Uveitis-Update-2024-Ramana-Moorthy (1).pdf-33333

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1. Clinical Update on Uveitis
Ramana S. Moorthy, MD FACS
Associated Vitreoretinal and Uveitis Consultants
Founding Partner
Clinical Professor of Ophthalmology
Indiana University School of Medicine
Indianapolis, Indiana

2. Financial Disclosure
I have no financial interests or relationships to disclose.

3. What is the purpose of Uveitis
Evaluation?
Assess current situation to determine acute,
recurrent, or chronic disease
–Important for prognostication
Find the etiology
–Infectious or Non- infectious
–Important Systemic Disease association and
Identification, Syndromes

Identify disease related complications

4. History
History – “ is everything”
–“Those who do not take a thorough history
will be lost in the fog of uveitis ignorance.”
–Speak with the patient
Time consuming
Teasing out relevant and contextual facts from
“Noise”

5. History
–HPI –Particulars
Timing –onset, duration, course
Inciting events
Associated non-ocular symptoms, illnesses
Treatment –past and current
–PMHx
Systemic Disease history
Medications
–PSHx
Ocular
Non-Ocular

6. Review of Systems
Integumentary

7. Review of Systems
Mucosal

8. Review of Systems
Pulmonary
–Fatigue
–Dyspnea
–Chronic Cough
–Fevers
.Karunanithi S, et al. Indian J Nucl Med (2015 Jan-Mar)

9. Review of Systems
Gastrointestinal
–Abdominal pain
–Chronic diarrhea with blood
–Bouts of tenismus

10. Review of Systems
Genitourinary – recurrent UTIs, Hematuria
Musculoskeletal – patterns of arthritis
Zoonotic/arthropod exposure – Cats, biting
insects
Travel history – knowledge of endemic
infectious diseases

11. Examination - TOOLS NEEDED

12. Examination
The Uveitis Specialist must be a master of the ophthalmic (and systemic)
examination
Periocular Skin / Motility/ Confrontational VF/ Pupils (APD, LND)–often
forgotten
Conjunctiva – often forgotten – granulomas (Biopsy) , KS lesions
Corneal – herpetic disease
AC – flare and cell – highest intensity illumination for cells
–Follow consistent grading schemes – SUN criteria
Iris – synechiae (PAS and PS) fresh or chronic; nodules; transillumination,
loss of crypts; rubeosis
Lens – PSC; inflammatory membranes
Gonioscopy – often forgotten – essential in Uveitic Glaucoma management

13. Anterior Uveitis: Signs
Acute
–Limbal injection
–KP (fine,tiny)
–AC reaction (may have
hypopyon)
–Posterior synechiae, PAS
–IOP often low
Chronic
–Usually no injection
–KP (large, medium)
–AC reaction (more flare)
–Posterior synechiae, PAS
–IOP often high
13
Photographs courtesy of Debra A. Goldstein, MD and Ramana S. Moorthy MD.

14. Examination
Vitreous – cells and haze – differentiate pigment, RBC, and WBC
Retina and choroid
–Inflammatory Lesions – active, old, combination
–Complication of disease – CME; CNV; NVE/NVD; ERM
Optic Nerve
–Lesions
–Cupping
–Pallor

15. Systemic Examination
Other parts of the body – Do we really
have to?... YES!!
Skin
Mucosa
Joints – axial and peripheral
Other – as indicated by history and Review
of Systems

16. What is the Diagnosis?
Still not sure?
–Pattern Recognition
Toxoplasmosis – unilateral, focal choroditis
VZV/HSV anterior uveitis – corneal scars, iris atrophy, IOP increased, diffuse KPs
Late onset endophthalmitis – Pseudophakia, history, capsular opacities
Aspergillus endophthalmitis– necrotic granuloma in posterior pole and “hyaloidal hypopyon” )
CMV retinitis – one of four patterns – “pizza pie”, granular, brushfire, frosted branch angiitis
Toxocariasis – peripheral granuloma, focal macular granuloma, diffuse endophthalmitis

17. What is the diagnosis?
Non-Ocular Clinical Clues
–Cutaneous
Vesicular and/or dermatomal rash
–HSV/VZV
Palmar or plantar exanthematous rash
– Secondary syphilis
Erythema chronicum migrans
– Lyme borreliosis
Photographs (1 and 2) courtesy of Debra A. Goldstein, MD
Photo 3 – Wiki-commons : Orig Uploader Jongarrison

18. Hypopyon
Photograph Copyright to American Academy of Ophthalmology – Focal Points

19. Vitritis
Photograph Copyright to American Academy of Ophthalmology – Focal Points

20. Toxoplasma Retinochoroiditis

21. Tuberculous Uveitis
21
Photograph courtesy of Debra A. Goldstein, MD

22. Tuberculosis:
Tuberculous Serpiginoid Choroditis

23. Ocular Bartonellosis
23
Photograph courtesy of Debra A. Goldstein, MD

24. Cytomegalovirus Retinitis
(© 2006 Ramana S Moorthy MD. Used by permission.)

25. NecrotizingHerpetic
Retinitis
25
(© 2006 Ramana S Moorthy MD. Used by permission.)

26. ANCA positive – Necrotizing Scleritis / Relapsing Polychondritis

27. Imaging – Qualitative and Quantitative Data
OCT retina
–CME
–CNV : SRF/IRF
–EDI – Quantitate Choroidal inflammation
RSFA
–UWF – looks for signs of vascular leakage, ischemia, NV
–Diseases with characteristic findings
ICG
–Choroidal inflammatory diseases
Ultrasound
–Bscan – media opacity
–UBM – evaluation of UGH

28. Synthesize Data
Summarize the patient’s condition in a one line statement
–e.g. 27 year old male with hypopyon uveitis, MCP joint redness, and
patchy psoriatic skin rash over extensor surfaces
Problem focused search for etiology
–If you think of something that you forgot based on your exam and
imaging, go back and ask and/or look again.
–This is a work in progress

29. Laboratory Testing
TESTING IS ONLY SUPPORTIVE OF YOUR PRESUMPTIVE
DIAGNOSIS
–TESTING IS NOT A SUBSTITUTE FOR HISTORY AND
EXAMINATION
YOU CAN NEVER GO WRONG WITH BASIC TESTING
–SST – SARCOID, SYPHILIS, TB
Remember – YOU GET MORE THAN ONE CHANCE
UVEITIS WORK UP EVOLVES WITH DISEASE
COURSE
LOOK FOR OTHER CAUSES IF SYSTEMIC OR
OCULAR CIRCUMSTANCES WARRANT

