Serum IL-17 and TNFα as prognostic biomarkers in systemic sclerosis patients: a prospective study.

Recent reports have demonstrated that endothelial injury is critical in the pathogenesis of systemic sclerosis (SSc) and is associated with increased levels of circulating inflammatory biomarkers. This study aims to analyze the serum concentrations of selected cytokines and evaluate their relationship with SSc clinics and the long-term course of the disease. This study included 43 SSc patients and 24 matched healthy controls. In both groups, we measured serum levels of inflammatory cytokines related to the inflammatory response, such as tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)-4, IL-6, IL-10, and IL-17, and fibroblast activation protein (FAP). Additionally, in SSc patients, we evaluated the presence of four single nucleotide polymorphisms (SNPs) located in the promotor region of the TNFA gene, namely rs361525, rs1800629, rs1799964, and rs1799724, which might be related to increased TNFα concentrations. The main aim consisted of associating inflammatory cytokines with (1) clinical disease characteristics and (2) longitudinal observation of survival and cancer prevalence. SSc patients were characterized by a 17% increase in serum TNFα. There was no other difference in serum cytokines between the studied groups and diffuse vs. limited SSc patients. As expected, evaluated serum cytokines correlated with inflammatory biomarkers (e.g., IL-6 and C-reactive protein). Interestingly, patients with higher IL-17 had decreased left ventricle ejection fraction. During the median 5-year follow-up, we recorded four cases of neoplastic diseases (lung cancer in two cases, squamous cell carcinoma of unknown origin, and breast cancer with concomitant multiple myeloma) and nine deaths. The causes of death included lung cancer (n = 2), renal crisis (n = 1), multiple-organ failure (n = 1), and unknown reasons in five cases. Surprisingly, higher TNFα was associated with an increased cancer prevalence, while elevated IL-17 with death risk in the follow-up. Furthermore, the AG rs361525 genotype referred to higher TNFα levels than GG carriers. Both AG rs361525 and CT rs1799964 genotypes were associated with increased cancer risk. Higher serum concentrations of TNFα characterize the SSc patients, with the highest values associated with cancer. On the other hand, increased IL-17 in peripheral blood might predict poor SSc prognosis. Further research is needed to validate these findings.

Use of Optical Coherence Tomography and Optical Coherence Tomography Angiography in the Diagnosis and Follow-Up of Endogenous Candida Endophthalmitis: A Case Report.

Background: Endogenous Candida endophthalmitis (ECE) is a rare but sight-threatening disease. Patients with ECE present with various clinical signs and symptoms, which can complicate the diagnosis. The aim of this report was to demonstrate the outcomes of treatment and to diagnose macular complications caused by intraocular inflammation. Case presentation: A 41-year-old woman with a history of acute intermittent porphyria presented with a progressive vision loss in her left eye. Left-eye OCT revealed findings consistent with a fungal etiology, which was confirmed by the culture of swabs collected from a central vein catheter. The outcomes of intravenous fluconazole treatment were not satisfactory, and the patient developed recurrent attacks of porphyria, suggesting a porphyrogenic effect of systemic antifungal therapy. Repeated intravitreal injections with amphotericin B led to a gradual regression of inflammatory lesions. However, follow-up examinations revealed active macular neovascularization (MNV) on both OCT and OCTA scans. The patient was administered intravitreal bevacizumab. At the 11th month of follow-up, OCT and OCTA scans showed significant inflammatory lesions regression with macula scarring, and no MNV activity was detected. Conclusions: This case highlights the importance of OCT and OCTA as valuable noninvasive imaging techniques for the identification of ECE, the monitoring of its clinical course, and the diagnosis of macular complications.

Diagnostic Challenges in Inflammatory Choroidal Neovascularization.

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

Circulating Anti-Endothelial Cell Antibodies in Patients with Geographic Atrophy Related to Dry Age-Related Macular Degeneration.

