[Corneal wound healing-Pharmacological treatment]. / Wundheilung der Kornea ­ Pharmakologische Therapie.

Physiological wound healing of the cornea is a complex process and involves numerous multifactorial tissue processes. A proper wound healing, especially without the formation of light-scattering scars, is essential to preserve the integrity and function of the cornea. Misdirected wound healing is of vast clinical relevance as it can lead to corneal fibrosis and the loss of optical transparency with subsequent reduction of visual acuity, up to blindness. In addition to the understanding of the pathophysiological mechanisms, the knowledge of therapeutic concepts and options for treating corneal wound healing disorders and fibrosis is essential to counteract a permanent damage of the cornea as early as possible. Nowadays, various pharmacological and surgical options are available for treatment. The decision, appropriate selection and indication for the optimal treatment depend primarily on the genesis and clinical appearance of the corneal wound, fibrosis or scar. The treatment of wound healing disorders ranges from the use of topical therapy and supportive measures up to tissue replacement procedures. As long as the mechanical stability of the cornea is intact and wound healing processes are still ongoing, a pharmacological modulation is reasonable, which is discussed in this article.

PREVALENCE OF SARS-CoV-2 RNA AND ANTIBODY DETECTION, AND VACCINATION STATUS IN PATIENTS WITH OCULAR VASCULAR OCCLUSION.

PURPOSE: To analyze the annual prevalence of ocular vascular occlusion in relation to COVID-19 infection and vaccination status in a prospective study. METHODS: All patients were examined for an active severe acute respiratory syndrome coronavirus 2 infection by RNA detection and for a previous infection by virus-specific antibody detection, and their vaccination status was documented. Data from pandemic year 2020 and previous years, before COVID-19 (2019, 2018, 2017), were retrospectively analyzed. RESULTS: In 2021, a total of 103 patients with the first diagnosis of ocular vascular occlusion were treated. Most frequent subdiagnoses were central retinal vein occlusion (20.4%), nonarteritic anterior ischemic optic neuropathy (18.4%), central retinal artery occlusion (13.6%), and branch retinal artery occlusion (12.6%). Thereof, only three patients (2.9%) presented with virus-specific severe acute respiratory syndrome coronavirus 2 antibodies, and none was PCR positive. Patients with preceded severe acute respiratory syndrome coronavirus 2 vaccination (59.2%) presented with comparable characteristics as unvaccinated patients with vascular occlusion regarding age, gender distribution, systemic risk factors, duration of symptoms, visual acuity, and the present subdiagnoses ( P > 0.05). The total number of cases in 2021 (103 cases) was comparable with the pandemic year 2020, at which no vaccination was available (114 cases), and to earlier years 2017, 2018, and 2019 without COVID-19 pandemic (100, 120, and 119 cases). Furthermore, we did not reveal any differences between pandemic and reference years regarding patients' characteristics ( P > 0.05). CONCLUSION: Our study did not reveal an increased annual prevalence of ocular vascular occlusions during COVID-19 pandemic years 2020 and 2021. Patients with previous COVID-19 vaccination did not present differences regarding the risk profile nor symptoms, compared with unvaccinated individuals.

Retinal and Choroidal Ultra-Widefield OCT - Technology, Insights, and Clinical Relevance. / Retinale und choroidale Ultra-Weitwinkel-OCT ­ Technologie, Einblicke und klinische Bedeutung.

As one of the most state-of-the-art procedures for retinal and choroidal imaging, ultra-widefield optical coherence tomography (UWF-OCT) offers significant gains in terms of information pertaining to peripheral retinal lesions and their differential diagnoses. In particular, it enables the presence of minimal accumulations of subretinal fluid to be assessed in detail and then documented. It also enables choroidal expansion of choroidal lesions to be precisely measured. Similar to conventional OCT, its only limitations relate to patient compliance and opacities of the ocular media. While the pupil width is somewhat less important here, the quality of the images is nevertheless better with the patient under medication-induced mydriasis. Used in combination with UWF fundus photography, UWF-OCT is a helpful tool for assessing and monitoring peripheral retinal and choroidal lesions.

DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber's hereditary optic neuropathy and optic atrophy.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) has been considered a prototypical mitochondriopathy and a textbook example for maternal inheritance linked to certain disease-causing variants in the mitochondrial genome. Recently, an autosomal recessive form of LHON (arLHON) has been described, caused by disease-causing variants in the nuclear encoded gene DNAJC30. METHODS AND RESULTS: In this study, we screened the DNAJC30 gene in a large Central European cohort of patients with a clinical diagnosis of LHON or other autosomal inherited optic atrophies (OA). We identified likely pathogenic variants in 35/1202 patients, corresponding to a detection rate of 2.9%. The previously described missense variant c.152A>G;p.(Tyr51Cys) accounts for 90% of disease-associated alleles in our cohort and we confirmed a strong founder effect. Furthermore, we identified two novel pathogenic variants in DNAJC30: the nonsense variant c.610G>T;p.(Glu204*) and the in-frame deletion c.230_232del;p.(His77del). Clinical investigation of the patients with arLHON revealed a younger age of onset, a more frequent bilateral onset and an increased clinically relevant recovery compared with LHON associated with disease-causing variants in the mitochondrial DNA. CONCLUSION: This study expands previous findings on arLHON and emphasises the importance of DNAJC30 in the genetic diagnostics of LHON and OA in European patients.

[Corneal wound healing-Pathophysiology and principles]. / Wundheilung der Kornea ­ Pathophysiologie und Grundlagen.

The cornea forms the anterior border of the eye and significantly contributes to a sharp optical image quality on the retina through its transparency, avascular nature and curvature. Because of its anatomical structure and as a barrier to the environment, the cornea is particularly exposed to various external factors, such as injuries and pathogens. A correct wound healing without the formation of light diverging scarring is therefore essential to preserve the integrity and function of the cornea. Misguided wound healing is of outstanding clinical relevance and can lead to corneal fibrogenesis. Corneal fibrosis results in scarring with a loss of optical transparency, which significantly reduces eyesight and can lead to blindness. Understanding the pathophysiological mechanisms of wound healing and fibrogenesis is of great importance for the diagnostics, treatment and evaluation of the subsequent healing process in order to prevent permanent damage as far as possible.

L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes.

Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK). We determined TRPV1-induced intracellular calcium transients using fluorescence calcium imaging, channel currents by planar patch-clamping, and cell migration by scratch assay for wound healing. The potential L-carnitine effect on TRPV1-induced myofibroblast transdifferentiation was evaluated by immunocytochemical detection of alpha smooth muscle actin. RT-PCR analysis confirmed TRPV1 mRNA expression in HCK. L-carnitine (1 mmol/l) inhibited either capsaicin (CAP) (10 µmol/l), hypertonic stress (450 mOsmol/l), or thermal increase (>43 °C) induced Ca2+ transients and corresponding increases in TRPV1-induced inward and outward whole-cell currents. This was accompanied by suppression of injury-induced increases in myofibroblast transdifferentiation and cell migration. In conclusion, L-carnitine contributes to inhibit stromal scarring through suppressing an injury-induced intrinsic TRPV1 activity that is linked with induction of myofibroblast transdifferentiation in HCK cells.

Recovery of Contrast Sensitivity After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charité-Universitätsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively. RESULTS: Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 µm, after 12 months 527 ± 29 µm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006). CONCLUSIONS: Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities.

Comparison of two extended depth of focus intraocular lenses with a monofocal lens: a multi-centre randomised trial.

