Treatment of uveitis

Suggested treatment scheme, one possible stepwise approach to ocular inflammation

Action Anti inflammatory Analgesic Anti pyretic Inhibit platelet aggregation

Indications CME Prevention of intraoperative miosis Post surgical inflammation Allergy Episcleritis Uveitis

o NSAIDs have no role during episode of acute anterior uveitis o May be useful in long term management of recurrent anterior uveitiso Adjuvant therapy with systemic NSAIDs was shown to reduce

inflammatory activity and allow reduction in dose of steroid in group of children with JRA associated uveitis

o For posterior uveitis with CME, oral NSAIDs showed good results once combined with local steroids injection, once it been used for 6-12 months to prevent recurrence

Dose and Route Topical TID-QID Oral

o Non-selectiveo Selective COX2 inhibitor

Celebrex 100-200 mg BID Vioxx 12.5-25-50 mg qd

Side effect Topical

o Irritationo Keratitiso Infiltrateo Thinningo Perforation

Systemico GIo CNSo Hematologicalo Renalo Hepatic

CorticosteroidsMechanism of actionThe anti-inflammatory actions of corticosteroids involve phospholipase A2 inhibitory proteins called lipocortins, which control the biosynthesis of inflammatory mediators, such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid.Phenotypic effect of steroid includes:

1. Constrict blood vessels, and decrease vascular permeability.2. Stabilization of intracellular lysosomal membrane and inhibition of expression of

various damaging enzymes.3. Stabilization of mast cells and basophil membrane is important in inhibiting the

process of degranulation and subsequent release of histamine, bradykinin, platelet activating-factor, protease, and eosinophil, chemotactic factor.

4. Suppression of lymphocytes proliferation.5. Reduction of circulating eosinophils and monocytes.6. Inhibition of macrophage recruitment and migration.

Suggested guidelines for use of prednisone for chronic ocular inflammation

Initial dose 1mg /kg/day

Maximum adult oral dose 60 to 80 mg/day

Maintenance dose (adult) ≤ 10mg/dayTapering schedule over 40mg/day, decrease by 10 mg/day

every 1-2 weeks40-20mg/day decrease by 5 mg/day every 1-2 weeks 20-10 mg/day decrease by 2.5mg/day every 1-2weeks10-0mg/day decrease by1-2.5 mg/day every

Monitor Blood pressure, weight, and glucose every 3 months Lipids (cholesterols and triglycerides) annually Bone density within first 3 months and annually thereafter1-4weeks

Supplemental treatmentBMD measurement needed to be done in the first 3 months and if it decreased or we are treating post menopausal women

supplement treatment neededBut as a role any patient who are on ≥7.5 mg for 6 months, should receive supplement treatment Calcium 1500 mg daily and vitamin D 800 IU daily (all patients on >7.5 mg steroid longer than 6 months)Estrogens (postmenopausal women)Antiresorpative (residronate 2.5 to 5mg/day. Etidronate, Calcitonin) as needed

In selected situations, where immediate effect is needed, some would begin with

IV methylprednisolone at a dosage of 1 gm/day (over 30 to 60 mins to avoid arrhythmia, cardiovascular shock, myocardial infarction, and severe infection) for 3 days and then start oral prednisone.

Typically high-dose oral steroid are continued for no longer than 1 month. If the patient disease worsens on high-dose prednisone, no response after 2-4

weeks, disease no completely quiet after 4 weeks with high-dose oral steroid, or if chronic suppression of disease requires more than 10mg/day of prednisone an immunosuppressive agents should started.

Ocular inflammation varies in their responses to steroid, some do response to short duration oral steroid 3-12 weeks, other need longer duration 6-12 months.

Children’s should not be on steroid longer than 3 months.