Background and Objectives: Age-related macular degeneration (AMD) is one of the leading causes of central vision loss among elderly patients, and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As inflammation and immune system involvement are strongly suggested to play a central role in promoting the degenerative process and stimulating the onset of complications, we aimed to analyze the frequency of serum anti-retinal (ARAs) and anti-endothelial cell antibodies (AECAs) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably the area of geographic atrophy (GA). Materials and Methods: This study included 41 patients with advanced-stage dry AMD and 50 healthy controls without AMD, matched for gender and age. ARAs were detected by indirect immunofluorescence using monkey retina as an antigen substrate, and the presence of AECAs was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARAs were detected in 36 (87.8%) AMD patients (titers ranged from 1:20 to 1:320) and in 16 (39.0%) (titers ranged from 1:10 to 1:40) controls (p = 0.0000). Twenty of the forty-one patients (48.8%) were positive for AECAs, while in the control group, AECAs were present only in five sera (10.0%). The titers of AECAs in AMD patients ranged from 1:100 to 1:1000, and in the control group, the AECA titers were 1:100 (p = 0.0001). There were no significant correlations between the presence of AECAs and disease activity. Conclusions: This study demonstrates a higher prevalence of circulating AECAs in patients with dry AMD; however, no correlation was found between the serum levels of these autoantibodies and the area of GA.

Diagnostic and Therapeutic Challenges in a Patient with Radiation Retinopathy Complicated by Corticosteroid-Induced Central Serous Chorioretinopathy.

Central serous chorioretinopathy (CSC) is a common chorioretinal disorder. It has been postulated that impaired retinal pigment epithelium and hyperpermeability of the choriocapillaris may be involved in the development of CSC, but the exact pathomechanism has not been established. We report an unusual case of a middle-aged man who developed CSC after triamcinolone acetonide injection for macular edema. Edema developed as a late complication of radiation retinopathy after brachytherapy for childhood retinoblastoma. Steroid treatment is an important risk factor for CSC, but the underlying causative mechanisms have not been fully elucidated. It is important to increase the awareness of this link among clinicians who prescribe exogenous corticosteroids, irrespective of the route of administration.

Changes in Plasma VEGF and PEDF Levels in Patients with Central Serous Chorioretinopathy.

Background and Objectives: Retinal pigment epitheliopathy and hyperpermeability of choroidal vessels were postulated to be involved in the pathogenesis of central serous chorioretinopathy (CSC). Imbalanced levels of vascular endothelial growth factor (VEGF) and pigment-epithelium-derived factor (PEDF) were previously implicated in the development of chorioretinal diseases characterized by increased vascular permeability. We aimed to compare the plasma levels of proangiogenic VEGF and antiangiogenic PEDF for 26 patients with acute CSC, 26 patients with chronic CSC, and 19 controls. Materials and Methods: VEGF and PEDF levels were measured using a multiplex immunoassay or enzyme-linked immunosorbent assay. Correlations with disease duration were assessed. Results: VEGF levels differed between groups (p = 0.001). They were lower in patients with acute CSC (p = 0.042) and chronic CSC (p = 0.018) than in controls. PEDF levels were similar in all groups. The VEGF-to-PEDF ratio was lower in CSC patients than in controls (p = 0.04). A negative correlation with disease duration was noted only for PEDF levels in the group with chronic CSC (rho = -0.46, p = 0.017). Discussion: Our study confirmed that patients with CSC have imbalanced levels of VEGF and PEDF. This finding may have important implications for the pathogenesis of CSC. VEGF-independent arteriogenesis rather than angiogenesis may underlie vascular abnormalities in these patients.

The use of mineralocorticoid receptor antagonists in chronic central serous chorioretinopathy.

