Viscoelastic, Optical, and Surgical Properties of Vitreous Body Replacement Hydrogels After Aging Compared to Porcine Vitreous Bodies And Silicone Oils.

Purpose: First- (monomers), second- (pre-gelated), and third- (in situ gelating after injection) generation hydrogels were previously introduced to replace the vitreous body after vitrectomy surgery. In this study, we evaluated the surgical, optical, and viscoelastic properties of vitreous body replacement hydrogels before and after an accelerated aging protocol previously applied to intraocular implants. Methods: Measurements of injection force, removal speed using a clinically established vitrectomy setup, as well as evaluation of forward light scattering and viscoelastic properties before and after an accelerated aging protocol were conducted. Results were compared to porcine and human vitreous bodies, as well as currently clinically applied lighter- and heavier-than-water silicone oils. Results: Removal speed of all tested hydrogels is substantially lower than the removal speed of porcine vitreous body (0.2 g/min vs. 2.7 g/min for the best performing hydrogel and porcine vitreous body, respectively). Forward light scattering in second-generation vitreous body replacement hydrogels was higher after the aging process than the straylight of the average 70-year-old vitreous body (9.4 vs. 5.5 deg2/sr, respectively). The viscoelastic properties of all hydrogels did not change in a clinically meaningful manner; however, trends toward greater stiffness and greater elasticity after aging were apparent. Conclusions: This study demonstrates surgical weaknesses of the hydrogels that need to be addressed before clinical use, especially low removal speed. Pre-linked hydrogels (second-generation) showed inferior performance regarding surgical properties compared to in situ gelating hydrogels (third-generation). Translational Relevance: This study highlights possible pitfalls regarding surgical and optical properties when applying vitreous replacement hydrogels clinically.

Clinical characteristics and management outcome of acute infectious endophthalmitis.

PURPOSE: This study aimed to investigate the demographics, clinical characteristics, and management outcomes of patients with acute infectious endophthalmitis (AIE). METHODS: This retrospective chart review was conducted on all patients admitted with the clinical diagnosis of infectious endophthalmitis from 2017 to 2022. Demographic data, patients' clinical characteristics, the type of acute infectious endophthalmitis (post-operative, post-traumatic, bleb-associated, and endogenous endophthalmitis), the type of surgical procedure in the post-operative cases, the microbiologic analysis results of vitreous samples, therapeutic measures, and visual outcomes of patients were recorded. RESULTS: In this study, 182 participants, including 122 male (67%) and 60 (33%) female, were involved. The mean age of patients was 54.56 ± 21 years, with a range of 1-88 years old. The most prevalent type of AIE was post-operative (59.9%), followed by endogenous (19.2%), post-traumatic (17%), and bleb-associated (3.8%). The most common type of intraocular surgery in the post-operative subgroups of AIE patients was phacoemulsification (57.8%). The median (interquartile range) of the primary and final BCVA of patients was 1.5 (1.35, 1.85) and 0.65 (0.35, 1.35), respectively. Vitreous haziness grade (OR, 2.89; 95% CI, 1.11-5.74; p = 0.009) and the primary VA (OR, 60.34; 95% CI, 2.87-126.8; p = 0.008) revealed statistical significance for final vision loss. CONCLUSION: AIE is a devastating condition with poor visual outcomes, which presents with acute inflammatory signs and symptoms regardless of its type. However, prompt and appropriate treatment leads to visual recovery to a functional level in many patients.

Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body.

BACKGROUND: The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive. RESULTS: In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood. We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia. Embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes. CONCLUSION: Our study identifies hyalocytes as long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye. As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases. Therefore, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface.

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in Rabbits.