30. Lab Testing
DO NOT ORDER TESTS THAT WILL
NOT HELP
–SLE and RA are clinical diagnoses – labs only
support
•ANA ; Rh F - Not a part of uveitis work up in
adults unless the patient has scleritis or retinal
vasculitis
–E.g. If a patient has a hypopyon anterior uveitis, do
not order HLA-A29

31. Invasive Laboratory testing
AC tap – ln Office
–PCR
Standard - HSV, VZV, CMV, Toxoplasma
more advanced Next Generation Sequencing (NGS); multiplex PCR
–Low risk - High Yield in selected cases
e.g. unilateral hypertensive uveitis
e.g. Necrotizing herpetic retinitis – ESSENTIAL – AFFECTS THERAPY
Vit tap – better performed in OR – Formal PPV
–Cytology, flow cytometry, Advanced immunohistochemical/ genetic testing – MYD 88 testing, PCR
for infectious entities
–Speak to pathologist before surgery
Tell them the clinical history and what you are looking for
Retinochoroidal biopsy – advanced PPV techniques

32. DIAGNOSIS : WHAT NOT TO
MISS…
Do not miss the diagnosis of Necrotizing herpetic retinitis
Do not miss the diagnosis of Syphilitic Uveitis
Do not miss the diagnosis of Tuberculous Uveitis
Do not miss the diagnosis of systemic vasculitis syndrome (ANCA positive)
Do not miss the diagnosis of Primary CNS Lymphoma
Do not miss the diagnosis of paraneoplastic uveitic syndromes associated
with advanced cancer – Small cell lung cancer, Cutaneous Melanoma
Do not miss other non-neoplastic masquerade syndromes
–Chronic retinal detachment
–Hereditary retinal dystrophies

33. What is the most important reason for performing a diagnostic work-
up of a uveitis patient?
1.To determine if the etiology autoimmune
2.To determine if topical steroids can be used safely
3.To determine if systemic immunosuppressives are needed
4.To determine of the etiology is infectious or non-infectious

34. Uveitis : Diagnostics
Etiology of Uveitis
–Infectious
–Non-Infectious
–Neoplastic

35. Uveitis : Advances in diagnostics
PCR – Polymerase
chain reaction – 1985
(Saiki et al.)
–Amplify specific region of
DNA of a single pathogen
by many orders of
magnitude in a short time
with a small sample
–Ideal for ocular samples
(often less than 1ml)
–Qualitative and Quantitative

36. Uveitis: Advances in Diagnostics
Multiplex PCR
–Qualitative analysis only
–Detect many different target genomic DNAs at one time
Panbacterial, panfungal, panviral, (Panpathogen)
–High sensitivity so High false positives due to contamination
Real-Time PCR
–Quantitative analysis – DNA copy number
–Broad-range real-time PCR –
Detect bacterial (16s rDNA) and fungal (18s or 28s rDNA)
Use conserved genomic regions of many different species of bacteria and
fungi

37. Uveitis : Advances in Diagnostics
Metagenomic Deep
Sequencing
–Broad identification of all
possible pathogens in a
sample
–Useful since not all pathogens
can be grown and cultured
–Needs many primers from a
large databank
–Rapid diagnosis

Environmental
Shotgun Sequencing
(ESS).
(A)Sampling from
habitat;
(B)Filtering particles,
typically by size
(C)Lysis and DNA
extraction;
(D)cloning and library
construction;
(E)sequencing the
clones
(F)sequence assembly
into contigs and
scaffolds.
Doan T, Wilson MR, Crawford ED, et al. Illuminating uveitis: metagenomic deep sequencing
identifies common and rare pathogens. Genome medicine 2016; 8(1): 90.

38. Uveitis : Advances in Diagnostics
21
st
century uveitis practice example of real- time multiplex PCR testing
–aqueous and vitreous samples
–panel of 9 common infectious uveitis pathogens (HSV1, HSV2, VZV, HTLV1,
HHV6, EBV, CMV, Toxoplasma gondii, and T. pallidum).
–Specificities and sensitivities >98% .
–The intent of the authors was to test a real time PCR that would provide high
level of fidelity to more expensive quantitative PCR instrumentation and
techniques. Operational fidelity was achieved when compared to qPCR with
correlation coefficient of r=0.838.
Nakano S, Tomaru Y, Kubota T, et al. Evaluation of a Multiplex Strip PCR Test for Infectious Uveitis: A
Prospective Multicenter Study. Am J Ophthalmol. 2020;213:252- 259.

39. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Indications
–Noninfectious ocular inflammatory disease
–Other diseases in which an inflammatory component exists, if
therapy directed against the primary etiology is also used (e.g.,
infectious disease)
Paradigm – Goal of Therapy
–Control of the inflammation
Eliminate the risk to vision from the structural and functional
complications resulting from uncontrolled inflammation
39

40. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Paradigm – Choice of Agent
–Based on a careful consideration of
Specific diagnosis
Concurrent ocular or systemic disease
Existing level of ocular function compromise
Monocular vs binocular disease
Patient desires
40

41. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Paradigm – Initial Therapy
–The initial goal of therapy
Control of inflammation rapidly
–Corticosteroids - most effective agent
Topically, regionally, and systemically
41

42. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Paradigm – Initial Therapy
–Corticosteroids - most effective agent
The Multicenter Uveitis Steroid Treatment Trial (MUST), a randomized, controlled,
superiority trial, comparing systemic anti-inflammatory therapy, versus fluocinolone
acetonide implant for intermediate, posterior and panuveitis was conducted and
recently published the following results
–In each treatment group, mean visual acuity improved over 24 months, with
neither approach superior, to a degree detectable with the study's power
–The specific advantages and disadvantages identified based on individual
patients' particular circumstances, should dictate selection between these two
alternatives
–Systemic therapy with aggressive use of corticosteroid- sparing
immunosuppression, was well tolerated
For certain conditions such as mild scleritis, non-steroidal anti- inflammatory agents
may be used instead of corticosteroids
42

43. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
–Certain conditions indications for the early initiation of immunomodulatory
therapy
Strongly consider early initiation in:
–Behçet’s with posterior segment, vision threatening involvement
–Sympathetic ophthalmia
–Necrotizing scleritis with systemic association
–Serpiginous choroidopathy with vision threatening involvement
Some consider early initiation for other conditions such as
–Birdshot uveitis; Juvenile Idiopathic Arthritis Associated chronic
uveitis, steroid-dependent; Multifocal Choroiditis with Panuveitis;
Vogt Koyanagi Harada Disease
43

44. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
–Tapering of Initial Therapy
If control of inflammation is achieved with initial therapy and
disease is considered to be of acute or limited duration, then an
appropriate taper of the initial agent(s) is warranted
If disease activity recurs with taper, then the dose of corticosteroid
at which the flare occurred determines whether long-term
corticosteroid therapy (baseline DEXA scan and bone preservation
measures implemented) or second line therapy is used.
–If control is not achieved with initial therapy, then transition to second
line therapy
44

45. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Paradigm – Second Line Therapy
–In chronic disease not controlled at a safe dose of corticosteroid
(actually, there is no chronic dose of systemic corticosteroid considered
by bone specialists to be safe for chronic use)
–acute or limited duration disease in which initial corticosteroid therapy
failed to achieve control
–individuals unable to tolerate doses of initial therapy
–Multiple drug classes and agents - data from randomized controlled
trials generally lacking
–Selection of agent is thus based on a consideration of an individual
patient’s comorbidities
45

46. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
–Drug Classes (as new agents are continually being developed and
released, this list may be incomplete). Refer to each individual agent’s
monograph for a complete discussion
Antimetabolites
–Methotrexate
–Azathioprine
–Mycophenolate mofetil or mycophenolic acid
Calcineurin inhibitors
–Cyclosporine
–Tacrolimus
–Sirolimus
46

47. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
–Alkylating agents
Cyclophosphamide
Chlorambucil
–Biological response modifiers
Infliximab
Adalimumab
Etanercept
Tocilizumab
Rituximab
Intravenous Immunoglobulin
47

48. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Paradigm – Beyond Second Line Therapy
–If use of initial and second line therapy are ineffective in controlling
inflammation
Considerations of the individual needs for each patient should guide
choices
–Options may include
Medical
–Combination IMT - multiple drugs from more than one class of
drugs
–Surgical therapy in specific uveitic entities ( i.e. therapeutic
PPV in pars planitis)
48

49. Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease
Special Considerations
–Pregnancy testing: As part of the systemic work-up, prior to
initiating systemic immunosuppressive therapy, a pregnancy test
should be done
–Vaccine recommendations
Patients receiving anti-TNF therapy should not have live
vaccines, including, but not limited to varicella zoster, oral
polio, or rabies vaccination, and the influenza vaccine made
with a live virus
49

50. Clinical Trials in Uveitis – NEI/NIH
Multicenter Uveitis Steroid Treatment (MUST) Trial
- RCT, Open label,
–Compare standard systemic therapy to fluocinolone
implant – outcomes, complications
Systemic Immunosuppressive Therapy for Eye Diseases
(SITE) Cohort Study – Retrospective
–Specific therapies, complications, and cancer mortality

51. Which of the following statements are true regarding corticosteroid
therapy for non-infectious uveitis?
1.The fluocinolone intravitreal steroid implant provides superior
quality of life compared to systemic immunosuppressive therapy.
2.Periocular corticosteroids are more likely to cause significant
elevations in IOP compared to intravitreal dexamethasone implant.
3.All local (periocular and intravitreal) corticosteroid therapies can
cause IOP elevation.
4.Corticosteroid therapy is not a first line therapy for non-infectious
uveitis

52. MUST :Steroid Implant vs. Systemic Therapy
NIH funded RCT that asked : Which is better for
treatment of chronic non- infectious uveitis?
Systemic therapy (steroids + IMT) - better visual
outcomes at 7 years (7 letter gain) compared to
Fluocinolone implant with comparable QOL and
safety data.
1.Kempen JH, Altaweel MM, Holbrook JT, Sugar EA, Thorne JE, Jabs DA. Association Between Long-Lasting Intravitreous
Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With
Intermediate, Posterior, or Panuveitis. Jama 2017; 317(19): 1993-2005.

53. Fluocinolone Acetonide Insert :
Yutiq
Phase 3 randomized multi- center clinical trial of Fluocinolone acetonide INSERT 0.18mg
(Yutiq)
Non-infectious intermediate, posterior, or panuveitis
-Significantly greater duration to first recurrence compared to sham (657 vs. 70.5 days)
-Fewer recurrences (1.7 vs. 5.3) 36 months after insertion
-Less need for adjunctive treatments
-Less macular edema (57.5% of treated vs 97.6% sham eyes)
-More frequent cataract surgery (74% vs 24%),
-LESS frequent need for glaucoma surgery (5.7% vs 11.9%) compared to sham group.
-This study confirms the utility of yet another potent local therapy in the uveitis arsenal.
Jaffe GJ, Pavesio CE. Effect of a Fluocinolone Acetonide Insert on Recurrence Rates in Noninfectious Intermediate, Posterior, or Panuveitis: Three-Year Results.
Ophthalmology 2020; 127(10): 1395-404. doi: 10.016/j.ophtha.2020.04.001. Epub Apr 17.

54. POINT Trial
Objective: To evaluate the comparative effectiveness of
three regional corticosteroid injections for uveitic macular
edema: periocular triamcinolone acetonide (PTA),
intravitreal triamcinolone acetonide (ITA), and the
intravitreal dexamethasone implant (IDI).
Design: Multicenter randomized clinical trial: 73 eyes 40
mg PTA ( day 0 and then every 8 weeks), 79 eyes 4 mg
IVTA(PF) ( day 0 and every 8 weeks), 78 eyes Intravit
0.7mg Dexamethasone Implant ( day 0 and every 12 weeks)
Participants: Patients with uveitic macular edema;
Thorne JE, Sugar EA, Holbrook JT, Burke AE, Altaweel MM, Vitale AT, Acharya NR, Kempen JH, Jabs DA; Multicenter Uveitis Steroid Treatment Trial Research Group. Periocular Triamcinolone vs.
Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) Trial.
Ophthalmology. 2019 Feb;126(2):283-295.

55. POINT Trial
Results: All treatment groups demonstrated improved CST during follow-up.
–At 8 weeks, reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which
translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively).
–Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, 99.87% Confidence Interval [CI]: 0.79,
0.65–0.96) and IDI (PropBL IDI/PropBL PTA, 99.87% CI: 0.69, 0.56–0.86) had larger reductions in CST
than PTA (p <0.0001).
–Intravitreal dexamethasone implant was non-inferior to ITA at 8 weeks (PropBL IDI/PropBL ITA,
99.87%CI: 0.88, 0.71–1.08).
–Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic
macular edema.
–All treatment groups demonstrated BCVA improvement throughout follow-up.
–Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than the PTA group at 8
weeks (p <0.004).
–The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the
periocular group (Hazard ratio [HR], 95% CI: 1.83, 0.91–3.65 and 2.52, 1.29–4.91 for ITA and IDI,
respectively);
however, there was no significant difference between the two intravitreal treatment groups.
Conclusions: Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic macular
edema with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal
treatments.