PURPOSE: The AT LARA 829MP is a next-generation extended depth of focus (EDOF) intraocular lens (IOL) providing continuous vision over a range of distances. The aim of this prospective multi-centre randomised trial was to compare two EDOF IOLs and one monofocal IOL. METHODS: Cataract patients between 50 and 80 years were randomised for bilateral implantation with either the AT LARA 829MP (EDOF), the TECNIS Symfony (EDOF) or the CT ASPHINA 409MP (monofocal). Follow-up was at 1 to 2 weeks, 1 month and 4 to 6 months. RESULTS: A total of 211 patients were randomised and included in the final analysis. Monocular depth of focus was significantly better for AT LARA 829MP eyes compared with that for TECNIS Symfony at all thresholds (p = 0.024, 0.001 and 0.006, for 0.1, 0.2 and 0.3 logMAR respectively) with no significant difference for binocular depth of focus. LARA eyes had significantly better monocular depth of focus at all levels compared with ASPHINA eyes (all p < 0.0001), while there was no significant difference between Symfony and ASPHINA eyes at 0.1 logMAR and 0.2 logMAR. Both EDOF IOLs were significantly better than the monofocal ASPHINA at all levels for binocular depth of focus (LARA: all p < 0.0001; Symfony: all p = 0.002). Distance visual acuity was similar for all IOLs at 6 months; intermediate and near visual acuity were significantly better for the EDOF IOLs than for the monofocal (p < 0.0001). Refraction improved in all groups relative to baseline. Contrast sensitivity was higher with the CT ASPHINA 409MP but both EDOF lenses had a better spectacle independence rate. At 6 months, all IOLs were well centred with no cases of tilt. No general safety issues were raised for any of the groups. CONCLUSION: The two EDOF intraocular lenses investigated provided good visual outcomes with comparable visual acuity at all distances. The AT LARA 829MP provided the widest monocular depth of focus at 0.1 and 0.2 logMAR, with a clear superiority compared with the monofocal IOL. TECNIS Symfony was superior to the monofocal control at 0.3 logMAR. Spectacle independence and patient satisfaction were comparable. TRIAL REGISTRATION: Trial registered on https://clinicaltrials.gov/ under the identification NCT03172351 (date of registration 1 June May 2017).

Dexamethasone Intraocular Suspension: A Long-Acting Therapeutic for Treating Inflammation Associated with Cataract Surgery.

Cataract surgery is the most commonly performed surgical procedure worldwide. Despite the availability of new technologies and enhanced surgical techniques, inflammation-related complications after even uneventful cataract procedures remain the most common cause of poor visual outcomes. In this review article, we discuss the recent development of an intraocular steroid-based suspension and its use in cataract surgery. A PubMed literature search was conducted through December 2018 using the terms "cataract surgery," "dexamethasone," "inflammation," "treatment," and "prevention." The search was supplemented with the results of clinical trials registered at ClinicalTrials.gov; outcomes from both experimental and clinical research were included. Because dexamethasone interferes at multiple steps of the inflammatory cascade, this application seems to be an interesting option in the prevention of postsurgical inflammation. A single drug deposit into the anterior chamber might be an attractive alternative to frequent drop installations. In addition, dexamethasone intravitreal inserts are an option in high-risk individuals-in particular, in those with preexistent macula edema. Nevertheless, a careful evaluation of the agents is required, because the present state of knowledge is based on only a few registered trials. Control of postoperative inflammation is one of the key factors in achieving satisfactory outcomes in cataract surgery. As the introduction of intracameral antibiotics has brought benefits to cataract surgery, dexamethasone intraocular suspension for anterior chamber steroid placement might assist in improving surgical outcomes. This could particularly refer to patients with a higher risk of postsurgical inflammation, especially in eyes with diabetic retinopathy or uveitis.

Systemic Rho-kinase inhibition using fasudil in mice with oxygen-induced retinopathy.

PURPOSE: To investigate the influence of the selective Rho-kinase (ROCK) inhibitor, fasudil, on the mRNA level of proinflammatory factors and the retinal vascular development in mice with oxygen-induced retinopathy (OIR). METHODS: C57BL/6J mice underwent standard protocol for OIR induction from postnatal days 7 to 12. Subsequently, they received a daily intraperitoneal injection of fasudil or sodium chloride from P12 to P16. Analyses were performed using vascular staining on retinal flat mounts, RNA expression by qPCR, and immunohistochemistry on paraffin sections. RESULTS: On retinal flat mounts, the proportion of avascular area and tuft formation did not differ between the fasudil and NaCl group. Immunohistochemical staining revealed a less intense staining with inflammatory markers after fasudil. Nevertheless, there were no differences on RNA level between the two groups. CONCLUSIONS: In conclusion, our findings support that daily systemic application of fasudil does not decrease retinal neovascularization in rodents with oxygen-induced retinopathy. The results of our study together with the controversial results on the effects of different ROCK inhibitors from the literature makes it apparent that effects of ROCK inhibition are more complex, and further studies are necessary to analyze its potential therapeutic effects.