Systemic side effect Musculoskeletal

Myopathy Osteoporosis Aseptic necrosis ( pts on 60 mg/day for 1 months or 20mg/day for 6 months have are

associated with 15% 20% risk of aseptic necrosis) Gastrointestinal

?Peptic ulcer ( 2 published studies showed that inc0idence of ulcer doesn’t increase by steroid and the use of H2 blocker is not necessary

Pancreatitis CNS

Psychiatric disorders Pseudotumor cerebri

Ocular Glaucoma Cataract Secondary infection Delay wound healing Mydriasis Ptosis Tissue atrophy

CVS/Renal HTN Na and water retention Hypokalemic alkalosis

Metabolic Ketoacidosis DM Hyperosmolar coma Hyperlipidemia Obesity

Endocrine Growth failure Amenorrhoea Suppression of hypothalamic-pituitary-adrenal system

Suppression of immune system

Agents commonly used to treat autoimmune inflammatory conditionsClass Type of Agen NamesAntimetabolites Folic acid analogue

Purine analogueMethotrexateAzathioprine

Pyrimidine analogueMycophenolate mofetil5 FluorouracilLeflunomide (Arava)

Alkylating agents Nitrogen mustards CyclophosphamideChlorambucil

Natural products Antibiotics

Antibodies

CyclosporineDapsoneTacrolimusMitomycin

Antilymphocytes serumAnti-T-cells antibodiesGamma globulin

Indication of immunosuppressive medicationAbsolute

Behcet disease with retinal involvement Sympathetic ophthalmia VKH RA with necrotizing Scleritis or PUK

Wegener’s granulomatosis Relapsing polychondritis with scleritis JRA OCP Bilateral Mooren’s Serpiginous choroidopathy

Relative Intermediate uveitis Retinal vasculitis Severs chronic iridocyclitis

Questionable Intermediate uveitis in children Sarcoid uveitis High risk graft

Antimetabolites

I. Methotrexate ( Rheumatrex)Mechanism of action

1. Antimetabolite2. Folic acid analogue3. Reversibly inhibit the enzyme Dihydrofolate reducatse (which convert folic

acid to tetrahydrofolic acid which is necessary for DNA replication4. Tissue with a high cellular turnover such as hair follicles, fetal cells,

gastrointestinal lining, bone marrow, and neoplasm are most sensitive5. MTX is excreted unchanged by the kidney6. Dosage doesn’t have to be adjusted in liver disease

Indication1. JRA2. Scleritis secondary to connective disease3. Sympathetic ophthalmia4. systemic SLE, RA, and Psoriatic arthritis

Suggested guidelines for use of MTXInitial doseOral formulation 2.5 mg tablet

most clinicians would start with 7.5mg/week in single Undivided dose, then increase the dose gradually to achieve an

effect. It can be given orally, IM, or IV.usual therapeutic dose is15 mg/week It has slow in onset, it might takes 3 to 4 weeks to see anti-inflammatory effect.

Maximum adult oral dose 25mg/week

Maintenance dose (adult) ≤ 25mg/week

Tapering schedule usually between 2.5-5 mg/week

Monitor CBC and platelet count should be taken every 3-4 weeks WBC <3500 per mm3, and platelet level below 125000 per mm3 may necessitate MTX to be discontinued or stopped LFT must be monitored Q 3-4 weeks (serum transaminase, alkaline phophatase, and bilirubin level), if LFT increased in 2 separate tests, then MTX dose should be reduced or discontinued. If LFT conti to be high after MTX been stopped then liver biopsy is indicated.Some suggest screening for Hep B/C before starting MTXAvoid alcohol

Supplemental treatment Folic acid 1 mg/day.

Contraindication Neutropenia, thrombocytopenia, pregnancy, and breast feeding women

Side effect1. Hepatotoxicity, LFT increase in 15%, but hepatic cirrhosis occurs in only 0.1%2. Neutropenia3. Thrombocytopenia 4. Ulcerative stomatitis, occur in 20% and can be minimized by 5 mg folic acid

weekly5. Pruritis, urticaria, alopecia, and erythema multiform6. Pneumonitis and pulmonary fibrosis7. Teratgenic

II. Azathioprine(Imuran)Mechanism of action

1. Purine analogue2. Metabolized by the liver into 6-mercaptopurine, 3. Immunologically, it decrease the peripheral T and B lymphocytes, and reduce

mixed lymphocytes reactivity, IL2 synthesis, and Ig M production

Indication1. Rarely in ophthalmology but have been tried in Behcet disease for ocular

inflammation in combination with steroid.2. OCP, also in combination with other medication3. SLE, Psoriatic arthritis, Reiter syndrome, and Transplant.

