Patterns of uveitis in a Philippine eye clinic

Harvey S. Uy, MD, Irene W. Tam, OD

UVEITIS refers to a spectrum of intraocular inflammatory disorders affecting the uveal tract, retina, optic nerve, sclera, and lens. Endogenous uveitis refers to types of uveitis where the antigenic stimuli or source of inflammation originates from within the eye wall or enters the eye hematogenously. There are about 60 recognized uveitis entities, varying in distribution within a given population according to geographic, racial, genetic, and environmental factors. The International Labor Organization reports that 8 million Filipinos work overseas, making the Philippines the largest supplier of migrant workers worldwide.1, 2 Because of the lack of published data on the patterns of endogenous uveitis among Filipinos, eye doctors in other countries who care for overseas Filipino workers afflicted with uveitis have limited sources of information to guide them in diagnosing and treating these patients. This situation prompted us to conduct this cross-sectional study using current classification systems and diagnostic techniques. The results of this study will update the clinical profile of Philippine uveitis patients and guide eye-care providers who serve the needs of this expanding migrant population.

All endogenous uveitis patients consulting for the first time at the Asian Eye Institute (AEI) from January 1, 2003 to June 30, 2004 were included. AEI is a private multispecialty ambulatory eye clinic whose primary catchment area is Metro Manila, a large urban center and home to 8 million people. Patients with traumatic uveitis, surgical uveitis and exogenous endophthalmitis were excluded except those with sympathetic ophthalmia. During the initial visit, a thorough ocular, medical, and family history was obtained and a standard uveitis questionnaire was administered as part of the review of systems. A comprehensive physical and ocular examination was conducted which included external eye examination, best-corrected Snellen visual acuity (BCVA), applanation tonometry, slitlamp biomicroscopy, and dilated fundus examination. Based on the patient’s history, review of systems and clinical characteristics, a list of differential diagnosis was systematically generated and appropriate imaging and laboratory tests were requested using a targeted approach.3, 4 When indicated, the following diagnostic tests were performed: fluorescein angiography, indocyanine green angiography (ICG), B-Scan ultrasonography, optical coherence tomography, visual-field (VF) testing, and radiological studies such as radiography, computed tomography, or magnetic resonance imaging (MRI). Laboratory testing may have involved complete blood count, urinalysis, erythrocyte sedimentation rate, serum fluorescent treponemal antibody absorption detection (FTA-ABS), human-leukocyte-antigen (HLA) typing, antinuclear antibodies, rheumatoid factor, liver-function tests, and serum antibody titers for Toxoplasma gondii, herpes simplex, and herpes zoster. Invasive tests may have involved biopsy of the skin, conjunctiva, sclera, aqueous, and vitreous. Culture and sensitivity and polymerase-chainreaction studies were performed when indicated. The anatomical sites of involvement were classified according to the International Uveitis Study Group (IUSG) system based on localization of the predominant site of intraocular inflammation.5 If the detailed history, review of systems, physical and ocular findings, and confirmatory laboratory test results pointed to a definite or highly probable etiological cause, a specific uveitis diagnosis was assigned and entered into the Registry. Otherwise the patient was classified as having idiopathic uveitis. The patients were treated according to published guidelines for immunosuppressive drugs.6 Topical steroids dexamethasone, prednisolone acetate, or fluoromethalone were administered to all patients at doses one drop daily to one drop hourly based on the severity of the uveitis flare up. Local periocular triamcinolone acetonide injections (Kenalog, Bristol Myers, New York, NY, USA) were given for severe (+3 or +4 cells) uveitis and for cystoid macular edema. Systemic corticosteroids or immunosuppressive drugs were indicated in the presence of bilateral intermediate or posterior or panuveitis, sight-threatening uveitis, recurrent uveitis, and intolerance for topical or local steroid injections. If systemic drugs were administered for longer than 3 months in an effort to control ocular inflammation, the patient was classified as necessitating long-term systemic therapy (LST). The last recorded BCVA was used to determine whether the patient was legally blind (20/200 or worse) in one or both eyes. The development of sight-threatening ocular complications such as cataract, glaucoma, retinal
detachment, vitreous hemorrhage, and cystoid macular edema (CME) was also recorded. Glaucoma for this series was defined as elevated IOP (>25 mmHg) leading to visualfield and optic nerve-head changes or necessitating at least 3 months of IOP-lowering medications. Descriptive statistics are reported. The probability values for the comparison of percentage values were calculated using the chi square test with p < 0.05 considered significant. Data analysis was performed using Microsoft Excel 2000 version 9.0 (Microsoft Corporation, Redmond, WA, USA).

