Ocular Immunology and Inflammation
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The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix Nicholas P. Jones FRCOphth To cite this article: Nicholas P. Jones FRCOphth (2015) The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix, Ocular Immunology and Inflammation, 23:2, 118-126, DOI: 10.3109/09273948.2013.855799 To link to this article: http://dx.doi.org/10.3109/09273948.2013.855799
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Date: 16 November 2016, At: 08:33
Ocular Immunology & Inflammation, 2015; 23(2): 118–126 ! Informa Healthcare USA, Inc. ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2013.855799
ORIGINAL ARTICLE
The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix Nicholas P. Jones,
FRCOphth
The Royal Eye Hospital, Manchester, UK
ABSTRACT Purpose: To demonstrate the demography, anatomical, and diagnostic classification of patients with uveitis attending the Manchester Uveitis Clinic (MUC), a specialist uveitis clinic in the northwest of England, UK. Methods: Retrospective retrieval of data on a computerized database incorporating all new referrals to MUC from 1991 to 2013. Results: A total of 3000 new patients with uveitis were seen during a 22-year period. The anatomical types seen were anterior 46%; intermediate 11.1%; posterior 21.8%; and panuveitis 21.1%. The most common diagnoses were Fuchs heterochromic uveitis (11.5% of total), sarcoidosis-related uveitis (9.7%), idiopathic intermediate uveitis (7.9%), idiopathic acute anterior uveitis (7.0%), and toxoplasmosis (6.9%). Syphilis and tuberculosisassociated uveitis increased markedly in frequency during the study period. Conclusions: The uveitis casemix in this region reflects a predominantly white Caucasian population in a temperate country, but with changing characteristics owing to increasing immigration, enhanced diagnostic techniques, changes in referral pattern, and some real changes in disease incidence. Keywords: Casemix, demography, epidemiology, uveitis
In 1991 the Manchester Uveitis Clinic (MUC) was created at the Manchester Royal Eye Hospital (MREH) to provide a specialist uveitis service to the population of Greater Manchester (GM) and the northwest of England. Immediately a database was created to record prospectively each new patient attending the clinic. Over 3000 patients have now been seen and the collected data provide information on the epidemiology and casemix of uveitis within this population. This represents the first major epidemiological study of uveitis in the United Kingdom for many years, and the largest single-center uveitis survey in the medical literature to date. A further paper will deal with uveitis manifestations, complications, and management.
in manifestations, diagnosis, and management. The fields are shown in Table 1. Data for this study were retrieved entirely from the MUC database, with catchment population epidemiology sourced from UK Census1 data available for 1991, 2001, and 2011. Diagnoses were made at the initial presentation for those forms of uveitis identifiable by clinical appearance only, or soon afterward for those requiring supportive serology or other investigation, being changed later if new clinical findings or investigations warranted. All diagnoses that include an etiology for uveitis were made on the basis of a qualifying clinical presentation, with positive supporting serology, radiology, microbiology, or biopsy where indicated by clinical appearance. Serological investigations for active or previous infection, including HIV, were performed in the presence of suggestive clinical appearance or significant risk factors. Radiology for joint, pulmonary, or CNS involvement was performed only on the basis of symptoms or where asymptomatic diagnostic changes were sought. Intraocular
METHODS The MUC database prospectively records 42 information fields on each new patient attending; for those continuing to attend, it records significant changes
Received 18 July 2013; revised 8 October 2013; accepted 11 October 2013; published online 25 November 2013 Correspondence: N. P. Jones, FRCOphth, Consultant Ophthalmic Surgeon, The Royal Eye Hospital, Oxford Road, Manchester M13 9WL, UK. E-mail: [email protected]
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TABLE 1. The data fields recorded in the Manchester Uveitis Clinic database. A. Patient identifiers
1. 2. 3. 4. 5. 6. 7. 8.
Hospital number Surname Forename Residence postcode (Zip) Sex Date of birth Age at first attendance at MUC Racial background
B. Management data
1. Date of first clinic attendance 2. Whether does or does not have uveitis (scleritis, screening patients also recorded) 3. Age at onset of uveitis 4. Referring ophthalmologist/physician name
C. Uveitis features
1. 2. 3. 4.
Location (anterior, intermediate, posterior, panuveitis) Granulomatous or nongranulomatous anterior uveitis Side affected Behavior over time (acute single/recurrent; chronic fluctuating/unremitting)
D. Associated systemic Involvement (Y or N)
1. 2. 3. 4. 5. 6. 7.
Fever Joints Skin Bowel Chest Neurological Other
E. Uveitis diagnosis
1. Descriptive term 2. Etiology if known 3. Diagnostic confidence (confirmed; presumed; possible)
F. Uveitis complications (Y or N)
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Band keratopathy Corneal decompensation Occlusio Glaucoma Cataract Retinal neovascularization Retinal detachment Subretinal fibrosis Macular edema Phthisis
G. Medical management (Y or N)
1. 2. 3. 4.
Depot steroid injection (orbital or intraocular) Systemic steroid Immunosuppressive (named) Antimicrobial
H. Surgical management (Y or N)
1. 2. 3. 4.
Cataract surgery Glaucoma surgery Vitreoretinal surgery Other surgery
I. Associated systemic disease (free text) J. Bone densitometry results
infection was confirmed with fluid sampling or biopsy for microscopy and culture or PCR, if possible, and masquerades by vitreous cytology.
RESULTS Between March 1, 1991 and March 6, 2013 there were 3301 patient entries to the database. Some patients on the database did not have uveitis. They included patients with scleritis but not uveitis (55), patients !
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with juvenile idiopathic arthritis on the uveitis screening program (162), patients with Behc¸et disease who attended for baseline examination (50), patients with HIV retinopathy but no uveitis (3), and sundry others referred from physicians with systemic inflammatory disease, but exhibiting nonuveitic ophthalmic manifestations (30). The remaining 3000 patients had uveitis and all subsequent data relate to this group. The patients attended the MUC via several routes of referral: 2324 (77%) were tertiary referrals from hospital consultants (2251 [75%] from
120 N. P. Jones TABLE 2. Areas of residence for patients with uveitis referred to Manchester Uveitis Clinic. Area 1. 2. 3. 4. 5. 6.
Greater Manchester Northwest, Cumbria, Isle of Man Other UK/International Midlands Merseyside, Cheshire, Wales Yorkshire, Humberside, Northeast
Number
Percentage of total
2364 294 108 92 88 54
78.8 9.8 3.6 3.1 2.9 1.8
Numbers correspond to marked areas on Figure 1.
ophthalmologists, 73 [2.4%] from physicians); 99 (3.3%) were from subconsultant ophthalmologists, streaming patients into the specialist service from outreach clinics or from a clinic for acute ocular inflammation; and 577 (19.2%) were either transferred to MUC urgently, direct from the MREH acute services, or were referred by their general practitioner, usually for a second opinion on management. The conurbation of Greater Manchester includes the cities of Manchester and Salford, and several surrounding towns, with a total and approximately stable population of 2.68M in the 2011 UK Census1 (population was 2.57 M in 1991). Of all patients with uveitis referred to MUC, 2364 (78.8%) resided within GM according to postcode. The areas of residence for all referred patients are shown in Table 2, and Figure 1 shows the areas referred to in this table. The incidence of referrals to MUC from GM over the study period was approximately 4.1:100,000/yr. However, the rate of referral increased by more than 60% over the study period: for the first decade (1991–2001) the rate was 3.46:100,000/yr; for the most recent decade (2003– 2013), 5.55:100,000/yr. The age at onset of uveitis and the age at presentation to MUC are shown in Figure 2. The onset of uveitis for 2334 patients (77.8%) was in adults of working age (between 16 and 65 years of age) and this included 1100 young adults (16–35 years of age, 36.7% of all patients); 401 (13.4%) were children with an onset age below 16 years, and 265 (8.8%) were of retirement age (more than 65 years at onset; oldest patient 90 years). Using the Standardisation of Uveitis Nomenclature (SUN),2 the number of patients with each anatomical type of uveitis is shown in Table 3. Fuchs heterochromic uveitis is classified in the MUC database as an ‘‘anterior’’ uveitis despite its usual significant vitreous involvement and occasional retinal vasculitis. It is identified as a subset of anterior uveitis in Table 3. Granulomatous anterior uveitis was seen in 332 patients (11.1% of total, 14.6% of those with anterior segment inflammation of any type). Uveitis was bilateral at presentation, or became bilateral, in 1550 patients (51.7%). Of those with unilateral uveitis, the left eye was involved in 722 cases (49.8%), the right in 728 (50.2%). The MUC database characterizes uveitis
FIGURE 1. Map of Greater Manchester (Zone 1) and surrounding areas of UK referring patients to Manchester Uveitis Clinic. Area numbers correspond to area descriptions in Table 2.
