Treatment of uveitis
•AST injection if
Unilateral inf lammation
If no response
unilater al
•Topical steroids
•If no response after 2-3 weeks or
f requent topical application needed t
o control inf lammation
Add oral NSAID if
mild recurrence , despite
low dose of topical steroid
No resons e
Multiple injection
needed
bilateral
Oral Corticosteroids
Mild cases controlled with
Low dose prednisone
15 mg/day or less
Sev ere inf lammation
Begin high dose and taper
No change may
continue long term
Non emergent
Emergent risk of
Immediate visual loss
Mild cases requiring
Moder ate inf lammation
more than 15 mg/day
f or more than 6-12 months despite corticosteroid therapy
•Add MTX or AZA
•Taper Pre dnisone to 15
mg/day
•Continue f or 6-12 months
•CsA may substitute f or MTX or
AZA
Especially on young patients
who may want to hav e children
Cy clophosphamide
•Add cyclophosphamide Or chlorambucil
•Slowly taper Prednisone f or 3months-1y ear
•Add CsA
•Continue f or 6-12 months
•Consider adding MTX or
AZA if Prednisone cannot be
To 15 mg/day
Suggested treatment scheme, one possible stepwise approach to ocular inflammation
Non steroidal anti-inflammatory
drugs
Phospholipids
inhibit
corticosteroids
Phosphlipase A2
Arachidonic acid
NSAIDs
Inhibit
Cyclo-oxygenase
Lipoxygenase
Endoperoxidase
Thromboxane A2
Prostacy clin
PGE2
PGF2
PGd2
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 uveitis
o 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-selective
o Selective COX2 inhibitor
 Celebrex 100-200 mg BID
 Vioxx 12.5-25-50 mg qd
Side effect
 Topical
o Irritation
o Keratitis
o Infiltrate
o Thinning
o Perforation
 Systemic
o GI
o CNS
o Hematological
o Renal
o Hepatic
Corticosteroids
Mechanism of action
The 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)
Tapering schedule
≤ 10mg/day
over 40mg/day, decrease by 10 mg/day
every 1-2 weeks
40-20mg/day decrease by 5 mg/day every
1-2 weeks
20-10 mg/day decrease by 2.5mg/day every
1-2weeks
10-0mg/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 treatment
BMD measurement needed to be done in
the first 3 months and if it decreased or we
are treating post menopausal women
supplement treatment needed
But 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