56. POINT Trial 24 week data
PTA – 73 eyes –
–36 eyes 2
nd
inj at 8 weeks
–4 eyes – 3

injections
–1 eye – 4

injections
IVTA – 79 eyes
–38 eyes 2
nd
injection
–8 eyes 3
rd
injection
–2 eyes 4
th
injection
–1 eye 5
th
injection
All treatments improved CST but Vision improvement and CST
improvement best with Intravitreal therapy (IVTA=DEXImplant)
Intravitreal therapies more likely to cause IOP>
24 compared to PTA

57. Steroid-sparing immunosuppressive agents increase the risk of
cancer mortality.
1.True
2.False

58. Do Immunosuppressive agents
increase risk of cancer mortality? SITE
Azathioprine, methotrexate, mycophenolate mofetil, cyclosporine,
systemic corticosteroids, or dapsone had overall cancer incidence
rates and cancer mortality similar to that of patients who never took
immunosuppressive drugs.
Cyclophosphamide, overall mortality was not increased and cancer
mortality was non-significantly increased.
Tumor necrosis factor inhibitors were associated with increased
overall risk (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98)
and cancer mortality.
Kempen JH, Daniel E, Dunn JP, et al. Overall and cancer related mortality
among patients with ocular inflammation treated with immunosuppressive
drugs: retrospective cohort study. BMJ (Clinical research ed) 2009; 339: b2480.

59. Which of the following clinical features of chronic anterior uveitis is a
determinant of reduced rates of disease remission?
1.Longer duration of disease at presentation (>2-5 years)
2.Unilateral disease
3.Older age at presentation
4.Absence of underlying systemic disease (JIA or
spondyloarthropathy)

60. SITE – Remission Predictors for Chronic Anterior Uveitis
SITE (Systemic Immunosuppressive Therapy for Eye Disease Cohort Study) Research Group retrospective study of 2795 eyes
of 1634 patients with chronic anterior uveitis (7936 eye years of follow up) and their long term clinical course.
A. About 1/3 of patients remit within 5 years.
B.Those 2/3 that had reduced remission incidence
1.a longer duration of disease at presentation (2-5 years vs 3-6 months),
2.more often bilateral
3.more often had one or more structural complications requiring
surgical intervention,
a.Keratic precipitates
b.Posterior synechiae
c.Cataracts
d.Glaucoma
4.Younger age at presentation tended to have a lower rate of remission.
5.Patients with systemic diagnosis of JIA and spondyloarthropathy had
reduced remission incidence.
** This data confirms many uveitis practitioners’ observations of patients with chronic anterior uveitis. It allows clinicians to
provide patients with more prognostic information based on characteristics at presentation and clinical course.
1.Sobrin L, Pistilli M, Dreger K, et al. Factors Predictive of Remission of Chronic Anterior Uveitis. Ophthalmology. 2020;127(6):826- 834.
doi: 810.1016/j.ophtha.2019.1011.1020. Epub 2019 Nov 1028.

61. Anti-Metabolites
Methotrexate

62. Anti-Metabolites
Methotrexate
Pharmacokinetics
–Subcutaneous injection - greater bioavailability and reduced gastrointestinal side effects
than oral
–Onset of action – slow- up to 3 to 6 months for full intraocular effect
Dosage
Maximum dosage in the range of 15 mg to 25 mg/week
Pediatric dosing 5-15 mg/m2
Level II- 2 evidence for Ocular Inflammatory Diseases (OID)
–SITE – 66% -no inflammation in 1 year and 58% reduced Pred <10mg/d
Gangaputra S, et al. Ophthalmology. 116: 2188-2198

63. Anti-Metabolites
Azathioprine

64. Anti-Metabolites
Azathioprine
•Pre-therapy evaluation
–Test for inherited thiopurine methyltransferase (TPMT) deficiency
•89% wild type; 11% heterozygous; 0.3% homozygous
•Dosage
–1 – 3.0 mg/kg/day (100-200mg/day typical dose)
–Reduced dose for Heterozygous TPMT deficiency
•Level II-2 evidence in OID
–SITE – 62% -no inflammation in 1 year and 47% reduced Pred <10mg/d
Pasadhika S, et al. Am J Ophthalmol. 148:500- 509. 2009

65. Anti-Metabolite :Mycophenolate Mofetil

66. Anti-Metabolite
Mycophenolate Mofetil
Dosage
–1000 to 1500 mg twice daily
Complications
•Gastrointestinal (GI) disturbance – 18%
•Leukopenia, pure red cell aplasia (PRCA)
•Possible increased long-term risk of malignancy (lymphoma, leukemia),
•Progressive multifocal leukoencephalopathy
Level II- 2 evidence for use in OID
–SITE – 73% -no inflammation in 1 year and 55% reduced Pred <10mg/d
–Level 1 evidence for rejection prevention in organ transplantation
Daniel E, et al. Am J Ophthalmol. 149: 423-432. 2010.

67. FAST Trial – 2019 Report – 12
month results
1.RCT (N=216)
1.similarity in steroid-sparing immunomodulatory efficacy of mycophenolate and methotrexate in the treatment of non -
infectious intermediate, posterior, and panuveitis.
2.Both drugs had similar rates of “success” at 6 months
1.defined as prednisone <=7.5 mg per day or 2 drops of topical prednisolone maintenance, <=0.5+ AC cells, <=0.5+
vitreous haze, no active retinal/choroidal lesions, and no failure due to declared intolerability or safety.
2.67% success with MTX vs 57% with MMF, P=0.2.
3.Subgroup analysis showed some treatment differences at 6 months based on anatomic location of inflammation.
1.Posterior or panuveitis treated with MTX demonstrated greater
treatment success (74.4%) vs. MMF (55.3% [p=0.02]).
2.Intermediate uveitis group, MMF demonstrated treatment success in
63.6% compared to MTX (33.3%) [p=0.07].
4.At 12-months, 80% of patients in the methotrexate group and 74% of patients in the mycophenolate group remained a
treatment success.
5.Approx 50% of methotrexate and 55% of mycophenolate group discontinued Prednisone.
6.Interestingly, there was greater treatment success at 12 months in the methotrexate group in patients who had
previously failed mycophenolate mofetil at 6 months and switched versus patients in the MMF group who had
previously failed MTX ( 69% versus 35%).
3.Although 14 serious adverse events occurred in the study, five were deemed related to the drug with 3 in the methotrexate
group and 2 in the mycophenolate mofetil group. All drug related adverse events were elevated liver function tests.
Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, et al. Effect of corticosteroid-sparing treatment with mycophenolate mofetil vs. methotrexate on
inflammation in patients with uveitis: a randomized clinical trial. JAMA 2019;322(10):936- 945.

