Efficacy and Safety of Mycophenolate Mofetil in the Treatment of Recalcitrant Intermediate Uveitis

Purpose: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in the treatment of recalcitrant intermediate uveitis in a tertiary referral eye-care center over a 1-year period.

Methods: Patients with at least three recurrences of intermediate uveitis per year, defined as relapse of disease after quiescent phase for >3 months after discontinuing all treatments and those with a minimum follow-up of 1 year, were analyzed retrospectively. MMF was initiated with oral steroids and the Standardization of Uveitis Nomenclature guidelines were used to evaluate patients at every visit. Response to treatment, worsening of uveitis, visual benefit, steroid withdrawal rates, and side-effect due to MMF were monitored.

Results: Data from 30 eyes of 19 patients were analyzed, of which 10 were men and 11 has bilateral disease. The mean age of presentation was 32.6 ± 15.4 years and the commonest presenting complaints were floaters (26 eyes). The mean vitreous haze was 3+ at presentation and reduced to 0 at last follow-up (24 eyes). Out of the 30 eyes, 80% had complete resolution of vitreous haze at the end of one year. Worsening intermediate uveitis was seen in six eyes (15.78%). Steroid withdrawal was successful in 85% of eyes. Vision improved in 56% of eyes. None of the patient developed serious systemic complications warranting withdrawal of MMF.

Conclusion: MMF in our series was a safe and effective drug in controlling disease and preventing worsening in majority eyes with the most severe forms of intermediate uveitis. Larger studies are required before MMF is widely adopted for the management of recalcitrant intermediate uveitis.     

Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis

Background We evaluated the outcomes of patients with different forms of chronic uveitis treated with mycophenolate mofetil (MMF) as an immunomodulatory and steroid-sparing agent. The multi-system side effects that arise after long-term treatment with corticosteroids and other immunosuppressants prompted us to use MMF. MMF is a selective inhibitor of inosine monophosphate dehydrogenase, thus blocking purine synthesis via the de novo pathway preferentially used by T and B lymphocytes.Methods Between 1998 and 2003, 106 patients were treated for uveitis (anterior n=26, intermediate n=51, posterior n=23, panuveitis n=6) with MMF at a dose of 1g twice daily. Treatment duration was at least 6 months (n=10), in most cases greater than 12 months (n=77) and in 25 cases between 24 months and 41 months, when the present retrospective evaluation was undertaken. Patient charts were analysed according to a standardized evaluation protocol.Results In 95 patients MMF was combined with prednisolone at a dosage of 2.5–10 mg per day. In 8 patients MMF was used as a monotherapy, and in 3 cases one further systemic immunosuppressant was required. The number of recurrences during MMF treatment was none or one in 92 patients, two in 6 cases and three or more in 8 patients. In none of the patients had MMF been stopped at the time of data analysis. The most frequently observed side effects were gastrointestinal upset (15%), followed by headache (9.3%), fatigue (5.7%), eczema (5%), and hair loss (3.5%). Other side effects were sporadic. Most of these phenomena were transitory. Forty-two patients experienced no side effects at all. In 4 patients MMF was judged ineffective due to failure to reduce the number of recurrences of severe inflammation compared with the previous therapeutic regime, or indeed occurrence of persistent macular oedema.Conclusions Our results show that MMF is an effective immunosuppressant in patients with uveitis. We provide evidence that MMF controls the disease in the majority of patients with an acceptable profile of side effects.     

Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis

Purpose: To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis.

Methods: In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients’ demographics, clinical course, response to treatment, and complications were assessed.

Results: A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing–remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity.

Conclusions: MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.     

Long-term control of cystoid macular oedema in noninfectious uveitis with Mycophenolate Mofetil

Purpose To evaluate the long-term safety and efficacy of Mycophenolate Mofetil (MMF) for the control of cystoid macular oedema (CMO) secondary to noninfectious uveitis (NU). Methods The medical records of 19 consecutive patients with inflammatory CMO treated with MMF were retrospectively reviewed. Patient demographics, best corrected visual acuity (BCVA), fluorescein angiography (FA), and optical coherence tomography (OCT) findings were evaluated. Results There were eight females and 11 males with a mean age of 32.9 ± 8.9 years. After a 1-year follow-up, 18/19 patients (31 eyes, 96.9%, P < 0.05) no longer had signs of CMO, as per their FA and OCT findings; the mean central foveal thickness (CFT) was 167.2 ± 12.8 μm. At the last follow-up, only 3/19 patients, all affected by Behçet panuveitis, had recurrences of CMO. Mean BCVA improved from 0.34 ± 0.14 SD at baseline to 0.65 ± 0.2 SD at last follow-up. Conclusions MMF was safe and effective in controlling CMO and in reducing the uveitis relapse rate in patients not responding to traditional immunosuppressants. Further case–controlled studies are mandatory to validate those preliminary results.     

