New therapies in development for the management of non‐infectious uveitis: A review

Uveitis is a spectrum of inflammatory disorders characterized by ocular inflammation and is one of the leading causes of preventable visual loss. The main aim of the treatment of uveitis is to control the inflammation, prevent recurrences of the disease and preserve vision while minimizing the adverse effects associated with the therapeutic agents. Initial management of uveitis relies heavily on the use of corticosteroids. However, monotherapy with high‐dose corticosteroids is associated with side effects and cannot be maintained long term. Therefore, steroid‐sparing agents are needed to decrease the burden of steroid therapy. Currently, the therapeutic approach for non‐infectious uveitis (NIU) consists of a step‐ladder strategy with the first‐line option being corticosteroids in various formulations followed by the use of first‐, second‐ and third‐line agents in cases with suboptimal steroid response. Unfortunately, the agents currently at our disposal have limitations such as having a narrow therapeutic window along with their own individual potential side‐effect profiles. Therefore, research has been targeted to identify newer drugs as well as new uses for older drugs that target specific pathways in the inflammatory response. Such efforts are made in order to provide targeted and safer therapy with reduced side effects and greater efficacy. Several specially designed molecular antibodies are currently in various phases of investigations that can potentially halt the inflammation in patients with NIU. In the review, we have provided a comprehensive overview of the current and upcoming therapeutic options for patients with NIU.     

Cyclosporin A therapy in refractory non-infectious childhood uveitis

AIMS—To assess the immunosuppressive efficacy, steroid sparing effect and adverse effects of cyclosporin A (CsA) therapy in refractory non-infectious childhood uveitis.
METHODS—A retrospective case series review of the medical records of children on CsA therapy attending a tertiary referral centre for refractory endogenous uveitis was performed. Low dose (5.0 mg/kg/day) CsA therapy was started either as monotherapy or in combination with other agents. The CsA immunosuppressive efficacy was assessed by visual acuity and binocular indirect ophthalmoscopy (BIO) score outcomes and steroid sparing effect by growth charts and ability to withdraw or maintain a low steroid dose. Possible CsA adverse effects were monitored by routine biochemistry (including serum creatinine) and haematological tests, blood pressure recordings, and symptoms.
RESULTS—14 patients (25 eyes, 10 males, four females) were recruited with steroid failure as the most common CsA indication. Age (mean (SD)) at start of CsA therapy was 8.7 (4.1) years with a duration of CsA therapy of 20.9 (range 3.5-88.3) months at a maintenance CsA dose of 4.0 (1.0) mg/kg/day. From baseline, visual acuity improved or was maintained in 23 (92%) eyes and BIO score improved in 19 (76%) eyes. Height centiles were preserved and the maintenance prednisolone dose was 6.3 (3.3) mg/day, where required, in 10 (71%) patients. Nephrotoxicity was not observed, with transient systemic hypertension developing in one patient. Minor adverse effects were more common but were well tolerated.
CONCLUSIONS—Cyclosporin A therapy is effective and safe in the medium term, if closely monitored, in refractory non-infectious childhood uveitis.

Keywords: cyclosporin A; childhood uveitis     

The use of low dose methotrexate in children with chronic anterior and intermediate uveitis

AIM: To assess the efficacy of low dose methotrexate (MTX) therapy for children with chronic anterior and intermediate uveitis. METHODS: A retrospective case review of 10 children who received MTX for chronic uveitis at a tertiary referral centre was performed. The following data were recorded for each patient: age, sex, race, duration of uveitis, primary diagnosis, anatomical localisation of uveitis, corticosteroid therapy, dose range of MTX, duration of MTX therapy, and side effects of MTX therapy. Several clinical parameters were evaluated to study the effect of MTX. These included visual acuity, anterior chamber inflammation, and topical and oral corticosteroid requirement. RESULTS: After MTX VA of 6/6 or better was present in 100% right eyes and 80% left eyes (p = 0.055 and p = 0.016, respectively). Anterior chamber inflammation decreased in 60% of children after MTX (p = 0.0168). The requirement of topical steroid decreased from a mean of 5.6 times a day before MTX to 1.5 times a day after MTX (p = 0.005). The dose of oral steroid decreased from a mean of 18 mg per day to 2.85 mg per day (p = 0.012). The most common adverse effect was nausea (20%). No patient required discontinuation of MTX because of side effects. CONCLUSION: MTX is effective and safe for chronic anterior and intermediate uveitis in children. An increase awareness of its efficacy is required among paediatricians and ophthalmologists to prevent sight threatening complication of chronic uveitis and its treatment with long term use of steroids.     