PURPOSE: Wet age-related macular degeneration (AMD) is a blinding retinal disease. Monthly intravitreal anti-VEGF antibody injections of bevacizumab (off-label) and ranibizumab (FDA approved) are the standard of care. Antibody aggregation may interfere with ocular absorption/distribution. This study assessed topical delivery of dilute antibodies to the posterior segment of rabbit eyes using a novel anti-aggregation formula (AAF). METHODS: Bevacizumab, or biosimilar ranibizumab was diluted to 5 mg/ml in AAF. All rabbits were dosed twice daily. Substudy 1 rabbits (bevacizumab, 100 µl eye drops): Group 1 (bevacizumab/AAF, n = 6); Group 2 (bevacizumab/PBS, n = 7) and Vehicle control (AAF, n = 1). Substudy 2 rabbits (ranibizumab biosimilar/AAF, 50 µl eye drops): (ranibizumab biosimilar/AAF, n = 8). At 14.5 days, serum was drawn from rabbits. Aqueous, vitreous and retina samples were recovered from eyes and placed into AAF aliquots. Tissue analyzed using AAF as diluent. RESULTS: Bevacizumab in AAF permeated/accumulated in rabbit aqueous, vitreous and retina 10 times more, than when diluted in PBS. AAF/0.1% hyaluronic acid eye drops, dosed twice daily, provided mean tissue concentrations (ng/g) in retina (29.50), aqueous (12.34), vitreous (3.46), and serum (0.28 ng/ml). Additionally, the highest concentration (ng/g) of ranibizumab biosimilar was present in the retina (18.0), followed by aqueous (7.82) and vitreous (1.47). Serum concentration was negligible (< 0.04 ng/ml). No irritation was observed throughout the studies. CONCLUSIONS: Bevacizumab and ranibizumab, in an AAF diluent eye drop, can be delivered to the retina, by the twice daily dosing of a low concentration mAb formulation. This may prove to be an adjunct to intravitreal injections.

Ferrous ascorbate as a potential biomarker for diabetic retinopathy: a vitreous humour metabolomics study.

BACKGROUND: This study aimed to explore differences in vitreous humour metabolites and metabolic pathways between patients with and without diabetic retinopathy (DR) and identify potential metabolite biomarkers. METHODS: Clinical data and vitreous fluid samples were collected from 125 patients (40 without diabetes, 85 with DR). The metabolite profiles of the vitreous fluid samples were analysed using ultra-high performance liquid chromatography, Q-Exactive mass spectrometry, and multivariate statistical analysis. A machine learning model based on Least Absolute Shrinkage and Selection Operator Regularized logistic regression was used to build a risk scoring model based on selected metabolite levels. Candidate metabolites were regressed to glycated haemoglobin levels by a logistic regression model. RESULTS: Twenty differential metabolites were identified between the DR and control groups and were significantly enriched in five Kyoto Encyclopedia of Genes and Genomes pathways (arginine biosynthesis; tricarboxylic acid cycle; alanine, aspartate, and glutamate metabolism; tyrosine metabolism; and D-glutamate metabolism). Ferrous ascorbate significantly contributes to poorer glycaemic control outcomes, offering insights into potential new pathogenic pathways in DR. CONCLUSIONS: Disorders in the metabolic pathways of arginine biosynthesis, tricarboxylic acid cycle, alanine, aspartate, glutamate metabolism, tyrosine metabolism, and D-glutamate metabolism were associated with DR. Risk scores based on vitreous fluid metabolites can be used for the diagnosis and management of DR. Ferrous ascorbate can provide insights into potential new pathogenic pathways for DR.

A sensitive bioanalytical ultra-high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation of lactone and carboxylate forms of topotecan in plasma and vitreous.

Topotecan (TPT) is used in the treatment of retinoblastoma, the most common malignant intraocular tumor in children. TPT undergoes pH-dependent hydrolysis of the lactone ring to the ring-opened carboxylate form, with the lactone form showing antitumor activity. A selective, and highly sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the determination of both forms of TPT in one mobile phase composition in plasma and vitreous humor matrices. The method showed an excellent linear range of 0.375-120 ng/mL for the lactone. For the carboxylate, the linear range was from 0.75 to 120 ng/mL. The matrix effect and the recovery for the lactone ranged from 98.5% to 106.0% in both matrices, for the carboxylate form, it ranged from 94.9% to 101.2%. The dynamics of the transition between TPT lactone and TPT carboxylate were evaluated at different pH environments. The stability of TPT forms was assessed in plasma and vitreous humor at 8 and 37°C and a very fast conversion of lactone to carboxylate form occurred at 37°C in both matrices. The method developed facilitates the investigation of TPT pharmacodynamics and the release kinetics in the development of the innovative local drug delivery systems.

