Mycophenolate Mofetil for Ocular Inflammation


To evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases.


Retrospective cohort study.


Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each.


Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation—sustained over consecutive visits spanning at least 28 days—was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy.


Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment-limiting side effects were observed in 12% of patients and typically were reversible.

Ocular inflammation is a common cause of ocular morbidity and vision loss, with uveitis alone accounting for approximately 10% of new cases of blindness in the United States. Because many of those affected are children or working-age adults, the years of potential vision lost and economic impact of each case of vision loss is higher, on average, than with eye diseases of the elderly. Immunosuppressive drugs are used to treat many potentially blinding cases of ocular inflammation, primarily in 3 settings: as corticosteroid-sparing therapy when the disease can be controlled with oral corticosteroids, but substantial toxicity is expected at the dose required; for inflammation that is recalcitrant to corticosteroids; and for management of specific diseases expected to fare poorly with corticosteroids alone.

Mycophenolate mofetil, an immunosuppressive drug that is increasingly popular for management of various types of noninfectious ocular inflammation, suppresses the immune system by selectively inhibiting the purine biosynthesis enzyme inosine monophosphate dehydrogenase (IMPDH), thereby resulting in depletion of guanosine nucleotides that are essential for purine synthesis used in the proliferation of B and T lymphocytes. .Extraocular applications of mycophenolate mofetil therapy include prevention of renal allograft rejection, psoriasis, and various autoimmune diseases.

Small to medium-sized studies evaluating mycophenolate mofetil for ocular inflammation suggest that it often is an effective corticosteroid-sparing agent in this setting, and may be faster acting than methotrexate and azathioprine. In children, the drug is generally well tolerated, typically without significant end-organ toxicity. However, the precision of these studies has been limited by the relatively small number of patients studied, and estimates of success may be inflated in some instances where some patients used additional immunosuppressive agents simultaneously.

In order to better characterize the effectiveness of mycophenolate mofetil for ocular inflammation in a large population of patients, we report here the outcomes of 236 patients followed from the point of initiation of mycophenolate mofetil as the only noncorticosteroid immunosuppressive therapy for patients with ocular inflammatory diseases at 4 tertiary ocular inflammation centers in the United States.


Study Population

All patients with noninfectious ocular inflammatory disease who had started receiving treatment with mycophenolate mofetil during the study as the sole noncorticosteroid immunosuppressive agent at 3 ocular immunology and uveitis clinics and an approximate 40% random sample of such patients from a fourth center were selected to be the study population. This group of patients was nested within a larger study, the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study, the methods of which have been reported previously. Patients from a fifth center participating in the parent study were excluded, because the co-management approach used by the center—wherein many follow-up visits were conducted outside the center—markedly biased ascertainment of the time-to-treatment response.

Data Collection

Trained, certified, expert reviewers reviewed the medical records of all patients and entered information for each eye of every patient at every visit into a custom Microsoft Access database (Microsoft Corporation, Redmond, Washington, USA). Demographic information obtained during the initial visit and details of all medications in use at every clinic visit were recorded. Details of ocular inflammation activity status—based on clinical evaluation using external, slit-lamp, and dilated fundus examination—also were recorded. Sequelae of ocular inflammation were noted when present.

Follow-up and Main Outcome Measures

Patients were followed until they stopped using mycophenolate mofetil or started using an additional noncorticosteroid immunosuppressive agent; had an event of interest; or stopped attending a study clinic; or until the end of data collection was reached—whichever occurred first. The primary outcome measures were: success in gaining control of inflammation; success in maintaining control of inflammation after tapering systemic corticosteroids to specified thresholds (“corticosteroid-sparing effects”); and discontinuation of treatment. Control of inflammation was categorized at each visit as “active,” “slightly active,” or “inactive” for every eye at every visit. Descriptors such as “active,” “uncontrolled,” “worsening inflammation,” or “disease progression” in the case notes were counted as indicating “active inflammation.” Inflammatory activity was scored as “slightly active” when inflammation was minimally present, described in the patient notes using descriptors such as “mild,” “few,” “trace cells,” or “trace activity.” Inflammation was defined as “inactive” when descriptors such as “quiet,” “quiescent,” “no cells,” and “no active inflammation” were used. When data regarding activity could not be ascertained from case notes, data regarding activity at the visit in question were entered as missing. Corticosteroid-sparing effects were evaluated based on the time to reduction of the prednisone dose to 10 mg, 5 mg, or 0 mg while maintaining inactivity of the ocular inflammation, among those not meeting each respective criterion for success at the outset. Prednisone-equivalent doses of alternative corticosteroids were included in these evaluations when required. When applicable, dates of discontinuation of mycophenolate mofetil and the reasons for the discontinuation documented in the charts were noted.

Statistical Methods

SAS version 9.1 (SAS Corporation, Cary, North Carolina, USA) was used for all analyses. The frequencies of demographic and clinical characteristics at enrollment among patients treated with mycophenolate mofetil were tabulated. The benefits of therapy were evaluated based on time to success (control of inflammation and corticosteroid-sparing effects). A time-to-failure approach was used for time to discontinuation of mycophenolate mofetil. In the primary analyses, outcomes were accepted only when observed at 2 or more visits spanning at least 28 days, to avoid the error of including transient improvements and brief interruptions in therapy as successes or failures.

