Yong Meng Hsien Lecturer & Ophthalmologist, UKM & HCTM, Malaysia yongmenghsien@ppukm.ukm.edu.my Last edited: Feb 202

1. Ophthalmic
Inflammatory Diseases
Dr Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM
yongmenghsien@ppukm.ukm.edu.my
Last edited: Feb 2022

2. Classification & Key Factors
• Orbital vs Ocular
• Systemic vs Local
• Infectious related or not
• Vasculitis related or not
• Chronicity and risk of recurrence

3. Orbital
• TED
• Non specific orbital inflammation
• Myositis
• Tolosa Hunt
• Bell’s palsy
• Trochleitis

4. Ocular
• Ocular surface
• MMP, GVHD
• VKC
• Scleritis
• Cornea
• Keratitis
• PUK, Mooren
• Graft rejection
• DLK diffuse lamellar keratitis post LASIK
• Uveitis
• TASS post surgery
• CMO/DME +-CNV
• Optic neuritis
• Vasculitis- small, medium, large vessels
• GCA, CTD

5. Inflammation ←→Infection
• FHU ← → CMV/rubella
• Eales dz (vasculitis) ← → TB
• Possner Schlossman ← → CMV
• GBS ← → Corynebacterium (GIT)
• POHS   Histoplasmosis

7. ImmunoModulator (IMT)
• Stimulant (IF/IL)
• Immunosuppressant
– Corticosteroid
– Antimetabolite (AZT/MTX/MPM)
– T cell/calcineurin inhibitor (CSA/Tacro-Siro-limus)
– Alkylating agents (cyclophosphamide/chlorambucil)
– Biologic (TNF-a AG, IL-1/IL-6 AG, IFN-a, IVIg)

8. Prednisolone
• Initiation
• 1 mg/kg/day up to a maximum of 60 mg/day
• range 0.5-2mg/kg/day
• >60 mg/day = increased risk of ischemic necrosis of bone
• IVMP 1g x 3d: if need immediate control, followed by oral steroid +-
IMT, avoid rapid IV (<30min) arrhythmia/MI/ifx
• Taper
• After 2 to 4 weeks
• of control/resolve/improve
• Target dose is =/<7.5mg/day
• Still increased risk of CVD
• 5 mg/day x 22yr
• 7.5 mg/day x 15yr

9. Prednisolone
• Flare/Exacerbation
• TRO ifx/non adherence/DDx/rapid taper with rebound
• If tapering  resume a higher dosage for another
month or until the disease is quiet  taper back to just
above the threshold at which the disease reactivated
• Taper slower/longer if =/<7.5mg OD <3mth still
• IMT if >7.5mg OD >3mth already
• Stop with remission
• hypothalamic–pituitary axis may not return for 6 to 12
months after tapering for chronic cases  adrenal crisis

10. Prednisolone- AE/Monitor/Supplement
• Short-term: ifx, BP, DXT
• Long-term: immune, bone, cushing, psychosis
• Eye: IOP, cataract, ifx
• Metabolic: HPT, fluid retention, DM, hyperlipidemia, atherosclerosis
• Cushingoid (moon facies, weight gain, fat redistribution, and increased acne)
• Immune: Infection
• Bone Skin: Osteoporosis, easy bruising, and poor wound healing, delay growth <15yo
• Psy: Anxiety, sleeplessness, mood changes
• Monitor
• BP and blood glucose q3mth
• Bone BMD yearly
• Lipid profile yearly
• Supplement
• 1500mg Ca, 800 IU Vit D daily (esp 1st 6-mth- greatest bone loss)
• If BMD=osteoporosis  antiresorptive e.g. calcitonin/alendronate
• H2 blockers for patients taking prednisone is unnecessary ?PPI