Psychiatric disorders
Pseudotumor cerebri





Glaucoma
Cataract
Secondary infection
Delay wound healing
Mydriasis
CNS
Ocular




 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 conditions
Class
Antimetabolites
Type of Agen
Folic acid analogue
Purine analogue
Names
Methotrexate
Azathioprine
Mycophenolate mofetil
5 Fluorouracil
Leflunomide (Arava)
Pyrimidine analogue
Alkylating agents
Nitrogen mustards
Natural products
Antibiotics
Cyclophosphamide
Chlorambucil
Cyclosporine
Dapsone
Tacrolimus
Mitomycin
Antibodies
•AZA
•Mycophenolate mofetil
Antilymphocytes serum
Anti-T-cells antibodies
Gamma globulin
MTX
Alkylating agents
Purine
Ribo nucl eo tid e
Deox yri bo nucl eoti de
DNA
RNA
Pyramidine
5 Fluorouracil
Leflunomide (Arava)
IL 2
Activated
CD4 cell
CD4 cell
CsA
B-cell
Corticosteroi
Site of action of immunosuppressive agents
Prot ein
Indication of immunosuppressive medication
Absolute
 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. Antimetabolite
2. Folic acid analogue
3. Reversibly inhibit the enzyme Dihydrofolate reducatse (which convert folic
acid to tetrahydrofolic acid which is necessary for DNA replication
4. Tissue with a high cellular turnover such as hair follicles, fetal cells,
gastrointestinal lining, bone marrow, and neoplasm are most sensitive
5. MTX is excreted unchanged by the kidney
6. Dosage doesn’t have to be adjusted in liver disease
Indication
1.
2.
3.
4.
JRA
Scleritis secondary to connective disease
Sympathetic ophthalmia
systemic SLE, RA, and Psoriatic arthritis
Suggested guidelines for use of MTX
Initial dose
Oral 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 MTX
Avoid alcohol
Folic acid 1 mg/day.
Supplemental treatment
Contraindication
Neutropenia, thrombocytopenia,
pregnancy, and breast feeding women
Side effect
1. Hepatotoxicity, LFT increase in 15%, but hepatic cirrhosis occurs in only 0.1%
2. Neutropenia
3. Thrombocytopenia
4. Ulcerative stomatitis, occur in 20% and can be minimized by 5 mg folic acid
weekly
5. Pruritis, urticaria, alopecia, and erythema multiform
6. Pneumonitis and pulmonary fibrosis
7. Teratgenic
II. Azathioprine(Imuran)
Mechanism of action
1. Purine analogue
2. 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
Indication
1. Rarely in ophthalmology but have been tried in Behcet disease for ocular
inflammation in combination with steroid.
2. OCP, also in combination with other medication
3. SLE, Psoriatic arthritis, Reiter syndrome, and Transplant.
Suggested guidelines for use of Azathioprine
Initial dose
1.5-2.5 mg/kg/day as single dose or BID
Oral formulation 50 mg tablet
some would start with 2.5-3 md/kg/day
slow onset, up to 3-4 weeks
rarely will be effective alone, usually will
be used with steroid
Dose 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)
Tapering schedule
Monitor
Therapeutic dose usually 2mg/kg/day
Decrease by 25-50mg
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 treatment
Contraindication
Preexisting hepatic disease
Active infection
pregnancy
Side effect
1. Neutropenia
2. Thrombocytopenia
3. Hepatic toxicity <2%
4. Malignancy risk esp non hodgkin lymphoma
5. GI upset (most common), nausea, vomiting, stomatitis.
6. Alopecia
III. Mycophenolate mofetil (Cellcept)
Mechanism of action
1. Purine analogue
2. 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
Indication
1. 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 Cellcept
Initial dose
Oral formulation 250 mg capsule
500 mg capsule
200 mg/ml suspension
Maximum adult oral dose
Maintenance dose (adult)
500 mg BID
expected onset 2 weeks to 3 months
1.5 gm BID
Tapering schedule
Monitor
Supplemental treatment
Caution
CBC weekly for 4 weeks, then every 2
weeks for 2 months then monthly
LFT every 3 months
in patient with renal disorders and GI
problems
Side effect
1. 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 Cyclophosphamide
Initial dose
1-5 mg/kg/day as single dose
Oral formulation 25 mg tablet
40-50 mg/kg IV once or twice a week or
50 mg tablet
monthly
But in uveitis oral therapy was more effective
than IV therapy
Expected onset is 2-8weeks
Maximum adult oral dose
3mg/kg/day
Maintenance dose (adult)
Tapering schedule
Monitor
Supplemental treatment
Contraindication
Therapeutic dose usually 2mg/kg/day
Usually not longer than 6-12 months
Decrease by 25-50mg
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 drug
Urine analysis weekly then q 4 weeks for
hematuria, which once discovered ,drug will
discontinued, if after 4 weeks no resolution
then consult urology
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 chlorambucil
Initial dose
0.1 mg/kg/day as single dose
Oral formulation 2 mg tablet
usually dose will increased by 2mg/day to
maximum 18 mg/day
expected onset 4-12 weeks
Maximum adult oral dose
0.2 mg/kg/day or 18mg/day
Maintenance dose (adult)
Tapering schedule
Monitor
Therapeutic dose usually 2mg/day
Usually not longer than 6-24 months
Decrease by 25-50mg
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 treatment
Contraindication
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 dose
Oral 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 doses
expected onset 2-6 weeks
Maximum adult oral dose
Maintenance dose (adult)
10 mg/kg/day
Therapeutic dose usually 10mg/kg/day
But this dose is nephrotoxic
Most patient would need 2.5-5mg/kg/day +
steroid for several years
Tapering schedule
Monitor
Decrease by 0.5-1 mg/kg
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 change
Serum creatinine should not be allowed to
increase more than 30%
Some clinician monitor CsA blood level
Supplemental treatment
Contraindication
Pregnancy, lactating women, malignancy, and
compromised renal function
Side effect
 Nephrotoxicity
o Most serious
o Occur mainly with 10mg/kg/day
o 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 Tacrolimus
Initial dose
Oral formulation 0.5,1,5 mg capsule
5 mg/ml oral suspension
Maximum adult oral dose
Maintenance dose (adult)
Tapering schedule
Monitor
Supplemental treatment
Contraindication
0.05 mg/kg/day as single dose for uveitis
0.15-0.3 mg/kg/day for organ transplant
0.3 mg/kg/day
0.1-0.15% mg/kg/day
BP monthly
CBC , LFT, Renal function, electrolytes,
glucose at least initially
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
Dapsone
Mechanism 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 dependent
o Most common adverse effect
o Always present in dose >200-300 mg/day
o Occurs after 4 weeks in normal individual
o Occurs earlier and more severely with G6PD deficiency
o 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
inflammation
o
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 sightthreatening 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 sightthreatening 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.
Colchicine
Mechanism 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