Aqueous Humor Cytokines in Non-Proliferative Diabetic Retinopathy.

Background and Objectives: Cytokines are cell-signaling proteins whose identification may serve as inflammatory markers or early indicators for progressive disease. The aim of our study was to quantify several cytokines in aqueous humor (AH) and their correlations with biochemical parameters in diabetic eyes with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: A total of 62 eyes from 62 patients were included in the study: 37 eyes from nondiabetic patients (group 1), 13 diabetic eyes with no retinopathy changes (group 2) and 12 diabetic eyes with early and moderate NPDR (group 3). AH samples were collected during uneventful cataract surgery. The cytokines IL-1ß, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, TNF-α and VEGF were quantified using multiplex bead-based immunoassay. Due to unreliable results, IL-1ß, TNF-α, IL-10 and IL-12 were excluded. Concentrations were compared between groups. Biochemical parameters (fasting blood sugar, glycated hemoglobin, C-reactive protein) and the duration of diabetes were recorded. Results: VEGF levels were significantly different between groups (p = 0.001), while levels of IL-6, IL-8, IP-10 and MCP-1 were comparable across all groups (p > 0.05). IL-6 concentration correlated with VEGF in group 1 (rho = 0.651, p = 0.003) and group 3 (rho = 0.857, p = 0.007); no correlation could be proved between IL-6, IL-8, IP-10, MCP-1 or VEGF and biochemical parameters. Duration of diabetes was not correlated with the cytokine levels in groups 2 and 3. The receiver operating characteristic (ROC) curve revealed that VEGF concentrations could discriminate early and moderate NPDR from diabetes, with an area under the curve (AUC) of 0.897 (p = 0.001, 95% CI = 0.74−1.0). Conclusions: Diabetes mellitus induces significant intraocular changes in the VEGF expression in diabetic patients vs. normal subjects, even before proliferative complications appear. VEGF was increasingly expressed once the diabetes progressed from no retinopathy to early or moderate retinopathy.

Choroidal Assessment in Patients with Type 2 Diabetes Mellitus and Non-Proliferative Diabetic Retinopathy by Swept-Source Ocular Coherence Tomography and Image Binarization.

Background and Objectives: The aim of this study was to evaluate choroidal structure and vascularity indices in patients with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: Sixty-three eyes from sixty-three patients were evaluated: 21 from healthy subjects, 20 with diabetes mellitus (DM) and no diabetic retinopathy (DR), and 22 with DM and non-proliferative diabetic retinopathy without diabetic macular edema (DME). Each patient underwent ocular examination, macular swept-source ocular coherence tomography (SS-OCT) imaging, glycemic control, and systemic high blood pressure (HBP) evaluation. Subfoveal choroidal thickness (SF-CT) was manually assessed on a line scan. Line scan OCT images were exported to ImageJ program. The areas under a 1.5, 3 and 6 mm horizontal line centered on the fovea were assessed by converting the OCT images to binary images, and total choroidal area (TCA), luminal area (LA), stromal area (SA), LA:SA ratio, and choroidal vascularity index (CVI) were evaluated. SF-CT and choroidal parameters were compared between groups, and correlations with ocular and systemic factors were analyzed. Results: SF-CT, TCA, LA, and SA were similar between groups. CVIs were significantly different between groups for all three studied areas (CVI-1.5: 66.21% vs. 66.06% vs. 63.74%, p = 0.003; CVI-3: 65.88% vs. 66.46% vs. 63.79%, p = 0.008; CVI-6: 64.79% vs. 65.40% vs. 63.61%, p = 0.032). NPDR patients had significantly lower CVIs compared to DM patients (p < 0.05). No association of choroidal parameters with glycemic control, DM duration and HBP was found significant (p < 0.05). Conclusions: Choroidal assessment by SS-OCT and image binarization in healthy subjects, subjects with DM without DR, and subjects with DM and NPDR indicated that CVI changes were identifiable and significant in early DR. The lack of association with ocular and systemic factors suggest that CVIs are reliable assessment parameters of choroidal vascular structure.

Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.

