The Complex Network of Cytokines and Chemokines in Pediatric Patients with Long-Standing Type 1 Diabetes.

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications.

Local T cell infiltrates are predominantly associated with corneal allograft rejection.

BACKGROUND: Corneal transplantations (CTXs) are a vision-saving procedure. Routinely, while CTXs' survival rates remain high, the risk of graft failure increases significantly for repeated CTXs. The reason is an alloimmunization following previous CTXs and development of memory T (Tm) and B (Bm) cells. METHODS: We characterized populations of cells present in explanted human corneas from patients receiving the first CTX and marked as a primary CTX (PCTX) or the second or more CTXs and marked as a repeated CTX (RCTX). Cells extracted from resected corneas and from peripheral blood mononuclear cells (PBMCs) were analyzed by the flow cytometry method using multiple surface and intracellular markers. RESULTS: Overall, the number of cells was similar in PCTX and RCTX patients. Extracted infiltrates from PCTXs and RCTXs contained similar numbers of T cell subsets, namely CD4+, CD8+, CD4+ Tm, CD8+ Tm, CD4+Foxp3+ T regulatory (Tregs), CD8+ Treg cells, while very few B cells (all p = NS). However, when compared to peripheral blood, PCTX and RCTX corneas contained significantly higher percentages of effector memory CD4+ and CD8+ T cells (both p < 0,05). In comparison to PCTX, RCTX group had the highest levels of Foxp3 in T CD4+ Tregs (p = 0,04) but decreased percentage of Helios-positive CD4+ Tregs. CONCLUSION: PCTXs and especially RCTXs are rejected mainly by local T cells. The accumulation of effector CD4+ and CD8+ T cells, as well as CD4+ and CD8+ Tm cells is associated with the final rejection. Furthermore, local CD4+ and CD8+ Tregs expressing Foxp3 and Helios are probably insufficient to impose the acceptance of CTX.

Cytomegaloviral Retinitis in a Heart Transplant Patient: Case Report and Review of the Literature.

Cytomegalovirus (CMV) poses a significant threat to solid organ transplant recipients (SOTR). The incidence of CMV disease in SOTR varies according to immunosuppressive therapy, antiviral prophylaxis, donor and recipient serologic compatibility, and the transplanted organ: 9% to 23%, 22% to 29% and 8% to 32% after heart, liver and kidney transplant, respectively. CMV retinitis (CMVR) is a rare manifestation of CMV with a high risk of blindness. Infection may vary in severity, from initially clinically silent cases to full-blown advanced changes involving the eye. The most characteristic effects are changes in the retina, which usually begin at the retina's periphery and are asymptomatic, then these changes spread toward the center as the disease progresses and impairs vision. We describe CMV vitritis and retinitis in a 74-year-old patient after heart transplantation conducted in 1992. The first symptom of the disease was low vision in the left eye. Initially no blood viremia was observed; then the CMV viral load in the blood and vitreous body of the right eye was 2454 and 26 million IU/mL.Despite the initiation of treatment (intravitreal and then intravenous ganciclovir), the inflammatory process progressed rapidly and vision in the left eye was lost, although functional visual acuity in the right eye was maintained. Systemic antiviral therapy with intravenous ganciclovir lasted 6 weeks until the eradication of CMV viremia. The patient was on prophylactic therapy with oral valganciclovir for 12 months. A clinically silent course of CMVR delays diagnosis and therapy. Therefore, it is recommended that all SOTR undergo periodic ophthalmologic control to avoid delayed diagnosis.

Corneal Allografts: Factors for and against Acceptance.

Cornea is one of the most commonly transplanted tissues worldwide. However, it is usually omitted in the field of transplantology. Transplantation of the cornea is performed to treat many ocular diseases. It restores eyesight significantly improving the quality of life. Advancements in banking of explanted corneas and progressive surgical techniques increased availability and outcomes of transplantation. Despite the vast growth in the field of transplantation laboratory testing, standards for corneal transplantation still do not include HLA typing or alloantibody detection. This standard practice is based on immune privilege dogma that accounts for high success rates of corneal transplantation. However, the increasing need for retransplantation in high-risk patients with markedly higher risk of rejection causes ophthalmology transplantation centers to reevaluate their standard algorithms. In this review we discuss immune privilege mechanisms influencing the allograft acceptance and factors disrupting the natural immunosuppressive environment of the eye. Current developments in testing and immunosuppressive treatments (including cell therapies), when applied in corneal transplantation, may give very good results, decrease the possibility of rejection, and reduce the need for retransplantation, which is fairly frequent nowadays.

Ophthalmologic Diseases in Kidney Transplant Recipients: A Single-Center Prospective Study.

