7. Anti-inflammatory agents
Treatment : stop inflammation
Use anti-inflammatory drugs
Most potent of such agents : Corticosteroids
Corticosteroids are the mainstay of therapy in
uveitis
6/21/2019Dr. Mohd N Khan
8. Complicating the issue
What if the cause is infectious--Specific anti-
infective agent is indicated and
Corticosteroids may even worsen the
infection when given alone
When the cause is immune related--
Corticosteroids will be effective but
Associated side effects maybe significant
6/21/2019Dr. Mohd N Khan
9. Finding the etiology
Narrow down list of differentials by history
and examination
Appropriate investigations (ocular and
systemic)
Referrals for systemic associations
Treating the inflammation by Specific therapy
or Non-specific therapy
6/21/2019Dr. Mohd N Khan
10. Few ocular investigations
Fundus fluorescein angiogram --Cystoid
macular edema (complication) • Serpiginous
choroidopathy (pattern of lesion)
OCT –-To assess macular edema
Ultrasonography --Especially in cases of
media opacities Ocular tissue analysis
Aqueous tap • Vitreous tap • Chorioretinal
biopsy
6/21/2019Dr. Mohd N Khan
11. Commonly ordered tests
Compete blood count (TLC & DLC)
Bacterial/Viral pathology/Malignancy
ESR—Non specific for inflammation
C-reactive protein
Rheumatoid Factor
Other tests depending on clinical suspicion
6/21/2019Dr. Mohd N Khan
12. Few Systemic investigations
Sarcoidosis-- Chest X-ray (Hilar
Lymphadenopathy), Serum Angiotensin
Converting Enzyme (ACE) but not specific,
raised serum calcium
Tuberculosis-- Mantoux test (Purified Protein
Derivative), QuantiFERON-TB Gold (QFT-G),
raised serum calcium
Syphilis – Non specific:VDRL & Rapid Plasma
Reagin (RPR), Specific:FTA-ABS & MHA-TP
6/21/2019Dr. Mohd N Khan
18. To preserve visual acuity
To relieve ocular pain
To eliminate the ocular inflammation or
identify the source of inflammation
To prevent formation of synechiae
To manage intraocular pressure.
6/21/2019Dr. Mohd N Khan
19. Specific – etiology dependent
Tuberculosis-- ATT
Syphilis-- Parenteral penicillin
Toxoplasmosis--Sulfa and pyrimethamine &
intravitreal clindamycin (1 mg/0.1ml) with
dexamethasone (0.4 mg/0.1ml)
Lyme disease—Tetracyclines
Acute retinal necrosis– I/V Acyclovir
CMV retinitis--IV Ganciclovir
6/21/2019Dr. Mohd N Khan
20. I. Corticosteroids: Corticosteroids are the first
line of therapy in patients with
noninfectious ocular inflammatory diseases.
Local delivery of corticosteroids:
Topical corticosteroids
Iontophoresis
Periocular injections
Intravitreal injections and inserts
Systemic oral steroids (oral and intravenous)
6/21/2019Dr. Mohd N Khan
21. II. Immunosuppressants
III. Biologics
IV. Adjuvant therapy: Cycloplegics
Newer nonsteroidal anti-inflammatory agents
Anti-vascular endothelial growth factor (anti-
VEGF) therapy
6/21/2019Dr. Mohd N Khan
22. To relieve pain by immobilizing the iris
To stabilize the blood-aqueous barrier and
help prevent further protein leakage (flare).
To relieve ciliary spasm and pain
To prevent posterior synechiae
break the ones already formed
Cycloplegia relieves pain and a mobile pupil
prevents posterior synechiae
6/21/2019Dr. Mohd N Khan
23. Atropine, 0.5%, 1%, 2%
Homatropine, 2%, 5%
Scopolamine, 0.25%
Cyclopentolate, 0.5%, 1%, 2%.
Phenylephrine, 2.5%, is an adrenergic agonist
that causes dilation by direct stimulation of
the iris dilator muscle. Because
phenylephrine has neither a cycloplegic nor
anti-inflammatory effect and may cause a
release of pigment cells into the anterior
chamber, it is generally not recommended as
an initial part of the therapeutic regimen.
Phenylephrine may, however, help break
recalcitrant posterior synechia.