68. FAST Trial – 2022 Report
1.Follow-up analysis
1.Time to reach treatment success, defined as 7.5 milligrams
of Prednisone per day maintenance or less, based on Kaplan
Meyer analysis
1.Both anti metabolite groups showed no difference between
methotrexate (125 days) and mycophenolate mofetil (133 days).
2.Likely that the 4- month time to success may differ from previous
reports because patients in this trial were started on 15mg weekly of
MTX and advanced to 25 milligrams weekly 2 weeks later. Similarly
mycophenolate mofetil dosage was started at 500 milligrams twice
daily orally and advanced to 1.5 grams twice daily after two weeks.
3.This is more rapid MTX dose advancement and more in keeping with
recent MTX dosing approaches in uveitis and rheumatology.
Bui AD, Kong CL, Kelly NK, Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan B, Vedhanayaki R, Lim LL, Suhler
EB, Al-Dhibi HA, Doan T, Acharya NR; First-Line Antimetabolites as Steroid-Sparing Treatment Research Group. Time to Uveitis
Control with Methotrexate and Mycophenolate Mofetil. Ophthalmology. 2022 Jun;129(6):721-723.

69. FAST Trial : Summary
TAKEAWAY :
1.Methotrexate and mycophenolate mofetil are both first line antimetabolites for steroid sparing
immunomodulatory therapy in the treatment of noninfectious uveitis.
1. Both appear to be equally effective in controlling inflammation
2. Both allow reduction of Prednisone maintenance dosage to 7.5 milligrams per day or less.
3. Choice of medication should be driven by
1. Patient tolerability
2. Physician comfort
4. Although early six-month data suggests that there may be some advantage in the treatment of posterior or pan uveitis with
methotrexate, This difference was not present at one year and 2 years
5. Regular laboratory testing including complete blood count and liver function tests are essential
6. It takes about four months for methotrexate and mycophenolate to become effective in controlling inflammation to allow successful
reduction of Prednisone maintenance dosage to 7.5 milligrams per day or less.
7. After a controlling for all other demographic characteristics, anatomic location of uveitis, and cystoid macular edema, it appears that
retinal vasculitis may be an independent risk factor for failure of both methotrexate and mycophenolate to work.
8. In cases of retinal vasculitis, it is important to rapidly transition the patients to more aggressive biologic therapy. This is particularly
important if the retinal vasculitis is associated with Behçet disease.

70. Calcineurin Inhibitors
Cyclosporine and Tacrolimus

71. Calcineurin Inhibitors
Cyclosporine and Tacrolimus
•Dosage
–2.0 to 5 mg/kg/day, typically in two divided doses with adjustment
depending on clinical response and toxicity
•USP modified cyclosporine is typically 4.0 mg/kg/day
•Unmodified cyclosporine A is typically 5 mg/kg/day
–Tacrolimus – 0.1-0.15mg/kg/day
•Level II-2 evidence for OID (Behçet)
–SITE – 52% -no inflammation in 1 year and 36% reduced Pred <10mg/d
–LEVEL 1 evidence for rejection prevention in organ transplantation
Kacmaz RO, et al. Ophthalmology. 117:576-584. 2010

72. Alkylating Agents
Cyclophosphamide
DNA Crosslinking
and cell death

73. Alkylating Agents
Chlorambucil
Mechanism of Action:
- Aromatic Alkylating Agent
- Similar to Cyclophosphamide –
Cross linking of DNA and inhibition of DNA replication
-Longer duration of effect
-Short term high dose and long term low dose therapy
Goldstein DA, et al. Ophthalmology. 109:370-377. 2002

74. Alkylating Agents
Cyclophosphamide
•Dosage
–Cyclophosphamide
•ORAL 100-150 mg/day typical initial dose increased to a
maximum 200mg/day if uveitis remains active
•IV pulse – 500-1000mg IV q monthly for 6- 12 months
•Target leukocyte count 3,000- 4,000 cells/µl off steroids
•Maximum cumulative cyclophosphamide dose 35gm
before risk of secondary leukemia substantially increases
•Level II-1 evidence of efficacy in OCP, I and II-1 systemic vasculitis
–SITE – 76% -no inflammation in 1 year and 61% reduced Pred <10mg/d
Foster CS. Tran Am Ophthalmol Soc. 84:527-663. 1986
Pujari SS, et al. Ophthalmology. 117:356-365. 2010.

75. Immunology of TNF-α

76. TNF-α Inhibitors

77. TNF-α Inhibitors
Etanercept (Enbrel®)
–LEVEL I - no better than placebo for the treatment of
uveitis
Infliximab (Remicade®) – IV infusions
–LEVEL II-1, II-2 - approved in Japan/EU for the treatment
of patients with Behcet’s Disease and associated uveitis
Adalimumab ( Humira®) – SQ Injections
–Level I, II-2 and III evidence – efficacy in treatment of
uveitis
Certolizumab (Cimzia®) (pegylated Fab)– Level III evidence
Golimumab (Simponi®) –Level III evidence

78. TNF-α Inhibitors
Complications
–TNF alpha inhibitors
Infusion reactions other than hypersensitivity reactions
Hypersensitivity reactions
Exacerbation of demyelinating disease
Congestive heart failure
Exacerbation of tuberculosis and other latent infections (e.g., histoplasmosis)
Drug induced lupus
Neoplasia (acute leukemia, lymphoma)
Production of neutralizing antibodies
De novo uveitis (etanercept)

79. Adalimumab therapy for non-infectious uveitis can cause which of the
following adverse effects ?
1.Chronic gastritis
2.Demyelinating disease of the CNS
3.Cardiac arrhythmias
4.Exacerbation of tinea capitis

80. Adalimumab : Humira: Visual I &II
Visual I and II studies
–Compared to tapering doses of oral corticosteroids,
–Adalimumab increases the interval to treatment failure from 13
weeks to 24 weeks,
–Adalimumab increases the interval to flare from 4.8 months to 10
months.
–Adalimumab Reduces risk of visual acuity loss.
Adalimumab FDA approved in 2016 for noninfectious
intermediate uveitis, posterior uveitis, and panuveitis
1. Jaffe GJ, Dick AD, Brezin AP, et al. Adalimumab in Patients with Active Noninfectious Uveitis. The New England journal of
medicine 2016; 375(10): 932-43.
2.Nguyen QD, Merrill PT, Jaffe GJ, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious
uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3
trial. Lancet (London, England) 2016; 388(10050): 1183- 92.