Predictive Factors for Clinical Outcomes after Primary Descemet's Membrane Endothelial Keratoplasty for Fuchs' Endothelial Dystrophy.

PURPOSE: The purpose of this study is to identify predictors for the best-corrected visual acuity (BCVA), central corneal thickness (CCT), and the endothelial cell density (ECD) after primary Descemet's membrane endothelial keratoplasty (DMEK). METHODS: In a prospective observational study, 108 eyes with Fuchs' endothelial dystrophy underwent a primary DMEK. Preoperative data, histologic parameters from host's Descemet's membrane, and follow-up data of the first eye were analyzed in regard to BCVA, CCT, and ECD, 12 months after surgery. RESULTS: Overall, 12 months postoperative, the BCVA improved to 0.11 ± 0.11 logMAR, the CCT declined to 529 ± 42 µm, and the ECD measured 1675 ± 418 cells/mm2. A significant influence of the preoperative CCT on postoperative BCVAs and CCTs was observed (r = 0.299, p = 0.014 and r = 0.507, p < 0.001, respectively). Especially eyes with a CCT <625 µm demonstrated a better BCVA (0.05 ± 0.07 logMAR) than eyes with a CCT ≥625 µm (0.13 ± 0.11 logMAR, p = 0.002). Furthermore, the identification of eyes with an early visual restitution was possible by considering follow-up data of the first eye. A preoperative CCT ≥625 µm was also sensitive to identify eyes with a persistent corneal swelling. The anterior banded layer thickness, which was obtained histologically, correlated to the preoperative CCT and the frequency of graft detachments (r = 0.601, p = 0.023 and r = 0.652, p = 0.041, respectively). Furthermore, a graft's baseline ECD ≤2100 cells/mm2 was found to be a risk factor for an ECD deterioration under 1000 cells/mm2 (1.8% vs. 15.8%, p = 0.020). CONCLUSIONS: Simple clinical parameters, such as the preoperative CCT, the course of visual restitution of the first eye, and the graft's baseline ECD, are efficient predictors for relevant outcome parameters after DMEK and therefore may be used for stratification. Furthermore, our findings indicate that a DMEK should be performed in eyes with Fuchs' endothelial corneal dystrophy, if possible, before the CCT exceeds 625 µm to maintain good clinical results.

Vascular Endothelial Growth Factor (VEGF) Induced Downstream Responses to Transient Receptor Potential Vanilloid 1 (TRPV1) and 3-Iodothyronamine (3-T1AM) in Human Corneal Keratocytes.

This study was undertaken to determine if crosstalk among the transient receptor potential (TRP) melastatin 8 (TRPM8), TRP vanilloid 1 (TRPV1), and vascular endothelial growth factor (VEGF) receptor triad modulates VEGF-induced Ca2+ signaling in human corneal keratocytes. Using RT-PCR, qPCR and immunohistochemistry, we determined TRPV1 and TRPM8 gene and protein coexpression in a human corneal keratocyte cell line (HCK) and human corneal cross sections. Fluorescence Ca2+ imaging using both a photomultiplier and a single cell digital imaging system as well as planar patch-clamping measured relative intracellular Ca2+ levels and underlying whole-cell currents. The TRPV1 agonist capsaicin increased both intracellular Ca2+ levels and whole-cell currents, while the antagonist capsazepine (CPZ) inhibited them. VEGF-induced Ca2+ transients and rises in whole-cell currents were suppressed by CPZ, whereas a selective TRPM8 antagonist, AMTB, increased VEGF signaling. In contrast, an endogenous thyroid hormone-derived metabolite 3-Iodothyronamine (3-T1AM) suppressed increases in the VEGF-induced current. The TRPM8 agonist menthol increased the currents, while AMTB suppressed this response. The VEGF-induced increases in Ca2+ influx and their underlying ionic currents stem from crosstalk between VEGFR and TRPV1, which can be impeded by 3-T1AM-induced TRPM8 activation. Such suppression in turn blocks VEGF-induced TRPV1 activation. Therefore, crosstalk between TRPM8 and TRPV1 inhibits VEGFR-induced activation of TRPV1.

