ARCH SOC ESP OFTALMOL 2009; 84: 523-528 ORIGINAL ARTICLE COMPLICATIONS OF UVEITIS: PREVALENCE AND RISK FACTORS IN A SERIE OF 398 CASES COMPLICACIONES DE LAS UVEÍTIS: PREVALENCIA Y FACTORES DE RIESGO EN UNA SERIE DE 398 CASOS PRIETO-DEL-CURA M 1, GONZÁLEZ-GUIJARRO J 2 ABSTRACT Objective: To estimate the rate of complications and establish risk factors for their development in patients with uveitis. Methods: Prospective study of a cohort of 398 patients (413 eyes) that were reviewed from January 2000 to October 2007 and monitored during a period of at least one month. Demographic data, laterality, course (acute, subacute, chronic), location, diagnosis (idiopathic, infectious, ocular origin, systemic origin, others) and development of complications (cataract, cystoid macular edema, macular complications, retinal complications and others) were evaluated. Results: After a mean follow-up of 35.2 months (range 1-160), 25% of patients developed one or more of the following complications: cataract 8.5%, macular edema 6.1%, macular complications (epiretinal membranes, choroidal neovascular membranes, macular necrosis) 4.1%, retinal complications (retinal detachment, retinal neovascularization, vitreous hemorrhage, retinal tears, retinal vascular occlusions) 4.1%, glaucoma or ocular hypertension 3.6%, and others 1.5%. Risk factors for development of uveitis complications were chronic course OR 6.37 (3.25-12.47) P <0.0001, bilaterality OR 1.98 (1.03-3.08) P =0.039, subacute course OR 1.94 (0.02-4.08) P=0.08, and panuveitis OR 1,92 (0.99-4.80) P=0.161. RESUMEN Objetivo: Estimar el porcentaje de complicaciones y establecer factores de riesgo para padecerlas en los pacientes con uveítis. Método: Estudio prospectivo de cohortes de 398 pacientes con seguimiento superior a 1 mes desde Enero del 2000 hasta Octubre del 2007. Se evaluaron los datos demográficos, lateralidad, curso (agudo, subagudo crónico), localización, diagnóstico (idiopática, infecciosa, de base ocular, de base sistémica, otras) y el desarrollo de complicaciones (catarata, edema macular quístico, complicaciones maculares, complicaciones retinianas y otras). Resultados: Tras un seguimiento medio de 35,2 meses (1-160), el 25% desarrollaron una o más de las siguientes complicaciones: catarata 8,5%, edema macular 6,1%, complicaciones maculares (membrana epirretiniana, membrana neovascular coroidea, necrosis macular) 4,1%, complicaciones retinianas (desprendimiento de retina, neovasos retinianos, hemovítreo, desgarros retinianos, oclusiones vasculares retinianas) 4,1%, glaucoma o hipertensión ocular 3,6% y otras 1,5%. Los factores de riesgo para desarrollarlas fueron el curso crónico OR 6,37 (3,25-12,47) P <0,0001, la bilateralidad OR 1,98 (1,03-3,08) P =0,039, el curso agudo recidivante OR1,94 (0,02-4,08) P=0,08 y la panuveítis OR 1,92 (0,99-4,80) P=0,161. Received: 31/5/08. Accepted: 28/10/09. Princesa Hospital. Ophthalmology Service. Madrid. Spain. 1 Graduate in Medicine. 2 Ph.D. in Medicine. Correspondence: M. Prieto del Cura Hospital de La Princesa. Servicio de Oftalmología C/. Diego de León, 62 28006 Madrid Spain E-mail: marprieto20@yahoo.com
PRIETO-DEL-CURA M, et al. Conclusions: In our patients, cases involving chronic and bilateral uveitis were more prone to develop complications, with cataracts being the most frequent complication (Arch Soc Esp Oftalmol 2009; 84: 523-528). Key words: Uveitis, cataract, risk factors, complications. Conclusiones: En nuestros pacientes las uveítis crónicas y las bilaterales son las que más riesgo tienen de sufrir complicaciones de las que la catarata es la más frecuente. Palabras clave: Uveítis, catarata, factores de riesgo, complicaciones. INTRODUCTION The number of uveitis cases in developed countries is 45 per 100,000 inhabitants/year, with a prevalence of 70 per 100,000 (1,2). In addition, uveitis is the cause of 10-15% of new cases of blindness in the USA. The complications caused by uveitis give rise to blindness and severe visual alterations in patients, including irreversible cystic macular