BACKGROUND: Kidney transplant (KTx) recipients usually experience many comorbidities (eg, hypertension, diabetes, cardiovascular disease, glaucoma). They usually are older and have some ophthalmologic disorders, which may deteriorate after Ktx and some others may develop. OBJECTIVE: We aimed to review a 1-year examination of the eyesight characteristics in patients after KTx. METHODS: The study encompassed 82 eyes in 41 patients who underwent KTx in the years 2014 to 2018. All patients had visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography. RESULTS: The most frequently observed changes during the 1-year observation were cataract (46%), hypertensive angiopathy (20%), and glaucoma (20%). One year after the renal transplant visual acuity declined in 22 patients (54%). In 45% of those with eyesight deterioration the cause was cataract, while in patients with no changes in eyesight (n = 9) cataract was not diagnosed. Patients with cataracts had been more often treated with high doses of steroids (steroid boluses), mainly because of acute rejection, which was significantly associated with cataract developing after Ktx (42% vs 11%; P = .019). On univariate analysis Charlson Comorbidity Index, total ischemic time, and steroid boluses were significantly associated with cataract developing after Ktx; none of these factors were an independent predictor on multivariate analysis. CONCLUSIONS: The most common ophthalmologic diagnoses in patients after Ktx include cataract, glaucoma, and hypertensive angiopathy. Visual acuity deterioration, seen so often in the studied group of the patients, was mainly the effect of cataract progress. The effect of steroid boluses on cataract progress was meaningful.

Pilot Study of Eyesight Characteristics and Thickness of the Retinal Nerve Fiber and Ganglion Cell-inner Plexiform Layers in Adolescent Patients with Type one Diabetes Mellitus on an Insulin Pump.

AIM: Estimation of the ocular status in adolescents with diabetes mellitus type 1 (DM1) treated with continuous subcutaneous insulin infusion (CSII), assessment of the development of the diabetic retinopathy (DR) and nephropathy (DN) within 10 years. METHODS: 37 patients (74 eyes) aged 16-33 years, treated with CSII were enrolled to the study. Baseline, and a 10- year follow-up evaluation included: best corrected visual acuity (BCVA), tonometry, slit lamp exam and fluorescein angiography (FLA). Additionally, spectral-domain optical coherence tomography (SD-OCT) was done in the 7th year of observation to assess the thickness of the retinal nerve fiber (RNFL) and the ganglion cellinner plexiform layers (GCL-IPL) complex thickness. Glycated haemoglobin (HbA1) and albuminuria were also analysed. RESULTS: During the 10-year observation period DR (non-proliferative - NPDR, proliferative - PDR, diabetic macular edema - DME) was diagnosed in 3 (8%) patients. In the DR group: BCVA was significantly lower, intraocular pressure (IOP) levels and albuminuria were higher. There were no differences in HbA1 in both groups. The thinning of RNFL was observed in both groups. Macular RNFL, GCL-IPL complex thickness assessment showed a significantly higher number of borderline results in the group with DR. CONCLUSIONS: Diabetic patients treated with CSII are at a lower risk of developing vascular complications even with poor metabolic control. Increased albuminuria may be a predictive sign for early ocular complications, and requires intense observation. Diagnosis of RNFL and GCL-IPL decreased values is crucial prior to diabetic retinopathy development. SD-OCT is a non-invasive, easy-to-perform, relatively inexpensive procedure, and can be a useful tool to monitor neuropathy progression.

The Level of Cytokines in the Vitreous Body of Severe Proliferative Diabetic Retinopathy Patients Undergoing Posterior Vitrectomy.

OBJECTIVE: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy. PATIENTS AND METHODS: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group). All patients underwent a comprehensive eye examination one day before and 3 weeks after the surgery, including measurements of: best-corrected visual acuity (BVCA) and intraocular pressure (IOP), slit-lamp examination and spectral domain optical coherence tomography (SOCT). Concentrations of cytokines: IL-6, IL-8, IL-12p70, TNF, IL-10, IL-1ß were measured in the vitreous body of patients with BD™ Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit. RESULTS: PDR patients who received pretreatment with aflibercept injection showed significantly lower concentrations of IL-12p70, TNF, IL-10 and IL-1ß in the vitreous body compared to the control group. Meanwhile, patients without prior aflibercept injection had a significantly higher concentration of IL-8. There was also a significant positive correlation between IOP before PPV and IL-8 concentration in both PDR patients' groups. CONCLUSION: Findings of our study suggest an important role of IL-8 in the development of severe PDR. Aflibercept administration on the day before elective vitrectomy facilitated the surgery.

The Influence of Silicone Oil on the Ganglion Cell Complex After Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment.