Suggested guidelines for use of AzathioprineInitial doseOral formulation 50 mg tablet

1.5-2.5 mg/kg/day as single dose or BIDsome would start with 2.5-3 md/kg/dayslow onset, up to 3-4 weeksrarely will be effective alone, usually will be used with steroidDose should be decreased if used with allopurinol( because azathioprine metabolism is dependent on xanthine oxidase, which can be inhibited by allopurinol)

Maximum adult oral dose 4mg/kg/day

Maintenance dose (adult) Therapeutic dose usually 2mg/kg/dayTapering schedule Decrease by 25-50mgMonitor CBC, and platelet Q 3-4 weeks

LFT Q 12 weeks ( if LFT increase by 1.5x normal then decrease the dose, if more than that then stop azathioprine)

Supplemental treatmentContraindication Preexisting hepatic disease

Active infectionpregnancy

Side effect1. Neutropenia2. Thrombocytopenia3. Hepatic toxicity <2%4. Malignancy risk esp non hodgkin lymphoma5. GI upset (most common), nausea, vomiting, stomatitis.6. Alopecia

III. Mycophenolate mofetil (Cellcept)Mechanism of action

1. Purine analogue2. Their major effects are on T and B lymphocytes. It prevent lymphocyte

proliferation, suppress antibody synthesis, interferes with cellular adhesions to vascular endothelium, and decrease recruitment of leukocytes to sites of inflammation

Indication1. Limited experience in ocular inflammation hasn’t been used as sole drug,

published studies showed it can be useful if used in combination with either steroid or cyclosporine to control graft rejection or ocular inflammation, the success was measured by being able to reduce the dose of steroid or cyclosporine but not stopping then, while we still control inflammation.

2. Most clinician use it as alternative to Azathioprine or Methotrexate when they are not tolerated

3. Systemic use for renal, cardiac transplant, and RA.

Suggested guidelines for use of CellceptInitial doseOral formulation 250 mg capsule 500 mg capsule 200 mg/ml suspension

500 mg BIDexpected onset 2 weeks to 3 months

Maximum adult oral dose 1.5 gm BIDMaintenance dose (adult) Tapering schedule Monitor CBC weekly for 4 weeks, then every 2

weeks for 2 months then monthlyLFT every 3 months

Supplemental treatmentCaution in patient with renal disorders and GI

problems

Side effect1. Nausea, vomiting, and diarrhea in 31%2. Leukopenia 19%3. Lymphoma 1%4. Non melanoma skin cancer 9%5. Opportunistic infection

Alkylating agents

I. Cyclophosphamide (Cytoxan)Mechanism of action

Nitrogen mustard derivative, alkylating agent Metabolize in the liver to an active metabolite that is capable of alkylating purines

in DNA and RNA, resulting in cross linking. This cross linking result in the inability of DNA to properly separate during cell division, and subsequently the cell dies

Cyclophosphamide inhibits both humoral and cellular immunity

Indication OCP Behcet Necrotizing and non necrotizing Scleritis ( Wegener’s, RA, Relapsing

polychondritis) Sympathetic ophthalmia Serpiginous choroiditis Refractory intermediate uveitis Mooren’s ulcer Systemic diseases…wegener’s granulomatosis (most common use in combination

with steroid), SLE, RA, and cancer.

Cyclophosphamide has rapid onset of action within days, and should be consider in sight threatening conditions, also can be used as IV for immediate effect

Suggested guidelines of use of CyclophosphamideInitial doseOral formulation 25 mg tablet 50 mg tablet

1-5 mg/kg/day as single dose 40-50 mg/kg IV once or twice a week or monthly But in uveitis oral therapy was more effective than IV therapyExpected onset is 2-8weeks

Maximum adult oral dose 3mg/kg/day

Maintenance dose (adult) Therapeutic dose usually 2mg/kg/dayUsually not longer than 6-12 months

Tapering schedule Decrease by 25-50mgMonitor CBC / Platelet q 1week , then after CBC

stabilize, it can be done q 4 weeks (minimum WBC 3000 per mm3,Neutrophils ( minimum 1500-2000 per mm3 )Once CBC decrease dose should decreased, but if WBC < 2500 hold the drugUrine analysis weekly then q 4 weeks for hematuria, which once discovered ,drug will discontinued, if after 4 weeks no resolution then consult urology