Clinical outcome of chronic immunosuppression in patients with non-infectious uveitis

AIM: To determine the visual outcome and corticosteroid dose requirement in patients with non-infectious uveitis affecting the posterior segment treated with corticosteroids and additional second-line immunosuppression. METHOD: A retrospective, non-comparative case series was carried out. Seventy-two patients (141 eyes) with uncontrolled non-infectious uveitis on systemic prednisolone were treated with at least one second-line immunosuppressive agent in addition to systemic prednisolone and followed for at least 3 months.Visual acuity (VA), clinical disease activity, corticosteroid-sparing effect, disease relapses requiring corticosteroid dose increase,and side-effects from second-line agents were evaluated. RESULTS: At the end of the follow-up period (mean: 55.5 months),70 eyes (49.6%) had VA of 6/9 or better. There was a reduction in the mean maintenance dose of prednisolone required before the introduction of the second-line agent (19 mg/day +/- 2 SE)when compared to the mean maintenance dose of prednisolone at the end of the data collection (9 mg/day +/- 1 SE; P <0.001).There was also a significant reduction in the number of disease relapses requiring an increase in prednisolone dose after starting the second-line agents as compared to the year before (P <0.02). CONCLUSION: In patients with uveitis affecting the posterior segment, the addition of all second-line immunosuppressive therapy was effective in allowing reduction of the dose of systemic prednisolone to 10 mg/day or less, in controlling intraocular inflammation, reducing the number of relapses and in maintaining vision. Because of their side-effects, immunosuppressive treatment should be individualized and monitored closely but its addition is beneficial in the short and longer term.     

重视葡萄膜炎药物治疗研究,提高葡萄膜炎药物治疗效果

各类非感染性葡萄膜炎的治疗,糖皮质激素是首选药物.但单一药物治疗对慢性或复发性葡萄膜炎的疗效欠佳,长期应用又具有明显的毒副作用,因此部分患者需辅助以免疫抑制剂或生物制剂治疗.不同类型免疫抑制剂和生物制剂的作用机制不完全相同,因此各自的适应证、疗效和毒副作用也不尽一样.在临床实践中,应根据葡萄膜炎的类型选择敏感的免疫抑制剂或生物制剂治疗,同时密切观察其疗效和毒副作用.葡萄膜炎治疗中的常用药物类型、疗效以及存在的问题值得我们进一步关注和深入研究,以提高葡萄膜炎药物治疗的效果.     

A role for methotrexate in the management of non-infectious orbital inflammatory disease

AIM: To evaluate the clinical usefulness of methotrexate for patients with non-infectious orbital inflammatory disease who fail to respond to systemic corticosteroids and/or orbital irradiation. METHODS: The medical records of patients with non-infectious orbital inflammatory disease who were treated with methotrexate at Oregon Health Sciences University between June 1993 and June 2000 were examined. Methotrexate was administered at a median maximum dose of 20 mg per week (range 15-25 mg per week) in conjunction with folate supplementation. Patients were followed with regular ophthalmic examinations, as well as serum liver enzyme levels and blood cell counts. Clinical signs of regression of the orbital inflammation, visual acuity, dosage and duration of methotrexate therapy, requirement for concurrent corticosteroid administration, and adverse drug reactions were recorded. RESULTS: The study cohort included 14 patients (24 eyes) with diagnoses including non-specific orbital inflammation (n=7), Tolosa-Hunt syndrome (n=1), thyroid orbitopathy (n=3), Wegener's granulomatosis (n=1), sarcoidosis (n=1), and Erdheim-Chester disease (n=1). In all cases, methotrexate was commenced as a corticosteroid sparing agent. 10 patients (71%) completed a 4 month therapeutic trial of methotrexate. Median duration of treatment for the nine (64%) patients who experienced clinical benefit was 25 months (range 10-47 months). Six responders were ultimately able to cease methotrexate, including the single patient who required concurrent long term corticosteroid therapy. Complications included fatigue, gastrointestinal disturbance, hair thinning and mild, reversible serum liver enzyme elevation. Two patients (14%) discontinued treatment because of adverse effects. CONCLUSION: Methotrexate is a well tolerated immunosuppressive medication which may benefit patients with recalcitrant non-infectious orbital inflammatory disease.     