Mycophenolate mofetil therapy in uveitis: analysis of eight cases in a tertiary ophthalmic care centre in India

Mycophenolate mofetil (MMF) is a relatively new immunomodulatory agent. The experience of MMF in inflammatory eye diseases is limited to a few case series. We report our experience of MMF in eight patients with uveitis. Control of inflammation was achieved in all patients. No patient had adverse side effects. Our study indicates that MMF is a safe and effective immunomodulatory agent.     

Cytomegalovirus Colitis and Viremia from Mycophenolate Mofetil Monotherapy in Birdshot Chorioretinopathy

Purpose: To describe a case of cytomegalovirus (CMV) viremia and colitis in a patient on mycophenolate mofetil (MMF) monotherapy for birdshot chorioretinopathy.

Design: Case report.

Methods: Retrospective chart review.

Results: Treatment with MMF 1.5?g twice daily for 5 years led to leucopenia and a CD4 count of 299, which resulted in active CMV infection.

Conclusions: Treatment with MMF alone may put otherwise immune-competent individuals at risk for opportunistic CMV infection. Greater awareness of this association may allow for better monitoring, earlier detection, and treatment of future cases.     

Recurrent Bilateral Inflammatory Idiopathic Optic Neuropathy Treated with Mycophenolate Mofetil: Clinical and Radiological Course

Objective: To report the clinical characteristics and radiological findings of a patient suffering simultaneous bilateral recurrent inflammatory optic neuritis, who has been free of relapses following treatment with mycophenolate mofetil (MMF). Background: Inflammatory simultaneous visual loss is unusual. It is more frequently seen in acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica (NMO). Evolution to multiple sclerosis (MS) after simultaneous bilateral optic neuritis is less frequent than after unilateral optic neuritis. Sequential optic neuritis has been described in Chronic Relapsing Inflammatory Optic Neuritis (CRION), which shows neither brain lesions nor oligoclonal bands in cerebrospinal fluid (CSF) and presents a relapsing course and a good response to immunosuppression. Case: A 41-year-old woman was evaluated for simultaneous bilateral visual loss. Magnetic resonance imaging showed enhancement of the chiasm and both optic nerves. No definite data of MS were found. We excluded infections, sarcoidosis, lupus, and other known causes of optic neuropathy. She was treated with intravenous methylprednisolone and tapering oral prednisone. After a partial recovery, she suffered two recurrences within three months. Following treatment with MMF, no further relapses have occurred during a 26 month follow-up. Discussion: Bilateral optic neuritis is part of two clinical syndromes: ADEM and NMO. Our patient differs from these entities on her clinical course and response to treatment. She is closer to the CRION cases (no oligoclonal bands, relapsing course, response to immunosuppression), except for her brain lesions and the bilateral involvement at onset. Conclusion: We suggest MMF as an effective treatment for idiopathic recurrent inflammatory optic neuritis not responsive to corticosteroids.     

Mycophenolate Mofetil and Fundus Autofluorescence in the Management of Recurrent Punctate Inner Choroidopathy

Purpose: To compare the frequencies of attacks before and after immunomodulatory therapy (IMT) with mycophenolate mofetil (MMF) in recurrent punctate inner choroidopathy (PIC) and to report fundus autofluorescence (FAF) findings.

Methods: Eight patients who had at least two recurrent episodes of increased activity before MMF and 12 months of documented clinical course before and after MMF were included. The frequencies of attacks before and after MMF were compared. FAF images evaluated.

Results: Before MMF, the 8 patients experienced 19 attacks of recurrent disease activity; during MMF therapy, 3 (38%) patients experienced 6 recurrent episodes. The attack frequencies were 1.09?±?0.75 before and 0.23?±?0.32 during treatment (p?=?.036). Among the 6 patients who had FAF, surrounding hyperautofluorescent halo was detected in 4 and recurrence occurred in 2 who did not show any changes on the intensity during treatment.