Supplemental treatmentContraindication Pregnancy, lactating women

Side effect Leukopenia Thrombocytopenia Lymphopenia Hemorrhagic cystitis can lead to bladder Ca Alopecia in 50%, reversible Malignancy Pulmonary fibrosis GI problems Ovarian suppression ( age <25 yrs risk is 30%, >30 yrs risk is 50%) Testicular atrophy and azospermia

o Cryopreservation of eggs and sperms may considered before starting Tx

II. Chlorambucil (Leukeran)Mechanism of action

Alkylating agent Slower in action than cyclophosphamide Metabolized in liver Clinical response in 3 weeks

Indication Mainly used as steroid sparing agent, esp in patient who cant tolerate

cyclophosphamide Behcet ( most common use in ophthalmology) Sympathetic ophthalmia Leukemia, non hodgkin lymphoma, and ovarian carcinoma.

Suggested guidelines for use of chlorambucilInitial doseOral formulation 2 mg tablet

0.1 mg/kg/day as single dose usually dose will increased by 2mg/day to maximum 18 mg/dayexpected onset 4-12 weeks

Maximum adult oral dose 0.2 mg/kg/day or 18mg/day

Maintenance dose (adult) Therapeutic dose usually 2mg/dayUsually not longer than 6-24 months

Tapering schedule Decrease by 25-50mgMonitor CBC / Platelet q 1week , then after CBC

stabilize, it can be done q 4 weeks (minimum WBC 24003000 per mm3,Platelet ( minimum 100.000 per mm3 )

Supplemental treatmentContraindication Pregnancy, lactating women

Side effect Leukopenia Thrombocytopenia Malignancy

Ovarian failure and azospermia

I. Cyclosporine (Sandimmune, Neoral)Mechanism of action

An oil soluble fungal metabolite Main function to suppress T-cell activation as well as the synthesis of variety of

cytokines, including IL2. The inhibitions of cytokines prevent clonal expansion of helper and cytotoxic T-cells. CsA also inhibits chemotaxis of inflammatory cells, especially eosinophils. Hematopoiesis and phagocytic cell functions are not affected

Metabolized in the liver by cytochrome P450

Indication CsA has been used as sole therapy for uveitis cases with effective results

Found to be superior to Colchicine for Behcet disease in Japan ( dose 10 mg /day)

Found to be similar to steroid in term of efficacy for endogenous uveitis ( dose 10 mg/day)

Was used in combination with oral steroid Behcet disease Bird shot retinochoroidopathy Sarcoidosis VKH Prophylaxis for high risk PKP Stem cells allograft Keratoconjunctivitis sicca Severe allergic eye diseases Necrotizing Scleritis Peripheral ulcerative keratitis Thygeson’s punctate keratitis Renal transplant, RA, and Psoriasis

Suggested guidelines for use of CsA

Initial doseOral formulation Sandimmune 25 , 50, 100 mg capsule 100mg/ml oral suspension Neoral l25, 100 mg capsule(better 100 mg/ml oral suspension absorption)

2.5-5 mg/kg/day divided dosesexpected onset 2-6 weeks

Maximum adult oral dose 10 mg/kg/dayMaintenance dose (adult) Therapeutic dose usually 10mg/kg/day

But this dose is nephrotoxicMost patient would need 2.5-5mg/kg/day + steroid for several years

Tapering schedule Decrease by 0.5-1 mg/kgMonitor Blood pressure, urea, and creatinine should be

checked q 2 weeks for first 3 months, then monthly thereafter, and then need to be checked after doses changeSerum creatinine should not be allowed to increase more than 30%Some clinician monitor CsA blood level

Supplemental treatmentContraindication Pregnancy, lactating women, malignancy, and

compromised renal function

Side effect Nephrotoxicity

o Most seriouso Occur mainly with 10mg/kg/dayo Can be irreversible

HTN Hyperuricemia Hepatotoxicity

o Dose dependent and reversible Parasthesia, temperature hypersensitivity, nausea, vomiting, and tremor Hypertrichosis, gingival hyperplasia, oral ulcer and hirsutism Topical side effect: redness, irritation, tearing, and burning