Review: uveitis and immunosuppressive drugs.

Uveitis, inflammation of the eye, is a common occurring disease resulting from a wide variety of traumatic and immunogenic insults and, in most cases, can be treated successfully by corticosteroids. However, corticosteroids have severe side effects. Alternative therapy is using nonsteroidal anti-inflammatory agents like indomethecin, diclofenac and flurbiprofen. The uveitic cases are prominent in the third world countries, and many of the patients are not responsive or become refractory to steroidal or nonsteroidal therapy. Therefore, there is another class of compounds "immunosuppressive drugs" found to be successful in treating uveitis. These include cyclosporin A, tacrolimus, and sirolimus. However, being immunosuppressive they also have side effects. Therefore, the effective therapy with lower side effects is the treatment with combination of these drugs in lower dosages. Cyclosporin A plus sirolimus or tacrolimus in threshold doses alleviate signs of uveitis with lower incidence of side effects.     

Ciclosporin-A-Therapie bei schweren anterioren Skleritiden Fünf schwere Verläufe ohne nachgewiesene assoziierte Systemerkrankung unter systemischer Ciclosporin-A-Therapie

BACKGROUND: Patients with severe scleritis who do not respond to high-dose corticosteroid therapy, or who require a daily corticosteroid maintenance dose higher than 30 mg prednisone should be treated by other immunosuppressants. PATIENTS AND METHODS: In five patients with various types of severe anterior scleritis a long-term high-dose steroid treatment failed to control scleral inflammation. They therefore received cyclosporin (CsA). Follow-up was 16-26 months. RESULTS: Scleral inflammation and ocular complications were controlled in all patients by a regimen of systemic CsA combined with a low maintenance steroid dose below the Cushing threshold. We observed no side effects under CsA serum levels of 120-150 ng/ml. In only one patient was scleral inflammation totally and lastingly eliminated. CONCLUSIONS: Systemic CsA therapy is of definite therapeutic value in the symptomatic management of steroid refractory severe anterior scleritis without associated systemic disease. Complete healing, however, is achieved only in a minority of cases.     

Practical approach to the use of corticosteroids in patients with uveitis

Corticosteroids constitute the first line of therapy for patients with noninfectious ocular inflammatory disease. We review factors contributing to the clinical effectiveness of various corticosteroid preparations in patients with uveitis and discuss practical aspects regarding treatment indications, when to administer various agents, and how best to dose and monitor for both treatment and adverse effects. Topically administered corticosteroids are typically indicated for the treatment of anterior uveitis, whereas periocular or intravitreal agents are employed most often in the management of intermediate or posterior intraocular inflammation. Patients with vision-threatening uveitis, bilateral inflammation, or uveitis occurring in the setting of systemic involvement may require oral or intravenous administration of corticosteroids. Noncorticosteroid immunosuppressive agents play an important role in limiting the toxic effects of long-term corticosteroid use.     

The outcomes of mycophenolate mofetil therapy combined with systemic corticosteroids in acute uveitis associated with Vogt–Koyanagi–Harada disease

Purpose: To study the effectiveness of mycophenolate mofetil (MMF) as first‐line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt–Koyanagi–Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy. Methods: This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease. Results: The mean follow‐up period was 27.0 ± 11.1 months (range 16–54 months). Corticosteroid‐sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3–7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3–41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed ‘sunset glow fundus’. Conclusions: Addition of MMF as first‐line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome.     

