from our scientific day

1. By
Hend M. Safwat, M.Sc
TA ophthalmology
Al-Azhar University
2017

2.  Uveitis is a small word, yet the condition itself
can devastate not only the life of patient, but
also the lives of his/her families.
 It is beyond the patient capacity as regard
vision, finance, and psychology.

5.  They inter ophthalmic
intervention by 1950 by
Gordon and McLean.
 Corticosteroids are the
mainstay of therapy.
 They are either topical,
ocular, or systemic.

7. For anterior uveitis, higher-potency drops,
specifically prednisolone acetate 1%,
should be used initially.
Lower-potency topical corticosteroids
should be avoided initially because of the
limited concentrations achieved in the
aqueous.

8. Start with one drop every one to two hours
and do not taper until a two-step
improvement in the grade of inflammation
has been achieved.
If the inflammation has not responded
within a reasonable period of time (i.e., one
month), drops are inadequate treatment
and therapy should be re-evaluated.

9. Local effect depends on many factors:
1- its ability to penetrate cornea, scleral, and
blood-ocular barrier.
2- its relative anti inflammatory potency and
duration of action
3- dose and frequency of administration
4- its side effects

10.  Topical potent steroid
is predinsolone acetate
1% ed, is characterized
by biphasic solubility.
 However, its
suspension form (must
shake before usage)
and frequency of
administration lower it
as 1st class !!

11.  Difluprednate is
diflourinate
predinsolone
derivative that not
inferior to pred.
acetate in power.
 It is emulsion form
and less frequently
administrated (4
times/day).

12.  The most potent drop but
the more ocular side effects
is dexamethasone .
 Flourmetholone and
rimexolone are weak !!
 Loteprednol etabonate(0.5
% suspension) is more or
less potent as predinsolone
but less IOP rise.

13. Uveitis patients are frequently steroid
responders. Since the inflammation must
be controlled, the temptation to reduce
topical corticosteroids should be avoided.
Elevated pressure should be treated with
pressure-lowering drops, reserving
prostaglandin analogs for last because of
their association with inflammation.

14. Steriods are not significant in treatment of
Fuch’s heterochromic iridocylitis.
NSAID’s are the first line of ttt in
episcleritis and scleritis.
Steroids are used in non infectious and
infectious (except the debate around
fungal).

15. Sub conjuctival in non compliant patients
in ant. uveitis !
Subtenon injections of triamcinolone
acetonide ,or orbital floor injections of
triamcinolone or methylprednisolone
acetate are useful in unilateral
intermediate or posterior uveitis, and in the
presence of macular edema.

16.  The dose of every injection is 40mg/ml of TA.
 Repeating injection every 2-4 weeks.
 Failure if successive 4 injections within 8-10
weeks without improvement !
 It’s not potent as intravitreal injection because
of limited diffusion of depot forms through
sclera.
 But associated with sever form of steroid
responding glaucoma (that must ttt by surgical
removal of steroid from subtenon)

17. Off label use of kenacort 40
mg/ml for unilateral IU or PU
especially with CME.
Intravitreal steroids such as
preservative-free triamcinolone
40 mg/ml(Triesence; Alcon,
USA).
It can be repeated every 3 ms.

18.  Ozurdex (Allegan, Irvine, CA,
USA), a 0.7 mg intravitreal
dexamethasone implant, can be
used in intermediate and posterior
uveitis, with effects lasting 3 to 6
months.
 Retisert (Bausch & Lomb) is a
corticosteroid implant over 2.5 ys
(with 0.59 mg fluocinolone
acetonide) which is associated with
high rates of glaucoma and
cataract.
 Iluvien (Alimera Sciences), a 0.19
mg fluocinolone acetonide implant,
is still undergoing clinical trials.

19.  is a 0.4 mm × 0.21 mm
titanium helical non
biodegradable implant
that contains 0.925 mcg
triamcinolone acetonide. It
is intended for a sustained
delivery of 2 years. The
helical design increases
the surface area for drug
release and stabilizes the
device onto the sclera .