Primary Descemet's Membrane Endothelial Keratoplasty for Fuchs Endothelial Dystrophy versus Bullous Keratopathy: Histopathology and Clinical Results.

PURPOSE: To investigate functional and anatomical results up to 12 months after Descemet's membrane endothelial keratoplasty (DMEK) for Fuchs' endothelial dystrophy (FED) versus bullous keratopathy (BK) in consideration of morphologic characteristics on host's endothelium-Descemet's membranes (EDM). METHODS: In a prospective consecutive case series, 119 eyes underwent a primary DMEK for FED or BK. Intraoperatively obtained EDM were investigated immunohistologically. Clinical and morphological parameters were compared between FED and BK. RESULTS: Overall, the 12-months best-corrected visual acuity (BCVA) was 0.14 logMAR, and 0.10 logMAR in eyes without vision-limiting comorbidities; thereby no differences were revealed between eyes with FED and BK up to 12 months postoperative (p = 0.186 and p = 0.095, respectively). Correspondingly, the mean central corneal thickness (CCT) measured 520 vs. 529 µm and the mean endothelial cell density (ECD) was 1743 vs. 1457 cells/mm2 for FED and BK, 12 months postoperative. Regarding CCT and ECD, no differences were observed between the groups (p = 0.181 and p = 0.112, respectively). The overall detachment rate was 40% (48/119). Comparing FED and BK the detachment rates did not differ, which were 41% vs. 39% and 43% vs. 35%, in pseudophakic eyes (p = 0.554 and p = 0.601, respectively). Yet, the distribution of recurring graft detachments differed between FED and BK; secondary re-detachments were more frequent in the FED group (7 cases). Regarding histologic investigations, a lower ECD was found in specimens with BK, no differences were revealed for EDM and anterior banded layer thicknesses. Immunohistologically, differences in the distribution of fibronectin and cytokeratin were observed. A rarification of matrix proteins was found in EDM complexes with FED. CONCLUSIONS: DMEK produces similar results for FED and BK. However, the postoperative course may differ with regard to the recurrence of secondary graft detachments that may be associated by histopathologic particularities.

Photochemical degradation of trypan blue.

PURPOSE: To investigate the photochemical degradation of trypan blue (TB) and to identify decomposition products. METHODS: Defined solution samples of TB and a mixture with lutein/zeaxanthin were exposed to blue light. Thermal degradation processes were ruled out using controls not subjected to irradiation. All samples were analyzed using optical microscopy, UV/Vis spectroscopy, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR) spectrometry. Degradation kinetics were determined based on changes in absorbance; intermediates were identified by analyzing mass differences of characteristic fragment ion peaks within the fragmentation patterns, and assignments were verified by NMR. RESULTS: TB demonstrated a photochemical degradation, which can be triggered by lutein/zeaxanthin. Intermediates vary depending on the presence of lutein/zeaxanthin. The self-sensitized photodegradation of TB occurs under generation of dimethyl sulfate and presumed formation of phenol. In contrast, within the presence of lutein/zeaxanthin the decomposition of TB indicates the formation of methoxyamine and sulfonyl arin. Thermal degradation processes were not observed. CONCLUSIONS: TB demonstrated a photodegradation that may be triggered by lutein/zeaxanthin and results in the formation of cytotoxic decomposition products. Our findings contribute to understand degradation mechanisms of TB and may elucidate previous clinical and experimental observations of cellular toxicity after TB application.

Clinical outcome and higher order aberrations after bilateral implantation of an extended depth of focus intraocular lens.