The Kaplan-Meier method was used to estimate the proportion of patients who achieved success or experienced failure at or before 6 and 12 months of therapy. Incidence rates, by person and/or by eye, were calculated as the number of events divided by the person- or eye-years of observation. Cox regression was used to calculate crude and adjusted hazard ratios (HRs) for occurrence of major outcome events, in relation to potentially explanatory covariates.


During follow-up, 236 patients started mycophenolate mofetil as a single (noncorticosteroid) immunosuppressive treatment. Their characteristics at the time when mycophenolate mofetil was started are given in Table 1 . The median age was 47.1 years (range, 8.1–84.2 years); 64% were female and 67% were Caucasian. The mean duration of inflammation prior to starting mycophenolate mofetil was 3 years. Bilateral involvement was present in 68% of patients; 130 patients (32.7%) had a visual acuity of 20/50 or worse. The primary site of ocular inflammation was as follows: 48 (20%) had anterior uveitis, 28 (12%) intermediate uveitis, 94 (40%) posterior uveitis or panuveitis, 33 (14%) scleritis, 18 (8%) mucous membrane pemphigoid, and 15 (6%) other forms of inflammation.


Patient- and Eye-Specific Characteristics at the Time of Starting Mycophenolate Mofetil

Characteristics Anterior Uveitis Intermediate Uveitis Posterior/Panuveitis Scleritis MMP Other Total
Person-specific Characteristics
Number of patients 48 28 94 33 18 15 236
Median age, years (range) 34.1 (8.1–71.4) 44.3 (19.8–75.4) 48.0 (8.5–80.3) 56.2 (19.3–72.7) 70.6 (45.9–84.2) 39.4 (13.2–69.1) 47.1 (8.1–84.2)
Gender, % female 38 (79.2%) 16 (57.1%) 56 (59.6%) 22 (66.7%) 9 (50.0%) 9 (60.0%) 150 (63.6%)
Race, % Caucasian 29 (60.4%) 20 (71.4%) 60 (63.8%) 22 (66.7%) 16 (88.9%) 11 (73.3%) 158 (66.9%)
Race, % Black 12 (25.0%) 5 (17.9%) 22 (23.4%) 9 (27.3%) 0 (0.0%) 2 (13.3%) 50 (21.2%)
Race, % other 7 (14.6%) 3 (10.7%) 12 (12.8%) 2 (6.1%) 2 (11.1%) 2 (13.3%) 28 (11.9%)
Duration of inflammation 4.1 (0.0–18.9) 5.9 (0.1–22.4) 3.0 (0.0–35.1) 1.8 (0.1–21.3) 1.3 (0.0–17.4) 3.0 (0.3–17.1) 3.0 (0.0–35.1)
Bilateral inflammation 34 (70.8%) 19 (67.9%) 67 (71.3%) 18 (54.5%) 13 (72.2%) 10 (66.7%) 161 (68.2%)
Corticosteroid dose less than or equal to 10 mg 34 (70.8%) 15 (53.6%) 53 (56.4%) 8 (24.2%) 12 (66.7%) 5 (33.3%) 127 (53.8%)
Prior mycophenolate 8 (16.7%) 6 (21.4%) 9 (9.6%) 2 (6.1%) 1 (5.6%) 0 (0.0%) 26 (11.0%)
Prior antimetabolites (other than mycophenolate) 23 (47.9%) 6 (21.4%) 21 (22.3%) 10 (30.3%) 3 (16.7%) 3 (20.0%) 66 (28.0%)
Prior alkylating agents 2 (4.2%) 1 (3.6%) 5 (5.3%) 3 (9.1%) 4 (22.2%) 2 (13.3%) 17 (7.2%)
Prior T cell inhibitors 9 (18.8%) 11 (39.3%) 13 (13.8%) 3 (9.1%) 0 (0.0%) 0 (0.0%) 36 (15.3%)
Prior biologics 5 (10.4%) 3 (10.7%) 4 (4.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 12 (5.1%)
Any prior immunosuppressive treatment 30 (62.5%) 15 (53.6%) 37 (39.4%) 14 (42.4%) 8 (44.4%) 5 (33.3%) 109 (46.2%)
Eye-specific characteristics
Number of affected eyes 82 47 161 51 31 25 397
20/50 or worse 23 (28.0%) 20 (42.6%) 67 (41.6%) 10 (19.6%) 10 (32.3%) 0 (0.0%) 130 (32.7%)
20/200 or worse 12 (14.6%) 8 (17.0%) 28 (17.4%) 5 (9.8%) 4 (12.9%) 0 (0.0%) 57 (14.4%)
Any ocular complication, affected eyes a 36 (43.9%) 37 (78.7%) 95 (59.0%) 14 (27.5%) 7 (22.6%) 1 (4.0%) 190 (47.9%)

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Jan 17, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Mycophenolate Mofetil for Ocular Inflammation
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