20.  MUST(multicenter uveitis steroid
treatment) trial is a randomized clinical trial
that compared the safety and effectiveness of
an intraocular fluocinolone cetonide implant
versus standard oral therapy among 255
patients with intermediate, posterior or
panuveitis.
 After 2 years, the vision of patients receiving
either treatment had improved similarly.
 It was established as an equivalent alternate
to systemic steroid therapy.

23.  Systemic steroids should be considered in patients
with bilateral involvement, severe uveitis, lack of
response or contraindications to periocular steroids.
 When systemic disease is present that also requires
treatment or for vision-threatening uveitis that is
poorly responsive to other methods of delivery, oral
or intravenous therapy is necessary.
 The most widely used systemic steroids for uveitis
are oral prednisolone and intravenous
methylprednisolone.

24. Prednisolone is usually initiated at a dose
of 1-1.5 mg/kg/day, while intravenous
methylprednisolone is dosed at 500-1000
mg/day for 1-3 days followed by oral
prednisolone, and tapered by 5-10 mg a
week according to clinical response until
the lowest dose for maintenance.

25. A short-term course of oral prednisone is
sometimes needed, in addition to drops or
injections for acute flares of uveitis.
Prolonged therapy with prednisone,
especially at doses greater than 10 mg
daily, can have significant side effects

27.  A stepwise approach in applying
corticosteroid sparing immunomodulatory
therapy to achieve durable, corticosteroid-free
remission is the standard of care.
 Immunomodulatory therapy is indicated for
acute non-infectious uveitis that is refractory
to high-dose corticosteroids for >2 weeks, or
inability to taper down prednisolone.

30. Never in infectious form of uveitis or
pediatric uveitis.

31.  Methotrexate has been widely
used in ophthalmic diseases,
systemically and locally. It has
been used for the treatment of
recurrent intraocular lymphoma.
 It was also used in the treatment
of non infectious ocular
inflammation: anterior uveitis,
intermediate uveitis, posterior or
panuveitis, scleritis, ocular
mucous membrane
pemphigoid , as well as
advanced proliferative diabetic
retinopathy .

32.  Local treatment of ocular inflammation via
intravitreal injection is preferred when possible,
especially for unilateral diseases. Intravitreal
MTX avoids systemic toxicity, and can provide
consistent therapeutic drug concentrations .
 Also, intravitreal MTX is able to maintain
therapeutic doses in the vitreous humor for
5 days.
 400 μg/0.1 ml were performed once monthly
for 3 months.

33.  A phase 3, double-masked,
multinational trial found that
low-dose sirolimus (rapamycin)
injected every 2 months can
reduce vitreous haze in non-
infectious posterior uveitis, with
low rates of ocular side effects.
 Sirolimus is a bacteria-derived
immunosuppressant that
inhibits the activation of T cells
and B cells and reduces
cytokine production.
 2 different doses of intravitreal
sirolimus (880 μg or 440 μg).

35. In animal models, the successful use of
intravitreal cyclosporine has been reported
in inflammatory eyes.
It was found that there were no toxic effects
in any animals treated with ⩽100 μg of
intravitreal cyclosporine.
Suprachoridal (deep lamellar scleral
pocket) cyclosporine implants now are
under trial .

36.  CsA eye drops have
recently been
approved by FDA for
use in dry eye
disease.
 Experience with CsA
eye drops has shown
little benefit in their
use for uveitis.

37.  Voclosporin: calcineurin inhibitor is more similar to CsA
than to a single functional group.
 It has been evaluated in phase 3 studies for use in non
infectious uveitis and has been found to be four times
more potent than CsA in vitro and in vivo studies.
 The adverse events of voclosporin have been found to be
much less than those of CsA.
 Additional phase 3 studies of voclosporin in active, non
infectious, intermediate, posterior, or panuveitis are being
conducted for approval by the FDA.

39.  Biologic response modifiers commonly referred to as
biologics, is a term used to describe therapeutic
proteins designed to block the activity of bioactive
mediators of the immune response.
 most notably recombinant antibodies and antibody-
derived proteins.
 Monoclonal antibodies (mAb), when used as
medications, are given a generic name ending in "-
mab" An antecedent "u"(-umab) indicates a human
antibody; "xi"(-ximab) indicates a mixed human-murine
antibody. Fusion proteins, which typically contain either
receptor domains or cell surface markers, are given a
generic name ending in "-cept."