PURPOSE: The purpose of this study was to assess the clinical outcome after a bilateral implantation of an extended depth of focus intraocular lens in comparison to a monofocal intraocular lens. SETTING: Department of Ophthalmology, Charité-Medical University Berlin, Germany. PATIENTS AND METHODS: A total of 60 eyes of 30 patients were enrolled in this prospective, single-center study. The cataract patients underwent phacoemulsification with bilateral implantation of a TECNIS® Symfony (Abbott Medical Optics, Santa Ana, CA, USA, 15 patients) or a TECNIS Monofocal ZCB00 (Abbott Medical Optics, Santa Ana, CA, USA, 15 patients). Postoperative evaluations were performed after 1 and 3 months, including visual acuities at far, intermediate, and near distance. Mesopic, scotopic vision, and contrast sensitivity were investigated. Aberrometry was performed using an iTrace aberrometer with a pupil scan size of 5.0 mm. RESULTS: After 3 months, the TECNIS Symfony group reached an uncorrected visual acuity at far distance of -0.02 logMAR compared to -0.06 logMAR in the TECNIS Monofocal group ( p = 0.03). Regarding the uncorrected vision at intermediate and near distance the following values were obtained: intermediate visual acuity -0.13 versus 0.0 logMAR (TECNIS Symfony vs TECNIS Monofocal, p = 0.001) and near visual acuity 0.11 versus 0.26 logMAR (TECNIS Symfony vs TECNIS Monofocal, p = 0.001). Low-contrast visual acuities were 0.27 versus 0.20 logMar (TECNIS Symfony vs TECNIS Monofocal, p = 0.023). CONCLUSION: The TECNIS Symfony intraocular lens can be considered an appropriate alternative to multifocal intraocular lenses because of good visual results at far, intermediate, and near distance as well as in low-contrast vision.

Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b-HSVTK mouse model.

PURPOSE: To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b-HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells. METHODS: We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b-HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14. RESULTS: The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2 ) and peripheral retina (53 ± 20.6 cells/mm2 ); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2 , p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups. CONCLUSION: The CD11b-HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected.

Spatial distribution of CD115+ and CD11b+ cells and their temporal activation during oxygen-induced retinopathy in mice.

PURPOSE: The model of oxygen-induced retinopathy (OIR) is widely used to analyze pathomechanisms in retinal neovascularization. Previous studies have shown that macrophages (MP) play a key role in vessel formation in OIR, the influence of microglia (MG) having been discussed. The aim of our study was to analyze the spatial and temporal distribution and activation of MP/MG expressing CD115 and CD11b during the process of neovascularization in OIR. METHODS: We used MacGreen mice expressing the green fluorescence protein (GFP) under the promoter for CD115. CD115+ cells were investigated in vivo by scanning laser ophthalmoscopy at postnatal days (P) 17 and 21 in MacGreen mice with OIR (75% oxygen from P7 to P12), and were compared to MacGreen room-air controls. In addition MP/MG were examined ex vivo using immunohistochemistry for CD11b+ detection on retinal flatmounts at P14, P17, and P21 of wild type mice with OIR. RESULTS: In-vivo imaging revealed the highest density of activated MP/MG in tuft areas at P17 of MacGreen mice with OIR. Tufts and regions with a high density of CD115+ cells were detected close to veins, rather to arteries. In peripheral, fully vascularized areas, the distribution of CD115+ cells in MacGreen mice with OIR was similar to MacGreen room-air controls. Correspondingly, immunohistochemical analyses of retinal flatmounts from wild type mice with OIR induction revealed that the number of CD11b+ cells significantly varies between vascular, avascular, and tuft areas as well as between the retinal layers. Activated CD11b+ cells were almost exclusively found in avascular areas and tufts of wild type mice with OIR induction; here, the proportion of activated cells related to the total number of CD11b+ cells remained stable over the course of time. CONCLUSIONS: Using two different approaches to monitor MP/MG cells, our findings demonstrated that MP/MG concentrate within pathologically vascularized areas during OIR. We were able to clarify that reactive changes of CD11b+ cell distribution to OIR primarily occur in the deep retinal layers. Furthermore, we found the highest proportion of activated CD11b+ cells in regions with pathologic neovascularization processes. Our findings support previous reports about activated MP/MG guiding revascularization in avascular areas and playing a key role in the formation and regression of neovascular tufts.

Corneal higher-order aberrations after phacoemulsification: a comparison of 3 different incision sizes.