Aqueous VEGF-A Levels as a Liquid Biopsy Biomarker of Retinoblastoma Vitreous Seed Response to Therapy.

Purpose: Regression of retinoblastoma vitreous seeds (VS) during intravitreal chemotherapy can be delayed, resulting in supernumerary injections. Similarly, VS relapse may not be clinically evident at first. A predictive biomarker of tumor regression and relapse could help guide real-time clinical decision making. Retinoblastoma is an oxygen-sensitive tumor; paradoxically, VS survive in the hypoxic vitreous. We hypothesized that VS elaborate pro-angiogenic cytokines. The purpose was to determine if pro-angiogenic cytokine signatures from aqueous humor could serve as a biomarker of VS response to treatment. Methods: Multiplex ELISA was performed on aqueous from rabbit eyes with human retinoblastoma VS xenografts to identify expressed proangiogenic cytokines and changes in aqueous cytokine levels during intravitreal treatment were determined. Confirmatory RNAscope in situ hybridization for VEGF-A was performed on human retinoblastoma tumor sections and VS xenografts from rabbits. For human eyes undergoing intravitreal chemotherapy, serial aqueous VEGF-A levels measured via VEGF-A-specific ELISA were compared to clinical response. Results: VEGF-A was highly expressed in human retinoblastoma VS in the xenograft model, and was the only proangiogenic cytokine that correlated with VS disease burden. In rabbits, aqueous VEGF-A levels decreased in response to therapy, consistent with quantitative VS reduction. In patients, aqueous VEGF-A levels associated with clinical changes in disease burden (regression, stability, or relapse), with changes in VEGF-A levels correlating with clinical response. Conclusions: Aqueous VEGF-A levels correlate with extent of retinoblastoma VS, suggesting that aqueous VEGF-A may serve as a predictive molecular biomarker of treatment response.

[Lamellar macular holes-In the center of vitreomacular interface diseases : Pathophysiology, spontaneous courses and treatment concepts]. / Makulaschichtforamen ­ im Zentrum der vitreomakulären Grenzflächenerkrankungen : Pathophysiologie, Spontanverläufe und Therapiekonzepte.

BACKGROUND: A lamellar macular hole (LMH) is characterized by a distinct morphologic configuration and can be distinguished from related entities such as macular pseudohole (MPH) and epiretinal membrane with foveoschisis (ERM-FS) by clear morphologic features. PURPOSE: Based on current knowledge, the pathophysiologic function of LMH in the spectrum of vitreomacular interface diseases will be described and therapeutic concepts will be presented. METHODS: Current studies are supplemented by case reports to provide a schematic overview of the natural history and therapeutic concepts at the vitreomacular interface. RESULTS: The LMH is as a retrospective marker for pathologic posterior vitreous detachment in adult patients and may be interpreted as the pathophysiologic center of tractional maculopathies. Various vitreomacular pathologies can result in LMH: a detached vitreomacular traction, a spontaneously closed penetrating macular hole, or an epiretinal membrane with foveoschisis. Pathophysiologically, a degenerative, progressive loss of the architecture of the foveal muller cell cone may be the underlaying mechanism, resulting in the typical undermining of the hole edges and occasionally in a full thickness macular hole. The optimal timing and the appropriate surgical method are the focus of current clinical studies. CONCLUSION: The pathophysiology of LMH indicates a smooth transition of tractive maculopathies. These should be prospectively evaluated in order to develop evidence-based treatment strategies for LMH.

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits.

Siponimod is a promising agent for the inhibition of ocular neovascularization in diabetic retinopathy and age-related macular degeneration. Siponimod's development for ophthalmological application is hindered by the limited information available on the drug's solubility, stability, ocular pharmacokinetics (PK), and toxicity in vivo. In this study, we investigated the aqueous stability of siponimod under stress conditions (up to 60 °C) and its degradation behavior in solution. Additionally, siponimod's ocular PK and toxicity were investigated using intravitreal injection of two different doses (either 1300 or 6500 ng) in an albino rabbit model. Siponimod concentration was quantified in the extracted vitreous, and the PK parameters were calculated. The drug half-life after administration of the low and high doses was 2.8 and 3.9 h, respectively. The data obtained in vivo was used to test the ability of published in silico models to predict siponimod's PK accurately. Two models that correlated siponimod's molecular descriptors with its elimination from the vitreous closely predicted the half-life. Furthermore, 24 h and 7 days after intravitreal injections, the retinas showed no signs of toxicity. This study provides important information necessary for the formulation and development of siponimod for ophthalmologic applications. The short half-life of siponimod necessitates the development of a sustained drug delivery system to maintain therapeutic concentrations over an extended period, while the lack of short-term ocular toxicity observed in the retinas of siponimod-treated rabbits supports possible clinical use.