41.  They initially developed to treat systemic inflammatory
diseases or to prevent organ transplant rejection, but have
been used off-label to treat uveitis or ocular inflammation.
 The preponderance of literature describing biologic
treatment of uveitis is with the tumor necrosis factor
inhibitors (infliximab, etanercept and adalimumab),
followed by the IL-2 receptor (IL2-R) blocker
daclizumab.

43.  A mixed monoclonal antibody
(mAb) composed of human-
murine sequences.
 Infliximab has been used
successfully in children with non
infectious uveitis.
 There are also excellent results
reported in adults with Behcet
(BD), and other causes of
posterior uveitis and scleritis.
 In Japan, recent studies have
supported the use of infliximab as
first-line therapy for BD.

44.  Besides BD and JIA, infliximab has been
reported anecdotally to be effective for the
treatment of uveitis associated with multiple
conditions, including IBD, AS,
psoriasis, sarcoidosis, Vogt- Koyanagi-
Harada disease, and Takayasu disease.
 It may also be effective to treat birdshot
retinochoroidopathy, recalcitrant uveitic
cystoid macular edema, pars planitis,
multifocal choroiditis, HLA-B27-related
anterior uveitis, and idiopathic uveitis.

45. Serious side effects include
myelosuppression, demyelinating
neurological disorders (eg, multiple
sclerosis), infectious diseases, activation
of latent infections (TB and HBV),
malignancies and immunological
disorders, such as drug-induced SLE and
immune hypersensitivity reactions.

46. Experimental animal models showed that
intravitreal injections of infliximab were
tolerated up to 2.0 mg. However, doses
higher than 3.3 mg may be potentially toxic
to the retina.
 Beer et al. suggested that infliximab may
be suitable for compounding and could be
a cost-effective intravitreal medication for
use in clinical practice.

48.  Etanercept is a genetically
engineered fusion protein of
TNF receptor p75.
 There have been few case
series reporting successful use
of etanercept in uveitis. Other
trials reported no difference in
inflammatory indices between
groups treated with etanercept.
 Given its low efficacy,
etanercept is not currently
being used often in
management of uveitis and
ocular inflammatory disease.

49.  Adalimumab (Humira)
is a fully human
monoclonal antibody
against TNF-á.
 Due to its promising
results and
subcutaneous route of
administration,
experience in both
rheumatologic and
ocular indications is
growing.

50.  Several reports have demonstrated a successful use
of adalimumab in management of BD, severe forms of
VKH syndrome, JRA-associated uveitis and idiopathic
pediatric uveitis.
 The most common side effect associated with
adalimumab is injection-site reaction (10%).
 It is relatively safe and tolerable with rare serious side
effects, including serious infections, lymphoma,
tuberculosis, herpetic keratitis, opportunistic infections,
demyelinating diseases, drug-induced SLE, elevated
hepatic enzymes and congestive heart failure.

51. HUMIRA is now the first and only FDA-
approved non-corticosteroid therapy
available for adults with non-infectious
intermediate, posterior and panuveitis.
It found be effective in off-label treatment
of pediatric uveitis and scleritis as well.

52.  Intravitreal Humura is still
off-label but with
promising results.
 Intravitreal injections of
adalimumab
2.0 mg/0.08 mL.
 No ocular side effects
were reported following
intravitreal injections of
adalimumab.

53.  Daclizumab is a recombinant mAb that
targets interleukin-2 (IL-2) receptors of
activated T- and B-lymphocytes, consequently
inhibiting the IL-2 signaling pathway.
 One trial found no benefits of daclizumab in
treating posterior inflammation associated with
BD.
 Another found that daclizumab allowed
control of inflammation with low-dose
corticosteroids or other immunosuppressive
agents in intermediate and posterior uveitis.
 Serious side effects reported with daclizumab
use were rare; however, it has been
discontinued in the United States. According
to the manufacturer, this decision was based
on the availability of alternative treatments and
the diminishing market demand.

54.  A recombinant human mAb
targeting the interleukin 1
(IL-1) receptors.
 Anakinra down regulates
the IL-1-mediated immune
response through
competitive inhibition of IL-
1 receptors of T- and B-
lymphocytes and NK cells.