FIGURE 2. The onset age for uveitis, and the age at presentation for 3000 patients referred to MUC. TABLE 3. Anatomical location of uveitis. Definition Anterior uveitis (excluding FHU (FHU Intermediate uveitis Posterior uveitis Panuveitis
Number
Percentage of total
1380 1037 343 332 654 634
46.0 34.6) 11.4) 11.1 21.8 21.1
FHU, Fuchs heterochromic uveitis.
behavior over time: a total of 757 (25.2%) patients had a single acute episode; 407 (13.6%) had acute recurrent uveitis; 607 (20.2%) had chronic fluctuating disease; and 1229 (41.0%) had chronic unremitting uveitis. The coexistence of systemic symptoms and/or signs at presentation was recorded and these are shown in Table 4. A total of 978 patients (32.6%) were Ocular Immunology & Inflammation
The Manchester Uveitis Clinic TABLE 4. Accompanying systemic symptoms and/or signs in patients at presentation. System
Number with concurrent systemic symptoms or signs (%)
Fever Arthropathy Skin lesions Bowel disorder Chest Neurological No symptoms/signs
135 407 274 89 193 153 2022
(4.5) (13.6) (9.1) (3.0) (6.4) (5.1) (67.4)
so affected, the most common being arthropathy (13.6% of all patients with uveitis). In addition to the SUN nomenclature of uveitis, the MUC database uses a comprehensive diagnostic system based on descriptive and/or etiological diagnoses. The data are shown in Table 5. The most common diagnoses were Fuchs heterochromic uveitis (FHU), which was diagnosed on clinical appearance (345 patients, 11.5% of total); sarcoidosis-related uveitis (292, 9.7%), which was diagnosed as a qualifying uveitis with supporting biopsy at any site (confirmed), raised ACE and hilar lymphadenopathy (presumed), or typical with only raised ACE or abnormal chest x-ray (possible); idiopathic intermediate uveitis (236, 7.9%), diagnosed by clinical appearance, without neurological symptoms and with no supportive evidence of sarcoidosis; idiopathic acute anterior uveitis (210, 7.0%), diagnosed with either HLA-B27 negative or untested; and toxoplasmosis (206, 6.9%), diagnosed mainly by clinical appearance, with supporting serology in most patients. These 5 diagnoses together accounted for 43% of all patients. There is deliberate overlap in some of the diagnoses shown in Table 5, as some are descriptive and some etiological; results can be found using either parameter. The most common type of anterior uveitis was FHU (24.8%); of intermediate uveitis, idiopathic (70.5%); of posterior uveitis, idiopathic (42.8%); and of panuveitis, idiopathic (42.1%). Table 5 also includes a description of the method of diagnosis for each listed entity. The total number of patients without either a proven etiology or a definite, well-recognized descriptive pattern was 935 (31.2%). However, where wellrecognized syndromes, including (idiopathic) FHU, were more appropriately included in the category with unknown etiology, this number rose to 1557 (51.9%). The MUC diagnostic system requires a statement on diagnostic confidence. Those with confirmed etiology include uveitis in association with biopsy-confirmed sarcoidosis at any site, and culture-proven or PCR-supported intraocular infection, and these amounted to 101 patients (3.4%). The etiology was presumed from supporting evidence (for example, a patient with raised ACE, hilar !
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lymphadenopathy, and a qualifying uveitis, with no evidence of another diagnosis, was presumed to have sarcoidosis-associated uveitis) in 952 (31.7%) and considered possible (with suggestive features and no other diagnosis identified) in 390 (13.0%). More females than males were referred to MUC: 54.1 and 45.9%, respectively (F1.17:1 M compared to UK population ratio of F1.01:0.99 M), 2 = 15.55, p 0.0001). The diagnoses with the most significant gender difference are shown in Table 6. The population demography of GM and the northwest of England (UK Census1 2001), compared with the number of referrals from three main ethnic groups, is shown in Table 7. Some uveitis diagnoses were clearly more frequent in patients with a particular ethnic or racial background, and these are also shown. The most significant of these discrepancies were birdshot retinochoroidopathy (100% of these patients were Caucasian, compared with 88.9% in the GM catchment population), tuberculosis (66.3% Asian compared with 6.5%), and toxoplasmosis (19.8% black compared with 1.7%). There was no evidence of significant seasonal variation in incidence for any diagnosis. Some diseases changed in incidence during the period of study. An epidemic of syphilis commenced in Manchester in 1999–2004,3 resulting in a surge of ophthalmic cases.4 During the first decade of this survey (1991–2001) only 2 cases of ocular syphilis were seen; during the most recent decade (2003–2013) there were 18. The diagnosis of tuberculosis has also increased, the figures for the same periods being 30 and 78. There was a ‘‘surge’’ in toxoplasmosis diagnosis during 1996–1998 (16.7 cases per year, against a mean of 9.4 per year over the whole period). Data on uveitis type, distribution, and diagnosis were compared with those from studies in other centers.5–19 The anatomical distributions of uveitis are shown in Table 8, and the relative frequencies of key uveitis diagnoses are shown in Table 9.
DISCUSSION There is no fixed catchment population for any specialist hospital service in the United Kingdom, which permits the patient a choice of hospital. However, the great majority of residents in the Greater Manchester conurbation choose the MUC if referred for the management of uveitis. The recording of residential postcode on the database permits comparison with the GM catchment population for the patients who reside in that area. Demographic studies on uveitis are substantially affected by the patient population, and the MUC is no exception. It is located in a large university hospital in a western city at 53 North latitude within an unusually temperate large island. Sarcoidosis is a common
122 N. P. Jones TABLE 5. Uveitis diagnoses in Manchester Uveitis Clinic 1991–2012. Diagnosis Acute anterior uveitis, unknown etiology Acute anterior uveitis, post-traumatic Acute macular neuroretinitis Acute panuveitis, unknown etiology Acute posterior multifocal placoid pigment epitheliopathy Acute zonal occult outer retinopathy Autoimmune corneal endotheliopathy Bacterial endophthalmitis Behc¸et disease with uveitis including retinal vasculitis Birdshot retinochoroidopathy Chronic anterior uveitis, unknown aetiology Chronic anterior uveitis, systemic vasculitis-related Chronic panuveitis, unknown aetiology Churg-Strauss syndrome with uveitis CINCA syndrome-related uveitis Cogan syndrome with uveitis Cytomegalovirus-associated uveitis (Chronic anterior (Retinitis Diabetes-related uveitis Drug-induced uveitis Focal choroiditis/choroidal granuloma, unknown etiology Focal retinitis, unknown aetiology Fuchs heterochromic uveitis Fungal endophthalmitis or retinitis (candidiasis Herpes simplex virus-associated uveitis (Acute anterior (Chronic anterior (Keratouveitis (ARN HLA-B27-related uveitis: (Anterior, recurrent (Anterior, chronic (Panuveitis, acute (Panuveitis, chronic Immune recovery uveitis post-CMV retinitis Inflammatory bowel disease-related: (Crohn disease (Ulcerative colitis Intermediate uveitis (Multiple sclerosis (Sarcoidosis (Tuberculosis (Unknown etiology Juvenile chronic iridocyclitis Juvenile idiopathic arthritis-related uveitis Leprosy with uveitis Masquerade syndromes Multifocal choroiditis, unknown etiology Multiple evanescent white-dot syndrome Multiple sclerosis-related uveitis Necrotising retinopathy, including ARN (HSV-related (VZV-related (CMV-related (Cause unknown Neuroretinitis, unknown etiology Phakoanaphylactic uveitis Posner-Schlossman syndrome Post-surgical uveitis, unknown etiology Psoriatic arthropathy-associated uveitis Punctate inner choroidopathy
Total (%)
Method of diagnosis
210 (7.0%) 2 1 29 31 10 4 13 81 36 197 (6.6%) 1 199 (6.6%) 1 2 2 25 2) 23) 3 4 6 10 345 (11.5%) 26 22) 58 6) 37) 9) 6) 135 (4.5%) 94) 27) 6) 7) 3 32 14) 18) 332 18) 58) 13) 234) (7.8% of total) 6 112 1 22 26 12 48 59 6) 27) 23) 3) 4 4 4 6 19 83
A E B A B B B Ci D Cvi A D A D D D B or Ci Ci Ciii Ci D E A A B Ci Ci B or Ci B or Ci B B =/ Ci Ci Cvi Cvi Cvi þ D Cvi þ Ci Cvi þ D B þ Ci D Cvi D Cvi D Cvi B BþD B þ Civ/v D Ciii/v D B B þ Ciii Ciii þ D Cv Cii/iv Cv B þ Ciii B D B Ci, or Ciii B þ Ci B þ Ci Ciii Ci B B B B E D Cvi B (continued )
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Table 5. Continued