Endogenous Endophthalmitis Caused by Aspergillus lentulus in an Immunocompromised Patient with Lung Cancer

A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks' duration in his right eye. There was multifocal, yellowish-white retinitis foci, vascular engorgement, and scattered intraretinal hemorrhages extending from posterior pole to retinal periphery in the right eye, whereas the left eye was normal. Intravitreal vancomycin, ceftazidime, clindamycin, and dexamethasone were given for endogenous endophthalmitis initially. Vitreous culture confirmed the presence of Aspergillus lentulus, and he was treated with intravitreal amphotericin-B and voriconazole injections together with systemic amphotericin-B, voriconazole, posaconazole, and micafungin therapy. During follow-up, vitreoretinal surgery was performed because of rhegmatogenous retinal detachment, and he received one additional cycle of chemotherapy due to recurrence of the cancer. Although the retina was attached, enucleation was eventually required due to painful red eye. Atypical squamous cells beneath the neurosensory retina suggesting metastasis were noted on histopathological examination. Timely ocular examination is crucial for any immunocompromised patient having ocular symptoms. High level of suspicion for a fungal etiology is a must in these patients.

CLINICAL CHARACTERIZATION OF AQUEOUS AND VITREOUS RETINOL-BINDING PROTEIN 3 CONCENTRATIONS IN RELATION TO DIABETIC RETINOPATHY SEVERITY, RETINAL STRUCTURES, AND SYSTEMIC COMPLICATIONS.

PURPOSE: To evaluate Retinol-Binding Protein 3 (RBP3) from photoreceptors in aqueous and its association with vitreous concentrations, diabetic retinopathy (DR) severity, retinal layer thickness, and clinical characteristics in people with diabetes. METHODS: RBP3 concentration was measured by custom-developed enzyme-linked immunosorbent assay in aqueous and correlated with vitreous concentrations in patients from the 50-Year Medalist study and Beetham Eye Institute at Joslin Diabetes Center. RESULTS: Aqueous RBP3 concentration (N = 131) was elevated in eyes with no to mild DR (mean ± SD 0.7 nM ± 0.2) and decreased in eyes with moderate to severe DR (0.65 nM ± 0.3) and proliferative DR (0.5 nM ± 0.2, P < 0.001) compared to eyes without diabetes. Aqueous and vitreous RBP3 concentrations correlated with each other (r = 0.34, P = 0.001) and between fellow eyes (P < 0.0001). History of retinal surgery did not affect aqueous RBP3 concentrations, but cataract surgery affected both vitreous and aqueous levels. Elevated aqueous RBP3 concentration associated with increased thickness of the outer nuclear layer (P = 0.004) and correlated with hemoglobin A1c, whereas vitreous RBP3 concentrations correlated with diabetic systemic complications. CONCLUSION: These findings suggest that aqueous RBP3 concentration may be an important endogenous clinical retinal protective factor, a biomarker for DR severity, and a promising VEGF-independent clinical intervention target in DR.

Light Scattering by Vitreous of Humans With Vision Degrading Myodesopsia From Floaters.

Purpose: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL. Methods: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission in vitro. Results: All indices of vitreous echodensity in vivo correlated positively with straylight at 0.5° (R = 0.708 to 0.775, P = 0.049 and 0.024, respectively). Straylight mean scatter index correlated with echodensity (R = 0.71, P = 0.04) and VQOL (R = -0.82, P = 0.0075). Dark-field measures in vitro correlated with degraded CS in vivo (R = -0.69, P = 0.04). VQOL correlated with straylight mean scatter index (R = -0.823, P = 0.012). Conclusions: Increased vitreous echodensity in vivo is associated with more straylight scattering in vitro, validating ultrasonography as a clinical surrogate for light scattering. Contrast sensitivity in vivo is more degraded in the presence of dark-field scattering in vitro and VQOL is decreased in patients whose vitreous has increased light scattering. These findings could form the basis for the development of optical corrections for VDM or support new laser treatments, as well as novel pharmacotherapy.