55.  It is not commercially
available .
 Therapy with AIN457,
an anti-IL-17 antibody
given either
systemically or via
intravitreal injections,
reduces inflammation
in mouse models of
uveitis.

56.  INF-α and INF-β are cytokines that have an
important role in treating severe sight-
threatening uveitis.
 INF-α, which is naturally secreted in response
to viral infection, is categorized into INF-α 2a
(Roferon-A®) and INF-α2b (Intron-A®).
 INF therapy can cause severe adverse effects
including sarcoidosis. Thus, this therapy is not
recommended for the treatment of sarcoid-
related uveitis.

57.  INF-β has been
successfully used in
treating intermediate
uveitis associated with
multiple sclerosis,
choroiditis, and
choroidal
neovascularization in
chronic recurrent
punctate inner
choroidopathy.

58.  the only report of intravitreal interferon
alpha-2b use in human,
Kertes et al. evaluated long-term effects
and safety of a single injection of 100,000
IU of the drug in two cases of neovascular
age-related macular degeneration.
 They did not report any clinical ocular or
systemic adverse effect; however, in both
treated eyes, they observed a marked
generalized reduction in the amplitude of
the bright-flash dark-adapted
electroretinogram.

59.  Intravenous immunoglobulin (IVIG) therapy
involves the use of immunoglobulin mixtures.
 It has multiple mechanisms of
immunomodulatory action and is used to treat
various autoimmune, infectious, and
idiopathic diseases
 According to a retrospective study it can treat
active non-infectious uveitis refractory to
steroids and immunomodulatory therapy.
 But treatment failed to induce long-term
remission .

60. Intravitreal either off-label
Avastin or on-label
Lucentis and Elea are
highly indicated in uveitic
CME and
neovascularization (2ry to
choroiditis)

63.  Ocular gene therapy offers advantages over biologic
agents by mediating long term therapeutic gene
expression without the potential risk of systemic side
effects.
 The cytokines interferon alpha (IFN-α), interleukin (IL)-10
and the IL-1 receptor antagonist (IL-1Ra) have all been
demonstrated to have anti-inflammatory effects. A few
reports have shown that gene therapy with virus vector
encoding the IL-1Ra or IL-10 gene can significantly
ameliorate experimental uveitis.
 Furthermore, Tsai et al. investigated the effectiveness of
adeno-associated virus 2 (AAV2)-Mediated Subretinal
Gene Transfer of human IFN-α in experimental
autoimmune uveoretinitis (EAU), with promising results.

64.  Although gene therapy
is a very attractive
therapeutic option, gene
therapy applied to
uveitis remains a
challenge, because its
success is highly
dependent on the gene
delivery system and on
the stability of
transgene expression.

65.  RNA interference (RNAi), a powerful tool for gene
silencing, is a process within living cells that moderates
the activity of their genes.
 Small-interfering RNAs (siRNAs) bind to the specific
messenger RNA (mRNA) molecules and decrease their
activity or trigger mRNA degradation to prevent mRNA
from producing inflammation proteins.
 The first clinical trials of RNAi were directed at the
treatment of age-related macular degeneration (AMD)
and respiratory syncytial virus infection.
 Nowadays, RNAi has been shown to be of great value in
decreasing ocular inflammation.

66.  In recent years, intravitreal injection of non-
steroidal anti-inflammatory drugs (NSAIDs)
has been under clinical investigation and
some are commercially available.
 ketorolac and diclofenac have potent anti-
inflammatory effects after intraocular injection
but they are rapidly cleared by 48h.
 Dose of a 4µg intravitreal injection is safe in
ocular disease.

67. Several reports are available in the
ophthalmic literature that address the issue
of therapeutic vitrectomy as a means of
moderating intraocular inflammation.
Vitrectomy may debulk the antigenic
stimulus in the eye, thus reducing
intraocular inflammation and CME, and
allow tapering or elimination of systemic
therapy.

68.  While the theoretical advantages of
vitrectomy in chronic uveitis seem apparent,
and although the body of evidence is growing,
the quality of the evidence is weak.
 Likewise, as polymerase chain reaction
(PCR) becomes more widely used,
diagnostic vitrectomy will be performed
more regularly to confirm or establish a
diagnosis and to guide therapy.