Diagnosis Radiotherapy-induced uveitis Reactive arthropathy-associated uveitis Retinal detachment-induced uveitis Retinal pigment epitheliitis Retinal vasculitis as predominant feature of uveitis (Primary (Behc¸et (Multiple sclerosis (Sarcoidosis (SLE (Susac syndrome (Systemic vasculitis (Tuberculosis Sarcoidosis-related uveitis (Anterior uveitis (Chronic panuveitis (Choroidal granuloma 8) (Intermediate uveitis (Multifocal choroids (Retinal vasculitis Scleritis with uveitis Serpiginous choroiditis Sympathetic uveitis: (Trauma-induced (Surgery-induced Syphilis-associated uveitis Systemic lupus erythematosus-related uveitis Toxocariasis Toxoplasmosis Tuberculosis-associated uveitis (Anterior uveitis (Intermediate (Keratouveitis (Multifocal choroids (Panuveitis (Retinal vasculitis (Serpiginous-like Tubulointerstitial nephritis and uveitis syndrome Uveal effusion syndrome Varicella-zoster virus-associated uveitis (Acute anterior (Chronic anterior (Panuveitis (Keratouveitis (ARN (Sclerouveitis (Retinal vasculitis Vogt-Koyanagi-Harada syndrome
Total (%) 1 22 7 7 136 (4.5%) 63) 22) 11) 24) 2) 1) 1) 12) 292 (9.7%) 79) 99) Ciii/iv/v D 58) 16) 24) 49 9 33 21) 12) 22 5 26 206 (6.9%) 99 14) 12) 1) 9) 28) 19) 16) 7 2 70 18) 16) 2) 3) 27) 3) 1) 23
Method of diagnosis E D Cvi E B B B þ Ciii/iv BþD BþD B þ Ciii/iv/v D B þ Ciii þ D B þ Civ þ D B þ Ciii þ D B þ Ci/iii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D B B E E E Ci/iii D B Ciii B Ci/Ciii Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Cv B B Ci/Ciii B B Ciii B Ciii B B þ Ci B Ci/Ciii B þ Ci B
APMPPE, acute posterior multifocal placoid pigment epitheliopathy; ARN, acute retinal necrosis; CINCA, chronic infantile neurological, cutaneous and articular; HLA, human leucocyte antigen. Methods of diagnosis: A, anatomical description of uveitis with unknown cause; B, unique or typical clinical appearance; C, qualifying clinical appearance with supporting investigation (i, microbiology; ii, cytology; iii, serology; iv, radiology; v, biopsy; vi, HLA type); D, qualifying uveitis with supporting systemic manifestations; E, typical uveitis with typical history.
disease and HLA-B27 is a common gene with a prevalence of about 7%. The population is mostly indigenous white Caucasian derived from AngloSaxon or Celtic genetics but there is a significant and increasing minority of those particularly from the Indian subcontinent but also from within the European Union, Eastern Europe, and Africa. Some immigrant populations have a high rate of tuberculosis infection, !
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and the incidence of newly diagnosed tuberculosis in GM is among the highest in the United Kingdom20 (440:100,000). As with most European cities there is a significant gay community with its HIV and syphilis risk, and an epidemic of syphilis in GM, beginning 12 years ago, placed ocular syphilis once more on the diagnostic agenda. Manchester has a large international airport, regularly importing those with new
124 N. P. Jones TABLE 6. Uveitis and gender for the whole survey and for the most common forms of uveitis. Diagnosis
Total
Male (%)
Female (%)
UK gender ratio 2013 (all ages) (49.5) (50.5) All patients 3000 1377 (45.9) 1623 (54.1) Chronic anterior uveitis 510 194 (38) 316 (62) Acute anterior uveitis 438 198 (45) 240 (55) Chronic panuveitis 396 181 (46) 215 (54) Fuchs heterochromic uveitis 345 173 (50) 172 (50) Intermediate uveitis 337 151 (45) 186 (55) Sarcoidosis-associated 292 151 (52) 141 (48) Toxoplasmosis 206 101 (49) 105 (51) Retinal vasculitis 145 76 (52) 69 (48) HLA B27-associated 135 70 (52) 65 (48) JIA-associated 112 25 (22) 87 (78) Tuberculosis-associated 99 46 (46) 53 (54) Punctate inner choroidopathy 83 20 (24) 63 (76) Behc¸et disease 81 44 (54) 37 (46) JIA, juvenile idiopathic arthritis.
TABLE 7. Uveitis and ethnic or racial origin. Diagnosis or category Greater Manchester populationa Northwest England populationa All patients referred to MUC AAU, unknown etiology Behc¸et disease Birdshot retinochoroidopathy Fuchs heterochromic uveitis HLA-B27-related uveitis Juvenile chronic arthritis Sarcoidosis Toxoplasmosis Tuberculosis VKH syndrome
% Caucasian % Asian % Black (no.) (no.) (no.) 88.9 92.9 80.0 (2400) 84.3 79.5 100.0 85.1 96.9 94.9 63.8 68.3 22.5 16.7
6.5 4.1 13.1 (393) 9.5 17.9 0.0 8.8 3.0 3.0 18.2 11.9 66.3 72.2
1.7 1.0 6.8 (205) 5.2 2.6 0.0 6.0 0.0 2.1 17.9 19.8 11.2 11.1
AAU, acute anterior uveitis; VKH, Vogt-Koyanagi-Harada syndrome. a Data from UK Census1 2001.
infections, but the UK climate does not yet permit the proliferation of arthropod-borne viral diseases. It is in this context that some comparison can be made between population and clinic figures. There is a highly significant preponderance of female patients (p 0.0001) when compared to the all-ages UK population sex ratio (Table 6). Female patients predominate in four common diagnostic categories, but in only the first of these does the difference reach clear statistical significance: chronic anterior uveitis (CAU, p 0.0001), acute anterior uveitis (p = 0.07), intermediate uveitis (p = 0.08), and chronic panuveitis (p = 0.13). The reasons for this high incidence of female patients with CAU are not known. There is a significant discrepancy in the high proportion of ethnic minority patients attending MUC (Table 7). Those of Asian origin account for 6.5% of the GM population, yet 13.1% of those attending MUC, and
for black patients the figures are 1.7 and 6.8%, respectively. It is clear that this overrepresentation is concentrated in certain areas of diagnosis, as shown in Table 7—in particular, tuberculosis for those of Asian origin and toxoplasmosis and sarcoidosis for those of Afro-Caribbean origin. We have previously reported the increasing incidence of ocular tuberculosis in this region.21 The metropolitan areas of the United Kingdom become more ethnically mixed as immigration increases, and it is necessary that such changes in disease pattern are highlighted to direct resources appropriately. Comparisons with surveys undertaken in uveitis clinics elsewhere in the world5–19 often present great contrasts in the numbers of patients affected within diagnostic categories. Some of these are obviously associated with climatic or genetic predisposition (such as for the Vogt-Koyanagi-Harada syndrome, which is rare in the United Kingdom), but to this should be added the subtle but important organizational aspects of each clinic. This clinic, the MUC, is part of a large university hospital complex and MREH provides walk-in emergency services for ophthalmology. Most uveitis is dealt with within that service and does not require referral to MUC. The number of patients with HLA-B27-related uveitis, for example, is therefore low in the MUC statistics, and generally for anterior uveitis as a proportion of the total (compared with higher figures for some other centers which may have different organization, Table 8). Within the towns of GM are 6 other ophthalmology units, each of which will deal with local uveitis to differing degrees, referring to MUC when considered necessary. Nevertheless, such differences as described between centers in Table 8 are unlikely to be explained solely by true diagnostic difference (for example, the proportion of those with intermediate uveitis varying from 3% in Italy7 to 18% in Iran14 and panuveitis varying from 7% in Switzerland9 to 41% in China13 seem most unlikely to be explained solely by the clinical diagnoses of uveitis most commonly affecting patients in those areas). It seems more likely that despite the introduction of the SUN anatomical classification system,2 different interpretations still exist over the anatomical categorization of intraocular inflammation. Fuchs heterochromic uveitis is a common cause of uveitis in the United Kingdom, and appears to be particularly common in this area of England, producing 11.5% of all patients attending this clinic. This author has expressed a longstanding research interest in the disease22 and that may cause a positive referral bias. However, the frequency of the disease even when compared to that in other European countries (2.2% in Portugal,6 2.1% in Italy7) is striking, and largely unexplained. Part of the reason may be underdiagnosis; countries with a high (sometimes almost universal) prevalence of dark brown-eyed Ocular Immunology & Inflammation
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TABLE 8. Comparisons of uveitis anatomical location with recent surveys in other countries (all percentages are rounded). Study Jones Rodriguez5 Palmares6 Mercanti7 Merrill8 Tran9 Oruc10 Barisani11 Singh12 Yang13 Soheilia14 Sengu¨n15 Kazokog16 Sittivara17
Period
Country
No.