Conclusion: In the index study, the employment of MMF has decreased frequency of attacks in recurrent PIC. FAF may be employed to monitor and predict the response to treatment.     

A Case of Primary Intraocular Lymphoma Treated by Intravitreal Methotrexate

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 µg/0.1 ml in the right eye, 400 µg/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.     

我国葡萄膜炎研究现状、问题及今后研究方向

我国葡萄膜炎研究的现状是眼科医生对葡萄膜炎的认识水平普遍有所提高；糖皮质激素使用逐渐趋于合理化；其他免疫抑制剂的应用逐渐得到重视；抗生素使用逐渐减少；葡萄膜炎研究的国际影响力扩大。但存在研究工作的地区差异较大, 并发症治疗中误区较多, 糖皮质激素玻璃体内注射的合理评价有待重视等问题。Behcet病和伏格特-小柳-原田综合征是我国常见的葡萄膜炎类型和重要的致盲类型，梅毒性葡萄膜炎、艾滋病、真菌性眼内炎、伪装综合征等原来少见的一些葡萄膜炎类型近年逐渐增多。开展多中心合作研究，探讨Behcet病和伏格特-小柳-原田综合征不同治疗方案的治疗效果，优化出最佳的治疗方案；重视近年来逐渐增多的葡萄膜炎类型的临床特征；探讨免疫耐受的诱导对葡萄膜炎的预防和治疗作用等是今后值得重视的研究课题。     

Bilateral Nongranulomatous Uveitis with Infective Endocarditis

A 32-year-old male who had infective endocarditis complained of photophobia and blurred vision in both eyes. Biomicroscopic examination and fundus examination revealed anterior chamber reaction, vitritis, optic disc swelling, and Roth spots. He was diagnosed with bilateral nongranulomatous uveitis and treated with topical steroid eye drops and posterior sub-Tenon injection of triamcinolone. His visual symptoms were resolved within 1 week, and inflammation resolved within 4 weeks after treatment.     

超声乳化摘除白内障治疗葡萄膜炎继发性青光眼的疗效观察

目的初步评价白内障超声乳化摘除联合人工晶体植入术治疗合并有葡萄膜炎引起的继发性青光跟和并发性白内障的疗效.方法对13例(15眼)同时患有葡萄膜炎、继发性青光眼和并发性白内障的患者行连续环形撕囊的白内障超声乳化摘除联合人工晶体植入术,观察术后并发症、眼压和视力的变化情况.结果所有患者术中、术后都没有出现严重的并发症;术后3个月的视力平均为0.34±0.19,明显好于术前0.05±0.07(P＜0.05);术后3个月跟压和使用抗青光眼药物的种类分别为2.03±0.31kPa(15.21±2.36mmHg)和0.83±0.32种,较手术前的2.33±0.14kPa(17.5±1.03mmHg)和2.7±0.21种减少(P＜0.05).结论白内障超声乳化摘除联合人工晶体植入术是治疗葡萄膜炎引起的继发性青光眼和并发性白内障的又一种新的理想的选择.     

幼年特发性关节炎伴发葡萄膜炎

幼年特发性关节炎（JIA）是指发生在16岁以下儿童以慢性关节炎为主要临床表现的全身多系统自身免疫性疾病,临床表现为不明原因的持续6周以上的关节肿胀或炎症。大约有10%的患者伴有葡萄膜炎症,具有发病隐匿、炎症反应轻、并发症多和视力损害重等特点。好发人群为关节炎发病年龄小、抗核抗体阳性的女性少关节型关节炎患者。典型临床表现为双眼不对称的慢性轻度前葡萄膜炎,常见致盲性并发症有角膜带状变性、虹膜后粘连、并发性白内障和继发性青光眼等。局部应用糖皮质激素、非甾体抗炎剂和散瞳剂是主要治疗措施,顽固性患者需全身加用糖皮质激素、免疫抑制剂或生物制剂治疗,并发性白内障患者在围手术期需加强抗炎治疗。对幼年关节炎患儿进行密切眼部随访和及早诊治,可减轻葡萄膜炎病情和降低致盲性并发症的损害。     

Combined Intravitreal and Systemic Antibiotic Therapy in a Patient with Syphilitic Uveitis

Purpose: To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis.