11. IMT- IndiC
Therapeutic needs, Uveitis type, Severity
• Steroid-sparing:
– prolonged steroid >3mth & >7.5mg/day
– SE, intolerate
– Poor response
– worsens on high-dose
– no response after 2-4wk
– better but not quiet after 4 wk of high dose
– relapse despite 7.5mg OD
• Initial Rx in:-
– Poor natural history
– OCP with ocular involvement
– Behcet with posterior segment involvement
– SO/VKH, serpiginous choroiditis, Birdshot
• Systemic protection
– necrotizing scleritis & PUK with systemic vasculitis
– Severe advanced inflammatory damage
– Reserved as 2nd line:
• SE & cancer risk
• bladder cancer (cyclophosphamide), leukemia, lymphoma, non melanoma skin
cancer (AZT & CSA for postTx case) and, possibly, overall cancer.

12. IMT- How to choose
• Availability/cost  AE vs efficacy
• Antimetabolite
• MMF & AZT- most effective
• AZT vs MMF – least & best tolerable
• MTX- best for paeds, worst for fetus
• MTX- not for hepatitis or alcoholic
• T cell inhibitors
• CSA- less effective vs antimetabolite
• > combination therapy w antimetabolite
• Not for CKD
• Alkylating
• most potent & potentially remission-inducing
• BUT most SE/cancer risk, IV pulse or oral daily

13. IMT- Pre & Starting
• baseline vital organ function (liver/kidney/BM)
• screen for active/latent infectious diseases
• TRO pregnancy & chance
• history of malignancy & testing for TB & HIV before
biologic therapy
• Administration
• bridging with steroid (wk-mth)- high dose if active/relapse, same
dose if stable
• Taper of steroid after 4-8wk
• monitoring blood tests (1wk-2wk-4wk-2mth-3mth)
• DDX inadequate suppression/ifx due to over suppression
– Other systemic features of ifx VS inflam
– Lymphocyte count 0.8-1.2 = adequate

14. IMT- Increase, Combine & Taper
• Step up dose
• Dose escalation: low dose  increments every 4-6weeks  optimal
dose
• Rapid incrementation: low dose  2wk to assess tolerability 
max/optimal dose (esp for MTX & MMF)
• Combination
• Antimetabolite + CSA
• Alkylating usually solo
• Antimetabolite + biologic
• Taper/off IMT/2nd line
• Usually after off the oral prednisolone
• Usually >3yr use & >2yr stable/control for non-alkylating
• Usually >3yr use & >1yr stable/control for alkylating
• Taper slowly with long duration each of step (3-6mth)

15. IMT- No response
• TRO:
• treatment nonadherence
• infections (syphilis, TB, vira)
• masquerade syndromes incl lymphoma
• Dose step-up, combine, switch

16. IMT in Pregnancy
• CI in pregnancy: cyclophosphamide, chlorambucil
and methotrexate.
• Esp MTX (category X)
• even in a male patient who may impregnate someone
• Evan also CI for BF
• use two forms of birth control.
• at least three months after it is stopped.
• But very good for paed uveitis/JIA
• Use topical/regional medication if possible
• Pregnancy = progresterone more = more anti-
inflammatory  but post partum flare

17. IMT- Paeds
• MTX
• +- CSA
• Growth
• should not receive live virus vaccine (MMR vaccine,
varicella-zoster virus vaccine, oral polio vaccine, BCG) while
on therapy for 3 months after stopping therapy or > 20 mg
prednisone daily
• If possible, varicella-zoster vaccine should be given before
the start of therapy.
• systemic viral diseases, they should receive a yearly
influenza vaccine, and if susceptible, varicella-zoster virus
immune globulin upon close exposure to chickenpox.
• If CD4 <200 cells per ml, consider P. carinii prophylaxis.