Ant (%)
Int (%)
Pos (%)
Pan (%)
1991–2013 1982–1992 1985–1989 1986–1993 1989–1994 1990–1993 1990–1995 1995–2009 1996–2001 1996–2003 1997–2000 52004 2004 2010–2011
UK USA Portugal Italy USA Swiss USA Austria India China Iran Turkey Turkey Thailand
3000 1237 450 655 385 558 853 2619 1233 1752 544 300 761 254
46 52 60 58 25 61 22 60 49 46 38 44 52 35
11 13 4 3 12 10 11 15 16 6 18 9 7 10
22 19 24 26 24 21 48 18 20 7 18 27 13 20
21 16 12 13 38 7 18 7 15 41 26 20 28 35
TABLE 9. Frequencies of key uveitis diagnoses in comparison with other studies (percentages, all rounded). Study
Country
No.
Beh
FHU
Sar
Toxo
TB
VKH
Jones Rodrigue5 Palmares6 Mercanti7 Merrill8 Tran9 Barisani11 Singh12 Yang13 Soheilia14 Sengu¨n15 Kazokog16 Sittivara17 Goto18 Ohguro19
UK USA Portugal Italy USA Swiss Austria India China Iran Turkey Turkey Thailand Japan Japan
3000 1237 450 655 385 558 2619 1233 1752 544 300 761 254 3060 2556
2.7 2.5 4.5 3.0
11.5 9.6 2.2 2.1
9.7
6.9
3.3
0.8
1.4
4.6
9.0 17.7 10.0 5.9 14.4 1.7
7.0
1.8
1.6 0.8 11.0 5.4 3.2
16.0 8.6 26.0 32.1 7.1 6.2 3.9
6.6 2.7 5.1 2.0
3.5 2.3 0.8 13.3 10.6
10.1 7.3 4.7 7.1 1.1
9.5 10.1 1.5 1.3 1.2
16.0 3.9 1.0 11.0 6.7 7.0.0
Beh, Behcet’s disease; FHU, Fuchs’ heterochromic uveitis; Sar, sarcoidosis; Toxo, toxoplasmosis; TB, tuberculosis; VKH, Vogt-Koyanagi-Harada syndrome.
patients tend to underdiagnose the disease, whereas those with a high prevalence of more lightly pigmented irides find diagnosis easier. Sarcoidosis is accepted to be a common disease at these latitudes, and it is notable that the highest proportions in uveitis surveys (Table 8) emanate from this UK center, the United States, and Japan. However, the strikingly lower incidence of sarcoidosis in a country close to Japan17 is also unexplained. Two classical causes of uveitis, which are very common in Asia and the Middle East, are Behc¸et disease and Vogt-Koyanagi-Harada disease. This study confirms their rarity in a predominantly Caucasian UK population. However, 65 of 81 patients (80%) in MUC with Behc¸et disease were Caucasian, which is a higher proportion than might have been anticipated. During the 22-year period of this study, some diagnoses have changed in frequency. In some cases this is clearly linked to an increase in the incidence of the disease, and this is clear for both tuberculosis and !
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syphilis causing uveitis. However, additional factors conspire to confuse the true change in incidence; during the period covered by this study, the gammainterferon test for tuberculosis has become available and has enhanced diagnosis; in addition, new forms of presentation of tuberculous uveitis (including serpiginous-like choroiditis23,24) have provoked investigation in a new subset of patients. For syphilis, an effective PCR has become available and has enhanced diagnosis in atypical cases and PCR of high quality is available for a greater range of microorganisms. The relationship between general ophthalmologists and the MUC has also changed during the 22-year period of study. Nonspecialists are no longer prepared to manage any intraocular inflammation other than acute anterior uveitis, and, in particular, have learned to refer patients requiring anterior segment surgery to specialists. The referral pattern has therefore changed and overall numbers are increasing; this probably reflects changes to the referral pattern, rather than an
126 N. P. Jones overall increase in the incidence of uveitis in this region. In conclusion, this study has presented data on the casemix of the Manchester Uveitis Clinic, the first specialist uveitis clinic to offer a service to the northwest of England. It represents the largest single-center survey worldwide to date, of a specialist uveitis service. It has demonstrated the casemix of uveitis over a 22-year period in a UK center, and is the first to do so for 17 years.25 It has compared the striking differences between casemix in various studies worldwide. Such comparisons are difficult26 and do not necessarily reflect accurate differences in casemix. A simultaneous multicenter prospective study organized through the aegis of the International Uveitis Study Group might elucidate casemix comparisons. A further paper from this center will deal with uveitis manifestations and complications and medical and surgical interventions.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. UK Census 1991, 2001, 2011. Office for National Statistics www.ons.gov.uk. 2. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardisation of Uveitis Nomenclature (SUN) working group. Am J Ophthalmol. 2005;140:509–516. 3. Communicable Disease Surveillance Centre. Increased transmission of syphilis in Manchester. Commun Dis Rep CDR Wkly. 2000;10:89. 4. Doris J, Saha K, Jones NP, Sukhanthar A. Ocular syphilis— the new epidemic. Eye. 2006;20:703–705. 5. Rodriguez A, Calonge M, Pedroza-Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol. 1996;114:593–599. 6. Palmares J, Coutinho MF, Castro-Correia J. Uveitis in northern Portugal. Curr Eye Res. 1990;9:31–34. 7. Mercanti A, Parolini B, Bonora A, et al. Epidemiology of endogenous uveitis in north-eastern Italy: analysis of 655 new cases. Acta Ophthalmol Scand. 2001;79:64–68. 8. Merrill PT, Kim J, Cox TA, et al. Uveitis in the southeastern United States. Curr Eye Res. 1997;16:865–874.
