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.

Screening for common eye diseases in the elderly with Optos ultra-wide-field scanning laser ophthalmoscopy: a pilot study with focus on ocular toxoplasmosis.

PURPOSE: Studies on the occurrence of ocular toxoplasmosis (OT) in a general population are rare. Therefore, we conducted this pilot study to assess whether a nonmydriatic ultra-wide-field (UWF) scanning laser ophthalmoscope (SLO) is suitable for a simple, rapid screening procedure. METHODS: The population of this cross-sectional study was randomly recruited from a cohort of hospital-based patients in an urban geriatric hospital. Ophthalmologic evaluation was performed on 201 eyes from 101 participants through nonmydriatic UWF-SLO (Optos Daytona) and assessed for suspicious lesions and other relevant ocular findings. All images were evaluated by two independent examiners. Individuals who presented lesions with a morphological appearance suggestive of OT underwent fundoscopy and serological analysis of Toxoplasma gondii-specific antibodies. RESULTS: The mean age of the study group was 76 years, and 63 (62%) were female. Despite many health restrictions, the SLO examination was carried out easily in this geriatric population. Three participants presented findings by SLO suspicious for T. gondii-related injury. Further clinical examination and serological investigation confirmed the diagnosis, with funduscopic evaluation and positive T. gondii ELISA testing. In addition, a high rate of arterial hypertension and dyslipidemias within the cohort led to a high incidence of vascular changes and age-related fundus findings. CONCLUSION: In our study, we confirm that UWF-SLO technology is helpful in the rapid detection of peripheral retinal injuries in elderly patients such as OT and may be used as a routine screening tool.

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.

[Pharmacotherapy of Non-neovascular AMD]. / Medikamentöse Therapieansätze für die nicht neovaskuläre AMD.

BACKGROUND: Non-neovascular age-related macular degeneration (AMD) is not yet treatable. This article summarises current clinical research approaches. The reasons for the current lack of success are analysed. METHODS: Literature and databank search. RESULTS: The number of therapeutic approaches and mechanisms is limited. Only reduction in lipofuscin containing deposits is specific for AMD. Further approaches include modulation of inflammation and neuroprotection. Confirmatory studies have failed to demonstrate efficacy in AMD, i.e. slowing or stopping AMD progression. DISCUSSION: To increase the probability of success for future developments, the pharmacological target space needs to be broadened. This may be achieved by application of molecular network analyses. As visual acuity is commonly not primarily affected by non-neovascular AMD, research on patient perspective is required to define reasonable target profiles for future therapies.

Myeloid cells contribute indirectly to VEGF expression upon hypoxia via activation of Müller cells.

Anti-VEGF-directed therapies have been a milestone for treating retinal vascular diseases. Depletion of monocyte lineage cells suppresses pathological neovascularization in the oxygen-induced retinopathy mouse model. However, the question whether myeloid-derived VEGF-A expression is responsible for the pathogenesis in oxygen-induced retinopathy remained unknown. We analyzed LysMCre-driven myeloid cell-specific VEGF-A knockout mice as well as mice with complete depletion of circulating macrophages through clodronate-liposome treatment in the oxygen-induced retinopathy model by immunohistochemistry, qPCR, and flow cytometry. Furthermore, we analyzed VEGF-A mRNA expression in MIO-M1 cells alone and in co-culture with BV-2 cells in vitro. The myeloid cell-specific VEGF-A knockout did not change relative retinal VEGF-A mRNA levels, the relative avascular area or macrophage/granulocyte numbers in oxygen-induced retinopathy and under normoxic conditions. We observed an insignificantly attenuated pathology in systemically clodronate-liposome treated knockouts but evident VEGF-A expression in activated Müller cells on immunohistochemically stained sections. MIO-M1 cells had significantly higher expression levels of VEGF-A in co-culture with BV-2 cells compared to cultivating MIO-M1 cells alone. Our data show that myeloid-derived cells contribute to pathological neovascularization in oxygen-induced retinopathy through activation of VEGF-A expression in Müller cells.

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.

[Ultra-Wide Field Retinal Imaging and Angiography in the Differential Diagnosis and Therapeutic Decisions in Vascular Diseases of the Peripheral Retina]. / Ultraweitwinkel-Fundusfotografie und -angiografie in der Differenzialdiagnose und zur Therapieplanung bei peripheren vaskulären Netzhauterkrankungen.

Investigation of vascular diseases of the peripheral retina requires imaging procedures that allow a comprehensive view of the periphery, as well as reproducible pictures. In particular, ultra-wide field fluorescence angiography facilitates diagnosis, therapeutic decisions and follow-up examinations. While vasculopathies such as Coats disease and familiar exudative vitreoretinopathy are diagnosed within the first and second decade of life, patients' compliance during fundus imaging is typically reduced within this age range. Compared to the repeated imaging procedures for composite formation, ultra-wide field imaging has significantly reduced recording time. Nevertheless, current imaging systems are not able to map the entire retina in scaled proportions. Therefore, the imaging frame must be guided by patients' gaze onto the affected retinal area. Moreover, the medical photographer must be aware of the clinical setting and the region of interest. Hence, previous detailed funduscopy by trained ophthalmologists will remain indispensable.