edema, cataracts, glaucoma, macular and optic nerve lesions, a number of retinal vascular anomalies or retina detachment (3). Frequently, complications are present at diagnostic time but when that is not the case the degree and characteristics of ocular inflammation can be an important prognostic factor for the development of ocular complications and accordingly of visual acuity loss during follow-up. The objective of our study is to estimate the percentage of complications and establish risk factors in a series of uveitis patients. SUBJECTS, MATERIAL AND METHODS A prospective, descriptive cohort study of 398 patients diagnosed with uveitis in the uvea section of the Ophthalmology Dept. of the Princesa University Hospital, aged over 14 with follow-up above 1 month, from January 2000 to October 2007. The data were obtained from a computerized database. The demographic variables comprised age in years and sex. The ophthalmological variables comprised: 1. Primary localization: following the anatomic classification criteria of the Standardization of Uveitis Nomenclature (SUN) Working Group (4) which are: anterior uveitis (iritis, iridocyclitis), intermediate uveitis (pars planitis, posterior ciclitis, hialitis) posterior uveitis and panuveitis. 2. Clinical course: as per the criteria of the SUN working group (4), each episode is divided in: acute, recurring or sub-acute and chronic. 3. Laterality: unilateral or bilateral. 4. Diagnostic: with a detailed patient profile, a list of diagnostic possibilities is drawn up. This list was grouped in: Idiopathic. Infectious. With ocular base: with the intention of unifying criteria we included glaucomatocyclitic crisis, pars planitis, Fuchs heterochromic ciclitis, associated to HLA B 27 without systemic expressions, white spot syndromes, spotted choroidopathy, Eales disease, post-surgical non-infectious and sympathetic ophthalmia. With systemic base: when accompanied by, or in the course of, a self-immune systemic disease (or with immunological etiopathogeny): Bechet syndrome, seronegative spondiloarthropathies, associated to ocular inflammation disease, Sjögren s disease, psoriasis, multiple sclerosis, Harada s disease, chronic juvenile arthritis, rheumatoid arthritis, sarcoidosis and diabetes. Others: we included the masquerade and pharmacological syndromes, idiopathic relapsing arterial branch occlusions. 6. Complications: 1) Cataract: defined as the presence of 1+ nuclear sclerosis or 1 + cortical or subcapsular posterior change. 2) Glaucoma or ocular hypertension: defined as IOP greater than 21 mmhg or glaucomatous damage in the optic nerve requiring anti-glaucomatous medical or surgical treatment. 3) Macular edema: presence of macular thickening with or without cystic formations which can be observed with clinical or angiographic exploration and/or via OCT. 524 ARCH SOC ESP OFTALMOL 2009; 84: 523-528
Uveitis complications: prevalence and risk factors in a series of 398 cases Table I. Age distribution Mean (RIC) With complications W/out complications P (Mann-Whitney) Age 44 (31-59) 41.5 (31-55) 44 (32-61) 0.35 4) Macular: choroidal neovascular membrane (CNVM), epiretinal membrane (ERM), macular necrosis. 5) Retinal: retina detachment, retinal tears, retinal neovessels, vascular occlusions and hemovitreous. 6) Others: comprising band keratopathy and posterior synechiae exceeding 180. To determine differences between the groups of patients with and without complications as well as the risk factors, we analyzed the studied variables. The statistical analysis was made with?2 tests to determine the association between qualitative variables and the development of complications and Mann-Whitney (after kurtosis and asymmetry test) for comparing the ages between patients with and without complications. As a measure of effect we utilized the OR (odds ratio) with its corresponding confidence interval at 95%. In order to determine the joint effect of variables we utilized logistical regression, verifying the match between the model and the Hosmer-Lemeshow test. In all cases we took p values over <0.05 to be statistically significant. All the analyses were made with the help of the SPSS v15.0 application (SPSS Inc Chicago Ill), Intercooled Stata 9.1 for Windows, and EpiDat 3.1. RESULTS We analyzed 398 patients with uveitis, 47% of episodes occurred in men, the mean age was of 44 years (RIC 31-59), and the mean follow-up was of 22 months (RIC 4-60). One hundred patients (25.1%) had one or more complications. 