9. Tran VT, Auer C, Guex-Crosier Y, et al. Epidemiology of uveitis in Switzerland. Ocul Immunol Inflamm. 1994;2: 169–176. 10. Oruc S, Kaplan AD, Galen M, Kaplan HJ. Uveitis referral pattern in a midwest university eye center. Ocul Immunol Inflamm. 2003;11:287–298. 11. Barisani-Asenbauer T, Maca SM, Mejdoubi L, et al. Uveitis—a rare disease often associated with systemic diseases and infections: a systemic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57–64. 12. Singh R, Gupta V, Gupta A. Pattern of uveitis in a referral eye clinic in north India. Indian J Ophthalmol. 2004;52: 121–125. 13. Yang P, Zhang Z, Zhou H, et al. Clinical patterns and characteristics of uveitis in a tertiary center for uveitis in China. Curr Eye Res. 2005;30:943–948. 14. Soheilian M, Heidari K, Yazdani S, et al. Patterns of uveitis in a tertiary eye care center in Iran. Ocul Immunol Inflamm. 2004;12:297–310. 15. Sengu¨n A, Karadag R, Karakurt A, et al. Causes of uveitis in a referral hospital in Ankara, Turkey. Ocul Immunol Inflamm. 2005;13:45–50. 16. Kazokoglu H, Onal S, Tugal-Tutkun I, et al. Demographic and clinical features of uveitis in tertiary centers in Turkey. Ophthalmic Epidemiol. 2008;15:285–293. 17. Sittivarakul W, Bhurayanontachai P, Ratanasukon M. Pattern of uveitis in a university-based referral center in southern Thailand. Ocul Immunol Inflamm. 2013;21:53–60. 18. Goto H, Mochizuki M, Yamaki K, et al. Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol. 2007;51:41–44. 19. Ohguro N, Sonoda KH, Takeuchi M, et al. The 2009 prospective multi-center epidemiologic survey of uveitis in Japan. Jpn J Ophthalmol. 2012;56:432–435. 20. Pedrazzoli D, Fulton N, Anderson L, et al. Tuberculosis in the UK: annual report on tuberculosis surveillance in the UK 2012. London, Health Protection Agency Centre for Infections, July 2012. 21. Sanghvi C, Jones NP, Bell C, et al. Presumed tuberculous uveitis: diagnosis, management and outcome. Eye. 2011;25: 475–480. 22. Jones NP. Fuchs’ heterochromic uveitis: a reappraisal of the clinical spectrum. Eye. 1991;5:649–661. 23. Gupta V, Gupta A, Arora S, et al. Presumed tubercular serpiginouslike choroiditis: clinical presentations and management. Ophthalmology. 2003;110:1744–1749. 24. Gan W-L, Jones NP. Serpiginous-like choroiditis as a marker for tuberculosis in a non-endemic area. Br J Ophthalmol. 2013;97:644–647. 25. Thean LH, Thompson J, Rosenthal AR. A uveitis register at the Leicester Royal Infirmary. Ophthalm Epidemiol. 1996;3: 151–158. 26. Miserocchi E, Fogliato G, Modorati G, Bandello F. Review of worldwide epidemiology of uveitis. Eur J Ophthalmol. 2013;3:705–717.
Ocular Immunology & Inflammation
ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: http://www.tandfonline.com/loi/ioii20
The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix Nicholas P. Jones FRCOphth To cite this article: Nicholas P. Jones FRCOphth (2015) The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix, Ocular Immunology and Inflammation, 23:2, 118-126, DOI: 10.3109/09273948.2013.855799 To link to this article: http://dx.doi.org/10.3109/09273948.2013.855799
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Ocular Immunology & Inflammation, 2015; 23(2): 118–126 ! Informa Healthcare USA, Inc. ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2013.855799
ORIGINAL ARTICLE
The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix Nicholas P. Jones,
FRCOphth
The Royal Eye Hospital, Manchester, UK
ABSTRACT Purpose: To demonstrate the demography, anatomical, and diagnostic classification of patients with uveitis attending the Manchester Uveitis Clinic (MUC), a specialist uveitis clinic in the northwest of England, UK. Methods: Retrospective retrieval of data on a computerized database incorporating all new referrals to MUC from 1991 to 2013. Results: A total of 3000 new patients with uveitis were seen during a 22-year period. The anatomical types seen were anterior 46%; intermediate 11.1%; posterior 21.8%; and panuveitis 21.1%. The most common diagnoses were Fuchs heterochromic uveitis (11.5% of total), sarcoidosis-related uveitis (9.7%), idiopathic intermediate uveitis (7.9%), idiopathic acute anterior uveitis (7.0%), and toxoplasmosis (6.9%). Syphilis and tuberculosisassociated uveitis increased markedly in frequency during the study period. Conclusions: The uveitis casemix in this region reflects a predominantly white Caucasian population in a temperate country, but with changing characteristics owing to increasing immigration, enhanced diagnostic techniques, changes in referral pattern, and some real changes in disease incidence. Keywords: Casemix, demography, epidemiology, uveitis
In 1991 the Manchester Uveitis Clinic (MUC) was created at the Manchester Royal Eye Hospital (MREH) to provide a specialist uveitis service to the population of Greater Manchester (GM) and the northwest of England. Immediately a database was created to record prospectively each new patient attending the clinic. Over 3000 patients have now been seen and the collected data provide information on the epidemiology and casemix of uveitis within this population. This represents the first major epidemiological study of uveitis in the United Kingdom for many years, and the largest single-center uveitis survey in the medical literature to date. A further paper will deal with uveitis manifestations, complications, and management.
in manifestations, diagnosis, and management. The fields are shown in Table 1. Data for this study were retrieved entirely from the MUC database, with catchment population epidemiology sourced from UK Census1 data available for 1991, 2001, and 2011. Diagnoses were made at the initial presentation for those forms of uveitis identifiable by clinical appearance only, or soon afterward for those requiring supportive serology or other investigation, being changed later if new clinical findings or investigations warranted. All diagnoses that include an etiology for uveitis were made on the basis of a qualifying clinical presentation, with positive supporting serology, radiology, microbiology, or biopsy where indicated by clinical appearance. Serological investigations for active or previous infection, including HIV, were performed in the presence of suggestive clinical appearance or significant risk factors. Radiology for joint, pulmonary, or CNS involvement was performed only on the basis of symptoms or where asymptomatic diagnostic changes were sought. Intraocular
METHODS The MUC database prospectively records 42 information fields on each new patient attending; for those continuing to attend, it records significant changes
Received 18 July 2013; revised 8 October 2013; accepted 11 October 2013; published online 25 November 2013 Correspondence: N. P. Jones, FRCOphth, Consultant Ophthalmic Surgeon, The Royal Eye Hospital, Oxford Road, Manchester M13 9WL, UK. E-mail: [email protected]
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TABLE 1. The data fields recorded in the Manchester Uveitis Clinic database. A. Patient identifiers
1. 2. 3. 4. 5. 6. 7. 8.
Hospital number Surname Forename Residence postcode (Zip) Sex Date of birth Age at first attendance at MUC Racial background
B. Management data
1. Date of first clinic attendance 2. Whether does or does not have uveitis (scleritis, screening patients also recorded) 3. Age at onset of uveitis 4. Referring ophthalmologist/physician name
C. Uveitis features
1. 2. 3. 4.
Location (anterior, intermediate, posterior, panuveitis) Granulomatous or nongranulomatous anterior uveitis Side affected Behavior over time (acute single/recurrent; chronic fluctuating/unremitting)
D. Associated systemic Involvement (Y or N)
1. 2. 3. 4. 5. 6. 7.
Fever Joints Skin Bowel Chest Neurological Other
E. Uveitis diagnosis
1. Descriptive term 2. Etiology if known 3. Diagnostic confidence (confirmed; presumed; possible)
F. Uveitis complications (Y or N)
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Band keratopathy Corneal decompensation Occlusio Glaucoma Cataract Retinal neovascularization Retinal detachment Subretinal fibrosis Macular edema Phthisis
G. Medical management (Y or N)
1. 2. 3. 4.
Depot steroid injection (orbital or intraocular) Systemic steroid Immunosuppressive (named) Antimicrobial
H. Surgical management (Y or N)
1. 2. 3. 4.
Cataract surgery Glaucoma surgery Vitreoretinal surgery Other surgery
I. Associated systemic disease (free text) J. Bone densitometry results
infection was confirmed with fluid sampling or biopsy for microscopy and culture or PCR, if possible, and masquerades by vitreous cytology.
RESULTS Between March 1, 1991 and March 6, 2013 there were 3301 patient entries to the database. Some patients on the database did not have uveitis. They included patients with scleritis but not uveitis (55), patients !
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with juvenile idiopathic arthritis on the uveitis screening program (162), patients with Behc¸et disease who attended for baseline examination (50), patients with HIV retinopathy but no uveitis (3), and sundry others referred from physicians with systemic inflammatory disease, but exhibiting nonuveitic ophthalmic manifestations (30). The remaining 3000 patients had uveitis and all subsequent data relate to this group. The patients attended the MUC via several routes of referral: 2324 (77%) were tertiary referrals from hospital consultants (2251 [75%] from
120 N. P. Jones TABLE 2. Areas of residence for patients with uveitis referred to Manchester Uveitis Clinic. Area 1. 2. 3. 4. 5. 6.