Long-term follow-up of patients with birdshot retinochoroidopathy treated with systemic immunosuppression

PURPOSE: Birdshot retinochoroidopathy (BRC) is a rare uveitis syndrome of presumed autoimmune etiology. Therapy with systemic and periocular corticosteroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Corticosteroid-sparing strategies with agents such as cyclosporine A or azathioprine have been suggested for this disease. METHODS: We retrospectively reviewed the medical charts of patients with BRC who were evaluated consecutively at a tertiary-care, referral-based North American uveitis clinic over a 15-year period. RESULTS: Eleven Caucasian patients (22 eyes) were diagnosed with BRC, representing approximately 1% of all cases seen at the uveitis clinic. HLA-A29 was positive in all 11 patients. We elected to treat five patients with azathioprine, methotrexate, cyclosporine A, mycophenolate mofetil, and/or IvIg, as well as systemic or periocular corticosteroid injections. The median period of follow-up for the five treated patients was six years (range: 8 months-13 years). Inflammation was reduced or stabilized in five of five patients. CONCLUSION: Although the definitive strategy for the management of BRC is unknown, control of intraocular inflammation and preservation of vision is possible with corticosteroid-sparing immunosuppressive agents.     

Intravitreal steroids for macular edema: the past, the present, and the future

Macular edema, a condition usually associated with an underlying disease process, is a common cause of severe visual loss. There have been a variety of approaches to the treatment of macular edema; within the past few years, however, intravitreal corticosteroid treatments have emerged as an increasingly used treatment option for patients with macular edema. Intravitreal delivery allows the steroid to bypass the blood–retinal barrier, leading to a more concentrated dose of steroid for a prolonged period of time. Corticosteroids have likely been successful in the treatment of various forms of macular edema, due to their known anti-angiogenic, anti-edematous, anti-inflammatory, anti-apoptotic, and anti-proliferative effects. Intravitreal triamcinolone acetonide has been repeatedly successful in reducing macular edema and improving visual acuity, although the duration of action is typically short-term. Due to the recurrent and chronic nature of macular edema, biodegradable implants may be the future of intravitreal steroids. Intravitreal corticosteroids are not without risks. Steroid-related side effects include cataract formation and elevated intraocular pressure. Injection-related side effects include retinal detachment, vitreous hemorrhage, bacterial endophthalmitis, and sterile endophthalmitis. This article reviews the evolving role of intravitreal corticosteroids in the treatment of macular edema secondary to uveitis, diabetes, and retinal vascular disorders.     

Long-Term Follow-Up of Patients with Birdshot Retinochoroidopathy Treated with Systemic Immunosuppression

Purpose: Birdshot retinochoroidopathy (BRC) is a rare uveitis syndrome of presumed autoimmune etiology. Therapy with systemic and periocular corticosteroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Corticosteroid-sparing strategies with agents such as cyclosporine A or azathioprine have been suggested for this disease. Methods: We retrospectively reviewed the medical charts of patients with BRC who were evaluated consecutively at a tertiary-care, referral-based North American uveitis clinic over a 15-year period. Results: Eleven Caucasian patients (22 eyes) were diagnosed with BRC, representing approximately 1% of all cases seen at the uveitis clinic. HLA-A29 was positive in all 11 patients. We elected to treat five patients with azathioprine, methotrexate, cyclosporine A, mycophenolate mofetil, and/or IvIg, as well as systemic or periocular corticosteroid injections. The median period of follow-up for the five treated patients was six years (range: 8 months–13 years). Inflammation was reduced or stabilized in five of five patients. Conclusion: Although the definitive strategy for the management of BRC is unknown, control of intraocular inflammation and preservation of vision is possible with corticosteroid-sparing immunosuppressive agents.     