PURPOSE: Pars plana vitrectomy (PPV) and silicone oil endotamponade have been used as a treatment in rhegmatogenous retinal detachment (RRD). Improvement in the modality of spectral-domain optical coherence tomography (SD-OCT) allows for the assessment of ganglion cell layer-inner plexiform layer (GCL-IPL) in the macular region. Information about the GCL-IPL status may be a response to the question as to why the visual recovery after PPV with silicone oil tamponade is incomplete. The aim of the study was to evaluate the impact of silicone oil on GCL-IPL and compare it with other endotamponade types such as Sulfur hexafluoride gas (SF6), Perfluoropropane gas (C3F8) used during PPV performed due to RRD. PATIENTS AND METHODS: The study involved 57 eyes after PPV and 57 healthy, control eyes of patients with primary RRD who had undergone successful PPV. The patients were divided into three subgroups depending on the endotamponade type, and were tracked with complete ophthalmological examination during a period of 6 months. PPV with internal tamponade silicone oil, 24% SF6 or 14% C3F8 was performed. The medical records were reviewed and compared between the groups. RESULTS: SD-OCT analysis detected a significant reduction of average GCL-IPL thickness and reduction of GCLIPL parameter in almost all examined sectors in the group with silicone oil endotamponade during all follow-up visits (P<0.05). The study showed a significant vision deterioration in the silicone oil group in comparison with the SF6 group on all follow-up visits (P<0.05). CONCLUSION: This is the first in vivo SD-OCT study describing the toxic effect of silicone oil endotamponade on GCL-IPL complex after PPV for RRD. The study confirmed that the GCL-IPL complex value can be a predictive factor for assessing the final visual acuity. SD-OCT should be recommended as a clinical standard in the followup treatment of patients after PPV for RRD, especially with the use of silicone oil endotamponade. Plain Language Summary: The aim of the study was to examine the impact of silicone oil on the ganglion cell complex. The ganglion cell is a neuron type located in the retina and takes part in transmitting visual information from the retina to the brain. Silicone oil is a substance used during eye surgery called pars plana vitrectomy. This tamponade type acts to hold the retina in a proper position. However, during the retinal detachment, which is the separation of the retina from the layer underneath, a reduction of neurons is observed. We decided to use a new technology device called SD-OCT to determine the thickness of the ganglion cell complex. We compared the impact of silicone oil with other tamponade types. We found that silicone oil causes a reduction in the ganglion cell complex. Moreover, we observed vision deterioration in eyes treated with a silicone oil tamponade. The research describes the toxic effect of silicone oil on ganglion cells. Ganglion cell values may be used to determine visual improvement or deterioration after eye surgery with silicone oil tamponade. SD-OCT should be a clinical standard in monitoring patients with silicone oil tamponade.

A 10-year monitoring of the eyesight in patients after kidney transplantation.

A pilot study of a 10-year analysis of the eyesight characteristics in patients after renal transplantation with a view to a later wider study of the same population.The study encompassed 50 eyes in 25 patients who underwent renal transplantation in the years 2007 and 2008. All patients underwent: visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography.Changes in the eyes observed during the 10-year observation period included mostly: cataract (48%), hypertensive angiopathy (28%), diabetic macular edema (16%), and glaucoma (16%). Ten years after the renal transplant visual acuity declined in 15 patients (60%). In 67% of those with eyesight deterioration the cause was cataract, while in patients with no changes in the eyesight (n = 10) cataract was diagnosed only in one. Patients with cataracts had been more often treated with cyclosporine, and that difference was statistically significant (73% vs 21%; P < .05). Comparing patients with hypertensive angiopathy with controls has shown that in the first group creatinine levels were statistically significantly higher (1.6 vs 1.16 mg/dL; P < .05). Patients with angiopathy had been also longer on renal replacement therapy before transplant (57 vs 26 months, P > .05), and this group included also statistically more persons after retransplantation (43% vs 5%, P < .05).Most frequent ophthalmological diagnoses in patients after a kidney transplant include cataract, diabetic retinopathy, and hypertensive angiopathy. Visual acuity deterioration was seen in 60% of patients and was mainly the effect of cataract progress. The effect of cyclosporine on cataract progress was significant. The diagnosis of hypertensive angiopathy corresponded with poorer function of the transplanted kidney.

Eye surgery in the elderly.

Extending life expectancy is a human achievement. It does however entail problems. Ophthalmic treatments are widely recognized as having a low risk of general complications. A classic example is cataract surgery, considered to be one of the safest and most frequently performed surgical procedures in the world. However, advanced age brings with it risks that should be considered before surgery. Eye operations, as with procedures on other organs, are largely dependent on the quality of surgical tissues. Therefore, the elderly are at increased risk of complications. Improved general health and postoperative follow-up with the use of noninvasive technologies such as optical coherence tomography translate into lower intraoperative risk and better postoperative prognosis. In this review, we discuss the impact of general health on operational prognosis, therapeutic problems, and technical difficulties which a surgeon and anesthesiologist may encounter in the process. We also consider new technology and strategies specifically aimed at treating eye conditions in the elderly.