Greater Manchester Northwest, Cumbria, Isle of Man Other UK/International Midlands Merseyside, Cheshire, Wales Yorkshire, Humberside, Northeast
Number
Percentage of total
2364 294 108 92 88 54
78.8 9.8 3.6 3.1 2.9 1.8
Numbers correspond to marked areas on Figure 1.
ophthalmologists, 73 [2.4%] from physicians); 99 (3.3%) were from subconsultant ophthalmologists, streaming patients into the specialist service from outreach clinics or from a clinic for acute ocular inflammation; and 577 (19.2%) were either transferred to MUC urgently, direct from the MREH acute services, or were referred by their general practitioner, usually for a second opinion on management. The conurbation of Greater Manchester includes the cities of Manchester and Salford, and several surrounding towns, with a total and approximately stable population of 2.68M in the 2011 UK Census1 (population was 2.57 M in 1991). Of all patients with uveitis referred to MUC, 2364 (78.8%) resided within GM according to postcode. The areas of residence for all referred patients are shown in Table 2, and Figure 1 shows the areas referred to in this table. The incidence of referrals to MUC from GM over the study period was approximately 4.1:100,000/yr. However, the rate of referral increased by more than 60% over the study period: for the first decade (1991–2001) the rate was 3.46:100,000/yr; for the most recent decade (2003– 2013), 5.55:100,000/yr. The age at onset of uveitis and the age at presentation to MUC are shown in Figure 2. The onset of uveitis for 2334 patients (77.8%) was in adults of working age (between 16 and 65 years of age) and this included 1100 young adults (16–35 years of age, 36.7% of all patients); 401 (13.4%) were children with an onset age below 16 years, and 265 (8.8%) were of retirement age (more than 65 years at onset; oldest patient 90 years). Using the Standardisation of Uveitis Nomenclature (SUN),2 the number of patients with each anatomical type of uveitis is shown in Table 3. Fuchs heterochromic uveitis is classified in the MUC database as an ‘‘anterior’’ uveitis despite its usual significant vitreous involvement and occasional retinal vasculitis. It is identified as a subset of anterior uveitis in Table 3. Granulomatous anterior uveitis was seen in 332 patients (11.1% of total, 14.6% of those with anterior segment inflammation of any type). Uveitis was bilateral at presentation, or became bilateral, in 1550 patients (51.7%). Of those with unilateral uveitis, the left eye was involved in 722 cases (49.8%), the right in 728 (50.2%). The MUC database characterizes uveitis
FIGURE 1. Map of Greater Manchester (Zone 1) and surrounding areas of UK referring patients to Manchester Uveitis Clinic. Area numbers correspond to area descriptions in Table 2.
FIGURE 2. The onset age for uveitis, and the age at presentation for 3000 patients referred to MUC. TABLE 3. Anatomical location of uveitis. Definition Anterior uveitis (excluding FHU (FHU Intermediate uveitis Posterior uveitis Panuveitis
Number
Percentage of total
1380 1037 343 332 654 634
46.0 34.6) 11.4) 11.1 21.8 21.1
FHU, Fuchs heterochromic uveitis.
behavior over time: a total of 757 (25.2%) patients had a single acute episode; 407 (13.6%) had acute recurrent uveitis; 607 (20.2%) had chronic fluctuating disease; and 1229 (41.0%) had chronic unremitting uveitis. The coexistence of systemic symptoms and/or signs at presentation was recorded and these are shown in Table 4. A total of 978 patients (32.6%) were Ocular Immunology & Inflammation
The Manchester Uveitis Clinic TABLE 4. Accompanying systemic symptoms and/or signs in patients at presentation. System
Number with concurrent systemic symptoms or signs (%)
Fever Arthropathy Skin lesions Bowel disorder Chest Neurological No symptoms/signs
135 407 274 89 193 153 2022
(4.5) (13.6) (9.1) (3.0) (6.4) (5.1) (67.4)
so affected, the most common being arthropathy (13.6% of all patients with uveitis). In addition to the SUN nomenclature of uveitis, the MUC database uses a comprehensive diagnostic system based on descriptive and/or etiological diagnoses. The data are shown in Table 5. The most common diagnoses were Fuchs heterochromic uveitis (FHU), which was diagnosed on clinical appearance (345 patients, 11.5% of total); sarcoidosis-related uveitis (292, 9.7%), which was diagnosed as a qualifying uveitis with supporting biopsy at any site (confirmed), raised ACE and hilar lymphadenopathy (presumed), or typical with only raised ACE or abnormal chest x-ray (possible); idiopathic intermediate uveitis (236, 7.9%), diagnosed by clinical appearance, without neurological symptoms and with no supportive evidence of sarcoidosis; idiopathic acute anterior uveitis (210, 7.0%), diagnosed with either HLA-B27 negative or untested; and toxoplasmosis (206, 6.9%), diagnosed mainly by clinical appearance, with supporting serology in most patients. These 5 diagnoses together accounted for 43% of all patients. There is deliberate overlap in some of the diagnoses shown in Table 5, as some are descriptive and some etiological; results can be found using either parameter. The most common type of anterior uveitis was FHU (24.8%); of intermediate uveitis, idiopathic (70.5%); of posterior uveitis, idiopathic (42.8%); and of panuveitis, idiopathic (42.1%). Table 5 also includes a description of the method of diagnosis for each listed entity. The total number of patients without either a proven etiology or a definite, well-recognized descriptive pattern was 935 (31.2%). However, where wellrecognized syndromes, including (idiopathic) FHU, were more appropriately included in the category with unknown etiology, this number rose to 1557 (51.9%). The MUC diagnostic system requires a statement on diagnostic confidence. Those with confirmed etiology include uveitis in association with biopsy-confirmed sarcoidosis at any site, and culture-proven or PCR-supported intraocular infection, and these amounted to 101 patients (3.4%). The etiology was presumed from supporting evidence (for example, a patient with raised ACE, hilar !
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lymphadenopathy, and a qualifying uveitis, with no evidence of another diagnosis, was presumed to have sarcoidosis-associated uveitis) in 952 (31.7%) and considered possible (with suggestive features and no other diagnosis identified) in 390 (13.0%). More females than males were referred to MUC: 54.1 and 45.9%, respectively (F1.17:1 M compared to UK population ratio of F1.01:0.99 M), 2 = 15.55, p 0.0001). The diagnoses with the most significant gender difference are shown in Table 6. The population demography of GM and the northwest of England (UK Census1 2001), compared with the number of referrals from three main ethnic groups, is shown in Table 7. Some uveitis diagnoses were clearly more frequent in patients with a particular ethnic or racial background, and these are also shown. The most significant of these discrepancies were birdshot retinochoroidopathy (100% of these patients were Caucasian, compared with 88.9% in the GM catchment population), tuberculosis (66.3% Asian compared with 6.5%), and toxoplasmosis (19.8% black compared with 1.7%). There was no evidence of significant seasonal variation in incidence for any diagnosis. Some diseases changed in incidence during the period of study. An epidemic of syphilis commenced in Manchester in 1999–2004,3 resulting in a surge of ophthalmic cases.4 During the first decade of this survey (1991–2001) only 2 cases of ocular syphilis were seen; during the most recent decade (2003–2013) there were 18. The diagnosis of tuberculosis has also increased, the figures for the same periods being 30 and 78. There was a ‘‘surge’’ in toxoplasmosis diagnosis during 1996–1998 (16.7 cases per year, against a mean of 9.4 per year over the whole period). Data on uveitis type, distribution, and diagnosis were compared with those from studies in other centers.5–19 The anatomical distributions of uveitis are shown in Table 8, and the relative frequencies of key uveitis diagnoses are shown in Table 9.