Of 12,250 new general-eye-clinic patients seen during the study period, 103 (0.84%) were diagnosed to have endogenous uveitis. Table 1 shows the demographic and clinical characteristics of the patients. The mean age at presentation was 43 ± 17 years (range 5 to 83; median age = 40 years). The mean age at presentation was similar for all four groups when the patients were classified according to the predominant site of involvement. The male to female ratio was 1:1.3. No gender predominance was observed for anterior, intermediate, and panuveitis; however, more females than males had posterior uveitis. All 5 patients with retinal vasculitis were female. Filipinos, who belong to the Malay race (77%), made up the predominant racial group, followed by Chinese (22%) and a single Indian patient (1%). Table 2 shows the sites of involvement according to racial group. Filipino patients developed uveitis in all sites of involvement but were particularly prone to develop anterior and panuveitis. The most common diagnoses among Filipinos were: idiopathic anterior uveitis, idiopathic pars planitis, VogtKoyanagi-Harada syndrome (VKH), Behcet’s disease, and multifocal choroiditis and panuveitis (MCP). The predominant type by site of involvement among Chinese patients was anterior uveitis. The most common diagnoses among chinese were: idiopathic anterior uveitis, HLA-B27- associated uveitis, MCP, and retinal vasculitis. Only one Chinese patient presented with intermediate uveitis; none developed VKH or Behcet’s disease. Anterior uveitis was the most common (40%), followed by panuveitis (27%), posterior uveitis (19%), and intermediate uveitis (14%). A specific diagnosis was established in 61 (59%) patients. The rest were diagnosed as having idiopathic uveitis. The most frequent specific descriptive disease entities were: multifocal choroiditis and panuveitis (MCP) (9%), Vogt-Koyanagi Harada (VKH) syndrome (9%), Behcet’s disease (8%), HLA B27-associated uveitis (5%), and serpiginous choroidopathy (4%). Idiopathic anterior uveitis (IAU) was diagnosed in 25 (24%), idiopathic intermediate uveitis in 14 (14%), and idiopathic retinal vasculitis in 3 (3%) patients (Table 3). An infectious etiology was identified in 9 (9%) patients while the rest presented with noninfectious autoimmune

uveitis. Among the infectious causes of uveitis, Toxocara and Toxoplasma were the most common identifiable etiologic agents (3 each) followed by one case each of herpes simplex, leprosy, and tuberculosis. None of the 32 patients tested for FTA-ABS were positive. Most patients (56%) experienced bilateral involvement. The number of eyes involved was affected by the site of involvement (p < 0.001). Bilateral involvement occurred less frequently among patients with anterior uveitis (34%) and more frequently among patients with intermediate (71%) and panuveitis (86%). For posterior uveitis, an equal number of patients experienced unilateral and bilateral involvement. Forty-two of 158 involved eyes had severely decreased BCVA of 20/200 or worse. Eighteen patients (18%) were blind in one eye while 12 (12%) were blind in both eyes. Only patients with panuveitis developed bilateral blindness. Systemic immunosuppressive drugs were required for control of intraocular inflammation in 66 (64%) patients (Table 1). Systemic medications were administered for most patients with intermediate, posterior, and panuveitis. Only a third of patients with anterior uveitis needed systemic medication. The most common agents used were oral nonsteroidal anti-inflammatory agents (celecoxib, valdecoxib, mefenamic acid, diclofenac sodium), corticosteroids, methotrexate, and pulse intravenous cyclophosphamide. Forty-seven of 103 (46%) patients developed sight-threatening complications. Cataract formation (34%) was the most frequent sight-threatening complication, except in patients with posterior uveitis. Thirteen patients developed glaucoma (13%) in the whole sample population. However, the patients with intermediate uveitis were spared from developing glaucoma. CME developed in 11 patients (11%). Less frequent complications included

retinal detachment, vitreous hemorrhage, hypotony, and optic neuritis (Table 1).