II. FK506 (Tacrolimus) (Prograf)Mechanism of action

Tacrolimus is a macrolide antibiotic produced by streptomyces tsukubaensis. Inhibit activation of T lymphocytes by mechanism similar to that of cyclosporine

Indication Cyclosporine sparing agent Behcet disease VKH SO Idiopathic retinal vasculitis Organ transplant

Suggested guidelines for use of TacrolimusInitial doseOral formulation 0.5,1,5 mg capsule 5 mg/ml oral suspension

0.05 mg/kg/day as single dose for uveitis0.15-0.3 mg/kg/day for organ transplant

Maximum adult oral dose 0.3 mg/kg/day Maintenance dose (adult) 0.1-0.15% mg/kg/dayTapering schedule Monitor BP monthly

CBC , LFT, Renal function, electrolytes, glucose at least initially

Supplemental treatmentContraindication Pregnancy, lactating women

Should never use with cyclosporine

Side effect Renal impairment 28% Neurological symptoms 21% , headache, tremor, dizziness, forgetfulness, and

seizure GI symptoms 19% Hyperglycemia 13% HTN

DapsoneMechanism of action

Diaminodiphenylsulfone Antibacterial sulfonamide Influence on immune system is unclear Some evidence that it stabilize lysosomal membranes, decreasing the release of

lysosomal enzymes

Indication OCP Leprosy Relapsing polychondritis Malaria Dermatitis herpetiform Cutaneous leishmaniasis

Dose and Route 25 mg BID for 1 week increase by 50 mg per day depending on therapeutic response and drug tolerance Response usually within 4 weeks of initiation of Tx

Contraindication sulfa allergy G6PD deficiency

Side effect Hemolytic anemia

o Dose dependento Most common adverse effecto Always present in dose >200-300 mg/day o Occurs after 4 weeks in normal individualo Occurs earlier and more severely with G6PD deficiencyo G6PD level must be determined before initiation of the therapy

Nausea

Daclizumab (Zenapex)Mechanism of action

IL2 receptor monoclonal antibody Suppress activated lymphocytes

Dose and Route

IV at usual dose of 1mg/kg every 2-4 weeks

Indication Renal transplant rejection Sight threatening intermediate and posterior uveitis in combination with other

immunosuppressive medication. One study only

Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial.

Nussenblatt RB, Fortin E, Schiffman R, Rizzo L, Smith J, Van Veldhuisen P, Sran P, Yaffe A, Goldman CK, Waldmann TA, Whitcup SM.

Laboratory of Immunology, National Institutes of Health, Bethesda, MD 20892-1858, USA. DrBob@intra.nei.nih.gov

To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 receptor mAb (Daclizumab) therapy in the treatment of patients with severe, sight-threatening, intermediate and posterior noninfectious uveitis, a nonrandomized, open-label, pilot study was performed. Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. All patients were able to tolerate the study medications without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2 receptor therapy may be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile.

Clinical trials with daclizumab

Therapy for severe chronic uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. A study recently published in the Journal of Autoimmunology by Nussenblatt et al suggests that intravenous anti-interleukin-2 (IL-2) receptor alpha (daclizumab) therapy remains effective for several years. The study also suggests that the medication can be administered subcutaneously with apparently therapeutic drug levels being attained.

Nussenblatt and colleagues have been studying the efficacy of daclizumab for a number of years. Their first paper on this subject, published in 1999 in the

Proceedings of the National Academy of Sciences USA, described how 10 patients were weaned off other immunomodulators and prednisone and switched to daclizumab infusions every 4 weeks. Patients were treated over a 12-month period, and in 8 of the 10, the therapy appeared to prevent further intraocular inflammatory disease and to result in improved visual acuity.

The current study by Nussenblatt follows these patients in an open-label extension of the initial study. In this study, 7 of the 10 patients completed 4 years of IV therapy, and none discontinued medication because of side effects. The patients did not appear to be susceptible to opportunistic infections. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not.

In another portion of the study, the researchers treated a different group of five patients with subcutaneously administered daclizumab, and found that 4 of 5 could be weaned off their other immunomodulators by 12 weeks, and all patients were weaned off by 26 weeks.