AIM: To assess the effect of eplerenone on macular structure and function in patients with chronic central serous chorioretinopathy. MATERIAL AND METHODS: 17 eyes of 16 patients (aged 32-66 years) with chronic central serous chorioretinopathy treated at the Department of Ophthalmology and Ocular Oncology, Jagiellonian University in Cracow were enrolled. The duration of symptoms ranged between 4 and 24 months. The patients were dosed with eplerenone according to the scheme: first 25 mg/day for a week, then 50 mg/day for 3 months. The baseline examination and two follow-up visits (after 1-1,5 months and after 3-4 months respectively) involved best corrected visual acuity (Snellen, decimal scale), central retinal thickness in optical coherence tomography and visual disturbances in Amsler test. RESULTS: The mean best corrected visual acuity improved from 0.61 (±0.25) to 0.67 (±0.28) and 0.72 (±0.28) at the first and second follow-up appointment, respectively. Central retinal thickness declined from 367 µm (±70) to 264 µm (±50) and 248 µm (±50) at the first and second follow up appointment, respectively (p<0.05). Amsler test findings improved in 10 eyes (58.8%), while the deterioration in central vision remained unchanged in 7 eyes (41.2%) at the first follow up appointment. During the second follow-up appointment, though, Amsler test improvement was reported in 7 eyes (50%), while the deterioration in central vision remained unchanged in 7 eyes (50%). CONCLUSIONS: Our study suggests that eplerenone may provide an alternative treatment of chronic central serous chorioretinopathy, especially in patients with known contraindications to or ineligible for other treatments (for instance, retinal laser photocoagulation). Further randomized controlled trial is required.

Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha.

BACKGROUND: Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc). OBJECTIVES: This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc. MATERIAL AND METHODS: This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer. RESULTS: The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9). CONCLUSIONS: The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.

Association between Subjective and Objective Assessment of Enucleation Outcome Depending on the Presence of an Orbital Implant in Patients with Uveal Melanoma.

We aimed to assess the cosmetic outcome of patients who underwent enucleation for uveal melanoma. The subjective assessment was based on a questionnaire, including four questions on postoperative cosmetic outcome. As part of the objective assessment, the following features were evaluated using a four-point scale: the symmetry of the upper eyelid sulcus, color matching between the prosthetic and healthy eye, prosthetic eye motility, and eyelid position. We enrolled 90 patients after enucleation (58 with and 32 without an orbital implant). The overall subjective assessment scores were 3.5/4 and 3.3/4 points in patients with and without an implant, respectively. The overall objective assessment scores were 3.3/4 and 2.3/4 in patients with and without an implant, respectively (p < 0.001). The cosmetic outcome was rated significantly higher by patients than by investigators (p < 0.05). There was no significant association between the overall subjective and objective assessment of the cosmetic outcome in any of the groups. Cosmetic outcome after enucleation for uveal melanoma was highly rated by patients. It was rated higher by patients than by investigators. The presence of an orbital implant was associated with higher objective assessment scores in terms of the symmetry of the upper lid sulcus, prosthetic eye motility, and eyelid position.

Acute Macular Neuroretinopathy in a Patient with Retinal Vascular Tortuosity.

We report a rare case of a young woman with acute macular neuroretinopathy (AMN) in the right eye and concomitant retinal vascular tortuosity in both eyes. A 19-years-old woman presented with a sudden loss of central vision in the right eye. Apart from flu-like infection 2 weeks before the onset of symptoms, she reported overall good health. She used oral contraceptive pills. Multimodal imaging techniques including color fundus photography, fundus autofluorescence, infrared reflectance imaging, fluorescein angiography, swept-source optical coherence tomography (SS-OCT), and visual field assessment were used for the diagnosis of AMN as well as disease monitoring during follow-up. At presentation, ophthalmoscopy revealed a reddish parafoveal lesion, while SS-OCT showed hyper-reflectivity in the outer plexiform and outer nuclear layers with a slightly disrupted inner segment/outer segment junction. All these imaging findings indicated AMN, but the interpretation was slightly difficult due to the presence of tortuous retinal arteries in both eyes. During the disease course, functional and morphological recovery was documented at 1- and 6-month follow-up. However, as the abnormal appearance of the retinal vessels did not change, congenital retinal vascular tortuosity was diagnosed. Since the pathogenesis of AMN has not been fully elucidated, there is currently no effective treatment. Numerous studies have emphasized a vascular origin and the key role of ischemia in AMN. Our rare case suggests that congenital tortuosity of the retinal vessels, although constituting a common finding in healthy individuals, may be involved in the pathophysiology of the disease.