Tolerability and pharmacokinetics of intravitreal sirolimus

Abstract Purpose: To evaluate the pharmacokinetics (PK) and tolerability of a proprietary sirolimus depot-forming ocular formulation in rabbits and humans after a single intravitreal (IVT) injection. Methods: New Zealand White (NZW) rabbits were intravitreally injected in both eyes with an injectable formulation in 5 (3 PK and 2 tolerability) studies. The rabbits received up to approximately 220?μg sirolimus per eye. At the desired timing post-injection, the animals were euthanized; both eyes were enucleated, frozen, and dissected to separate sclera, retina/choroid, and vitreous humor (VH). Whole blood (WB) samples were obtained at each time point before euthanasia. In clinical trials, patients received an IVT injection of approximately 352?μg sirolimus. Sirolimus concentrations in ocular tissues and WB samples were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). In both single- and repeat-dose tolerability studies, systemic and ocular adverse effects were evaluated. Results: After IVT administration, sirolimus formed a depot in the VH. During dissolution, concentrations in VH were dose related and exhibited continuous release from the depot. This was characterized by a gradient of sirolimus concentration in the order of VH > retina/choroid > sclera > WB, and the concentrations were maintained for approximately 2 months after the IVT injection. After repeat dosing (132?μg), no drug accumulation was seen in the ocular tissue or systemically. In clinical studies, the highest blood levels were <2?ng/mL at day 2, and half-time (t(1/2)) was 8-9 days. There was no accumulation at day 30 after the IVT injection (up to 352?μg). Safety studies conducted on rabbits indicated good local tolerability. Sirolimus-related effects were limited to minor incipient cataract findings and mild lenticular changes. In the clinical studies where sirolimus was intravitreally administered up to 352?μg, injections were well tolerated. Conclusions: Sustained IVT delivery was achieved in a dose-dependent fashion after the IVT injection of a proprietary sirolimus depot-forming ocular formulation. Across the tolerability and safety studies, no significant findings were observed for systemic and ocular tolerability. The human WB levels were well below the daily trough systemic blood level range required for systemic immunosuppression. An IVT injection of sirolimus has a PK and safety profile that is favorable for treating inflammatory conditions of the eye, such as non-infectious uveitis, and warrants further investigation in humans.     

Antituberculosis therapy in the treatment of peripheral uveitis

Tuberculous uveitis usually appears as chronic anterior uveitis or disseminated choroiditis. From 1982 to 1989, we conducted a retrospective study of 23 patients with presumed tuberculous uveitis. All patients had a positive tuberculin purified protein derivative skin test. The diagnosis was based on history, positive skin test, and physical examination. We excluded other conditions that could induce uveitis, based on the absence of signs, symptoms, or laboratory results suggesting any other diagnosis. Tuberculous uveitis was also considered in the differential diagnosis when progressive ocular inflammation was resistant to corticosteroid therapy. The patients received the following treatment: (1) isoniazid (300mg/day) and rifampin (600mg/day) for nine to 12 months, (2) ethambutol (1200mg/day) in some cases for two to three months, and (3) corticosteroids orally where indicated. In cases with anterior uveitis, we added local instillation of mydriatics and corticosteroids. There was no regression, nor were there any side effects of antituberculosis therapy in all 23 patients. We noted clinical improvement in 78% of cases. Five patients had other conditions (cataract or retinal detachment) that worsened their vision.     

Nonsteroidal drugs for the treatment of noninfectious posterior and intermediate uveitis

PURPOSE OF REVIEW: This review summarizes current nonsteroidal drug therapies for noninfectious posterior and intermediate uveitis. RECENT FINDINGS: Continuing evidence shows that second-line agents including antimetabolites, T-cell inhibitors and alkylating agents, are effective in many patients, allowing reduction in steroid dose and preservation of visual function. There is an increased use of mycophenolate mofetil. Biologic therapies, including the antitumour necrosis factor-alpha agents and interferons, have demonstrated a high degree of efficacy in controlling uveitis refractory to immunosuppressants. SUMMARY: There are an increasing number of treatment options. As the vast majority of published studies in uveitis are case series or nonrandomized trials, there remains a lack of level 1 evidence to guide the choice and duration of therapy. Standard initial treatment for steroid-resistant disease is to add a single immunosuppressant to the regime, with additional agents being substituted or added as required. Combination of two immunosuppressants in addition to steroids may be indicated especially in chronic uveitis. High cost and limited long-term experience with biologic agents have restricted their use to uveitis refractory to immunosuppressants, but evidence suggests a potential therapeutic role earlier in Bechet's disease.     

Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis

AIM: To compare the efficacy and side-effects of posterior sub-Tenon injection of triamcinolone acetonide (Kenalog) with orbital floor injection of methylpredisolone acetate (Depomedrone) in the management of posterior uveitis. METHODS: Non-randomized comparative prospective clinical study. Sixty-four eyes from 60 consecutive patients with non-infectious posterior uveitis requiring treatment were allocated on an alternate 1:1 basis to receive either orbital floor methylprednisolone or sub-Tenon triamcinolone using standard procedures and assessed at 6 and 12 weeks. RESULTS: After five eyes of five patients who had received the same treatment bilaterally were excluded from the statistical analysis, 14 out of 29 eyes treated with orbital floor methylprednisolone and 10 out of the 30 eyes given sub-Tenon triamcinolone improved at 6 weeks. There was no statistically significant difference in the improvement rate between the two groups. However, two patients given triamcinolone had prolonged upper lid ptosis, which required surgery, and another two developed markedly raised intraocular pressure, neither of which occurred in the methylprednisolone-treated group. CONCLUSIONS: Although the two drugs and routes compared were of similar efficacy, lid ptosis occurred in the triamcinolone-treated but not the methylprednisolone group. This should be borne in mind when choosing the preferred route of delivery of periocular corticosteroid in the treatment of posterior uveitis.     

Usefulness of the Laser FLare Cell Meter (LFCM, Kowa FC-1000) for evaluating inflammation of the anterior chamber in clinical practice

The Laser Flare Cell Meter (LFCM, Kowa FC-1000), an instrument measuring aqueous flare and cells in a quantitative, objective and non-invasive way, has been mainly used so far to measure inflammation in clinical and experimental research. In the light of some illustrative examples, its practical clinical usefulness is presented; the LFCM was found to be specially helpful in 3 types of situations. 1. In acute anterior uveitis (AAU) patients, precise LFCM monitoring of inflammation made it possible to avoid excessive corticosteroid therapy, mainly by more rapid and controlled tapering at the end of an inflammatory episode, so possibly minimizing steroid side effects in a group of patients prone to numerous uveitis recurrences. In a steroid-responder patient it allowed successful treatment of a flare-up of AAU with a combination of systemic and topical diclofenac (Voltaren), a potent nonsteroidal antiinflammatory drug. 2. LFCM monitoring of inflammation in patients undergoing laser treatments allowed optimal adjustment of antiinflammatory therapy. Diclofenac drops (Voltarene Ophta), were sufficient to treat inflammation in all patients, undergoing Nd-YAG laser posterior capsulotomy or Argon laser trabeculoplasty. 3. In patients with acyclovir treated herpes simplex or herpes zoster uveitis corticosteroid treatment should be avoided whenever possible, because of the tendency to develop steroid dependency. LFCM monitoring of this group of patients gave a precise evolutionary pattern of inflammation and permitted to avoid steroid treatment in many patients.     

Treatment of uveitis with immunosuppressives: antimetabolites and alkylating agents

Oral corticosteroids remain the main therapeutical choice in patients with uveitis not responding to topical treatment, however their chronic use can be very toxic, especially for bones (osteoporosis or growth retardation). Immunosuppresive agents are used as corticosteroid sparing agents and/or as agents able to control refractory uveitis in sight threatening uveitis. Cyclosporin A is very efficacious but is nephrotoxic, in particular in old people. Methotrexate is well tolerated in young people, is not carcinogenic but not very active. Azathioprine is well tolerated but it's carcinogenic effect and its delayed action are helpful in chronic uveitis of old women. Cyclophosphamide and intravenous steroids are helpful for emergencies. Chlorambucil is toxic and carcinogenic but might lead to an increased rate of remission and might be useful as a short treatment. In any case, a careful and regular follow-up in collaboration with a competent internist is mandatory.     

Long-term results of treatment of macular complications in eyes with immune recovery uveitis using a graded treatment approach

PURPOSE: To evaluate the results of a graded treatment approach in a cohort of eyes with macular complications of immune recovery uveitis. METHODS: A cohort of 18 eyes of 13 patients representing all eyes with these complications at the University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes were classified into three groups and treated according to a graded protocol. RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better) were observed. These six eyes maintained good vision with only one dropping to 20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 9 patients), repository sub-Tenon steroid injections were used repeatedly. There were no complications of steroid use but visual improvement occurred in only 40% of eyes. Macular edema persisted. In eyes with structural macular changes, such as epiretinal membrane, vitrectomy resulted in vision improvement in three of four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild cases of immune recovery uveitis and macular edema may be observed. In eyes with reduction of vision due to cystoid macular edema, there was only a modest treatment effect using repository corticosteroids. Eyes with immune recovery uveitis that develop epiretinal membrane undergo some visual improvement after removal of the membrane. The macular edema of immune recovery uveitis is resistant to corticosteroid treatment.