Chrysanthos Symeonidis

Retinal vasculitis in rheumatic diseases: an unseen burden

Retinal vascular inflammation, a potentially blinding condition (herein: retinal vasculitis (RV)) is commonly associated with a heterogeneous group of diseases characterized by systemic inflammatory cell infiltration and/or necrosis of blood vessel walls. RV may arise as an isolated ocular disorder, as part of systemic vasculitis (Wegener’s granulomatosis and Adamantiadis–Behcet Disease), or it can be secondary to an underlying connective tissue disease (systemic lupus erythematosus, sarcoidosis, and rheumatoid arthritis), systemic infection, or malignancy. Depending on the type of RV, it can be a potentially disabling condition, in the short or long term. Early diagnosis is the key to successful treatment and better prognosis. However, early diagnosis can be difficult, because these conditions usually present with nonspecific visual symptoms for a long period before diagnostic manifestations occur. The retina should be examined in warranted patients with verified rheumatic disease, since retinal vasculitis may be asymptomatic at the beginning (peripheral retinal disease). RV can be detected clinically (often accompanied by uveitis, scleritis, or macular edema) or revealed on fluorescein fundus angiography, even if minimal signs of retinal vessel inflammation are present. RV may also represent one of the possible extra-articular manifestations of the rheumatic disease. Rheumatologists should be familiar with the ocular manifestations of these disorders, since they may not only be sight-threatening, but more importantly, could be the presenting or even the very first manifestations of active, potentially lethal systemic disease in a patient with nonspecific rheumatologic presentation.

Coats' disease: treatment with intravitreal bevacizumab and laser photocoagulation.

Editor, C oats’ disease is characterized by retinal telangiectasia, macular oedema, exudation and, consequently, exudative retinal detachment. In its advanced stages, it may be complicated by total retinal detachment and glaucoma and may lead to phthisis bulbi (Shields et al. 2001). It usually presents unilaterally in 8–16-year-old males, although it may occur in patients as young as 4 months (Haller 2004). Exudation characterizing Coats’ disease can be attributed to increased vascular permeability caused by telangiectasia and aneurysms in the posterior pole and ⁄or the periphery, facilitating release of vascular endothelial growth factor (VEGF). This growth factor has been shown to cause telangiectasia, microvascular occlusion, microaneurysms, and, consequently, vascular leakage, thus promoting exudation (Sun et al. 2007). Recently, antibodies against VEGF (bevacizumab [Avastin ; Genentech], ranibizumab [Lucentis ; Novartis AG] and pegaptanib [Macugen ; Pfizer, Inc.]) have been employed in managing conditions characterized by exudation, such as age-related macular degeneration (AMD) and diabetic macular oedema (DMO) (Minnella et al. 2007). Corticosteroids have been known to reduce intraocular inflammation, tighten capillary walls and suppress cell proliferation. Intravitreal triamcinolone acetonide has been shown to be useful in increasing visual acuity (VA) in patients with diffuse DMO (Sivaprasad et al. 2006). We describe the management of Coats’ disease in a young adult male, in which laser photocoagulation along with bevacizumab ⁄ triamcinolone intravitreal injection were employed. A 17-year-old male was referred with a severe decrease in VA OD occurring over some weeks. Ophthalmic evaluations included non-standardized Snellen VA, and complete ophthalmic and fundus examination. Active neovascularization in the optic disc and ⁄or elsewhere was confirmed with fluorescein angiography (FA). The patient’s VA OD was 20 ⁄ 1000. Fundus examination revealed considerable exudation involving the posterior pole, and macroaneurysms and telangiectases in the temporal periphery (Fig. 1A). Localized telangiectases in the periphery combined with the overall clinical picture was compatible with Coats’ disease diagnosed in adulthood. These findings were confirmed in FA (Fig. 2A). Treatment