PURPOSE: To analyze the impact of different incision sizes for phacoemulsification on corneal higher-order aberrations (HOA). METHODS: Patients seeking cataract surgery were randomly assigned to one of the following groups: 1.4 mm with biaxial microincision phacoemulsification (25 eyes), 1.8 mm with coaxial phacoemulsification (27 eyes), and 2.2 mm with coaxial phacoemulsification (62 eyes). Inclusion criteria were a minimum age of 18 years and uncomplicated cataract. Exclusion criteria were history of ocular trauma or intraocular surgery, any sign of inflammation or infection, pseudoexfoliation syndrome, glaucoma, optic atrophy, diabetic retinopathy, lens dislocation, cataracta intumescens, cataracta matura, and corneal diseases. Patients underwent phacoemulsification with implantation of an intraocular lens. Aberrometry was performed using an iTrace aberrometer with a pupil scan size of 5.0 mm preoperatively and at postoperative follow-up visits after 1 month. The paired sample t test and analysis of covariance were used for statistical analysis. RESULTS: Ninety patients (114 eyes) were enrolled (mean age 73.7 ± 8.9 years). In all groups, an increase of total HOAs could be measured. The strongest increase was seen in the 2.2 mm group (mean difference 0.031 [95% confidence interval (CI) 0.006-0.056], p = 0.014) and in the 1.4 mm group (mean difference 0.035 [95% CI -0.007 to 0078], p = 0.097). No important difference was found in the 1.8 mm group. CONCLUSIONS: The 2.2 mm and the 1.4 mm incisions seem to have a higher impact on corneal HOAs in comparison to the 1.8 mm incision.

Progressive idiopathic tractional corectopia with iris thinning.

A 2-month-old boy presented with an irregular left pupil. Over the course of 3 months, progressive pupil ovalization, corectopia, and ballooning of the thinned superior iris tissue caused obstruction of the visual axis. Because of concern for deprivational amblyopia, a sectoral pupilloplasty and sphincterotomies were performed, restoring pupil shape and clearing the visual axis. On postoperative examinations, the pupil remained round, the visual axis clear, and visual acuity of the left eye improved. Findings and clinical course suggested the diagnosis of idiopathic tractional corectopia, a rare congenital disorder of unknown cause that may lead to isolated unilateral progressive corectopia and visual axis obstruction. Patients should receive regular follow-up examinations.

PREDICTORS OF TREATMENT RESPONSE OF VASOPROLIFERATIVE RETINAL TUMORS TO RUTHENIUM-106 BRACHYTHERAPY.

PURPOSE: To identify predictors of treatment response by evaluating long-term outcomes of vasoproliferative retinal tumors after ruthenium-106 brachytherapy. METHODS: In a retrospective case series, 39 eyes of 38 patients with vasoproliferative retinal tumors received ruthenium-106 brachytherapy between 2001 and 2013. Baseline clinical and morphologic parameters were analyzed regarding posttreatment tumor activity status. RESULTS: Within a median follow-up period of 2.9 ± 2.9 years, overall, a tumor inactivation was achieved in 72% of cases and visual acuity remained stable in 69%. The mean apex dose was 90 ± 23 Gy (range, 51-140 Gy). Mean tumor thickness decreased significantly, from 2.9 ± 0.9 mm to 1.5 ± 1.0 mm (P < 0.001; paired t-test). Persistence or recurrence of tumor activity occurred in 28% of cases, requiring secondary intervention with intravitreal drug injections, vitrectomy, cryotherapy, or repeated brachytherapy. Comparison of inactive and active vasoproliferative retinal tumors revealed significant correlation between both initial basal tumour diameter and area and subsequent tumour activity status. In particular, a diameter >7.5 mm was associated with an 8-fold risk of persistent or recurrent activity, whereas basal area >40 mm demonstrated a 6-fold risk (P = 0.009 and 0.021, respectively; Fisher's exact-test). In contrast, tumor thickness was not found to be of prognostic relevance. CONCLUSION: Ruthenium-106 brachytherapy is an effective and safe therapeutic option for vasoproliferative retinal tumors. Additionally, tumor diameter and area are efficient predictors of persistence or recurrence of tumor activity.