[The use of aflibercept (Eylea) in the treatment of polypoidal choroidal vasculopathy--case report]. / Zastosowanie afliberceptu (leku Eylea) w leczeniu polipoidainej waskulopatii naczyniówkowej--opis przypadku.

The paper presents a case of a 25-year-old woman referred to the Outpatient Clinic at the Department of Ophthalmology, University Clinical Centre in Gdansk, with sudden vision impairment in her right eye. Clinical manifestation and diagnostic tests gave a basis for the preliminary diagnosis of polypoidal choroidal vasculopathy. Polypoidal choroidal vasculopathy is a type of choroidal neovascularisation, frequently confused with age-related macular degeneration. Standard treatment includes photodynamic therapy and intravitreal injections of anti-vascular endothelial growth factor agents. 2.0 miligrams of aflibercept was administered as an intravitreal injection, causing a rapid, significant improvement of visual function and proper anatomical relationships within the retina.

[Pigmented paravenous retinochoroidal atrophy--a case report]. / Barwnikowy okolozylny zanik siatkówkowo-naczyniówkowy--opis przypadku.

Pigmented paravenous retinochoroidal atrophy is a rare dystrophy, which is usually asymptomatic and limited to the paravenous area. Due to the slow progression of eye fundus changes, typically without the macular involvement, pigmented paravenous retinochoroidal atrophy is not thought to be a vision-threatening ocular disease. We report a case of a 64-year-old man with sudden unilateral reduction of vision and binocular diplopia, diagnosed with bilateral pigmented paravenous retinochoroidal atrophy. The diagnosis was based on a characteristic fundus appearance, additionally accompanied by the bilateral mild macular changes, minor optic disc pallor and moderate retinal artery narrowing. The presented case posed a diagnostic challenge due to the sudden onset and atypical manifestation.

Glycemic control influences serum angiogenin concentrations in patients with type 2 diabetes.

OBJECTIVE: Because diabetes is the most frequent factor responsible for microvascular and macrovascular disease, we investigated angiogenin serum levels within the diabetic patient group. RESEARCH DESIGN AND METHODS: We investigated 49 patients who met the criteria to be in the diabetic group. Forty nondiabetic patients were included in the control group. We set A1C <7% as well-controlled diabetes. Serum angiogenin level was measured using the enzyme-linked immunosorbent assay method. RESULTS: Serum angiogenin levels of poorly controlled patients with type 2 diabetes were significantly lower than those of group with well-controlled diabetes (361.23 +/- 126.03 ng/ml vs. 446.37 +/- 134.10 ng/ml; P = 0.001). Moreover, they were characterized by a significantly longer duration of the disease (P = 0.006), higher BMI (P = 0.0003), and higher systolic blood pressure (P = 0.01). Levels of total cholesterol, triglycerides, LDL, and HDL were not significantly different in both groups. CONCLUSIONS: Patients with poorly controlled type 2 diabetes (A1C >7%) have lower angiogenin levels than patients with well-controlled diabetes.

[Traumatic hyphema caused by eye injuries]. / Krwawienia do komory przedniej oka jako nast pstwo urazów mechanicznych gatki ocznej.

Hyphema is a common consequence of mechanical ocular trauma. Blood in the anterior chamber (hyphema)can occur after blunt or lacerating trauma. Traumatic hyphema is a diagnostic and therapeutic emergency. Major complications of hyphema include secondary hemorrhage, secondary glaucoma, corneal staining and disturbances in visual acuity. The aim of our study was the retrospective analysis of patients with posttraumatic hyphema. According to a prospective protocol we studied 428 patients who were examined and treated at the Emergency Department of Department of Ophthalmology Medical University of Gdansk between 1998-2004 years (ears). Data obtained included age and sex. 81% of patients were man, 19% of patients were women. Mean age of patients with ocular hyphema 6-72 years. We determined initial and final visual acuities (visual acuity - distance Snellen acuity test), intraocular pressure measurement, biomicroscopy, fundus indirect ophthalmology, gonioscopy and US- examinations (sometimes). Data obtained also were: slitlamp examinations for hyphema size, hyphema grading and corneal clarity. Most hyphemas were small, occupying less than one- third of the volume of the anterior chamber. The most common associated injuries to the eye hyphema included corneal oedema, glaucoma (secondary glaucoma), cataract and mydriasis. Traumatic hyphema is therapeutic emergency. More preventive efforts (hospitalization) were necessary, especially for children. In our study we observed 89% patients with traumatic hyphema due to non - penetrating eye injury. The assault were responsible for hyphema in 30.1% of cases and traffic accidents in 38.7% of all hyphemas. Treatment of the hyphema is generally topical. Outcome is good (in more cases), if medical treatment was quickly instituted. Surgical treatment must be reserved for a special cases, but it needs more further investigations.