87. VISUAL III
1.424 patients enrolled, 371 were included in intent-to-treat analysis.
a.At study entry, 242 of 371 (65%) patients had active uveitis;
b.60% (145/242, NRI) achieved quiescence at week 78,
1. 66% (95/143, as-observed) of those were corticosteroid free.
c.At study entry, 129 of 371 (35%) patients had inactive uveitis;
1. 74% (96/129, NRI) achieved quiescence at week 78,
2. 93% (89/96, as-observed) of those were corticosteroid free.
d.BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR).
e.Mean corticosteroid dose
1. Active Uveitis at entry : decreased from 13.6 mg/day (week 0) to 2.6
mg/day (week 78)
2. Inactive Uveitis At entry : remained stable (1.5-1.2 mg/day).
f.AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient -years) were
comparable with previous VISUAL trials.
2.Important follow-up data confirming the efficacy of adalimumab in the treatment of noninfectious
intermediate, posterior, and pan -uveitis.
Suhler EB, Adán A, Brézin AP, et al. Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an
Ongoing Open-Label Study: VISUAL III. Ophthalmology. 2018;125(7):1075- 1087.

88. Adalimumab – Weekly
Retrospective 7 year review of cohort of 25 patients from a single academic
institution with non-infectious uveitis
–Treated with weekly adalimumab after failing every 2 week therapy.
–54% - Inflammation “controlled" at 12 months on weekly therapy.
**This is important information and essential peer- reviewed published
evidence needed for the practitioner to obtain insurance authorization and
medication coverage for patients.
Lee J, Koreishi AF, Zumpf KB, Minkus CL, Goldstein DA. Success of Weekly Adalimumab in Refractory Ocular Inflammatory Disease. Ophthalmology 2020; 127(10): 1431-3.

89. SYCAMORE - Trial
Primary end point was the time to treatment failure (as assessed by means of a multicomponent intraocular inflammation
score), At least one of the following criteria being met:
–a two-grade increase from baseline in the SUN cell-activity score (anterior chamber cell count) over
two consecutive visits;
–no change in the SUN cell- activity score in patients with an entry grade of 3 or higher for two
consecutive readings (apart from baseline);
–only partial improvement (decrease of one grade) or no change from baseline, with the
development of another ocular coexisting condition that was sustained over a period of two
consecutive visits;
–the worsening of an existing (on enrollment) ocular coexisting condition after 3 months;
–an entry grade of 1 or 2 - still present after 6 months of therapy and that had been sustained over a
period of two consecutive visits;
–the use of ineligible concomitant medications (medications not listed in the prespecified
acceptable criteria or those that were not allowed);
–the intermittent or continuous suspension of the trial regimen for a cumulative period of more
than 4 weeks.

90. SYCAMORE TRIAL : UK based
METHODS
–Multicenter, double-blind, randomized, placebo-controlled trial,
–Assessed the efficacy and safety of adalimumab in children and adolescents >2
years of age with A ctive JIA-associated uveitis.
–Those taking stable dose of methotrexate were randomly assigned in a 2:1 ratio
to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body
weight) or placebo, administered subcutaneously every 2 weeks.
–Patients continued the trial regimen until treatment failure or until 18 months had
elapsed.
–Followed for up to 2 years after randomization.
–Primary end point was the time to treatment failure, defined according to a
multicomponent intraocular inflammation score that was based on the
Standardization of Uveitis Nomenclature criteria.

91. SYCAMORE Trial
RESULTS
The prespecified stopping criteria were met after the enrollment of 90 of 114 patients.
–16 treatment failures in 60 patients (27%) in the adalimumab group
versus 18 treatment failures in 30 patients (60%) in the placebo group
(hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49;
P<0.0001 [the prespecified stopping boundary]).
–Adverse events were reported more frequently in patients receiving
adalimumab than in those receiving placebo (10.07 events per patient-
year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI,
5.26 to 7.77]), as were serious adverse events (0.29 events per patient-
year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI,
0.00 to 0.40]).

92. SYCAMORE Trial
CONCLUSIONS
Adalimumab therapy controlled inflammation and was associated
with a lower rate of treatment failure than placebo among children
and adolescents with active JIA-associated uveitis who were taking a
stable dose of methotrexate. Patients who received adalimumab had a
much higher incidence of adverse events and serious adverse events
than those who received placebo.

93. Rituximab
Anti-CD20 monoclonal antibody
chimeric monoclonal antibody directed
against CD20-positive B-lymphocytes.
B-cell Apoptosis

94. Rituximab
•Level and I and II-1 evidence of efficacy in
–Refractory Scleritis
–Systemic vasculitides (GPA)
–OCP
–Pediatric uveitis
– Orbital inflammation
Suhler EB, et al. Ophthalmology . 121:1885-1891. 2014
Foster CS, et al. Ophthalmology 117:861-9. 2010
Taylor SR, et al. Arthritis Rheum. 60:1540-1547. 2009
Specks U, et al. N Engl J Med. Aug;369(5):417- 27. 2013

95. Rituximab
Complications
–Profound Lymphopenia
–Hypersensitivity reactions
–Infusion reactions – Fevers, Nausea

96. Biologic Response Modifiers
–Cytokine receptor blockade
•Abatacept (Orencia)– useful in refractory JIA uveitis
–Soluble fusion protein CTLA-4+Fc IgG1 fragment
–Binds CD80/CD86 ; binds B7 on antigen presenting cells, effectively
preventing binding of the APC to T-lymphocytes and preventing T cell
activation
–Blocks the CD28 costimulatory signal and inhibits T-call activation.
–Interferons : Recombinant human cytokine/cytokine
analogues
•Mechanism of action of the interferons is poorly
understood
•antiviral, antineoplastic, and antiangiogenic effects
•Treat mucocutaneous, articular, and ocular Behçet Disease

97. Th-Cell Subsets and Functions
Xu S, Cao X. Cellular & Molecular Immunology (2010) 7, 164–174; doi:10.1038/cmi.2010.21; published
online 19 April 2010

98. Biological Activities of IL-17
Xu S, Cao X. Cellular & Molecular Immunology (2010) 7, 164–174; doi:10.1038/cmi.2010.21; published
online 19 April 2010

99. Biologic Response Modifiers :
Emerging Therapies
Secukinumab
–Fully humanized antibody to IL17 A
–2 infusions 3 weeks apart
–sustained anti-inflammatory activity for 2
months

100. Uveitis : Complications
Glaucoma
Cataract
CME

101. Uveitic Glaucoma

102. Uveitic Glaucoma : Risk Factors - SITE
Statistically significant risk factors for incident OHT >/=30 mmHg included
–Prior use of fluocinolone acetonide implants (aHR, 9.75).
–History of OHT in the other eye: and;IOP>/=30 mmHg (aHR, 4.86)
–Prior/current use of IOP-lowering drops/surgery in other eye (aHR, 4.17)
–History of OHT in the other eye: and;IOP >/=21 mmHg (aHR, 2.68),
–Current topical corticosteroid use [>/=8x/day vs. none] (aHR, 2.58);
–Periocular corticosteroids in the last 3 months (aHR, 2.23);
–Pars plana vitrectomy (aHR, 1.87);
–Current use of prednisone >7.5 mg/day (aHR, 1.86);
–peripheral anterior synechiae (aHR, 1.81); anterior chamber cells: 1+ (aHR, 1.43)
and >/=2+ (aHR, 1.59) vs. none;
1. Daniel E, Pistilli M, Kothari S, et al. Risk of Ocular Hypertension in Adults with
Noninfectious Uveitis. Ophthalmology 2017; 124(8): 1196- 208.

