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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Marcus Kernt*, Raoul E Cheuteu*, Sarah Cserhati, Florian Seidensticker, Raffael G Liegl, Julian Lang, Christos Haritoglou, Anselm Kampik, Michael W Ulbig, Aljoscha S Neubauer Department of Ophthalmology, Ludwig Maximilian University of Munich, Germany*These authors contributed equally to this studyAim: To investigate treatment-related pain and the accuracy of navigated laser photocoagulation in the treatment of clinically significant macular edema.Methods: Focal laser treatment of diabetic macular edema in 54 consecutive patients was digitally planned on fundus images and performed using the navigated laser photocoagulation system Navilas® (OD-OS GmbH, Teltow, Germany). Treatment-related pain was quantified on a visual analog scale directly after treatment and compared with a matched control group who received conventional laser treatment (n = 46). In addition, for Navilas-treated patients, the accuracy of spot placement on color images was analyzed 1 month after treatment.Results: In total, 5423 laser spots (mean 100 per eye) were analyzed. With navigated treatment, 90% of laser spots were visible on color images, of which 96% were within 100 µm from the target. Eighty percent of the laser spots were placed and visible within the 100 µm target on an intention-to-treat basis for color imaging. Optical coherence topography confirmed that laser effects were limited to the outer retina. Treatment-related pain following navigated laser photocoagulation was significantly lower than that of conventional laser treatment (1.6 vs 4.4 on a visual analog scale, P < 0.001).Conclusion: Navigated laser effects could be visualized to a high percentage on post-treatment color images, and their location showed a high concordance to targeted areas. Patients reported that treatment-related pain following Navilas laser photocoagulation was significantly lower than pain following conventional laser treatment.Keywords: diabetic retinopathy, navigated laser therapy, pattern laser, diabetes

Background Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor is the main target of current antiangiogenic treatment strategies in AMD. However, other growth factors, such as platelet-derived growth factor (PDGF) and placenta growth factor (PlGF), have a substantial impact on development of AMD. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on lightinduced overexpression of growth factors in human retinal pigment epithelial (RPE) cells. Methods Primary human RPE cells were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reactions, immunohistochemistry and enzyme-linked immunosorbent assays. Results Light exposure decreased cell viability and increased expression and secretion of VEGF-A, PDGF-BB and PlGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 mg/ml. Conclusion The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.