Combined Osteopontin Blockade and Type 2 Classical Dendritic Cell Vaccination as Effective Synergetic Therapy for Conjunctival Melanoma.

Angiogenesis and immune protection are essential at the onset of tumorigenesis. Angiogenesis serves to nourish the tumor, and prevention of immune defenses, for example, by dendritic cells (DCs), allows tumor growth. In this study, we investigated whether there are factors with dual functions that are both angiogenic and immunomodulatory and represent a therapeutic target. We analyzed 1) innate immune responses intratumorally and in draining lymph nodes and 2) angiogenic factors in conjunctival melanoma (CM), a potentially lethal malignant tumor at the ocular surface whose immune and vascular responses are largely unknown. For this purpose, an HGF-Cdk4R24C model in immunocompetent C57BL/6 mice was used and revealed that CD103- type 2 classical DC (cDC2s) were the most abundant DC subtype in healthy conjunctiva, whereas in CM, CD103- cDC2s, CD103+ type 1 cDCs, monocyte-derived DCs, and plasmacytoid DCs were significantly increased. In our analysis of angiogenic factors in CM, the examination of 53 angiogenesis-related factors that might interact with DCs identified osteopontin (OPN) as a major tumor-derived protein that interacts with DCs. Consistent with these findings, 3) a dual therapeutic strategy that inhibited tumor cell function by an OPN blocking Ab while enhancing the immune response by cDC2 vaccination resulted in 35% failure of tumor development. Moreover, tumor progression, monocyte-derived DC infiltration, and intratumoral angiogenesis were significantly reduced, whereas survival and CD8+ T cell infiltration were increased in treated mice compared with the control group. Therefore, we identified OPN blockade in combination with cDC2 vaccination as a potential future therapeutic intervention for early stages of CM by combining antiangiogenic and host immune stimulating effects.

Intraday repeatability of macular layers measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography.

PURPOSE: To assess the intraday repeatability of macular architecture measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography (SD-OCT) and to evaluate the independence from intraindividual intraocular pressure (IOP) fluctuations. METHODS: In this single-center, time-point comparison study, 88 eyes with glaucoma, 53 eyes with ocular hypertension (OHT), and 253 healthy eyes underwent two standardized SD-OCT and intraocular pressure (IOP) measurements on the same day with a 5-h time gap. Bland-Altman plots, intraclass correlation coefficients (ICC), and random-effects model were used to analyze repeatability of entire retinal thickness, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer measurements. RESULTS: Intraday measurements were highly reproducible in all 3 groups. ICC were greater than 0.90, respectively. The pairwise comparisons of morphometric parameters showed a statistically significant difference (P < 0.001, respectively) between groups (glaucoma vs. control, glaucoma vs. OHT) and a significant influence of time points. No correlation was found between IOP fluctuations and morphometric parameters (P > 0.05, respectively), except for a weak positive correlation with GCL (rho = 0.109, P = 0.031). CONCLUSIONS: The evaluation of macular morphometric parameters of SD-OCT showed a high intraday repeatability and an excellent degree of agreement in glaucoma, ocular hypertension, and healthy groups. The fixed effects of time points were statistically significant. Except for a weak positive correlation of ganglion cell layer, variability did not appear to be affected by intraday IOP changes. Additional research is required to fully understand the impact of IOP fluctuations on macular morphometric parameters, considering the small observed IOP changes.

Periocular Asymmetry Index in Caucasian Populations Using Three-dimensional Photogrammetry Assessment.

OBJECTIVE: To quantitatively assess the periocular asymmetry and investigate its sex and age-related differences in a Caucasian population using three-dimensional (3D) stereophotogrammetry. METHOD: Standardized 3D photos of the periocular region of 301 Caucasians were taken using the VECTRA M3 3D Imaging System. Standardized landmarks were positioned, and data measurements in the periocular region were obtained from these images using VAM software and assessed using intraclass correlation coefficients (ICC) for reliability. Absolute differences and asymmetry index between the right and the left periocular region were calculated with a focus on gender and age-related differences. RESULT: Fissure height asymmetry was positively correlated with age (p < 0.01). Furthermore, reflex distance asymmetry was positively correlated with age in the elderly group (p < 0.05). Absolute differences of upper eyelid crease were 0.65 ± 0.79 mm for females and 0.90 ± 0.94 mm for males (p < 0.05). In the elderly group, the absolute differences of reflex distance were 0.664 ± 0.471 mm for males and 0.470 ± 0.408 mm for females (p < 0.05), while the absolute differences of fissure height were 0.619 ± 0.469 mm and 0.436 ± 0.372 mm, respectively (p < 0.05). All measurements had an inter-rater ICC and intra-rater ICC between 0.761 and 0.957. CONCLUSION: Periocular asymmetry is more prominent in older and male people. 3D photogrammetry is a reliable tool to detect periocular asymmetry and might provide an accurate and effective reference for periocular cosmetic, plastic, and reconstructive surgery in the clinical routine. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

Postoperative Pain Following Eye Enucleation: A Prospective Observational Study.

