Uveitis is inflammation of the middle layer of the eye (iris, ciliary body and choroid), although other structures (sclera, retina, optic nerve) can also be affected. The condition can be of endogenous origin, associated or otherwise with systemic diseases, or exogenous.1 Classification is based on the anatomical site of the inflammation, its time course and aetiology.2–4 The incidence of uveitis in developed countries is 17–52 cases per 100,000 inhabitants per year, with a prevalence of 38–714 cases per 100,000 inhabitants.5–7 The incidence is similar in males and females, although more prevalent in females.6,8

These conditions are significant in that they cause notable morbidity, and principally affect young adults,1,8 with major socioeconomic consequences.1,9 In fact, they are the fourth cause of blindness among the active population, and the second cause of potentially treatable and preventable blindness in the developed countries.9 Loss of vision is mainly due to the development of cystic macular oedema.10

Non-infectious uveitis is usually treated initially with topical corticosteroids, which are particularly effective for anterior uveitis.11 However, it is occasionally necessary to resort to systemic therapy, both oral corticosteroids and immunomodulatory drugs,12,13 which are used for cases that are refractory to corticosteroids or to minimise their side effects,12,14 and it is often necessary to use several of them successively or in combination.1,12 However, possibly due to the heterogeneity of presentation, the emergence of new drugs, and the aetiology and prognosis of this set of diseases, there are still no clear action guidelines or protocols. Multidisciplinary uveitis clinics have emerged to improve the approach to these patients, where ophthalmologists and rheumatologists interact to contribute within their area of knowledge. This should result in better diagnosis and treatment and promote advances in this area.15–17

The aims of this paper were to analyse the features of the patients attending our hospital's multidisciplinary uveitis clinic, and to study the use of immunomodulators in treating the condition, to establish the level of response according to the type of uveitis, and thus acquire the knowledge to improve the treatment and prognosis of our patients.

A retrospective, observational study was undertaken of the patients attended by the rheumatologist in the multidisciplinary uveitis clinic of a tertiary referral hospital from January 2012 to December 2015. Infectious, postsurgical, posttraumatic, and masquerading syndromes were excluded. The study was approved by the hospital's Research Ethics Committee (PI-2246).

We gathered the demographic data, age of onset of the ocular symptoms, relevant personal and family history, details of the ophthalmological examination, and the results of complementary tests.

The types of uveitis were classified according to their aetiology (without systemic involvement, with systemic involvement), anatomical site (anterior, intermediate, posterior, panuveitis), laterality (unilateral, bilateral), and course (acute, recurrent, chronic).2–4

Data relating to the treatments given were also collected: local (topical eye drops, peri-ocular and intra-ocular injections), and systemic (oral corticosteroids, immunomodulatory drugs). The response to treatment was also recorded: lack of response or improvement in the eye disease according to the judgement of the ophthalmologist, based on the usual response parameters according to the pattern of uveitis (anterior Tyndall, vitreous Tyndall, macular oedema, chorioretinitis, vasculitis, etc.). Intolerance or toxicity were also recorded, and discontinuation of treatment or lack of follow-up. Immunomodulatory treatments prescribed for other manifestations of the associated systemic disease were excluded from the analysis, and those started prior to the uveitis consultation.

The most common non-infectious uveitis cases in our clinic are those with no idiopathic systemic involvement, and those associated with spondylarthritis, similar to that described in other studies.15,17–19 The high percentage of idiopathic uveitis in our sample compared to other reviews performed in our country is because we excluded infectious, postsurgical, posttraumatic uveitis and masquerading syndromes, which appear in high percentages in other series.20 There are other areas where cases of uveitis associated with Behçet's syndrome, sarcoidosis, and VKH are more prevalent.8,21

According to anatomical site, anterior forms of uveitis were most common and, among them, the acute recurring types. The intermediate and posterior types, and panuveitis were less common, similar to other studies.8,15,17–19 However, there are populations where the posterior types and panuveitis are more frequent than the intermediate,8,18,19 probably due to a greater prevalence in these areas of uveitis cases with posterior involvement, such as those associated with Behçet's and VKH syndromes, and because infectious uveitis was not excluded in these studies.