DISCUSSION There is no fixed catchment population for any specialist hospital service in the United Kingdom, which permits the patient a choice of hospital. However, the great majority of residents in the Greater Manchester conurbation choose the MUC if referred for the management of uveitis. The recording of residential postcode on the database permits comparison with the GM catchment population for the patients who reside in that area. Demographic studies on uveitis are substantially affected by the patient population, and the MUC is no exception. It is located in a large university hospital in a western city at 53 North latitude within an unusually temperate large island. Sarcoidosis is a common
122 N. P. Jones TABLE 5. Uveitis diagnoses in Manchester Uveitis Clinic 1991–2012. Diagnosis Acute anterior uveitis, unknown etiology Acute anterior uveitis, post-traumatic Acute macular neuroretinitis Acute panuveitis, unknown etiology Acute posterior multifocal placoid pigment epitheliopathy Acute zonal occult outer retinopathy Autoimmune corneal endotheliopathy Bacterial endophthalmitis Behc¸et disease with uveitis including retinal vasculitis Birdshot retinochoroidopathy Chronic anterior uveitis, unknown aetiology Chronic anterior uveitis, systemic vasculitis-related Chronic panuveitis, unknown aetiology Churg-Strauss syndrome with uveitis CINCA syndrome-related uveitis Cogan syndrome with uveitis Cytomegalovirus-associated uveitis (Chronic anterior (Retinitis Diabetes-related uveitis Drug-induced uveitis Focal choroiditis/choroidal granuloma, unknown etiology Focal retinitis, unknown aetiology Fuchs heterochromic uveitis Fungal endophthalmitis or retinitis (candidiasis Herpes simplex virus-associated uveitis (Acute anterior (Chronic anterior (Keratouveitis (ARN HLA-B27-related uveitis: (Anterior, recurrent (Anterior, chronic (Panuveitis, acute (Panuveitis, chronic Immune recovery uveitis post-CMV retinitis Inflammatory bowel disease-related: (Crohn disease (Ulcerative colitis Intermediate uveitis (Multiple sclerosis (Sarcoidosis (Tuberculosis (Unknown etiology Juvenile chronic iridocyclitis Juvenile idiopathic arthritis-related uveitis Leprosy with uveitis Masquerade syndromes Multifocal choroiditis, unknown etiology Multiple evanescent white-dot syndrome Multiple sclerosis-related uveitis Necrotising retinopathy, including ARN (HSV-related (VZV-related (CMV-related (Cause unknown Neuroretinitis, unknown etiology Phakoanaphylactic uveitis Posner-Schlossman syndrome Post-surgical uveitis, unknown etiology Psoriatic arthropathy-associated uveitis Punctate inner choroidopathy
Total (%)
Method of diagnosis
210 (7.0%) 2 1 29 31 10 4 13 81 36 197 (6.6%) 1 199 (6.6%) 1 2 2 25 2) 23) 3 4 6 10 345 (11.5%) 26 22) 58 6) 37) 9) 6) 135 (4.5%) 94) 27) 6) 7) 3 32 14) 18) 332 18) 58) 13) 234) (7.8% of total) 6 112 1 22 26 12 48 59 6) 27) 23) 3) 4 4 4 6 19 83
A E B A B B B Ci D Cvi A D A D D D B or Ci Ci Ciii Ci D E A A B Ci Ci B or Ci B or Ci B B =/ Ci Ci Cvi Cvi Cvi þ D Cvi þ Ci Cvi þ D B þ Ci D Cvi D Cvi D Cvi B BþD B þ Civ/v D Ciii/v D B B þ Ciii Ciii þ D Cv Cii/iv Cv B þ Ciii B D B Ci, or Ciii B þ Ci B þ Ci Ciii Ci B B B B E D Cvi B (continued )
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Table 5. Continued
Diagnosis Radiotherapy-induced uveitis Reactive arthropathy-associated uveitis Retinal detachment-induced uveitis Retinal pigment epitheliitis Retinal vasculitis as predominant feature of uveitis (Primary (Behc¸et (Multiple sclerosis (Sarcoidosis (SLE (Susac syndrome (Systemic vasculitis (Tuberculosis Sarcoidosis-related uveitis (Anterior uveitis (Chronic panuveitis (Choroidal granuloma 8) (Intermediate uveitis (Multifocal choroids (Retinal vasculitis Scleritis with uveitis Serpiginous choroiditis Sympathetic uveitis: (Trauma-induced (Surgery-induced Syphilis-associated uveitis Systemic lupus erythematosus-related uveitis Toxocariasis Toxoplasmosis Tuberculosis-associated uveitis (Anterior uveitis (Intermediate (Keratouveitis (Multifocal choroids (Panuveitis (Retinal vasculitis (Serpiginous-like Tubulointerstitial nephritis and uveitis syndrome Uveal effusion syndrome Varicella-zoster virus-associated uveitis (Acute anterior (Chronic anterior (Panuveitis (Keratouveitis (ARN (Sclerouveitis (Retinal vasculitis Vogt-Koyanagi-Harada syndrome
Total (%) 1 22 7 7 136 (4.5%) 63) 22) 11) 24) 2) 1) 1) 12) 292 (9.7%) 79) 99) Ciii/iv/v D 58) 16) 24) 49 9 33 21) 12) 22 5 26 206 (6.9%) 99 14) 12) 1) 9) 28) 19) 16) 7 2 70 18) 16) 2) 3) 27) 3) 1) 23
Method of diagnosis E D Cvi E B B B þ Ciii/iv BþD BþD B þ Ciii/iv/v D B þ Ciii þ D B þ Civ þ D B þ Ciii þ D B þ Ci/iii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D Ciii/iv/v D B B E E E Ci/iii D B Ciii B Ci/Ciii Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Ci/iii/iv/v D Cv B B Ci/Ciii B B Ciii B Ciii B B þ Ci B Ci/Ciii B þ Ci B
APMPPE, acute posterior multifocal placoid pigment epitheliopathy; ARN, acute retinal necrosis; CINCA, chronic infantile neurological, cutaneous and articular; HLA, human leucocyte antigen. Methods of diagnosis: A, anatomical description of uveitis with unknown cause; B, unique or typical clinical appearance; C, qualifying clinical appearance with supporting investigation (i, microbiology; ii, cytology; iii, serology; iv, radiology; v, biopsy; vi, HLA type); D, qualifying uveitis with supporting systemic manifestations; E, typical uveitis with typical history.
disease and HLA-B27 is a common gene with a prevalence of about 7%. The population is mostly indigenous white Caucasian derived from AngloSaxon or Celtic genetics but there is a significant and increasing minority of those particularly from the Indian subcontinent but also from within the European Union, Eastern Europe, and Africa. Some immigrant populations have a high rate of tuberculosis infection, !
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and the incidence of newly diagnosed tuberculosis in GM is among the highest in the United Kingdom20 (440:100,000). As with most European cities there is a significant gay community with its HIV and syphilis risk, and an epidemic of syphilis in GM, beginning 12 years ago, placed ocular syphilis once more on the diagnostic agenda. Manchester has a large international airport, regularly importing those with new
124 N. P. Jones TABLE 6. Uveitis and gender for the whole survey and for the most common forms of uveitis. Diagnosis
Total
Male (%)
Female (%)
UK gender ratio 2013 (all ages) (49.5) (50.5) All patients 3000 1377 (45.9) 1623 (54.1) Chronic anterior uveitis 510 194 (38) 316 (62) Acute anterior uveitis 438 198 (45) 240 (55) Chronic panuveitis 396 181 (46) 215 (54) Fuchs heterochromic uveitis 345 173 (50) 172 (50) Intermediate uveitis 337 151 (45) 186 (55) Sarcoidosis-associated 292 151 (52) 141 (48) Toxoplasmosis 206 101 (49) 105 (51) Retinal vasculitis 145 76 (52) 69 (48) HLA B27-associated 135 70 (52) 65 (48) JIA-associated 112 25 (22) 87 (78) Tuberculosis-associated 99 46 (46) 53 (54) Punctate inner choroidopathy 83 20 (24) 63 (76) Behc¸et disease 81 44 (54) 37 (46) JIA, juvenile idiopathic arthritis.