A Focus on the Epidemiology of Uveitis

ABSTRACT Purpose: Uveitis is a common, sight-threatening inflammatory ocular disease and includes multiple heterogeneous clinical entities. The prevalence of various types of uveitis depends upon multiple factors, such as age, sex, race, geographic distribution, environmental influence, genetics, and social habits. Epidemiologic research of uveitis is necessary to understand the etiology and immunopathogenesis of this group of diseases. The present study attempts to concentrate on the most recent information on the epidemiology of uveitis and compare it with previous knowledge. Methods: An extensive literature search was performed in the Medline database (PubMed) and included surveys completed until 2015. Articles that reported prevalence and incidence were studied. References cited in the articles were also studied. Results: The incidence and prevalence of uveitis differs based on age, anatomic location of the inflammatory process (anterior, intermediate, posterior uveitis, panuveitis), gender, histopathology (granulomatous, non-granulomatous), type of inflammatory process (acute, chronic, recurrent), and etiology (infectious, non-infectious). Prevalence differs by geographic location. Idiopathic anterior uveitis is the most common form of uveitis in the community. Infectious causes are common (30–60%) in the developing countries. Herpes and toxoplasmosis are the leading infectious causes of uveitis. Non-infectious uveitic conditions are generally more common in the developed world. An increase in the prevalence of infectious etiologies, including tuberculosis and syphilis, has been seen in developed countries. Introduction of new treatment options has also changed patterns of disease. Conclusions: Introduction of new uveitis entities, changes in the incidence of already known disease and increased availability of diagnostic testing have all altered the epidemiology of uveitis in recent years. Knowledge of regional patterns of disease is essential. A more detailed classification of uveitis with the establishment of uniform diagnostic criteria and prospective population based studies would certainly benefit epidemiologic research and clinical practice.

Interleukin-6 and the matrix metalloproteinase response in the vitreous during proliferative vitreoretinopathy.

PURPOSE To investigate the levels of IL-6 in the vitreous of patients with RRD complicated with PVR and correlate the IL-6 levels with matrix metalloproteinase (MMP)-1,-2,-3,-8,-9 and tissue inhibitor of metalloproteinases (TIMP)-1 with respect to RRD extent, duration and PVR grade. DESIGN Cohort study. PARTICIPANTS Twenty-eight vitreous samples from 28 eyes of 28 patients with RRD complicated with PVR. METHODS Institutional study. Twenty-eight vitreous samples from 28 eyes of 28 patients with RRD complicated with PVR were collected during pars plana vitrectomy (PPV) and were compared to vitreous control samples. IL-6, MMP-1,-3,-8 and TIMP-1 levels were measured using ELISA while enzymatic activity of MMP-2, and -9 was determined employing gelatin zymography. RESULTS Protein IL-6 (p=0.030), MMP-1 (p=0.003), MMP-3 (p=0.003), TIMP-1 (p=0.001) levels as well as enzymatic activity of proMMP-9 (p=0.013), MMP-9 (p=0.017) and proMMP-2 (p=0.010), were significantly increased in PVR patients as compared to controls. IL-6 levels correlated with MMP-1 (p=0.002), proMMP-2 (p=0.006), MMP-3 (p=0.001) and TIMP-1 (p=0.006). Regression analysis revealed positive correlations between IL-6 and all MMPs and TIMP-1. CONCLUSIONS Taking into account the previously established effect of interleukins in MMP activity, the findings of this study suggest a role of IL-6 in MMP stimulation during PVR development.

Correlation of the extent and duration of rhegmatogenous retinal detachment with the expression of matrix metalloproteinases in the vitreous.