Anterior uveitis was statistically significantly in the majority among the patients controlled with local treatment, as is also reflected in other papers.11,14 According to the aetiology, it was observed that uveitis with no systemic involvement is controlled better, which is consistent with the above, since the majority are anterior. Therefore, the patients with uveitis associated with systemic disease, posterior uveitis or panuveitis are more likely to need systemic treatment. When we analyse the anatomical pattern and the aetiology (Table 1), in the cases with systemic involvement the anatomical pattern has little influence, and generally requires more systemic treatment.

It is also worth highlighting that the patients who required systemic treatment were younger than those controlled with local treatment. This might be explained by the asymmetric distribution of the different types of uveitis according to age. In our clinic, the patients aged over 50 had more uveitis with no extraocular association, anterior uveitis and panuveitis, and those under 50 were diagnosed with more uveitis associated with systemic disease, intermediate and posterior uveitis. We think that these findings are interesting, but we have found no information in the literature in this regard.

Of the patients given systemic treatment, the females were controlled less well than the males, and more of them required immunomodulatory drugs. This might be explained by the greater frequency of males with acute, non-recurrent uveitis.

The cases of posterior uveitis in our clinic required oral corticosteroids and immunomodulatory drugs in equal measure, unlike other studies, where the majority are controlled with oral corticosteroids.1 This might be due to the change in treatment guidelines in recent years, with the reduction of systemic corticosteroid doses, and the earlier introduction of immunomodulators. Moreover, 45% of patients diagnosed with uveitis in our clinic, and who had not received previous immunosuppressive therapy for their baseline disease, started immunomodulatory treatment. This information is different to other papers,22 where the need for immunomodulators is less (14%), probably due to the inclusion of infectious, postsurgical and posttraumatic uveitis in these studies.

Methotrexate is the drug most used in our clinic, as in other studies, probably due to its good efficacy-cost-toxicity ratio.12,23 Cyclosporine is the second most used drug for uveitis with no systemic involvement, as in other papers,24,25 especially for the intermediate and posterior types. Sulfasalazine is important for uveitis associated with systemic disease and anterior uveitis, due to its good results for anterior uveitis associated with spondyloarthritis.26

The biological treatments are drugs with demonstrated efficacy as well.1,12,27 The most used drugs in our patients were infliximab and adalimumab, which are also the most used in other series in recent papers.12,13,28

With regard to change of immunomodulator, the first controlled ocular inflammation in 45% of our patients, which is similar to other studies.29 However, this varies according to the type of uveitis. According to sex, the women responded more poorly to the first drug, and required a second in 60% of cases, compared to 40% of the males. This, as we mentioned, is probably due to the differences in aetiology and the involvement pattern detected.

We also found differences in terms of anatomical site. Seventy-five percent of the anterior uveitis cases were controlled with a first or second drug, while more than half the posterior cases required at least three. We also observed a poorer response in the intermediate uveitis compared to the anterior cases. Forty percent of the intermediate uveitis cases required a fourth immunomodulator to control the disease, compared to 15% of the anterior cases. We were not able to contrast these data in the literature because there are no studies that analyse the response of these uveitis cases to the successive immunomodulatory drugs. However, the greater severity and poorer prognosis of posterior uveitis is known.1,9

A recent study evaluated the discontinuation rate of the various immunosuppressive drugs in 110 patients, and showed a retention rate for these drugs at one year and at 10 years of 74% and 16% respectively. The reasons for discontinuation were inefficacy or adverse effects in almost half the cases, similar to our frequency, and clinical improvement in 38%.24

A limitation of this study is that it is retrospective with the restrictions that this involves in terms of data collection, of ophthalmological examination, and the characterisation of the types of uveitis, since not all the information was gathered systematically. Another limitation is the number of patients, which reduced when they were classified into subgroups, diminishing the statistical power of the study.

The use of immunosuppressive therapy and the new biological treatments with their potential side effects, advances in the early diagnosis of rheumatic diseases and the need for in-depth knowledge of ocular pathology, together with the need for precise measurement of ocular outcomes, evidence the importance of multidisciplinary clinics, where the knowledge of rheumatologists and ophthalmologists combine to enhance the follow-up and management of these patients.

In sum, almost half the patients with non-infectious uveitis required immunomodulators. The patients often required a change of combination of these drugs, and the percentage of patients who required a third change of medication ranged from 15% for the anterior uveitis cases to 42% for the intermediate cases.

The authors have no conflict of interests to declare.