6/21/2019Dr. Mohd N Khan
24. Cycloplegic & Mydriatics
Shorter acting --Tropicamide eye drops
(effective up to 3 hrs) & Cyclopentolate drops
(up to 24 hrs)
Longer acting --Homatropine eye drops (up
to 4 days) & Atropine eye drops (up to 7-14
days)
6/21/2019Dr. Mohd N Khan
25. The mainstay of therapy
Depending on the site of inflammation and
severity Topical Periocular Systemic
Topical drops will not be effective for
intermediate, posterior and panuveitis
‘Use enough soon enough’
To always start with a higher dose and taper
before stopping
To investigate before starting
6/21/2019Dr. Mohd N Khan
27. Elevation of IOP
Susceptibility to infections
Impaired corneal
Scleral wound healing
Corneal epithelial toxicity
Crystalline keratopathy
6/21/2019Dr. Mohd N Khan
28. Methylprednisolone Prednisone
What class is it? corticosteroid corticosteroid
What are the brand-
name versions?
Medrol, Depo-Medrol,
Solu-Medrol
Rayos
Is a generic version
available?
yes yes
What forms does it
come in?
oral tablet, injectable
solution*
oral tablet, oral
solution
What is the typical
length of treatment?
short-term for flare-
ups, long-term for
maintenance
short-term for flare-
ups, long-term for
maintenance
Is there a risk of
withdrawal with this
drug?
yes yes
6/21/2019Dr. Mohd N Khan
29. A noninvasive method of application of low
current to an ionizable substance (drug) to
increase its mobility across a surface by
electrochemical repulsion.
Dexamethasone phosphate (40 mg/ml, EGP-
437) is a prodrug and is a good candidate for
iontophoresis delivery, as it possesses two
acidic protons (pK values of 1.9 and 6.4)
The Eye Gate II Delivery System (EGDS) is a
novel ocular iontophoresis system designed
to deliver substantial levels of drug
noninvasively into the anterior segments of
the eye while minimizing systemic
distribution.
6/21/2019Dr. Mohd N Khan
31. Increased IOP
Glaucoma
Ptosis
Cataract
Inadvertent globe perforation
6/21/2019Dr. Mohd N Khan
32. Triamcinolone acetonide - 4 mg in 0.1 ml,
The effects are usually short-lived and may
last for 6–8 weeks
Retisert (Bausch and Lomb)-Fluocinolone
acetonide 0.59 mg, requires a surgical
procedure to suture the implant to the scleral
wall, that achieves sustained release of
approximately 2.5 years, 90% risk of cataract
formation in phakic patients and about 40%
of patients will have to undergo glaucoma
surgery after 3 years of drug exposure
6/21/2019Dr. Mohd N Khan
33. Ozurdex(Allergan)-Dexamethasone
intravitreal implant, 0.7 mg, a sustained
release of dexamethasone over 3–6 months,
given intravitreally via an injector
Side effects include cataract, increased IOP,
glaucoma, retinal detachment, vitreous
hemorrhage, and endophthalmitis
6/21/2019Dr. Mohd N Khan
34. The Multicenter Uveitis Steroid Trial—which
compared Retisert with immunomodulation
therapies—
reported comparable visual acuity outcomes
with more control of inflammation in the local
therapy arm of the study
but a higher rate of ocular complications with
the fluocinolone acetonide intravitreal
implant.
6/21/2019Dr. Mohd N Khan
37. In corticosteroid resistant or intolerant cases
In vision threatening inflammations - as first
line
Specific cases -- Behcet’s syndrome
Sympathetic ophthalmitis
VKH syndrome
Necrotizing sclerouveitis
Adverse reactions can be severe and life
threatening
6/21/2019Dr. Mohd N Khan
38. Steroid-sparing drugs are efficacious,
Methotrexate, azathioprine, mycophenolate
mofetil, and cyclosporine were all evaluated in
the Systemic Immunosuppression Therapy for
Eye Disease Study.
“All of the drugs show roughly the same
efficacy—about 60% to 70%—for the achieving
steroid-sparing dose of less than 10 mg
prednisone daily
These drugs have serious adverse effects but
not be as frequent as many believe
6/21/2019Dr. Mohd N Khan
40. Being studied and the drug is effective for
treating intermediate and posterior uveitis.
Corneal toxicity, however, is a possibility with
the 0.4-mg dose.
The optimal dose remains unknown.
A recent study from Moorfields Eye Hospital
(Retina. 2013;33:2149-2154) reported that
70% of patients who responded to one
methotrexate injection had extended
remission of non-infectious uveitis.
6/21/2019Dr. Mohd N Khan
41. American Uveitis Society (2014;121:785-796)
recommended these drugs as first-line
therapies and as steroid-sparing therapies in
patients with Behçet’s disease
To be used early in the treatment of juvenile
idiopathic arthritis in patients for whom
methotrexate was not successful
6/21/2019Dr. Mohd N Khan
43. Difluprednate (Durezol, Alcon Laboratories) is
a difluorinated corticosteroid emulsion that
was approved to treat anterior uveitis.