Methods: Case report

Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1 month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. The patient denied history of genital lesions or rash, but did complain of difficulty hearing bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512 dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was made based on the clinical and laboratory findings. The patient was admitted for systemic intravenous antibiotic therapy, but was noted to have a penicillin allergy. Intravitreal ceftazidime was promptly administered bilaterally to achieve treponemacidal levels of antibiotic therapy. After penicillin desensitization protocol, the patient received 14 days of intravenous penicillin with clinical resolution.

Conclusions: There are increasing reports of ocular syphilis in the United States and delay in diagnosis and management can lead to severe visual impairment and blindness. We report the first case of adjunct intravitreal antibiotic therapy in a penicillin allergic patient. As ocular syphilis is a form of bacterial endophthalmitis, combination intravitreal and systemic antibiotics may be considered.     

Patterns of Exacerbations of Chronic Non-Infectious Uveitis in Pregnancy and Puerperium

Purpose: To determine patterns of exacerbations of recurrent non-infectious uveitis during pregnancy and puerperium. Design: Retrospective cohort study. Methods: The medical records of 32 women with a history of chronic non-infectious uveitis, who were pregnant during their follow-up at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary, from 1983 through 2003, were reviewed. The uveitis relapse rate during pregnancy was compared to the relapse rate during pregnancy-free periods in these women and to the relapse rate in a control group of women of childbearing age with recurrent non-infectious uveitis. Results: Among the 32 women who were pregnant during follow-up (40 pregnancies), the rate of flare-ups during pregnancy (1.0 recurrence per year) was lower than that observed during non-pregnant periods (2.4 per year; p < 0.001) and lower than that observed in the non-pregnant control group (3.1 per year; p < 0.001). Flare-ups were most frequent in the first trimester of pregnancy and decreased markedly in the second and third trimesters (2.3, 0.5, and 0.4 recurrences per year, respectively; p < 0.001). Conclusions: Pregnancy is associated with lower numbers of flare-ups of non-infectious uveitis compared to the non-pregnant state. If flare-ups do occur during pregnancy, they happen predominantly in the first trimester.     

Efficacy of Tocilizumab in Two Patients with anti-TNF-alpha Refractory Uveitis

Purpose: To report on two patients with refractory uveitis treated with tocilizumab; a new humanized monoclonal antibody against the interleukin-6 receptor (IL-6R).

Design: Retrospective interventional case series.

Methods: Both patients received a monthly infusion of tocilizumab 8?mg/kg; associated with corticosteroids. Outcome measures were visual acuity and central retinal thickness evaluated with optical coherence tomography.

Results: An improvement in visual acuity and a decrease in macular edema were observed in these two patients.

Conclusions: Tocilizumab seems to be a promising treatment in refractory uveitis. A prospective study is needed to evaluate the role of this new agent in the management of refractory uveitis.     

玻璃体切割在梅毒性葡萄膜炎中的试探性应用:附病例报告一例

目的:报道玻璃体切割在梅毒性葡萄膜炎中的应用。观察其治疗效果及安全性。方法:文献复习及病例报道。结果:一双眼梅毒性葡萄膜炎患者经药物治疗后,左眼视力明显提高而右眼停滞不前。右眼经标准三切口玻璃体手术后半个月,右眼视力大幅提高并超过左眼。结论:玻璃体切割手术在部分晚期梅毒性葡萄膜炎患者的治疗中有积极作用。尽管在本例患者中未见任何并发症,但其安全性及作用机制仍有待进一步研究证实。     

Changes in Inflammatory Activity after Glaucoma Filtration Surgery in Children with Chronic Anterior Uveitis

Purpose: To evaluate changes in inflammatory activity over time in patients with juvenile idiopathic arthritis (JIA)-associated anterior uveitis after two different types of glaucoma surgery.

Methods: Retrospective analysis of 32 patients with JIA who had trabeculectomy (TE, 21 eyes) or Ahmed glaucoma valve implantation (AGV, 11 eyes). Inflammatory activity and use of anti-inflammatory medication were evaluated 1 year prior to surgery and in the first, third, and fifth years after surgery.

Results: In both groups IOP decreased significantly from pre-surgery to 2 years after surgery (TE, 31.1 ± 6.7 to 12.8 ± 6.1 mmHg, p<0.0001; AGV, 28.5 ± 8.5 to 14.9 ± 6.6 mmHg, p<0.001). In the TE group flare, anterior chamber cells, and uveitis activity decreased significantly after surgery, whereas with AGV there was no sustained reduction of flare.

Conclusions: The degree of inflammation in JIA-associated uveitis is significantly reduced after trabeculectomy.