Papaliodis, Chu, and Foster also published a study of treatment with daclizumab in the April 2003 issue of Ophthalmology. In their study, 44% of patients had improvement in visual acuity, and 59% improved based on degree of inflammation.

These data certainly suggest that a randomized clinical trial for daclizumab in uveitis is warranted. Only with further study on a larger patient group (and under masked conditions) can the relative merits and deficits of daclizumab be compared to existing immunomodulators and other biologics, such as infliximab.

REFERENCES:

Nussenblatt RB, Fortin E, Schiffman R, et al. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial. Proc Natl Acad Sci U S A. 1999;96:7462-7466.

Nussenblatt RB, Thompson DJ, Li Z, et al. Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. J Autoimmun. 2003;21:283-293.

Papaliodis GN, Chu D, Foster CS. Treatment of ocular inflammatory disorders with daclizumab. Ophthalmology. 2003;110:786-789.

Etanercept (enbrel)Mechanism of action

Tumor necrosis factor alpha/beta antagonist Competitive inhibitor that bind and inactivate TNF

Indication

RA JRA associated uveitis

Dose and route 0.4 mg/kg , 25 mg SC dose twice weekly

Side effect Infection

Infliximab (Remicade)Mechanism of action

Human-murine antibody to tumor necrosis factor , it neutralize the biological activity of TNF alpha by binding to the soluble and membranous forms of the TNF alpha

Indication Crohn’s RA

Dose and Route IV during a 2 hours period as single dose to achieve control on severe

inflammationo Permanent loss of vision resulting from relapsing ocular inflammation occurs frequently

in patients with Behcet's disease, despite intensive, chronic immunosuppressive therapy. Since tumour necrosis factor (TNF) might have an important pathogenetic role in Behcet's disease, we decided to give a single infusion of infliximab-a monoclonal antibody against TNF-to five patients with relapsing panuveitis, at the immediate onset of last relapse. Remission of ocular inflammation was evident within the first 24 h, and complete suppression was seen 7 days after treatment in all patients. No side-effects were noted. We suggest that infliximab is a rapid and effective new therapy for sight-threatening ocular inflammation in Behcet's disease.

Dose 5mg/kg , second dose can be given after 2 weeks, third dose 4 weeks later, then asses patient response if patient had remission then relapse, u can repeat same regimen, but if there were no remission from the beginning then switch to another treatment.

o PURPOSE: To determine the efficacy and safety of infliximab in the treatment of refractory posterior uveitis. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Five patients with posterior uveitis were treated: 3 had Behcet's syndrome, and 2 had idiopathic posterior uveitis. INTERVENTIONS: Patients with sight-threatening uveitis refractory to other immunosuppressive agents were treated with infliximab. MAIN OUTCOME MEASURES: Intraocular inflammation, by using binocular indirect ophthalmoscopy score, retinal vasculitis, and visual acuity. Adverse effects of infliximab were documented. RESULTS: Within 2 weeks of the first infusion of infliximab, 4 of 5 patients showed marked improvement in vitreous haze and visual acuity. By the 6-month follow-up, the same four patients had achieved remission of

posterior uveitis and had successfully withdrawn all other immunosuppressive therapy. Further infusions of infliximab were required in 3 patients. One patient developed ocular and systemic tuberculosis, which responded to antituberculous treatment. CONCLUSIONS: Infliximab is effective in the treatment of sight-threatening refractory posterior uveitis. However, patients should be thoroughly screened for tuberculosis before treatment and followed up closely during and after therapy with infliximab.

ColchicineMechanism of action

Alkaloid derived from the autumn crocus Colchicum autumnale It has both antiinflammatory and antimiotic properties, mediated mainly through

inhibition of micro tubular formation Depression of neutrophils motility, adhesiveness, chemotaxis, and lysosomal

degranulation

Indication In ophthalmology, it has been used as prophylaxis for ocular and systemic

manifestation of Behcet disease in Japan, either alone or in combination with other immunosuppressive

Gout Psoriasis

Dose and Route 0.5- 0.6 mg orally 2-3 times daily

Side effect GI upset Watery diarrhea Leukopenia Aplastic anaemia Thrombocytopenia Myopathy Alopecia azospermia