Kaposi's sarcoma is a rare disease with four known variants: classic, epidemic, endemic and iatrogenic (transplant-related), all caused by an oncogenic virus named Human Herpes Virus 8. The viral infection in itself, along with the oncogenic properties of HHV8 and with immune system dysfunction, forms the grounds on which Kaposi's Sarcoma may develop. Infection with HHV8 occurs through saliva via close contacts, blood, blood products, solid organ donation and, rarely, vertical transmission. Chronic inflammation and oncogenesis are promoted by a mix of viral genes that directly promote cell survival and transformation or interfere with the regular cell cycle and cell signaling (of particular note: LANA-1, v-IL6, vBCL-2, vIAP, vIRF3, vGPCR, gB, K1, K8.1, K15). The most common development sites for Kaposi's sarcoma are the skin, mucocutaneous zones, lymph nodes and visceral organs, but it can also rarely appear in the musculoskeletal system, urinary system, endocrine organs, heart or eye. Histopathologically, spindle cell proliferation with slit-like vascular spaces, plasma cell and lymphocyte infiltrate are characteristic. The clinical presentation is heterogenic depending on the variant; some patients have indolent disease and others have aggressive disease. The treatment options include highly active antiretroviral therapy, surgery, radiation therapy, chemotherapy, and immunotherapy. A literature search was carried out using the MEDLINE/PubMed, SCOPUS and Google Scholar databases with a combination of keywords with the aim to provide critical, concise, and comprehensive insights into advances in the pathogenic mechanism of Kaposi's sarcoma.

Posterior choroidal boundary morphology and segmentation errors influence on choroidal thickness assessment in diabetic patients - a swept-source OCT study.

Objective: to evaluate the choroidal morphology and choroidal thickness (CT) in normal and diabetic subjects and to compare the differences between automated segmentation (AS) and manual segmentation (MS) of the choroid. Methods: in this observational cross-sectional study we included 48 eyes: 24 normal eyes (group 1), 9 eyes with DM without diabetic retinopathy (DR) (group 2) and 15 eyes with DM and DR (group 3). Swept-source OCT line scans images were analyzed for the presence of the suprachoroidal layer (SCL), choroidal morphology and the CT was measured manually subfoveal and at 750 µ both nasal and temporal to the fovea after AS and MS. SCL was not included in the CT evaluation. CT values were compared between the groups and between the three points of evaluation. Results: SCL was visualized in 21 eyes (43.8%). In diabetic patients, SCL was visible in 11 (45.83%) cases and in nondiabetic patients, in 10 eyes (41.66%). There was a good AS of Bruch's membrane, which was not further corrected manually. There were statistically significant differences between AS and MS at the level of CSJ for all three locations in all three groups (P ≤ 0.01). After MS, the choroid was statistically significantly thicker. Group 2 and group 3 showed a higher CT thickness. There were no statistically significant differences in the CT between groups in all three locations. Conclusions: Defining posterior choroidal boundary and the applied segmentation method can result in differences in CT measurements. Diabetic patients have altered CT and choroidal morphology. Abbreviations: CT = choroidal thickness, AS = automated segmentation, MS = manual segmentation, CSJ = choroidoscleral junction, SCL = suprachoroidal layer, SCS = suprachoroidal space, DM = diabetes mellitus, DR = diabetic retinopathy, RPE = retinal pigmented epithelium, BM = Buch's membrane.

Odontogenic orbital inflammation.

Objective: This study aimed to determine the most frequent clinical aspects in patients with odontogenic orbital inflammation, the computed tomography (CT) aspect, and the most appropriate treatment. Material and Methods: This is a retrospective case-series study conducted on 3 patients with ages between 16 and 55 years old, in the Ophthalmology and Oro-Maxillo-Facial Clinics of "Sf. Spiridon" Emergency Hospital, Iași, Romania. The following investigations were performed in all selected cases: visual acuity (VA), ocular motility examination, anterior segment examination at slit-lamp, fundus examination, intraoral clinical examination, sinus and orbital involvement on CT scan, pathogens involved. Results: All three patients presented swelling of the genic and periorbital regions, conjunctival chemosis, hyperemia of the conjunctiva, proptosis, pain, decreased vision and extraocular movement restriction. The CT examination identified orbital and periorbital cellulitis and ethmoidal expanded maxillary sinusitis or pansinusitis. Dental extraction, transalveolar drainage and orbital decompression were performed in all three cases. The evolution was favorable with remission of proptosis, edema of the genic and periorbital regions and conjunctival chemosis. Visual acuity remained poor in one case due to total optic nerve atrophy. Conclusions: Our study had a small number of patients, but the data was pertinent to ophthalmologists and maxillofacial surgeons who need to be aware of typical clinical features and the most common etiologies. Late treatment of dental infections can lead to severe ocular manifestations such as orbital cellulitis. Odontogenic orbital inflammation management involves a long-term and multidisciplinary approach. Abbreviations: CT = computed tomography, VA = visual acuity, CBCT = cone beam computed tomography, TED = thyroid eye disease, MRI = magnetic resonance imaging, OOC = odontogenic orbital cellulitis, RAPD = relative afferent pupillary defect.