Background and Objectives: Enucleation of an eye is the most invasive procedure in ophthalmologic surgery. It can be the result of various diseases (malignant/chronic/trauma/infection) and is nevertheless relatively rare, but leads to the loss of a strongly innervated neuronal organ. This study systematically evaluates postoperative pain levels following enucleation of the eye globe. Materials and Methods: This prospective single-center study enrolled twenty-four patients undergoing enucleation of the eye globe. Perioperatively all patients completed (preoperative day, day of surgery, 1st, 2nd, and 3rd day following surgery) standardized questionnaires concerning their pain experience and treatment-related side-effects (internal protocol, QUIPS, painDETECT®). Patients received usual pain therapy in an unstandardized individual manner. Results: Preoperatively, mean average pain intensity of all included patients was 3.29 ± 2.46 (range, 0-8), 3.29 ± 3.24 (range, 0-8) on the day of surgery, 4.67 ± 1.90 (range, 2-10) on day 1, 3.25 ± 1.39 (range, 1-6) on day 2, and 2.71 ± 1.30 (range, 1-6) on day 3 after surgery. Mean maximum pain intensity was 4.71 ± 3.28 (range, 0-10) preoperatively, 4.04 ± 3.78 (range, 0-10) on the day of surgery, 5.75 ± 2.01 (range, 2-10) on day 1, 4.25 ± 1.89 (range, 2-10) on day 2, and 3.88 ± 1.54 (range, 2-8) on day 3 after surgery. Nineteen patients (79.2%) stated that they would have preferred more pain therapy. Conclusions: Patients undergoing eye enucleation report pain sensations in need of intervention in this university hospital. Thus, effective standardized pain treatment concepts are now a high priority to be established in an interdisciplinary manner containing standardized regimens and continuous regional procedures. Awareness of this problem in the medical team should be sharpened through targeted training and information.

A comparative study of cystoid macula edema following glaucoma drainage device surgery versus trabeculectomy.

PURPOSE: To assess and compare the risk for development of cystoid macula edema (CME) after glaucoma drainage device (GDD) implantation versus conventional trabeculectomy with mitomycin (trab) for glaucoma. METHODS: Retrospective review of consecutive patients receiving trab or GDD implantation between 2016 and 2018. Inclusion criteria were availability of pre- and postoperative spectral domain optical coherence tomography (SD-OCT) of the macula. SD-OCT images were evaluated for presence of CME qualitatively, central subfield thickness (CST) and macular volume (MV). RESULTS: 73 eyes could be included, 42 received trab and 31 GDD surgery. Eyes receiving trab on average had 0.8 ± 0.8 previous intraocular operations, while eyes with GDD implantation had 3.1 ± 1.9 (p < 0.001). Occurrence of postoperative CME was significantly more frequent after GDD implantation (6 out of 31 (19.4%)) than after trab (2 out of 42 eyes = 4.8%), (p = 0.049). Mean preoperative CST as well as MV was comparable in both groups (CST before trab: 282.7 ± 23.0 µm, CST before GDD 284.2 ± 27.3 µm, p = 0.287; MV before trab: 7.8 ± 1.1 mm3, MV before GDD: 8.0 ± 0.8mm3, p = 0.305). Mean postoperative CST and MV were significantly higher after GDD (CST 338.5 ± 129.3 µm, MV 8.8 ± 2.6 mm3) than after trabeculectomy (CST 290.6 ± 60.2 µm, p = 0.038; MV 7.8 ± 1.2mm3, p = 0.039). CONCLUSIONS: In real-life conditions, GDD surgery seems to be associated with a higher risk to develop CME when compared to conventional trabeculectomy. This information may be helpful for glaucoma surgeons to advise the patients on postoperative risks of surgery.

VEGF-D-mediated signaling in tendon cells is involved in degenerative processes.