19. Azathioprine (Imuran)
• Purine (A&G) analogue
• MOA: activated to 6-mercaptopurine (6-MP) by thiopurine
S-methyltransferase (TPMT, enzyme activity = Rx response)
→ false coding → - DNA replication/RNA transcription
• Dose: start 50 mg/day x 1wk → most effective at
2mg/kg/day (aim)  3-4mg/kg/day (unusual)
• IndiC:
– Ocular: Behçet disease (1st)/VKH/SO, IU, necrotizing scleritis,
Wegener
• SE:
– GI (25%), BMS/pancytopenia, hepatotoxic (2%) → FBC/LFT!!
– Use lower dose if +allopurinol
– LFT q12 weeks. When toxicity occurs (> 1.5 times upper limit of
normal), the dose should be decreased by 25 to 50 mg per day, and
LFT 2 weeks. If > 5x upper limit  discontinued

20. Methotrexate
• Preferably 1st choice for paeds uveitis & sarcoidosis
• Folic acid analogue
• MOA: - dihydrofolate reductase (DHFR) → - thymidylate/purine
synthesis → - DNA/RNA/AA & adenosine release (anti-inflammation)
• IndiC:
– Systemic CTD esp RA, sarcoidosis
– Ocular esp JIA & paeds uveitis (1st line!), scleritis
– Lymphoma
• Dose
– Weekly dose: 2.5mg-7.5mg weekly, 10mg (Start) → 15mg (aim)  25mg
(max) (need 6wk for effect  6/12 to peak effect)
– + folinic acid/folate 1mg OD (except on day of MTX)
– IVT 400ug for refractory uveitis/uveitic CME
• SE
– GI (10%), BMS, hepatotoxic (15%), teratogenic → FBC/LFT/no pregnant/no
hepatitis/no alcohol, or need to stop >3/12 before pregnant!, double
contraceptive

21. Mycophenolate Mofetil/MMF (CellCept)
• Preferably 1st choice for adult uveitis
• Active: MPA (mycophenolic acid)
• MoA: -inosine monophosphate dehydrogenase → -
purine synthesis/DNA replication
• IndiC:
– chronic uveitis @adult/paeds esp Wegener
• Dose:
– 250mg BD  500mg BD (start) 1g BD (aim)  1.5g BD
(unusual)
– fast to peak effect (4mth)
• SE:
– relatively safe- >GI/esp diarrhea, less BM suppress, reduce
contraception effect, 1st trimester risk, renal toxic

22. Cyclosporin
• Preferably as add-on after antimetabolite
• Fungal Baeuveria
• MOA: - T cell signal → - transcription of IL/cytokines
• Indication:
– systemic: CTD (RA/SLE), nephrotic syndrome
– ocular: VKC/AKC/rosacea/blepharitis, uveitis/graft vs host,
dry eye, Behcet (2nd)
• Dose
– RA: start 1mg/kg BD (50-100mg/day) → step up q4wk →
max 2mg/kg BD  2.5mg/kg BD (unusual)
– Excrete biliary
• SE: HPT, renal/neuro-toxic, gingival hyperplasia →
BP/RP/LFT/FBC!! +Mg/lipid profile

23. Tacrolimus & Sirolimus
• Fungal Streptomyces
• Tacro= calcineurin inhibitor (-T/-IL)
– Dose: 0.05–0.15 mg/kg/day
– Vs CSA: lower dose/more potent/less SE (still need
FBC/RP)
• Siro= non-calcineurin inhibitor (-T/-AB & B
cell)

24. Cyclophosphamide
• Alkylating agent
• most potent & potentially remission-inducing
• MOA: cross link/alkylate purine (>G) of DNA → cytotoxic/- rapid
proliferating/mitosis cells → - T/B cell
• IndiC:
– Systemic: CTD esp SLE/Wegener/GPA/vasculitis/RPC
– Ocular: Mooren, MMP, Behcet/VKH/SO
• Dose
– Oral OD, or pulse IV monthly (oral > effective than pulse IV)
– Oral 2mg (1-3)/kg/day (peak effect 1yr) --> dose is adjusted to achieve a
white blood count in the 3000 to 4000 cells/ml range when the patient
is not taking prednisone.
– Treatment is continued for 1 year and then tapered to determine if a
remission has been induced
• SE
– cystitis/hematuria, sterility, teratogenic, malignancy risk (leukemia/bladder
CA), BMS/leucopenia, increase IOP
– Monitor: FBC/UFEME & drink >2L H2O
– Opp ifx: +- PCP  consider bactrim prophylaxis

25. Chlorambucil
• Alkylating agent
• Dose: 0.1–0.2 mg/kg/day adjust similar to
cyclophosphamide
• “high-dose, short-term”: start at 2 mg/day 
escalated weekly until uveitis controlled or bone
marrow suppression  treatment is discontinued;
the mean maximum dose with this approach is 20
mg/day
• Less SE/risk of cancer
• SE: BMS, sterility, teratogenic → FBC!