Inflammatory model in patients with primary open angle glaucoma and diabetes.

AIM: To assess the inflammatory cytokines expression in aqueous humor in diabetic primary open angle glaucoma (POAG) patients. METHODS: A cross-sectional study on 87 eyes, distributed as following: 26 eyes from diabetic patients, 16 eyes with POAG and 21 eyes from diabetic POAG patients; healthy controls (24 eyes) were recruited from patients undergoing conventional cataract surgery. A volume of 100 µL of aqueous humor (AH) was collected during phacoemulsification and 21 inflammatory markers were quantified using a Luminex® cytometric bead assay: IL-1Ra, IL-1α, IL-1ß, IL-5, IL-6, IL-10, IL-17, GM-CSF, IFNγ, CCL2, CCL3, CCL4, CXCL5, CXCL8, bFGF, VEGF, TNFα. Main changes in cytokine profile were analyzed and compared between groups. Data on demographics, duration of glaucoma, intraocular pressure (IOP), number of anti-glaucoma substances were recorded for correlation analysis and prediction models. RESULTS: Significant differences in cytokine expression between groups were detected for CXCL5 (P<0.001), CXCL8 (P=0.004), IL-1α (P<0.001), IL-2 (P<0.001), CCL4 (P=0.003), CCL5 (P<0.001) and TNFα (P=0.05). Post-hoc analysis identified IL-2 (P=0.009) and CXCL5 (P<0.001) as "separation markers" between POAG and diabetic POAG eyes. In POAG patients, the "separation markers" could highly predict the TNFα levels F(1, 16)=14.639, P<0.001, whereas in diabetic patients F(1, 24)=4.844, P=0.006 and diabetic POAG patients F(1, 19)=2.358, P=0.05 the level of prediction was inferior. CONCLUSION: Our results reveal an inflammatory model based on increased TNFα levels in POAG eyes. Simultaneous co-stimulatory molecules and additional inflammatory pathways need to be further explored in diabetic POAG cases, since the prediction model could only partially explain the increased TNFα level in this category of patients.

OUTCOMES OF SURGERY IN PROLIFERATIVE VITREORETINOPATHY.

AIM: To present the anatomical and functional outcomes of surgery in cases of rhegmatogenous retinal detachment complicated (at presentation) by proliferative vitreoretinopathy (PVR). MATERIAL AND METHODS: Retrospective study of the cases operated upon by a single surgeon between October 2012 and September 2014. RESULTS: A total of 49 eyes of 49 patients had PVR at presentation (12 cases with PVR stage B, 21 with stage C and 16 with stage D). 82% had a VA < or = 0.05 at presentation. Peripheral retinectomy was the primary surgery in 57% of cases. Reinterventions was required in 16.3% of the cases (silicon oil extraction was not considered reintervention). Although at the first postoperative examination 32% of eyes had an IOP > 21 mmHg without medication, only 8% retained a high lOP at the last visit. At the last visit 73.4% of eyes presented attached retina (an additional 6% had an attached macula under silicone oil, but sub retinal fluid in the inferior quadrants). A final VA > or = 0.05 was recorded in 67.3% of eyes (of which half had VA > or = 0.1) CONCLUSIONS: In cases presenting with retinal detachment complicated by PVR the possibility of reinterventions and the risk of intraocular hypertension should be considered. Unfortunately, even some cases with favorable anatomical outcome will not present ambulatory vision. Keywords:

Difference of refraction values between standard autorefractometry and Plusoptix.