Vascular endothelial growth factor (VEGF) signaling is crucial for a large variety of cellular processes, not only related to angiogenesis but also in nonvascular cell types. We have previously shown that controlling angiogenesis by reducing VEGF-A signaling positively affects tendon healing. We now hypothesize that VEGF signaling in non-endothelial cells may contribute to tendon pathologies. By immunohistochemistry we show that VEGFR1, VEGFR2, and VEGFR3 are expressed in murine and human tendon cells in vivo. In a rat Achilles tendon defect model we show that VEGFR1, VEGFR3, and VEGF-D expression are increased after injury. On cultured rat tendon cells we show that VEGF-D stimulates cell proliferation in a dose-dependent manner; the specific VEGFR3 inhibitor SAR131675 reduces cell proliferation and cell migration. Furthermore, activation of VEGFR2 and -3 in tendon-derived cells affects the expression of mRNAs encoding extracellular matrix and matrix remodeling proteins. Using explant model systems, we provide evidence, that VEGFR3 inhibition prevents biomechanical deterioration in rat tail tendon fascicles cultured without load and attenuates matrix damage if exposed to dynamic overload in a bioreactor system. Together, these results suggest a strong role of tendon cell VEGF signaling in mediation of degenerative processes. These findings give novel insight into tendon cell biology and may pave the way for novel treatment options for degenerative tendon diseases.

Novel point-of-care biomarkers of the dry anophthalmic socket syndrome: tear film osmolarity and matrix metalloproteinase 9 immunoassay.

PURPOSE: To compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of the MMP-9 and TFO as objective biomarkers for the dry anophthalmic socket syndrome (DASS). METHODS: In this prospective single-center study, the anophthalmic sockets and healthy fellow eyes of 98 unilateral anophthalmic patients were assessed using the ocular surface disease index (OSDI) questionnaire, InflammaDry® MMP-9 point-of-care immunoassay, TFO with TearLab™ Osmolarity System, and clinical conjunctival inflammation. MMP-9 concentration and conjunctival inflammation were graded semi-quantitatively. Differences between anophthalmic sockets and the healthy fellow eyes for OSDI scores, MMP-9, TFO values, clinical conjunctival inflammation, and eyelid abnormalities as well as the correlation between these factors and demographic data were evaluated. RESULTS: Patients had significantly higher OSDI, MMP-9, and TFO values, as well as higher conjunctival inflammation on the anophthalmic side, compared to the healthy side (p ≤ 0.002, respectively). For anophthalmic sockets, there was a significant positive correlation between OSDI scores and TFO values (p = 0.007), between the grade of posterior blepharitis and TFO values (p = 0.026), and between the conjunctival inflammation and MMP-9 values (p < 0.001), as well as between MMP-9 levels and time since eye loss (p = 0.004). CONCLUSIONS: Measuring MMP-9 and TFO may be helpful tools as efficient, quantifiable biomarkers, disease course parameters, or predictors for treatment response in the clinical management of patients with DASS or future therapy studies. Ophthalmologists should consider the updated diagnosis criteria including TFO and the definition for DASS proposed in this study.

Age-related changes of the periocular morphology: a two- and three-dimensional anthropometry study in Caucasians.

PURPOSE: To determine age-and sex-related changes in periocular morphology in Caucasians using a standardized protocol. METHODS: Healthy Caucasian volunteers aged 18-35 and 60-90 years old were recruited from the Department of Ophthalmology, Faculty of Medicine and University Hospital, Cologne, between October 2018 and May 2020. Volunteers with facial asymmetry, facial deformities, history of facial trauma, facial surgery, botox injection, eyelid ptosis, strabismus, or nystagmus, were excluded. Standardized three-dimensional facial photos of 68 young volunteers and 73 old volunteers were taken in this clinical practice. Position changes of endocanthion, pupil center, and exocanthion were analyzed in different age and gender groups, including palpebral fissure width (PFW): distance between endocanthions (En-En), pupil centers (Pu-Pu), exocanthions (Ex-Ex), endocanthion and nasion (En-Na), pupil center and nasion (Pu-Na), exocanthion and nasion (Ex-Na), endocanthion and pupil center (Pu-En), exocanthion and pupil center (Pu-Ex), and palpebral fissure inclination (PFI); angle of endocanthions to nasion (En-Na-En), pupils to nasion (Pu-Na-Pu), exocanthions to nasion (Ex-Na-Ex); endocanthion inclination (EnI), and exocanthion inclination (ExI). RESULTS: PFW, En-En, Ex-Na, Pu-Ex, PFI, ExI, and Ex-Na-Ex were significantly different between the young and old groups (p ≤ 0.004). There were sex-related differences in PFW, Ex-Ex, En-Na, Pu-Na, Ex-Na, Pu-En, PFI, and EnI between both groups (p ≤ 0.041). CONCLUSION: The position change of the pupil is minimal relative to age; it is preferred to establish the reference plane to describe periocular changes. The endocanthion tends to move temporally and inferiorly, while the exocanthion tends to shift nasally and inferiorly with age.