104. Cataract Surgery – MUST Trial Results
Of 479 enrolled eyes-117 underwent primary cataract surgery alone
(28 in systemic group and 89 and implant group)
Overall 23 letter gain by 3 months stable through 9 months
–Denser cataracts (unable to judge vitreous haze) gained additional 42 letters
beyond the ones that gained 13 letters in whom vitreous haze was gradable
–No preoperative factors for poor pre-op vision had an impact on final visual
outcomes.
Systemic therapy or Fluocinolone implant had similar visual
outcomes
Sen HN, Abreu FM, Louis TA, Sugar EA, Altaweel MM, Elner SG, Holbrook JT, Jabs DA, Kim RY, Kempen JH (2016) Cataract Surgery Outcomes in
Uveitis: The Multicenter Uveitis Steroid Treatment Trial. Ophthalmology, 123, 183-190.

105. Cataract Surgery - Outcomes
Uveitis - 1.2% of all eyes undergoing cataract surgery.
–Eyes in the uveitic group had worse preoperative visual acuity (0.87 vs 0.65
logarithm of the minimum angle of resolution (logMAR) units),
–Younger patients
–Shorter axial lengths
–Higher incidence of ocular copathology
Glaucoma.
Small pupils,
–Required additional surgical procedures
–Developed more intraoperative complications
–Poorer postoperative visual acuity –
up to 6 months (0.41 vs 0.27 logMAR units at 12- 24 weeks).
. Chu CJ, Dick AD, Johnston RL, Yang YC, Denniston AK (2017) Cataract surgery in uveitis: a
multicentre database study. The British journal of ophthalmology, 101, 1132-1137.

106. Which of the following is NOT an important risk factors for cataract
formation in children with uveitis?
1.Greater number of uveitis flares per year
2.Use of systemic immunosuppressive therapies
3.Presence of posterior synechiae
4.Local corticosteroid injections

107. Cataract Risk Factors in Children with
Uveitis
The main factors related with cataract development were
–Number of uveitis flares per year (hazard ratio [HR] = 3.06 [95% confidence interval {CI},
2.15-4.35], P < .001)
–Cystoid macular edema (HR = 2.87 [95% CI, 1.41- 5.82], P = .004)
–Posterior synechiae at presentation (HR = 2.85 [95% CI, 1.53- 5.30], P = .001)
–Use of local injections of corticosteroids (HR = 2.37 [95% CI, 1.18- 4.75], P = .02).
–Treatments with systemic and topical corticosteroids were not significant risk factors.
Controlling the inflammation, even using higher doses of systemic and
topical corticosteroids, is of importance in preventing ocular complications,
such as cataract.
Blum-Hareuveni T, Seguin-Greenstein S, Kramer M, Hareuveni G, Sharon Y, Friling R, Sharief L, Lightman S, Tomkins-Netzer O
(2017) Risk Factors for the Development of Cataract in Children with Uveitis. Am J Ophthalmol, 177, 139-143.

108. Cataract Risk Factors in Children with Uveitis
a.This retrospective cohort study from a single academic center (Johns
Hopkins) of 60 eyes of 40 patients treated with topical corticosteroids with
JIA associated chronic anterior uveitis
a.topical steroid use alone was associated with cataract development independent of disease
activity
b.using more than 3 drops of corticosteroids daily increased the incidence of cataract 16 fold (
from 0.01/ Eye Year(EY) to 0.16/EY).
c.Other Risk factors for Cataract Formations:
a.posterior synechiae
b.active uveitis
c. topical corticosteroid use at presentation were all associated with cataract formation.
b. The authors concluded that use of topical corticosteroid <3 drops daily was
associated with an 87% lower risk of cataract development in JIA patients compared
to those that received more than 3 drops daily.
Thorne JE, Woreta FA, Dunn JP, Jabs DA. Risk of Cataract Development among Children with Juvenile Idiopathic Arthritis-Related Uveitis
Treated with Topical Corticosteroids. Ophthalmology. 2020;127(4S):S21- S26.

109. Uveitic cataract: factors
complicating surgery
Posterior synechiae
Poor pupillary dilation
Epilenticular membranes
White cataract
Hypermature lens

110. Uveitic cataract: factors
complicating surgery
Band keratopathy
Friable iris vessels
Shallow anterior
chamber
Hypotony
Prior glaucoma or
vitrectomy surgery
Weak zonules, zonular
dialysis

112. Cataract Extraction for Uveitis Patients
Pre-op assessment: Determine if decrease in vision is secondary to lens opacity
–If possible, rule out CME, macular atrophy, macular scar, subretinal
neovascularization, glaucomatous loss as cause for decrease in vision
–Fundus exam, ultrasound, OCT, fluorescein angiography
Photographs courtesy of Ramana S. Moorthy, M.D. and Debra A. Goldstein,MD.

113. MUST Trials – Macular Edema
Longitudinal follow up of 248 eyes of 177 patients from MUST with uveitic ME
–Even when macular edema and uveitis were brought under control, episodes of relapse
cumulatively occurred commonly in 43% of eyes in 7 years.
–Also evaluated incident and recurrent ME annually.
Eyes that had annual incident improvement in ME gained 6 letters of vision,
those that remained free of ME remained stable visually
 those who developed (incident or relapsed) ME lost nearly 9 letters of vision.
TAKEAWAY:
–Uveitic macular edema must be controlled long-term to achieve stable visual outcomes in
chronic non-infectious uveitis.
–Uveitic macular edema can episodically relapse even when uveitis appears to be clinically
controlled
–These relapses result in further visual loss and visual instability.
Tomkins-Netzer O, Lightman SL, Burke AE, et al.Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis
Steroid Treatment Trial and Follow-up Study Results.Ophthalmology2021;128(5): 719-28.