TABLE 7. Uveitis and ethnic or racial origin. Diagnosis or category Greater Manchester populationa Northwest England populationa All patients referred to MUC AAU, unknown etiology Behc¸et disease Birdshot retinochoroidopathy Fuchs heterochromic uveitis HLA-B27-related uveitis Juvenile chronic arthritis Sarcoidosis Toxoplasmosis Tuberculosis VKH syndrome
% Caucasian % Asian % Black (no.) (no.) (no.) 88.9 92.9 80.0 (2400) 84.3 79.5 100.0 85.1 96.9 94.9 63.8 68.3 22.5 16.7
6.5 4.1 13.1 (393) 9.5 17.9 0.0 8.8 3.0 3.0 18.2 11.9 66.3 72.2
1.7 1.0 6.8 (205) 5.2 2.6 0.0 6.0 0.0 2.1 17.9 19.8 11.2 11.1
AAU, acute anterior uveitis; VKH, Vogt-Koyanagi-Harada syndrome. a Data from UK Census1 2001.
infections, but the UK climate does not yet permit the proliferation of arthropod-borne viral diseases. It is in this context that some comparison can be made between population and clinic figures. There is a highly significant preponderance of female patients (p 0.0001) when compared to the all-ages UK population sex ratio (Table 6). Female patients predominate in four common diagnostic categories, but in only the first of these does the difference reach clear statistical significance: chronic anterior uveitis (CAU, p 0.0001), acute anterior uveitis (p = 0.07), intermediate uveitis (p = 0.08), and chronic panuveitis (p = 0.13). The reasons for this high incidence of female patients with CAU are not known. There is a significant discrepancy in the high proportion of ethnic minority patients attending MUC (Table 7). Those of Asian origin account for 6.5% of the GM population, yet 13.1% of those attending MUC, and
for black patients the figures are 1.7 and 6.8%, respectively. It is clear that this overrepresentation is concentrated in certain areas of diagnosis, as shown in Table 7—in particular, tuberculosis for those of Asian origin and toxoplasmosis and sarcoidosis for those of Afro-Caribbean origin. We have previously reported the increasing incidence of ocular tuberculosis in this region.21 The metropolitan areas of the United Kingdom become more ethnically mixed as immigration increases, and it is necessary that such changes in disease pattern are highlighted to direct resources appropriately. Comparisons with surveys undertaken in uveitis clinics elsewhere in the world5–19 often present great contrasts in the numbers of patients affected within diagnostic categories. Some of these are obviously associated with climatic or genetic predisposition (such as for the Vogt-Koyanagi-Harada syndrome, which is rare in the United Kingdom), but to this should be added the subtle but important organizational aspects of each clinic. This clinic, the MUC, is part of a large university hospital complex and MREH provides walk-in emergency services for ophthalmology. Most uveitis is dealt with within that service and does not require referral to MUC. The number of patients with HLA-B27-related uveitis, for example, is therefore low in the MUC statistics, and generally for anterior uveitis as a proportion of the total (compared with higher figures for some other centers which may have different organization, Table 8). Within the towns of GM are 6 other ophthalmology units, each of which will deal with local uveitis to differing degrees, referring to MUC when considered necessary. Nevertheless, such differences as described between centers in Table 8 are unlikely to be explained solely by true diagnostic difference (for example, the proportion of those with intermediate uveitis varying from 3% in Italy7 to 18% in Iran14 and panuveitis varying from 7% in Switzerland9 to 41% in China13 seem most unlikely to be explained solely by the clinical diagnoses of uveitis most commonly affecting patients in those areas). It seems more likely that despite the introduction of the SUN anatomical classification system,2 different interpretations still exist over the anatomical categorization of intraocular inflammation. Fuchs heterochromic uveitis is a common cause of uveitis in the United Kingdom, and appears to be particularly common in this area of England, producing 11.5% of all patients attending this clinic. This author has expressed a longstanding research interest in the disease22 and that may cause a positive referral bias. However, the frequency of the disease even when compared to that in other European countries (2.2% in Portugal,6 2.1% in Italy7) is striking, and largely unexplained. Part of the reason may be underdiagnosis; countries with a high (sometimes almost universal) prevalence of dark brown-eyed Ocular Immunology & Inflammation
The Manchester Uveitis Clinic
125
TABLE 8. Comparisons of uveitis anatomical location with recent surveys in other countries (all percentages are rounded). Study Jones Rodriguez5 Palmares6 Mercanti7 Merrill8 Tran9 Oruc10 Barisani11 Singh12 Yang13 Soheilia14 Sengu¨n15 Kazokog16 Sittivara17
Period
Country
No.
Ant (%)
Int (%)
Pos (%)
Pan (%)
1991–2013 1982–1992 1985–1989 1986–1993 1989–1994 1990–1993 1990–1995 1995–2009 1996–2001 1996–2003 1997–2000 52004 2004 2010–2011
UK USA Portugal Italy USA Swiss USA Austria India China Iran Turkey Turkey Thailand
3000 1237 450 655 385 558 853 2619 1233 1752 544 300 761 254
46 52 60 58 25 61 22 60 49 46 38 44 52 35
11 13 4 3 12 10 11 15 16 6 18 9 7 10
22 19 24 26 24 21 48 18 20 7 18 27 13 20
21 16 12 13 38 7 18 7 15 41 26 20 28 35
TABLE 9. Frequencies of key uveitis diagnoses in comparison with other studies (percentages, all rounded). Study
Country
No.
Beh
FHU
Sar
Toxo
TB
VKH
Jones Rodrigue5 Palmares6 Mercanti7 Merrill8 Tran9 Barisani11 Singh12 Yang13 Soheilia14 Sengu¨n15 Kazokog16 Sittivara17 Goto18 Ohguro19
UK USA Portugal Italy USA Swiss Austria India China Iran Turkey Turkey Thailand Japan Japan
3000 1237 450 655 385 558 2619 1233 1752 544 300 761 254 3060 2556
2.7 2.5 4.5 3.0
11.5 9.6 2.2 2.1
9.7
6.9
3.3
0.8
1.4
4.6
9.0 17.7 10.0 5.9 14.4 1.7
7.0
1.8
1.6 0.8 11.0 5.4 3.2
16.0 8.6 26.0 32.1 7.1 6.2 3.9
6.6 2.7 5.1 2.0
3.5 2.3 0.8 13.3 10.6
10.1 7.3 4.7 7.1 1.1
9.5 10.1 1.5 1.3 1.2
16.0 3.9 1.0 11.0 6.7 7.0.0
Beh, Behcet’s disease; FHU, Fuchs’ heterochromic uveitis; Sar, sarcoidosis; Toxo, toxoplasmosis; TB, tuberculosis; VKH, Vogt-Koyanagi-Harada syndrome.
patients tend to underdiagnose the disease, whereas those with a high prevalence of more lightly pigmented irides find diagnosis easier. Sarcoidosis is accepted to be a common disease at these latitudes, and it is notable that the highest proportions in uveitis surveys (Table 8) emanate from this UK center, the United States, and Japan. However, the strikingly lower incidence of sarcoidosis in a country close to Japan17 is also unexplained. Two classical causes of uveitis, which are very common in Asia and the Middle East, are Behc¸et disease and Vogt-Koyanagi-Harada disease. This study confirms their rarity in a predominantly Caucasian UK population. However, 65 of 81 patients (80%) in MUC with Behc¸et disease were Caucasian, which is a higher proportion than might have been anticipated. During the 22-year period of this study, some diagnoses have changed in frequency. In some cases this is clearly linked to an increase in the incidence of the disease, and this is clear for both tuberculosis and !
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syphilis causing uveitis. However, additional factors conspire to confuse the true change in incidence; during the period covered by this study, the gammainterferon test for tuberculosis has become available and has enhanced diagnosis; in addition, new forms of presentation of tuberculous uveitis (including serpiginous-like choroiditis23,24) have provoked investigation in a new subset of patients. For syphilis, an effective PCR has become available and has enhanced diagnosis in atypical cases and PCR of high quality is available for a greater range of microorganisms. The relationship between general ophthalmologists and the MUC has also changed during the 22-year period of study. Nonspecialists are no longer prepared to manage any intraocular inflammation other than acute anterior uveitis, and, in particular, have learned to refer patients requiring anterior segment surgery to specialists. The referral pattern has therefore changed and overall numbers are increasing; this probably reflects changes to the referral pattern, rather than an
126 N. P. Jones overall increase in the incidence of uveitis in this region. In conclusion, this study has presented data on the casemix of the Manchester Uveitis Clinic, the first specialist uveitis clinic to offer a service to the northwest of England. It represents the largest single-center survey worldwide to date, of a specialist uveitis service. It has demonstrated the casemix of uveitis over a 22-year period in a UK center, and is the first to do so for 17 years.25 It has compared the striking differences between casemix in various studies worldwide. Such comparisons are difficult26 and do not necessarily reflect accurate differences in casemix. A simultaneous multicenter prospective study organized through the aegis of the International Uveitis Study Group might elucidate casemix comparisons. A further paper from this center will deal with uveitis manifestations and complications and medical and surgical interventions.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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