Immediate postoperative topical lidocaine gel for the treatment of eye pain following corneal abrasion in descemet membrane endothelial keratoplasty (DMEK) under general anaesthesia: a pilot retrospective analysis.

BACKGROUND: Patients undergoing corneal abrasion as part of Descemet membrane endothelial keratoplasty (DMEK) under general anesthesia suffer from early burning pain postoperatively. This pain appears to be poorly treatable with systemic analgesics. This study aims to evaluate postoperative pain management using topical lidocaine gel after DMEK with iatrogenic corneal abrasion. METHODS: Retrospective analysis of 28 consecutive patients undergoing DMEK with corneal abrasion from October 19, 2021, to November 12, 2021, at a German university hospital. Patients during week 1 and 2 received peri-operative standard pain treatment (cohort S) and additional local lidocaine gel during week 3 and 4 immediately postoperatively (cohort L). RESULTS: 13 patients were included in cohort S and 15 patients in cohort L. At awakening all patients (100%) in cohort S reported burning pain, and six of 15 patients (40%) in cohort L reported burning pain. Burning pain scores were significantly lower in cohort L (p < 0.001 at awakening, p < 0.001 at 10 min, p < 0.001 at 20 min, p < 0.001 at 30 min, p = 0.007 at 40 min after awakening, and p < 0.001 at leaving recovery room). No significant differences between cohort S and cohort L were detected concerning surgical outcome during 1-month-follow-up (p = 0.901 for best corrected visual acuity). CONCLUSION: Patients undergoing DMEK with corneal abrasion suffer significant pain in the recovery room. A single dose of topic lidocaine gel reduces the early postoperative burning pain sufficiently and does not affect the surgical outcome.

Current management of uveal melanoma: A review.

Uveal melanoma is the most frequent primary intraocular cancer in adulthood and is mostly localised to the choroid. It can be treated using radiation therapy, laser therapy, local resection and enucleation, with the best results achieved by combining these procedures. However, up to half of patients develop metastatic disease. There are no efficacious treatment methods for patients in advanced stage or with metastasis. In recent years, several novel treatment modalities aimed at improving tumour control and reducing adverse events have emerged. This review summarises current clinical treatment methods and new therapeutic perspectives for uveal melanoma.

Quantifying Dermatochalasis Using 3-Dimensional Photogrammetry.

BACKGROUND: Creating an appropriate treatment plan for patients with dermatochalasis requires careful investigation of the periocular region. Utilizing photographic documentation can assist physicians in conducting preoperative analysis and managing expectations regarding surgical outcomes. OBJECTIVES: This study aimed to quantify the periocular characteristics of dermatochalasis patients using standardized 3D imaging and to compare age and sex-related changes in periocular features. METHODS: In this cross-sectional study, we recruited 145 Caucasian patients with periocular dermatochalasis, comprising 48 men and 97 women, aged between 35 and 91 years. Standardized three-dimensional facial photographs were taken using the 3D Imaging system VECTRA M3. Linear dimensions, curve length, angle, indices, and sizes were measured and analyzed, including palpebral fissure height (PFH), palpebral fissure width (PFW), upper lid fold-palpebral margin distance (FPD), upper palpebral margin length (UPML), lower palpebral margin length (LPML), canthal tilt (CT), palpebral fissure index (PFI), upper eyelid area, and ocular surface area. RESULTS: In the female group, the left-side PFH was slightly larger than the right-side PFH (P = 0.023), but the difference was less than 1mm. The corresponding PFI also showed a difference in the female group (P = 0.009). Statistically significant differences were shown in genders for specific parameters, except PFI (P = 0.251) and CT (P = 0.098). Among males, PFW (R = -0.523, p < 0.001) and LPML (R = -0.514, P = 0.264) decreased moderately with age. The correlation between UPML and age was weak (R = -0.367, P = 0.010). Similarly, among females, moderate correlations were found between age and PFW (R = -0.566, P < 0.001) and LPML (R = -0.537, P < 0.001). Additionally, PFH (R = -0.315, P = 0.002), UPML (R = -0.381, P < 0.001), and ocular surface area (R = -0.457, P < 0.001) showed weak correlations with age. CONCLUSIONS: The study found that dermatochalasis usually affects both eyes simultaneously, and age is a significant factor in the morphological changes of certain periocular features regardless of sex. The PFI is not influenced by age or sex. These findings may provide useful information for surgical planning and understanding age-related changes in the periocular area. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Viral Conjunctivitis: Findings, Therapy, and Prophylaxis]. / Virale Bindehautentzündungen: Befunde, Therapie und Prophylaxe.

