay). By treating TMC, CEC, and RPE cells either with oxidative stress or tumor necrosis factor-alpha (TNF-a), lipopolysaccharide (LPS), and interleukin-6 (IL-6), the effects of moxifloxacin on cellular viability under conditions of inflammation were investigated.ResultsNo corneal endothelial toxicity could be detected after 30 days of treatment with moxifloxacin 500 μg/ml. Primary RPEs, TMCs, LECs, and CECs showed adverse effects on proliferation and viability only at concentrations higher than 150 μg/ml moxifloxacin. After preincubation with TNF-a, LPS, and IL-6 for 24 h and subsequent treatment with moxifloxacin at concentrations of 10-150 μg/ml for 24 h, no significant decrease in proliferation or viability was observed. H 2 O 2 exposure did not increase cellular toxicityConclusionVigamox® did not show significant toxicity on primary RPEs, TMCs, LECs, CECs, or human corneal endothelium at concentrations up to 150 μg/ml. The MIC90 of moxifloxacin for pathogens commonly encountered in endophthalmitis is known to be in the range of 0.25-2.5 μg/ml. Therefore, intracameral use of Vigamox® at concentrations up to 150 μg/ml may be safe and effective for preventing endophthalmitis after intraocular surgery.

Purpose To compare the possible protective effects of the ultraviolet (UV)-filtering and blue light–filtering SN60AT intraocular lens (IOL) and the untinted UV-filtering SA60AT IOL with regard to light-induced stress on human retinal pigment epithelium (RPE). Setting Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. Methods Primary human RPE cells were exposed to white light, and a tinted or untinted IOL was placed in the light beam. After 15 to 60 minutes of irradiation, cell viability was determined by a colorimetric test (tetrazolium dye-reduction assay) and a microscopic live/dead assay. The expression of vascular endothelial growth factor-α (VEGF-α), Bax, and Bcl-2 and their mRNA was determined by reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. Results Without an IOL, white-light exposure decreased cell viability compared with the decrease with the nonirradiated control in a time-dependent manner. Light-induced cell death was significantly reduced by both the tinted IOL and untinted IOL. The combined UV and blue-light filtering attenuated light-induced cell damage significantly more than UV filtering alone. Results of RT-PCR and Western blotting showed a significant time-dependent decrease in Bcl-2 and increase in Bax and VEGF-α that were significantly less with the tinted IOL than with the untinted IOL. Conclusions Both IOLs reduced light-induced RPE damage. The UV- and blue light–filtering IOL reduced damage more than the conventional IOL. This supports the hypothesis that blue light–filtering IOLs may prevent retinal damage in clinical use.

Purpose: To assess the impact of laminin and collagen IV on the proliferation of human lens epithelial cells (LECs) and the performance of two hydrophilic and one hydrophilic IOL with a hydrophobic surface coated with erufosine on their properties to inhibit LEC proliferation and migration in a well-established in vitro anterior chamber model of PCO. Setting: Research Laboratory for Experimental Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. Design: Experimental study. Methods: Three IOLs were selected after pre-evaluation for their properties to inhibit LEC proliferation in vitro. All three IOLs were then coated with erufosine while uncoated IOLs of the same type and lot served as controls. Twelve well cell culture inserts were coated with either laminin or collagen IV and erufosine coated or uncoated IOLs were placed on these inserts into the wells. The wells were inserted into 12 well plates and kept under standard cell culture conditions for 6 days. After removal of the IOLs, the cell culture inserts were analyzed for LEC proliferation and migration. Conclusions: Collagen IV has a stronger impact on LEC proliferation in vitro than laminin has. All tested erufosine coated IOLs were able to significantly decrease the formation of PCO in an in vitro anterior chamber model.

This study indicates that in addition to the significant improvement in visual acuity and reduction of central retinal thickness in patients with center-involving diabetic macular edema, intravitreal anti-VEGF treatment with Ranibizumab may also lead to a significant stabilization or even improvement of diabetic retinopathy.

OBJECTIVE: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME). RESEARCH DESIGN AND METHODS: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12. RESULTS: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p

The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.

Aljoscha S Neubauer,1,* Julian Langer,1,* Raffael Liegl,1 Christos Haritoglou,1 Armin Wolf,1 Igor Kozak,2 Florian Seidensticker,1 Michael Ulbig,1 William R Freeman,2 Anselm Kampik,1 Marcus Kernt,1 1Ludwig-Maximilians University, Department of Ophthalmology, Munich, Germany; 2Jacobs Retina Center, University of California San Diego, La Jolla, CA, USA*These authors contributed equally to this workBackground: The purpose of this study was to evaluate and compare clinical outcomes and retreatment rates using navigated macular laser versus conventional laser for the treatment of diabetic macular edema (DME).Methods: In this prospective, interventional pilot study, 46 eyes from 46 consecutive patients with DME were allocated to receive macular laser photocoagulation using navigated laser. Best corrected visual acuity and retreatment rate were evaluated for up to 12 months after treatment. The control group was drawn based on chart review of 119 patients treated by conventional laser at the same institutions during the same time period. Propensity score matching was performed with Stata, based on the nearest-neighbor method.Results: Propensity score matching for age, gender, baseline visual acuity, and number of laser spots yielded 28 matched patients for the control group. Visual acuity after navigated macular laser improved from a mean 0.48 ± 0.37 logMAR by a mean +2.9 letters after 3 months, while the control group showed a mean −4.0 letters (P = 0.03). After 6 months, navigated laser maintained a mean visual gain of +3.3 letters, and the conventional laser group showed a slower mean increase to +1.9 letters versus baseline. Using Kaplan-Meier analysis, the laser retreatment rate showed separation of the survival curves after 2 months, with fewer retreatments in the navigated group than in the conventional laser group during the first 8 months (18% versus 31%, respectively, P = 0.02).Conclusion: The short-term results of this pilot study suggest that navigated macular photocoagulation is an effective technique and could be considered as a valid alternative to conventional slit-lamp laser for DME when focal laser photocoagulation is indicated. The observed lower retreatment rates with navigated retinal laser therapy in the first 8 months suggest a more durable treatment effect.Keywords: navigated focal laser, macular laser, Navilas®, diabetic macular edema, diabetes mellitus, diabetic retinopathy

More than 450,000 babies are born prematurely in the USA every year. The improved survival of even the most vulnerable low body weight preterm infants has, despite improving health outcomes, led to the resurgence in preterm complications including one of the major causes for blindness in children, retinopathy of prematurity (ROP). The current mainstay in ROP therapy is laser photocoagulation and the injection of vascular endothelial growth factor (VEGF) antibodies in the late stages of the disease after the onset of neovascularization. Both are proven options for ophthalmologists to treat the severe forms of late ROP. However, laser photocoagulation destroys major parts of the retina, and the injection of VEGF antibodies, although rather simple to administer, may cause a systemic suppression of normal vascularization, which has not been studied in sufficient depth. However, the use of neither VEGF antibody nor laser treatment prevents ROP, which should be the long-term goal. It should be possible to prevent ROP by more closely mimicking the intrauterine environment after preterm birth. Such preventive measures include preventing the toxic postbirth influences (eg, oxygen excess) as well as providing the missing intrauterine factors (eg, insulin growth factor 1) and are likely to also reduce other complications of premature birth as well as ROP. This review is meant to summarize the current knowledge on the prevention of ROP with a particular emphasize on the use of insulin growth factor 1 supplementation.