50.4% of them occurred in women, the mean age was of 41.5 years (RIC 31-55), with a mean follow-up of 49 months (RIC 19-72) (table I). None of the demographic variables (age and sex) could be considered to be a risk factor for developing complications. For the study we analyzed the complications, which involved doubling the number of patients who had more than one. The studied complications are shown in table II and Graph 1. Graph 1: Prevalence of complications. Of the studied variables, chronicity (OR 6.37 [IC95% 3.26-12.47%] P < 0.001) and bilaterality (OR 1.78 [IC95% 1.03-3.09] P= 0.039) are statistically significant risk factors for developing complications in our patients. There is a tendency in relapsing uveitis (OR 1.94 [IC95% 0.92-4.08] P= 0.08) which does not achieve statistically significance. Table II. Prevalence of complications Complication Patients Percentage Cataract 34 8.50% Macular edema 25 6.10% Macular complications Total 17 4.10% Choroidal neovascular membrane 8 Epiretinal membrane 5 Macular necrosis 4 Retinal complications Total 17 4.10% Retina detachment 8 Retinal tears 1 Hemovitreous 1 Retinal neovessels 2 Retinal vascular occlusions 5 Glaucoma or ocular hypertension 15 3.60% Others Total 6 1.50% Band keratopathy 2 Posterior synechiae over 180% 4 ARCH SOC ESP OFTALMOL 2009; 84: 523-528 525
PRIETO-DEL-CURA M, et al. Table III. Distribution of variables and analysis of association with complications Analysis univariado Analysis multivariado % % Variable Category of sample of Complications OR (CI 95%) P value OR (CI 95%) P value Sexo Women 53 26.5 0.87 (0.56-1.32) 0.512 Does not improve the model Men 47 29.4 Laterality Unilateral 62.7 18.5 3.53 (2.26-5.62) <0.001 1 Bilateral 37.3 45.1 1.78 (1.03-3.09) 0.039 Localization Anterior 58.1 20.4 1 1 Intermediate 9.7 40.0 2.59 (1.28-5.26) 0.008 0.73 (0.32-1.68) 0.464 Posterior 24.5 37.6 2.35 (1.41-3.91) 0.001 1.58 (0.83-3.03) 0.164 Panuveitis 7,8 37.5 2.34 (1.07-5.11) 0.033 1.92 (0.77-4.80) 0.161 Total 100 0.001 Clinical courseacute 42 12.6 1 1 Acute relapsing 24.9 20.2 1.76 (0.91-3.42) 0.096 1.94 (0.92-4.08) 0.080 Chronic 33.2 51.5 7.39 (4.19-13.02) <0.001 6.37 (3.26-12.47) <0.001 Total 100 1 <0.001 Diagnostic Idiopathic 26.9 25.5 1 Does not improve the model Infectious 28.1 24.3 0.94 (0.52-1.72) 0.848 Ocular self-immune 13.7 39.3 1.89 (0.96-3.75) 0.066 Systemic self-immune 25.9 30.2 1.27 (0.70-2.29) 0.437 Others 5.4 22.7 0.86 (0.30-2.47) 0.787 Total 100 0.268 In the analysis of the localization of the inflammation, posterior localization is the one with most associated complications, followed by panuveitis which has a high association value with complications without being statistically significant (OR 1.92 [0.77-4.80] P= 0.161) (table III). The result of the analysis to find a statistical association between a given complication with the demographic and ophthalmological variables of the study was that none was significant. DISCUSSION The complications of uveitis are a cause of important ocular morbidity. In 1996, Rothova (1) observed in a series of 582 cases that 35% of patients with uveitis had a significant visual loss and 4% had legal blindness, where complications appeared in over 50% (1). In our study with a mean follow-up of four years, similar to that of Rothova, complications appeared in 25% of patients. This difference could be due to the fact that in one decade and improve the knowledge of the natural history of uveitis and the efficiency of new immunosuppressant treatments have caused a reduction of this percentage. Another reason explaining this difference