Viral conjunctivitis is one of the most common acute eye diseases. The fall and winter months are known to be the main season for viral infections which is also reflected in the ophthalmological outpatient clinics. Viral conjunctivitis is often accompanied by symptoms of the upper and lower respiratory tract, fever, chills, arthralgia or skin lesions. The spectrum of pathogens comprises DNA viruses such as Adeno-, Herpes simplex and Molluscum contagiosum as well as RNA viruses. Symptoms caused by pandemic pathogens such as SARS-CoV-2 and mpox viruses can also cause ocular manifestation. Viral conjunctivitis is often self-limiting leaving no residual symptoms, however an ophthalmologist should be consulted if there are inflammatory symptoms of the anterior eye accompanied by visual disturbance. It is particularly important to recognize the affection of corneal or even intraocular structures early to initiate an adequate and effective therapy. Affection of the cornea, vitreus or retina can result in temporary or permanent impairment of the field of vision and visual acuity. The diagnosis is usually made without further tests on the basis of the typical clinical presentation. Rapid tests or PCR diagnostics are also available for confirmation. In most patients the treatment is symptomatically with artificial tears and antibiotic eye drops in cases accompanied by secondary bacterial infections, not prophylactically. If the cornea or other ocular structures are affected by certain viruses, local as well as systemic virostatic therapy is initiated. The most important prophylactic measure is meticulous and consistent hygiene.

Clinical Signs for Differential Diagnosis of Eyelid Tumours.

This article aims to present the differential diagnostics of benign and malignant eyelid tumours. The most common malignant eyelid tumour is basal cell carcinoma, followed by squamous cell carcinoma. The common signs of malignity are loss of lashes, ulceration, and infiltration of the lesion. Often the clinical appearance is various and therefore only a histological analysis gives the proper diagnosis. For most tumours, surgical resection is the gold standard of therapy. The reconstruction of the defects should be performed by an experienced oculoplastic surgeon. In malignant tumours that require large safety margins, the defect can be easily very large, and the reconstruction must then be performed with advanced ophthalmic plastic reconstruction techniques.

Evaluation of the Portable Next-Generation VECTRA H2 3D Imaging System for Measuring Upper Eyelid Area and Volume.

BACKGROUND: Although a portable 3-dimensional (3D) imaging system has been used for periocular measurement analysis, this system has yet to be tested and validated for periocular area and volume measurements. OBJECTIVES: The aim of this study was to define the upper eyelid and upper eyelid fold region through a modified landmark strategy and validate a portable 3D imaging system for area and volume measurements in this periocular region. METHODS: Eighty-one healthy adult Caucasians underwent 3D facial imaging with the VECTRA M3 (static) and VECTRA H2 (portable) 3D imaging systems (Canfield Scientific, Inc., Parsippany, NJ). Subsequently, the upper eyelid and upper eyelid fold regions were selected according to a modified landmark localization strategy. Direct measurements of area and volume were performed to assess intrarater, interrater, intramethod, and intermethod reliability, and to compare the agreement between the 2 devices. RESULTS: The VECTRA M3 and H2 showed high reliability on upper eyelid area measurements. Excellent intra-, inter-, and intramethod reliability agreements were observed in intraclass correlation coefficient; very good agreement in intrarater reliability was observed in the relative error of measurement (REM) and relative technical error of measurement (rTEM); and good inter- and intramethod reliability were observed in the REM and rTEM. For area measurement of the upper eyelid fold, the intrarater, interrater, and intramethod reliability of the M3 was lower than that of the H2. Both systems had poor intrarater, interrater, and intramethod reliability for volume measurements in the upper eyelid and upper eyelid fold region. CONCLUSIONS: This new portable 3D imaging system achieved excellent or very good reliability values for standardized direct measurements of the upper eyelid and upper eyelid fold region, although volume measurements seem less reliable.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

[Congenital anomalies in lacrimal drainage]. / Angeborene Fehlbildungen der ableitenden Tränenwege.