Imbalance in the Levels of Angiogenic Factors in Patients with Acute and Chronic Central Serous Chorioretinopathy.

BACKGROUND: The pathogenesis of central serous chorioretinopathy (CSC) remains a subject of intensive research. We aimed to determine correlations between plasma levels of selected angiogenic factors and different forms of CSC. METHODS: Eighty patients were enrolled in the study including 30 with a chronic form of CSC, 30 with acute CSC, and 20 controls. Presence of active CSC was determined by fluorescein angiography (FA), indocyanine green angiography (ICGA), and swept-source optical coherence tomography (SS-OCT). Plasma concentrations of angiopoietin-1, endostatin, fibroblast growth factor, placental growth factor (PlGF), platelet-derived growth factor (PDGF-AA), thrombospondin-2, vascular endothelial growth factor (VEGF), VEGF-D, and pigment epithelium-derived factor were measured, and the results were compared between groups. Additionally, mean choroidal thickness (CT) was measured in all patients. RESULTS: Levels of angiopoietin-1 (p = 0.008), PlGF (p = 0.045), and PDGF-AA (p = 0.033) differed significantly between the three groups. Compared with the controls, VEGF (p = 0.024), PlGF (p = 0.013), and PDGF-AA (p = 0.012) were downregulated in the whole CSC group, specifically PDGF-AA (p = 0.002) in acute CSC and angiopoietin-1 (p = 0.007) in chronic CSC. An inverse correlation between mean CT and VEGF levels was noted in CSC patients (rho = -0.27, p = 0.044). CONCLUSIONS: Downregulated angiopoietin-1, VEGF, PDGF-AA, and PlGF levels may highlight the previously unknown role of the imbalanced levels of proangiogenic and antiangiogenic factors in the pathogenesis of CSC. Moreover, downregulated VEGF levels may suggest that choroidal neovascularization in CSC is associated with arteriogenesis rather than angiogenesis.

Diagnostic Algorithm for Conjunctival Melanocytic Lesions.

BACKGROUND/AIM: This study aimed to develop an algorithm allowing the differentiation between conjunctival melanoma and other melanocytic infiltrations of the conjunctiva, on the basis of a dermatoscopic examination. PATIENTS AND METHODS: A total of 160 conjunctival pigmented lesions were studied (40 melanomas and 120 non-melanoma conjunctival infiltrations). The clinical characteristics of the tumours were assessed with the use of dermatoscopic characteristics as described by Kittler, and with taking into consideration the typical characteristics of conjunctival lesions. RESULTS: On the basis of modified dermatoscopic criteria, an algorithm was generated consisting of an assessment of the presence of 9 suspicious characteristics, e.g. more than two colours, colour asymmetry, pattern asymmetry, vascular polymorphism, presence of short vessels, linear vascular pattern, the presence of a peripheral structureless area, the presence of a grey structureless area and black dots in any part of the lesion. The presence of any of these characteristics scores 1 point. If a melanocytic lesion scores ≥3 points, the probability of diagnosing melanoma is on the level of p>0.001. CONCLUSION: The use of the proposed algorithm, based on modified dermatoscopic characteristics, may be a valuable tool for the diagnosis of conjunctival melanoma.

Quality of life of patients with central serous chorioretinopathy - a major cause of vision threat among middle-aged individuals.

INTRODUCTION: The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was designed to measure the vision-related quality of life (QoL). We aimed to assess the effect of disease duration, disease type (i.e., acute vs. chronic and unilateral vs. bilateral), and selected sociodemographic data on the QoL of patients with central serous chorioretinopathy (CSC). MATERIAL AND METHODS: The study included 79 patients diagnosed with CSC. The QoL was assessed using the NEI VFQ-25. The statistical analysis was performed using IBM SPSS Statistics 24. RESULTS: A significant positive correlation was found between deterioration in peripheral vision as assessed by the NEI VFQ-25 and duration of CSC (r = -0.22, p = 0.046). Compared with women, men obtained higher scores on the scales assessing general health, mental health, ocular pain and role limitations (p = 0.018, p = 0.027, p = 0.009 and p = 0.007, respectively). Patients with acute CSC reported higher levels of social functioning as compared with those with chronic CSC (p = 0.04). There were no differences in any of the scales between patients with unilateral and bilateral CSC. Elderly patients obtained lower scores on 9 of the 12 analyzed scales, as compared with younger patients (p < 0.05). CONCLUSIONS: Patients with CSC do not assess their QoL in negative terms, which may be related to the fact that the disease presents with transient symptoms. However, the QoL deteriorated with longer disease duration. Men with CSC have better vision-related QoL than women.