[Biomechanics of diabetic vitreopapillary traction syndrome]. / Biomekhanika diabeticheskogo vitreopapillyarnogo traktsionnogo sindroma.

Diabetic vitreopapillary traction syndrome (VPT) is a variant of diabetic retinopathy (DR) that can lead to vision loss in advanced stages. This review reports on the biomechanics of the vitreous in the pathogenesis of proliferative DR, in particular diabetic VPT. The article analyzes and summarizes literature data, presents the views of different authors on this problem, and provides the results of Russian and foreign scientific research on this pathology. It is concluded that further research in this area can lead to a significant improvement in the results of therapy, timely diagnosis, and preservation of vision in patients with DR.

Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1ß induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect from diabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a "ceramidopathy" reversible by anti-ceramide immunotherapy.

[Vitreomacular traction: diagnostics, natural course, treatment decision and guideline recommendations]. / Vitreomakuläre Traktion: Diagnostik, natürlicher Verlauf, Therapieentscheidung und Leitlinienempfehlungen.

Vitreomacular traction is a tractive foveolar adhesion of the posterior vitreous limiting membrane, resulting in pathological structural alterations of the vitreomacular interface. This must be differentiated from physiological vitreomacular adhesion, which exhibits a completely preserved foveolar depression. Symptoms depend on the severity of the macular changes and typically include reduced visual acuity, reading problems and metamorphopsia. High-resolution spectral domain optical coherence tomography (SDOCT) imaging enables classification of the sometimes only subtle morphological changes. If pronounced vitreomacular traction is accompanied by epiretinal gliosis and alterations to the outer retina, it is referred to as a vitreomacular traction syndrome. Vitreomacular traction has a high probability of spontaneous resolution within 12 months. Therefore, treatment should only be carried out in cases of undue suffering of the patient and with symptoms during bilateral vision and a lack of spontaneous resolution. In addition to pars plana vitrectomy, alternative treatment options, such as intravitreal injection of ocriplasmin and pneumatic vitreolysis are discussed for vitreomacular traction with an associated macular hole; however, ocriplasmin is no longer available in Germany. The best anatomical results in comparative investigations were achieved by vitrectomy. Pneumatic vitreolysis is controversially discussed due to the increased risk of retinal tears. In one of the current S1 guidelines of the German ophthalmological societies evidence-based recommendations for the diagnostics and treatment of vitreomacular traction are summarized.

Interferons in vitreoretinal diseases; a review on their clinical application, and mechanism of action.

PURPOSE: This review investigates the therapeutic benefits of interferons (IFNs) in vitreoretinal diseases, focusing on their regulatory roles in innate immunological reactions and angiogenesis. The study aims to categorize the clinical outcomes of IFN applications and proposes a molecular mechanism underlying their action. METHODS: A systematic review was conducted using MEDLINE/PubMed, Web of Science, EMBASE, and Google Scholar databases to identify randomized clinical trials, case series, and case-control studies related to IFNs' impact on vitreoretinal diseases (1990-2022). The data synthesis involved an in-depth analysis of the anti-inflammatory and anti-angiogenesis effects of IFNs across various studies. RESULTS: Our findings indicate that IFNs exhibit efficacy in treating inflammation-associated vitreoretinal disorders. However, a lack of sufficient evidence exists regarding the suitability of IFNs in angiogenesis-associated vitreoretinal diseases like choroidal neovascularization and diabetic retinopathies. The synthesis of data suggests that IFNs may not be optimal for managing advanced stages of angiogenesis-associated disorders. CONCLUSION: While IFNs emerge as promising therapeutic candidates for inflammation-related vitreoretinal diseases, caution is warranted in their application for angiogenesis-associated disorders, especially in advanced stages. Further research is needed to elucidate the nuanced molecular pathways of IFN action, guiding their targeted use in specific vitreoretinal conditions.