Congenital dacryostenosis is the most common reason for ophthalmic consultation in childhood. It is most often caused by persisting of Hasner's membrane. However, congenital malformations of the lacrimal drainage system can also occur in rare cases. In the area of the proximal lacrimal drainage system, supernumerary lacrimal puncta and canaliculi can arise as well as diverticula, fistula, and atresia. The distal lacrimal drainage system can be affected by fistulas, amniotoceles, and cysts. Association of lacrimal malformations with congenital systemic diseases is reported in about 10% of cases. Depending on the severity of the symptoms, surgical rehabilitation can be performed, and endoscopic procedures and modern lacrimal drainage intubation systems may be employed.

Recent advances in graves ophthalmopathy medical therapy: a comprehensive literature review.

Graves ophthalmopathy (GO), which occurs in autoimmune thyroid disease, can reduce patients' quality of life due to its impact on visual function, physical appearance, and emotional health. Corticosteroids have been the first-line treatment for GO. More recently, the pathogenesis of GO has made significant progress. Various targeting biological agents and immunosuppressive agents make GO management more promising. Fully understanding GO pathogenesis and precise clinical management are beneficial for the prognosis of patients. Therefore, we conducted a comprehensive review of the medical management of GO and summarized research developments to highlight future research issues.

A Narrative Review - Therapy Options and Therapy Failure in Retinoblastoma.

Retinoblastoma (RB) management has evolved over the last three decades. Goals of modern RB treatment are first to protect life and prevent metastatic disease, then preservation of the globe and useful vision. With modern treatment protocols and early disease detection success rates can reach up to 100% of disease-free-globe and eye preservation. Treatment of advanced cases remains complex, requiring aggressive chemotherapy or/and external beam radiation. Treatment protocols are extremely diverse and dependent on local resources thus success rates are variable. Here we review narratively current treatment protocols and failure rates based on a PubMed search using keywords of retinoblastoma, retinoblastoma seed, retinoblastoma treatment, enucleation.

Therapy Failure and Resistance Mechanism in Eyelid and Ocular Surface Tumors.

Malignant tumors of the eyelids and ocular surface are common ocular malignancies. At present, surgical treatment is mostly the first choice for these types of tumors. However, postoperative tumor recurrence and metastasis are still regarded as failures in the treatment of such malignancies. Based on this, malignant tumors of the eyelid and ocular surface are sometimes accompanied by local adjuvant chemotherapy and systemic chemotherapy to treat patients with relapse, invasion of adjacent tissues, and systemic metastases. Still, drug resistance greatly affects the treatment effect. This review lists several mechanisms of recurrence and metastasis of ocular surface and eyelid tumors after surgery, as well as mechanisms that may lead to non-surgical treatment or drug resistance.

Membrane-bound IL-6R is upregulated on Th17 cells and inhibits Treg cell migration by regulating post-translational modification of VASP in autoimmune arthritis.

Autoimmune arthritis is characterized by impaired regulatory T (Treg) cell migration into inflamed joint tissue and by dysregulation of the balance between Treg cells and Th17 cells. Interleukin-6 (IL-6) is known to contribute to this dysregulation, but the molecular mechanisms behind impaired Treg cell migration remain largely unknown. In this study, we assessed dynamic changes in membrane-bound IL-6 receptor (IL6R) expression levels on Th17 cells by flow cytometry during the development of collagen-induced arthritis (CIA). In a next step, bioinformatics analysis based on proteomics was performed to evaluate potential pathways affected by altered IL-6R signaling in autoimmune arthritis. Our analysis shows that membrane-bound IL-6R is upregulated on Th17 cells and is inversely correlated with IL-6 serum levels in experimental autoimmune arthritis. Moreover, IL-6R expression is significantly increased on Th17 cells from untreated patients with rheumatoid arthritis (RA). Interestingly, CD4+ T cells from CIA mice and RA patients show reduced phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Bioinformatics analysis based on proteomics of CD4+ T cells with low or high phosphorylation levels of VASP revealed that integrin signaling and related pathways are significantly enriched in cells with low phosphorylation of VASP. Specific inhibition of p-VASP reduces the migratory function of Treg cells but has no influence on effector CD4+ T cells. Importantly, IL-6R blockade restores the phosphorylation level of VASP, thereby improving the migratory function of Treg cells from RA patients. Thus, our results establish a link between IL6R signaling and phosphorylation of VASP, which controls Treg cell migration in autoimmune arthritis.