Aim: Comparison between the objective refraction measurement results determined with Topcon KR-8900 standard autorefractometer and Plusoptix A09 photo-refractometer in children. Material and methods: A prospective transversal study was performed in the Department of Ophthalmology of "Sf. Spiridon" Hospital in Iași on 90 eyes of 45 pediatric patients, with a mean age of 8,82 ± 3,52 years, examined with noncycloplegic measurements provided by Plusoptix A09 and cycloplegic and noncycloplegic measurements provided by Topcon KR-8900 standard autorefractometer. The clinical parameters compared were the following: spherical equivalent (SE), spherical and cylindrical values, and cylinder axis. Astigmatism was recorded and evaluated with the cylindrical value on minus after transposition. The statistical calculation was performed with paired t-tests and Pearson's correlation analysis. All the data were analyzed with SPSS statistical package 19 (SPSS for Windows, Chicago, IL). Results: Plusoptix A09 noncycloplegic values were relatively equal between the eyes, with slightly lower values compared to noncycloplegic auto refractometry. Mean (± SD) measurements provided by Plusoptix AO9 were the following: spherical power 1.11 ± 1.52, cylindrical power 0.80 ± 0.80, and spherical equivalent 0.71 ± 1.39. The noncycloplegic auto refractometer mean (± SD) measurements were spherical power 1.12 ± 1.63, cylindrical power 0.79 ± 0,77 and spherical equivalent 0.71 ± 1.58. The cycloplegic auto refractometer mean (± SD) measurements were spherical power 2.08 ± 1.95, cylindrical power 0,82 ± 0.85 and spherical equivalent 1.68 ± 1.87. 32% of the eyes were hyperopic, 2.67% were myopic, 65.33% had astigmatism, and 30% eyes had amblyopia. Conclusions: Noncycloplegic objective refraction values were similar with those determined by autorefractometry. Plusoptix had an important role in the ophthalmological screening, but did not detect higher refractive errors, justifying the cycloplegic autorefractometry.

[Long-term clinical course after cataract surgery in patients with diabetes mellitus]. / Evolutia functionala pe termen lung dupa operatia de cataracta la pacientii cu diabet.

PURPOSE: To determine the visual outcome at 5 years postoperatively in patients operated for cataract associated with diabetes mellitus. PATIENTS AND METHODS: Retrospective study on a group of 41 eyes in patients with diabetes, who were operated for cataract (the same surgeon) by facoemulsification and IOL implantation in the capsular bag, without intraoperative complications, for 60 months (during 2003-2007). RESULTS: 27 patients with diabetes were included in the study, the average duration of diabetes was 10, 3 years. Average postoperative visual acuity (VA) was 0.5 at six weeks postoperatively. Preoperative VA improvement was observed in 78%. There was a decrease in VA of 85% at more than 5 years after surgery and 15% of eyes had preserved VA. VA decrease was due to the occurrence, progression and worsening of retinopathy (69%) and diabetic maculopathy, posterior capsular opacification (34%), glaucoma, age-related macular degeneration (12%). CONCLUSIONS: Visual acuity was maintained in 15% and decreased in 85% of patients due to diabetic retinopathy, glaucoma, age-related macular degeneration.

[Long-term course of visual acuity in patients with cataract surgery]. / Evolutia pe termen lung a acuitatii vizuale la pacientii operati de cataracta.

PURPOSE: To compare immediate and 5 years postoperatively visual acuity (VA), after uncomplicated cataract surgery and emphasizing the main causes of visual acuity loss. MATERIAL AND METHODS: This is a retrospective study that included 475 eyes that underwent uncomplicated cataract surgery between 2003-2007 by the same surgeon. 51 patients (73 eyes) returned to the last followup visit, 5 years postoperatively. RESULTS: Of 73 eyes, 18 eyes (24.66%) had VA < 0.5, 53 eyes (72.60%) had VA between 0.5-1 and 2 eyes (2.74%) had VA > 1, 5 years postoperatively. 26% (19 eyes) revealed reduced best corrected visual acuity in comparison to that from 6 weeks postoperatively Causes that led to reduced VA are: posterior capsular opacification (46.57%), age related macular degeneration (26.02%), glaucoma (10.95%), diabetic retinopathy (9.58%). CONCLUSIONS: Approximately a quarter of patients showed reduced VA after more than 5 years postoperatively; more than three quarters had VA > 0.5 on the last follow-up visit. The most frequent causes of reduced VA are age-related macular degeneration, glaucoma, appearence or worsening of diabetic retinopathy, posterior capsular opacification.