Background: Investigation of the activity of matrix metalloproteinase (MMP)-2 and -9 and protein levels of MMP-1, -3, -8, and the tissue inhibitor of MMPs (TIMP)-1 in the vitreous of patients with rhegmatogenous retinal detachment (RRD) and establishment of potential correlations of MMPs with clinical parameters. Methods: Thirty-two vitreous samples from patients with RRD and 9 vitreous samples from human organ donors (controls) were assayed for MMP-1,-3, -8, and TIMP-1 levels using enzyme-linked immunosorbent assay and MMP-2 and -9 activity employing gelatin zymography. Results: MMP-1, MMP-3, proMMP-2, proMMP-9, MMP-9, and TIMP-1 were higher in vitreous from patients with RRD as compared to organ donors. Overall, MMPs and TIMPs were differentially expressed in vitreous from RRD with respect to the duration and extent of RRD. Regression analysis for all data indicated that a model consisting of MMP-2 and TIMP-1 could estimate the extent of RRD. Conclusion: Levels of MMPs and TIMP-1 studied are elevated in vitreous during RRD. MMP-2 and TIMP-1 may have a more prominent and persistent role than other MMPs in the wound healing process of the retina during RRD. A regression model consisting of MMP-2 and TIMP-1 may prove to be of potential use in providing information for the evaluation of the extent of RRD.

Expression of matrix metalloproteinases in the subretinal fluid correlates with the extent of rhegmatogenous retinal detachment

BackgroundWe investigated the activity of matrix metalloproteinase (MMP)−2 and −9 and the protein levels of MMP−1, −3, −8 and the tissue inhibitor of MMPs (TIMP)−1 in the subretinal fluid (SRF) of patients with rhegmatogenous retinal detachment (RRD) and establishment of potential correlations with clinical parameters.MethodsThirty-seven SRF from RRD patients and nine vitreous samples from the human eye of organ donors (controls) were collected and assayed for MMP−1,−3,−8 and TIMP−1 levels using ELISA and for MMP−2 and −9 activity employing gelatin zymography.ResultsMMP−1, MMP−3, MMP−8, proMMP−2, proMMP−9, MMP−9 and TIMP−1 levels were higher in SRF compared with vitreous fluid. Overall, MMPs and TIMPs were differentially expressed in SRF with respect to duration and extent of RRD, as well as to stage of proliferative vitreoretinopathy. Regression analysis for all data indicated that a model consisting of MMP−3, MMP−8 and proMMP−9 could estimate the extent of RRD.ConclusionsMMPs and TIMP−1 levels are elevated in SRF during RRD. A regression model consisting of MMP−3, MMP−8 and proMMP−9 may be proved to be of potential use in providing information for evaluation of the extent of RRD.

Correlation of matrix metalloproteinase levels with the grade of proliferative vitreoretinopathy in the subretinal fluid and vitreous during rhegmatogenous retinal detachment

Purpose:  We investigated the activity of matrix metalloproteinase (MMP)‐2 and ‐9 and their latent pro‐forms (proMMP‐2, ‐9), and protein levels of MMP‐1, ‐3, ‐8 and tissue inhibitor of MMPs (TIMP)‐1 in the subretinal fluid (SRF) and vitreous of patients with rhegmatogenous retinal detachment (RRD). Potential correlations with proliferative vitreoretinopathy (PVR) grade were determined.

Matrix metalloproteinase (MMP-2, -9) and tissue inhibitor (TIMP-1, -2) activity in tear samples of pediatric type 1 diabetic patients

BackgroundThe presence of matrix metalloproteinase (MMP-2, -9) and tissue inhibitor (TIMP-1, -2) activity in tear samples of pediatric type 1 diabetes mellitus (DM) patients and potential correlations with clinical parameters (Schirmer testing, glycosylated hemoglobin-HBA1C) were investigated.MethodsTear samples from the right eyes of 27 type 1 DM patients and 17 healthy control subjects were included in this study. The MMP gelatinolytic activity was determined by gelatin zymography analysis using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE), while MMP and TIMP concentrations (in ng/ml) were quantified in tears of type 1 diabetic patients and healthy controls, with the use of enzyme-linked immunosorbent assay (ELISA).ResultsMMP-9, TIMP-1, -2 levels, MMP-9/TIMP-1, and MMP-9/TIMP-2 ratios in the patient group were significantly elevated. There was a significant correlation between TIMP-2 and HBA1C values, as well as between MMP-2 and MMP-9.ConclusionsSignificant correlations between TIMP-2 and HBA1C and between Schirmer test results and HBA1C were revealed. Significant increase in tear MMP and TIMP levels in pediatric type 1 diabetic patients may be suggestive of disease progression and localized pathologic remodelling. Further studies are required in order to ascertain whether MMPs and TIMPs could be employed as indicators of early disease progression.