[Multimodal Imaging of the Choroidal Melanoma, with Differential Diagnosis, Therapy (Radiation Planning) and Follow-up]. / Multimodale Bildgebung des Aderhautmelanoms mit seinen Differenzialdiagnosen, Therapie (Bestrahlungsplanung) und Verlaufskontrolle.

Imaging of intraocular tumors is multimodal, multi-purpose, and in continuous development. Therefore, imaging is indispensable for the detection, diagnosis, therapy and monitoring of intraocular tumours. A broad spectrum of imaging procedures is available for diagnostic testing and follow-up. This includes colour image acquisition, infrared imaging, autofluorescence imaging, fluorescence and indocyanine green angiography, optical coherence tomography (OCT) and sonography (US). In this article, the various investigations and their benefits are described using individual examples for the differential diagnosis of choroidal melanoma and retinal vascular tumours located in the fundus periphery.

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.

In vivo analysis of the time and spatial activation pattern of microglia in the retina following laser-induced choroidal neovascularization.

Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach the immune response in the retina in vivo.

Intravitreal inhibition of complement C5a reduces choroidal neovascularization in mice.

PURPOSE: To investigate the influence of complement component C5a inhibition on laser-induced choroidal neovascularization (CNV) in mice using a C5a specific L-aptamer. METHODS: In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor (NOX-D20) was intravitreally injected in three concentrations: 0.3, 3.0, and 30 mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 mg/ml; the vehicle (5 % glucose) was injected in controls. Vascular leakage was evaluated using fluorescence angiography, CNV area was examined immunohistochemically. Activated immune cells surrounding the CNV lesion and potential cytotoxicity were analyzed. RESULTS: Compared to controls, CNV areas were significantly reduced after NOX-D20 injection at a concentration of 0.3 and 3.0 mg/ml (p = 0.042; p = 0.016). NOX-D20001 significantly decreased CNV leakage but not the area (p = 0.007; p = 0.276). At a concentration of 30 mg/ml, NOX-D20 did not reveal significant effects on vascular leakage or CNV area (p = 0.624; p = 0.121). The amount of CD11b positive cells was significantly reduced after treatment with 0.3 and 3.0 mg/ml NOX-D20 (p = 0.027; p = 0.002). No adverse glial cell proliferation or increased apoptosis were observed at effective dosages. CONCLUSIONS: Our findings demonstrate that the targeted inhibition of complement component C5a reduces vascular leakage and neovascular area in laser-induced CNV in mice. NOX-D20 was proven to be an effective and safe agent that might be considered as a therapeutic candidate for CNV treatment. The deficiency of activated immune cells highlights promising new aspects in the pathology of choroidal neovascularization, and warrants further investigations.

Development of very large electrode arrays for epiretinal stimulation (VLARS).

BACKGROUND: Retinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments. METHODS: Large area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices. RESULTS: Large area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices. CONCLUSIONS: Large flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity.

[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.

Anatomical and functional results after vitrectomy with conventional ILM peeling versus inverted ILM flap technique in large full-thickness macular holes.

BACKGROUND: Aim of the study was to compare success rate and functional outcome following pars plana vitrectomy (PPV) with conventional internal limiting membrane (ILM) peeling versus ILM flap technique for full-thickness idiopathic macular holes (FTMH). METHODS: Retrospective analysis of consecutive eyes with FTMH having undergone vitrectomy with sulfur hexafluoride (SF6) endotamponade 25% at the University Medical Center Rostock, Germany (2009-2020). Eyes were divided according to applied surgical technique (ILM peeling [group P] versus ILM flap [group F]). Inclusion criteria were macular hole base diameters (MH-BD) ≥ 400 µm plus axial length ≤ 26.0 mm. Each group was divided into two subgroups based on macular hole minimum linear diameter (MH-MLD): ≤ 400 µm and > 400 µm. Exclusion criteria were FTMH with MH-BD < 400 µm, trauma, myopia with axial length > 26.0 mm or macular schisis. Demographic, functional, and anatomical data were obtained pre- and postoperatively. Preoperative MH-BD and MH-MLD were measured using optical coherence tomography (OCT; Spectralis®, Heidelberg Engineering GmbH, Heidelberg, Germany). Main outcome parameter were: primary closure rate, best-corrected visual acuity (BCVA), and re-surgery rate. RESULTS: Overall 117 eyes of 117 patients with FTMH could be included, thereof 52 eyes underwent conventional ILM peeling (group P) and 65 additional ILM flap (group F) technique. Macular hole closure was achieved in 31 eyes (59.6%) in group P and in 59 eyes (90.8%) in group F (p < 0.001). Secondary PPV was required in 21 eyes (40.4%) in group P and in 6 eyes (9.2%) in group F. Postoperative BCVA at first follow-up in eyes with surgical closure showed no significant difference for both groups (MH-MLD ≤ 400 µm: p = 0.740); MH-MLD > 400 µm: p = 0.241). CONCLUSION: Anatomical results and surgical closure rate following ILM flap technique seems to be superior to conventional ILM peeling for treatment of FTMH.