It is especially potent, excellent penetration
and can treat uveitic cystoid macular edema
even in phakic patients.
“However, a substantial risk for elevated IOP
and cataract formation, especially in children.
It requires close monitoring.
6/21/2019Dr. Mohd N Khan
44. Sirolimus (Santen Pharmaceuticals), a mammalian
target of rapamycin inhibitor similar to
cyclosporine and tacrolimus, is in a phase III trial
for local ophthalmic use. The 6-month results of
the Sirolimus (SAVE trial) showed encouraging
results.
Voclosporine (LX211, Lux Biosciences)—a
cyclosporine–family calcineurin inhibitor—was
tested in a phase III trial of uveitis that required
steroid-sparing drugs. The drug did not meet its
endpoint of decreased vitreous haze, and the
new drug application was withdrawn.
6/21/2019Dr. Mohd N Khan
45. Rituximab (anti-CD20, Rituxan, Genentech)
for scleritis and granulomatosis with
polyangiitis and rheumatoid arthritis,
AIN457 (anti-interleukin 17) (Novartis
Pharmaceuticals).
Other biologics that may have off-label uses
for uveitis are oclizumab, toclizumab,
certolizumab, canakinumab, abatacept,
golimumab, and tofacitinib.
6/21/2019Dr. Mohd N Khan
46. Bromfenac ophthalmic solution 0.09%: It can
be used (twice daily dosage) as either
monotherapy or as an adjunct therapy to
steroids.
Nepafenac 0.1%: It is a prodrug. It penetrates
the cornea six times faster than diclofenac. It
is converted to Amfenac in ocular tissues. It
has been approved for thrice daily dosage
beginning 1 day before cataract surgery.
6/21/2019Dr. Mohd N Khan
51. HUMIRA is administered by subcutaneous
injection INITIAL DOSE 80 mg FOLLOWED BY
40 mg given every other week starting 1
week after the initial dose
6/21/2019Dr. Mohd N Khan
52. Cataract surgery --If no active inflammation
for at least 3 months, Perioperative steroids,
Heparin surface modified IOLs
Glaucoma --Anti-glaucoma topical
medication, Peripheral iridotomy / iridectomy
in iris bombé, Trabeculectomy with
mitomycin C or 5 fluorouracil, AGV
6/21/2019Dr. Mohd N Khan
53. Cystoid macular edema --Control of
inflammation with corticosteroids or NSAIDs
Pars plana vitrectomy if persistent vitritis and
Vitreous Opacification
Hypotony --Intensive corticosteroids and
cycloplegia
Pars plana membranectomy for cyclitic
membrane
6/21/2019Dr. Mohd N Khan
55. 35 yr old male –in right eye
Ciliary congestion
Fine KPs, AC flare
pupil round
Posterior synechiae and
Hypopyon
Similar history of redness a year ago
spot.com
6/21/2019Dr. Mohd N Khan
56. Management
History and examination to narrow the
differentials – nothing significant
The core lab tests – Mantoux highly
significant
Referral to pulmonologist – confirm diagnosis
of tuberculosis
Co-management
6/21/2019Dr. Mohd N Khan
57. Ocular management
Topical corticosteroids --Prednisolone eye
drops hourly, tapered as per response
Homatropine/Cyclopentolate eye drops 3
times a day
Follow up for Inflammation Intraocular
pressure Complications
Systemic management --Anti-tuberculosis
therapy
6/21/2019Dr. Mohd N Khan
58. 3 year old girl –
Fever of unknown origin 1 month
Redness both eyes1 week
Eye examination Spill-over anterior uveitis
Anterior vitreous exudates / snowballs
Systemic examination --Lymphadenopathy
6/21/2019Dr. Mohd N Khan
59. Management
Lymph node biopsy --Caseating
granulomatous lesions
Physician diagnosis -- tuberculosis
Systemic management -- ATT
fever responded within 4 days
6/21/2019Dr. Mohd N Khan
60. Ocular management
On 1 week follow up
Vision drop of 2 lines
Systemic corticosteroids under cover of ATT
for short period (1mg/kg body wt of
prednisone, tapered and stopped within 4
weeks)
6/21/2019Dr. Mohd N Khan
61. 35 year old –
HIV positive female
Sudden painless loss of vision RE
Ocular examination --Spill over fine KPs and
CMV retinitis in the fundus
CD4 count – 50
6/21/2019Dr. Mohd N Khan
62. CMV retinitis – granular retinal necrosis,
frosted branch angiitis
Management with Antiretroviral therapy
Induction --I/V Ganciclovir 5mg/kg body
weight/ bid – 2 weeks
Maintenance – 5mg / kg body weight/day
6/21/2019Dr. Mohd N Khan