Surgical outcomes in phacoemulsification after application of a risk stratification system

Background The purpose of this study was to determine whether application of a risk stratification system during preoperative assessment of cataract patients and subsequent allocation of patients to surgeons with matching experience may reduce intraoperative complications. Methods Nine hundred and fifty-three consecutive patients (1109 eyes) undergoing phacoemulsification cataract surgery were assigned to two groups, ie, group A (n = 498 patients, 578 eyes) and group B (n = 455 patients, 531 eyes). Patients from group A were allocated to surgeons with varying experience with only a rough estimate of the complexity of their surgery. Patients from group B were assigned to three risk groups (no added risk, low risk, and moderate-high risk) according to risk factors established during their preoperative assessment and were respectively allocated to resident surgeons, low-volume surgeons, or high-volume surgeons. Data were collected and entered into a computerized database. The intraoperative complication rate was calculated for each group. Results The intraoperative complication rate was significantly lower in group B than in group A (group A, 5.88%; group B, 3.2%; P < 0.05). Patients from group B with no added risk and allocated to resident surgeons had a significantly lower rate of intraoperative complications than those from group A allocated to resident surgeons (group A, 7.2%; group B, 3.08%; P < 0.05). Conclusion Our study demonstrates that allocation of cataract patients to surgeons matched for experience according to a uniform and reliable preoperative assessment of their risk of complications allows for better surgical outcomes, especially for resident surgeons.

Interleukin-6 and matrix metalloproteinase expression in the subretinal fluid during proliferative vitreoretinopathy: Correlation with extent, duration of RRD and PVR grade

PURPOSE To investigate interleukin (IL)-6 protein levels in the subretinal fluid (SRF) of patients with rhegmatogenous retinal detachment (RRD) complicated by proliferative vitreoretinopathy (PVR); to correlate the IL-6 levels with matrix metalloproteinases (MMP)-1, -2, -3, -8, -9 and tissue inhibitor of metalloproteinases (TIMP)-1 with respect to RRD extent, duration and PVR grade. METHODS Thirty-one SRF samples from 31 eyes of 31 patients with RRD complicated with PVR and five SRF samples from five eyes of five patients suffering from RRD not complicated with PVR were collected during treatment by scleral buckling. Enzyme-Linked Immunosorbent Assay was employed for the measurement of IL-6, MMP-1, -3, -8 and TIMP-1 levels while the enzymatic activity of MMP-2 and MMP-9 was assessed by gelatin zymography. RESULTS Protein levels of IL-6 (p=0.050), MMP-1 (p=0.001), MMP-3 (p=0.005), MMP-8 (p=0.003), TIMP-1 (p=0.001) as well as enzymatic activity of proMMP-2 (p=0.001), MMP-2 (p=0.023) and MMP-9 (p=0.015), were significantly higher in the SRF of PVR patients compared to controls. IL-6 levels correlated significantly with TIMP-1 (r=0.528, p=0.035). Regarding clinical parameters of the detachment, IL-6 levels correlated with RRD extent (r=0.592, p=0.016), but not with RRD duration (p=0.857) and PVR grade (p=0.594). Regression analysis revealed positive correlations between IL-6 and MMP-2. CONCLUSIONS There was a significant correlation between IL-6 and TIMP-1 levels in the SRF of PVR patients. The findings of this study are in agreement with relevant studies concerning IL-6 involvement in the modulation of MMP expression and are indicative of IL-6 and MMP activity during PVR, mainly that of MMP-2 and TIMP-1.