26. Infliximab (Remicade)
Adalimumab (Humira)
• TNF-alpha inhibitor
• IndiC:
– JIA, AS/spondyloarthropathies/HLA B-27
– idiopathic uveitis/behcet (2nd)/VKH/SO
• Administration
– Infli- IVI 5-8mg/kg @ D1/wk2/wk6 then q8wk
– Adali- subcutaneous 80mg stat  40mg weekly x1  40mg q2wk
• SE
– Malignancy  cervical CA (need yearly pap smear)
– Ifx  TB reactivation → Mantoux/CXR + for prophylaxis!
FBC/HepB/HepC/HIV screen
– Worsen MS
– New hypersensitivity/autoimmune dx  lupus, demyelinating dz, VH
– CCF, thrombosis
– less BMS

27. Others Biologic Agents
• Rituximab: B cell/CD 20 inhibitor
• Anakinra: IL-1 inhibitor
• Tocilizumab: IL-6 inhibitor
• IFN-alpha 2a/2b: antiviral, immunomodulatory,
and antiangiogenic effects

28. Common Treatment ladder
• Steroid
• Topical for surface or anterior
• Systemic for posterior or systemic associated
• Supratarsal for ocular surface/VKC
• Subtenon or orbital floor or IVT for IU/PU
• IMT
• Biologic

29. Out from common Rx ladder
• Infection related- anti-microbial first/together
• Scleritis- oral NSAIDs first
• MMP- oral dapsone first
• TED/NSOI- pulse IVMP
• PUK/Mooren- conj recession& resection
• VKC- CSA first, pulse topical steroid
• Demyelinating O-neuritis- 1g 3day + 10mg’kg
11days then stop

30. Topical steroid
• high potency and penetration  prednisolone
acetate or prednisolone phosphate, difluprednate
• surface activity  fluorometholone, loteprednol

31. PPI or H2A with steroid? Or No
need

32. Taper
• When resolved?
• When improved?

33. TPA (tissue plasminogen activator)
• IVT (experimental) for
• occluded pars plana glaucoma tube (case report, blocked despite systemic steroid, successfully restore GDD flow)
• 30-gauge needle 3.5 mm posterior to the limbus. A total of 0.1 cc (12.5 μg) was injected.
• Intraop displacing submacular hemorrhages, reducing post-vitrectomy fibrin formation, and maintaining patent
inferior iridectomies in eyes with silicone oil
• in both animal studies and one human case report, photoreceptor toxicity was noted following 50 μg of
intravitreal tPA
• most authors agree that intravitreal application of rtPA should be restricted to concentrations of 50 to 100 g/mL
to avoid toxic effects
• subconjunctivally and intracamerally following glaucoma surgery
• Intracameral
• fibrinous exudates encountered in uveitic patients
• a dose-dependent toxic effect of rtPA on HCECs, with significant cell death at concentrations higher than125
g/mL
• intracameral tPA for occluded or near-occluded limbal glaucoma drainage devices with 89% of subjects
(n = 36) achieving success
• mean of 1.6 injections with a mean mean ± SD tPA dose per injection was 9.8 ± 3.1 µg
• only used tPA on patients who had a visibly occluded or visibly near-occluded tube, defined as fibrin or blood
within 2 mm of the tube tip.
• complications (severe hyphema, hypotony, anterior chamber flattening), which all occurred after
injections that were administered within 5 days after glaucoma surgery.