The distribution of uveitis differs according to geographic, genetic, and environmental factors. As in published reports, the age at presentation to the clinic occurs in the third or fourth decade in this series.7-10 Because the Philippines has a young population, the number of uveitis
cases is expected to increase over time as more children enter the third or fourth decade of life. Filipino patients with anterior uveitis tend to manifest unilateral involvement while patients with intermediate and panuveitis were more prone to experiencing bilateral involvement. The patterns of uveitis in this series are markedly different from those of the 1978 series reported by Fajardo et al. (Table 4). Other studies have shown that patterns of uveitis in a certain geographic area change over time.8, 10 In the 1978 series, the most frequent types of endogenous uveitis by cause were idiopathic, tuberculous, lens-induced,
rheumatoid, and sympathetic ophthalmia. In this series, these were: idiopathic, MCP, VKH, Behcet’s disease, and HLA B27-associated uveitis. The reduction in frequency of idiopathic cases from 53.8% in 1978 to 41% in 2004 is likely related to advances in the diagnostic technologies including PCR, antibody assays, genetic testing, MRI, VF, and ICG. Improvements in the delivery of public-health services may have led to changes in uveitis patterns. Over the past 2 decades, government programs that provide free antituberculosis medicines may have led to decreasing frequency of tuberculous uveitis. The local detection rate of TB has improved from 10% in 1998 to 58% in 2002, and the treatment success rate from 84% to 88%.11 The increasing availability of ophthalmic care as practising Filipino ophthalmologists grow in number, especially in highly populated urban centers, is a possible reason for the near disappearance of lens-induced uveitis and sympathetic ophthalmia. We cannot compare the frequencies of infectious endogenous uveitis (eg. Toxocara, Toxoplasma, Tuberculous) with other series because we did not screen all patients in this series for these diseases. The evolution and acceptance of uveitis classification systems, diagnostic tests, and diagnostic criteria have led to higher recognition of specific disease entities like MCP, SLE, Behcet’s disease, and the white-dot syndromes. For example, this study reveals that Behcet’s disease and VKH are significant causes of uveitis in the Philippines. The frequency of rheumatoid-disease-related uveitis has remained essentially the same. The absence of human
immunodeficiency (HIV) virus related ocular infections is likely to be multifactorial and may include a reluctance by patients to seek consultation, sequestration of HIV infected patients in specialized care centers, or short life expectancy. Systemic immunosuppressive drugs were needed for control of intraocular inflammation in 2 of every 3 patients. The site of involvement greatly influenced the need for systemic therapy. Only 1 in 3 patients with anterior uveitis needed systemic medications while most patients with intermediate, posterior, and panuveitis needed systemic therapy. In our practice, topical or local corticosteroid injections were preferred for anterior uveitis patients with only unilateral involvement in order to avoid systemic side effects. Corticosteroids for local injection, such as triamcinolone acetonide, are now readily available in the Philippines and have been used with great efficacy by our service in the treatment of severe disease flare up
and resolution of CME. Systemic therapy, including use of corticosteroids, was aggressively implemented for patients with intermediate, posterior and panuveitis especially when both eyes were involved. Steroid-sparing immunosuppressive drugs were given for recurrent or chronic cases of uveitis. The most common sight-threatening complications were cataract, glaucoma, and CME. Anterior-uveitis patients mostly developed cataracts while intermediateuveitis patients tended to develop cataracts and CME. None of the intermediate-uveitis patients developed glaucoma. None of the posterior-uveitis patients developed cataracts. Those with panuveitis, which has been associated with poorer visual outcomes in previous studies,12 developed more severe ocular complications like glaucoma and retinal detachment. In this series, only panuveitis patients developed bilateral blindness. Because of the great risk for poor outcomes, we recommend that aggressive treatment with corticosteroids and immunosuppressive medications be started early for these patients. Uveitis is a major cause of blindness worldwide. It has been estimated that uveitis accounts for 30,000 new cases or 10% of blindness in the United States annually.13 This study shows that many Filipino patients lose vision from uveitis. However, it does not estimate the socioeconomic and psychological costs of blindness among these young (<50 years) members of society. This is a prospective clinic-based case series and its findings should be interpreted with caution. Clinic-based studies provide dissimilar estimates of disease incidence, prevalence, or patterns of distribution as compared to community-based studies.14 A clinic-based study is subject to referral bias. Because the study site is a specialty eyecare center, the patients in this study probably suffer from more serious disease compared with the general population. Therefore, these patients are more likely to require systemic medications and develop more severe complications. Because the study site is in an urban center, the results and recommendations are not applicable to a rural setting. Nevertheless, in the absence of recent community or clinic-based studies, this study may provide the best representation of the current patterns of uveitis in the Philippines. In summary, this study demonstrated the changing disease patterns of uveitis in a Philippine urban center.  We have also shown that significant rates of ocular complications and blindness occur among Filipino uveitis patients. We recommend that aggressive ocular and systemic therapy be given for patients with panuveitis who are at great risk for developing binocular blindness.

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