Altered plasma cytokine levels in acute and chronic central serous chorioretinopathy.

PURPOSE: To evaluate plasma levels of selected cytokines and investigate their correlation with choroidal thickness (CT) in patients with acute and chronic central serous chorioretinopathy (CSC). METHODS: We enrolled 30 patients with acute CSC, 30 patients with chronic CSC and 20 controls. Plasma concentrations of 12 cytokines, interleukins IL-8, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10 and IL-12 p70, granulocyte-macrophage colony-stimulating factor, interferon-γ, tumour necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), were measured using multiplex immunoassays. Differences in cytokine levels between groups were assessed. We also investigated correlations between cytokine levels and CT using swept-source optical coherence tomography, as well as an association between plasma cytokine profile and systemic hypertension. RESULTS: We noted differences in IL-6 (p = 0.005), IL-10 (p = 0.03), IL-12 p70 (p = 0.028) and VEGF (p = 0.029) levels between groups. Pro-inflammatory IL-12 p70 and multidirectional IL-10 cytokines were upregulated, while pro-angiogenic VEGF was downregulated in chronic CSC as compared with controls (p = 0.005, p = 0.025 and p = 0.027, respectively). Interleukin-6 (IL-6) was upregulated in acute and chronic CSC (p = 0.030 and p = 0.005, respectively). Interleukin-5 (IL-5), IL-6 and IL-12 levels correlated with mean CT in acute CSC (p = 0.008, p = 0.003 and p = 0.044, respectively), while IL-8, IL-6 and TNF-α plasma levels correlated with hypertension in chronic CSC (p = 0.005, p = 0.033 and p = 0.001, respectively). CONCLUSION: We provided new evidence for the possible role of plasma cytokines in the pathogenesis of CSC. Our results suggest that IL-6 may be important in the pathophysiology of acute and chronic CSC. The association between inflammatory response and hypertension in patients with CSC was also confirmed.

Toxocara Optic Disc Granuloma: Deep Range Imaging Optical Coherence Tomography Findings.

We aimed to present a unique case of a child with an optic disc granuloma with exudative retinal detachment as a manifestation of ocular toxocariasis. The response to systemic therapy was assessed using deep range imaging optical coherence tomography. This imaging technique was the most accurate for identification of retinal, macular and vitreous changes associated with this intraocular pathology.

Sudden Visual Deterioration as the First Symptom of Chronic Kidney Failure.

PURPOSE: We report here a unique case of a sudden loss of vision as the first symptom of an advanced chronic nephropathy. METHODS AND RESULTS: A 25-year-old man was referred to the Department of Ophthalmology with sudden visual deterioration presumptively diagnosed as bilateral retinitis. The patient had never been under any medical care before and had never had any clinical signs of any chronic disease. He underwent an ophthalmic examination with optical coherence tomography (OCT). Based on the clinical features, OCT scans and systemic blood pressure (BP) assessment (225/145 mm Hg), the patient was definitely diagnosed with hypertensive retinopathy and choroidopathy due to hypertensive crisis. After urgent diagnostic procedures, the patient was diagnosed with a chronic kidney disease at stage 5 in the course of chronic glomerulonephritis. Immediately, a renal replacement therapy was started and the patient was qualified for renal transplantation. CONCLUSION: Adolescents with an unclear picture of retinal lesions, who have neither a history nor clinical signs of a systemic disease, should undergo careful systemic screening with BP assessment. A sudden deterioration of vision may be the first symptom of a previously undiagnosed severe systemic disease (very rare chronic) that requires immediate treatment.