between both studies is that our hospital is not a reference centre for uveitis patients and we probably manage a higher percentage of acute episodes and therefore the characteristics of patients may not be comparable. Our percentage is somewhat higher (20%) when comparing it with a series carried out in Japan in 2003 with a lower follow-up (2 years) and with a higher percentage of posterior uveitis (5). The patients between 25 and 44 years the age group having the highest prevalence (1), although the mean age in our study is of 44 years because it was carried out in a hospital to which children are not usually taken. When the inflammation does not revert with treatments or it courses with relapse episodes the risk of complications increases, and this is the line demonstrated by the results of our study. Accordingly, the risk of complications is greater when uveitis becomes chronic or is bilateral and in addition there is an important association (without being statistically significant) in those cases having a relapsing acute clinical course. 526 ARCH SOC ESP OFTALMOL 2009; 84: 523-528
Uveitis complications: prevalence and risk factors in a series of 398 cases It has been described that patient with panuveitis are those with most associated complication and worse visual prognosis (1,6). This also occurs in our series, with a strong statistical association with the presence of complications. Accordingly, in these patients we must establish an aggressive treatment strategy to try to avoid them. Of all the complications developed in our study, cataracts was the most frequent, accounting for 30% of all complications, followed by macular edema with 21.3% and ocular hypertension/glaucoma with 13%. The distribution is not too different than that described previously (1) although with a higher percentage of cataracts (against 19%) and less macular edema (against 26%). In other series, cystic macular edema is the main cause of central visual acuity reduction in intermediate uveitis and the most frequent complication (21.7%) followed by cataracts (13%) which can be secondary to corticoids treatment as well as to the inflammation disease itself (6). This difference in distribution between series can be conditioned by the same factors described above. It is admitted that the initial inflammation as well as its persistence, and therefore the associated complications, are the result of a complex combination of genetic, environmental and immunological factors (3). One of the aims of this study is to shed more light on this complex combination of causative factors or associated to the possibility of developing complications in the course of uveitis, because there are very few publications on the matter, particularly in our environment. To conclude, in our experience chronic and bilateral uveitis have the highest risk of developing complications and, of these, cataracts was the most frequent. The other variables of the study could not be considered as statistically significant risk factors even though some categories exhibit interesting tendencies. This is probably related to the small sample size of some groups which hinders statistically significance in moderate associations. REFERENCES 1. Rothova A, Suttorp-van Schulten MS, Frits Tretters W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996; 80: 332-336. 2. Foster SC, Vitale AT. Diagnosis and treatment of uveitis. 1st ed. USA: W.B. Saunders company; 2002. 3. Gegúndez Fernández JA. Ancillary tests in uveitis. Arch Soc Esp Oftalmol 2003; 78: 643-646. 4. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of uveitis nomenclatura (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140: 509-516. 5. Wakabayashi T, Morimura Y, Miyamoto Y, Okada AA. Changing patterns of intraocular inflammatory disease in Japan. Ocul Immunol Inflamm 2003; 11: 277-286. 6. Frau Rotger E, Corretger Ruhi X, Mateos Poch JM, Olea Vallejo JL. Intermediate uveitis. Retrospective study. Arch Soc Esp Oftalmol 1999; 74: 519-523. ARCH SOC ESP OFTALMOL 2009; 84: 523-528 527