Development of surgical techniques for implantation of a wireless intraocular epiretinal retina implant in Göttingen minipigs.

BACKGROUND: The aim of this study was to develop surgical methods for the implantation of a wireless intraocular epiretinal retina implant (EPI RET3) in Göttingen minipigs. This animal model resembles closely the anatomical conditions in humans, and is thus suitable for investigating the EPI RET3 implant as designed for the application in humans. METHODS: Phacoemulsification and vitrectomy was performed on the right eye of 16 Göttingen minipigs under general anesthesia. The implants, consisting of a receiver module and an electrode array connected via a flexible micro cable, were inserted through a corneoscleral incision. The receiver module was placed into the sulcus ciliaris and the electrode array was fixed onto the retina temporal to the optic disc with a retinal tack. Minipigs were monitored for intra- and postoperative ocular complications. Follow-up times were 3 (seven minipigs) and 12 weeks (nine minipigs). RESULTS: Implantation was successfully performed in all 16 minipigs. The complete implantation surgery required on average 2 hours. Intraoperative findings were a minor hemorrhage of the anterior chamber angle in two eyes, one minor iris hemorrhage, and one minor punctiform retinal hemorrhage, which were all reversible. Postoperatively, the corneoscleral incision showed good wound healing in all eyes. Intraocular reactions included mainly fibrin exudation (six eyes) and formation of iris synechiae with the receiver module of the implants (three eyes). CONCLUSIONS: The performed implantation procedures of the intraocular EPI RET3 implant are feasible and reproducible within an acceptable surgical time. The development of inflammatory responses is a specific predisposition of the minipig following any intraocular intervention; nevertheless, the surgical techniques should be further improved to minimize procedure-related reactions. Our results provide a step towards the application of the EPI RET3 system in clinical studies.

Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study.

BACKGROUND: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). METHODS: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. RESULTS: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window. CONCLUSIONS: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

Angiographic findings following tack fixation of a wireless epiretinal retina implant device in blind RP patients.

BACKGROUND: The fixation of polyimide stimulator foils as the basic substrate of epiretinal prostheses by using retinal tacks may cause retinal or choroidal alterations such as retinal proliferations or choroidal neovascularizations. During the prospective trial for the semichronical testing of a wireless intraocular retinal implant (EPIRET3) we investigated alterations in angiographic findings during implantation and after explantation of the device, to detect potential vascular pathologies at the fixation site or elsewhere. METHODS: As the final step of the implantation surgery in six blind patients, the stimulator was placed on the retinal surface using retinal tacks. For the detection of possible morphological or vascular alterations committed by the implant fluorescein angiography (FA) was performed 1 day before and 4 weeks after implantation surgery, as well as at the final visit 5 months after explantation. RESULTS: Following implantation surgery funduscopy and FA did not reveal any evidence of either vascular pathologies or choroidal neovascularisations (CNV), in addition, no cystoid macular edema (CME) occurred after 4 weeks. At the 6-month follow-up visit, we found a mild epiretinal gliosis formation in four patients. In one patient a retinal break occurred during explantation, requiring a temporary silicone-oil endotamponade. At the final visit, we observed a focal proliferative vitreoretinopathy (PVR) reaction without activity, while there was no evidence for a CNV formation in that area. CONCLUSIONS: The FA findings confirm our previous results on the safety of the EPIRET3 system, which was tolerated in all patients but revealed a certain risk profile in regard to the stimulator fixation. While there was no evidence for newly occurred CME or CNV during the follow-up visits, nevertheless gliosis or even PVR reaction at the tack's fixation site suggests the need to develop alternative fixation procedures of epiretinal stimulators.

Surgical Results and Microscopic Analysis of the Tissue Reaction following Implantation and Explantation of an Intraocular Implant for Epiretinal Stimulation in Minipigs.

AIMS: For the purpose of visual rehabilitation of subjects with photoreceptor degeneration, an implantable microelectronic device for epiretinal stimulation was developed. Our study aimed to show whether implantation and explantation could be conducted safely and to investigate tissue compatibility. METHODS: The device was implanted in 5 Göttinger minipigs. Four weeks later, the implant was surgical- ly removed. Histopathological examination that followed aimed at detecting inflammatory or proliferative changes. Stains used were hematoxylin and eosin, leukocyte common antigen, CD68 and glial fibrillary acidic protein. A grinding technique was used to visualize the retinal tissue in conjunction with the retinal tacks. RESULTS: The implantation of the devices was successful in all cases. The explantation was complicated by intraoperative hemorrhages. Complete explantation could only be achieved after modifying the implantation strategy. Histopathology revealed a mild degree of cystic disaggregation of the retina. Immunohistochemically, an increased glial fibrillary acidic protein expression of Müller cells was found, which shows a moderate glial cell activation. Inflammatory cells were absent. Using the grinding technique, tissue adjacent to the retinal tacks showed a mild gliosis. DISCUSSION: The viability of implantation and explantation of the implant in minipigs has been shown. The absence of immunoreactive cells or a considerable glial reaction suggest that the device may be considered safe and suitable for further implantation in humans.

[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.