114. Cataract surgery in uveitis:
General principles
Quiet eye for 3 months
–Does not mean off all medications
Control of inflammation pre and post-op is at least as
important as surgical technique

115. Cataract Extraction for Uveitis Patients
Pre-Operative Management
–Optimize uveitis status prior to surgery
Treat CME that may be worsened by surgery
Treat anterior segment inflammation that will result in worse
postoperative result
–Quiet eye for 3 months, patient should have an examination to confirm
the eye is quiet. (in JIA – 71% vs 22% >20/40 if well controlled)
May need to increase anti-inflammatory therapy
–Additional perioperative oral steroids often used (e.g. prednisone
1mg/kg/d, begin 3-7 days pre -op)
–Control of inflammation pre and post-op is at least as important as
surgical techniques
Mehta S, Linton MM, Kempen JH. Am J Ophthalmol. 2014; 158:676-692.

116. Cataract Extraction in Uveitis Patients
Pre-op steroids – Oral+topical or topical alone for prophylaxis?
–52 eyes in 50 patients were randomized:
–28 eyes were assigned to group A (topical) and 24 eyes to group B (topical +
oral).
–Results:
Mean relapse-free survival time was 131 +/ - 11 days in group A
Mean relapse-free survival time was 150 +/ - 13 days in group B.
not statistically significant (p = 0.42).
–Both groups had similar significant improvement in visual acuity (p < 0.01),
mean central macular thickness (CMT) and IOP variation.
Mora P, Gonzales S, Ghirardini S, Rubino P, Orsoni JG, Gandolfi SA, Majo F, Guex-Crosier Y (2016) Perioperative prophylaxis to
prevent recurrence following cataract surgery in uveitic patients: a two- centre, prospective, randomized trial. Acta ophthalmologica,
94, e390-394.

117. Cataract Extraction for Uveitis Patients
Intraoperative considerations
–Clear corneal wound preferred
–Removal of pupillary membranes
–Synechiolysis
–“Wide enough” capsulorrhexis
–Complete cortical clean up
–“In the bag” IOL Implantation
–Acrylic or PMMA only
–Intravitreal triamcinolone – Triescence 4mg at end of procedure
– trans pars plana

118. Cataract Extraction for Uveitis Patients
Special surgical
considerations
–Posterior synechiae
–Poor pupillary
dilation
–Epilenticular
membranes
–White cataract
–Hypermature lens
Photographs courtesy of Debra A. Goldstein, MD.

119. Cataract Extraction for Uveitis Patients
Special surgical
considerations
–Band keratopathy
–Friable iris
vessels/rubeosis
–Shallow anterior chamber
–Hypotony
–Prior glaucoma or
vitrectomy surgery
–Weak zonules, zonular
dialysis
Photographs courtesy of Debra A. Goldstein, MD.

120. Photograph courtesy of Debra A. Goldstein, MD.
Cataract Extraction for Uveitis Patients

121. Cataract Extraction for Uveitis Patients
Additional operative techniques
–Synechiolysis (cyclodialysis spatula)
–Peripheral iridectomy may be required to gain access to pupil,
and to prevent recurrence of pupil block (peripheral, non self-
sealing incision)
–Excision epilenticular membranes
–Pupil stretching
–Iris hooks or ring
–Trypan blue to stain capsule

122. Cataract Extraction for Uveitis Patients
Techniques
–Clear corneal surgery
Preserve conjunctiva for future
glaucoma procedures, which are
more common in uveitis patients
Avoid contact with sclera in eyes
with scleritis
Photograph courtesy of Debra A. Goldstein, MD.

123. Cataract Extraction for Uveitis Patients
Image courtesy of Debra A. Goldstein, MD.
Synechiolysis through
PI

124. Cataract Extraction for Uveitis Patients
Image courtesy of Debra A. Goldstein, MD.
Capsular dye and iris
hooks

125. Cataract Extraction for Uveitis Patients
Photograph courtesy of Debra A. Goldstein, MD.
Malyugin ring

126. Cataract Extraction for Uveitis Patients
Capsular tension ring
–Morcher, Cionni
–With or without scleral
fixation
–Need intact capsular bag
and rhexis
Capsular support hooks
–Mackoolcapsular support
system
Photograph Courtesy of Debra A. Goldstein, M.D.

127. Cataract surgery in uveitis:
additional operative techniques
Capsular tension ring (Morcher, Cionni)
–With or without scleral fixation

128. Cataract surgery in uveitis:
additional operative techniques
Trypan blue, ICG to stain capsule
May need capsular support hooks
(Mackool capsular support system)

129. IOL in uveitis patients
Can use IOL in almost all patients
–Acrylic
–PMMA
Location
–In the bag preferred
–One series suggests sulcus IOL to prevent recurrence
of posterior synechiae
–No AC IOL
–Sutured PCIOL if insufficient capsular support

130. IOL in Uveitis Patients
Wound closure
–Because of the likely need for frequent topical
corticosteroid use in the postoperative period
with their attendant inhibition of wound
healing, serious consideration should be given
to a sutured wound closure, even if end of
case wound testing suggests “water-tightness”

131. Peer Pressure

132. Cataract Extraction for Uveitis Patients
Who doesn’t get an IOL?
–Rare adult patients may do better without an IOL
–Consider aphakia in young children with uveitis
–Consider leaving aphakic those patients with all of the following
360 degrees of posterior synechiae
Significant flare
Hypotony
Non-compliance
–Also consider leaving aphakic those patients who have failed
IOL in contralateral eye

133. Cataract Extraction for Uveitis
Patients
Risk of IOL in uveitis patients
–Dense IOL precipitates
–Cyclitic membranes
–Cocooned IOL
–Ciliary body detachment
–Irreversible hypotony

134. Cataract Extraction for Uveitis
Patients
IOL in JIA
–Older child
–Well-controlled inflammation (complete quiescence)
–Good compliance with meds, follow-up
–Worse prognosis
Younger age
Extensive posterior synechiae
Significant flare
Hypotony

135. Cataract Extraction for Uveitis Patients
Photograph courtesy of Debra A. Goldstein, MD.
IOL precipitates

136. Cataract Extraction for Uveitis Patients
Photograph courtesy of Debra A. Goldstein, MD.
Epilenticular membranes, PAS, posterior
synechiae

137. Cataract Extraction for Uveitis Patients
Photograph courtesy of Debra A. Goldstein, MD.
Cocooned IOL

138. Cataract Surgery in Uveitis
Post-operative considerations
–Control inflammation
Aggressive use of topical and systemic corticosteroids
Taper based on response
Closer follow-up
–Fibrin – Use Intracameral tPA – 12.5-25mcg/0.1ml
Usually first 1-2 days post-op if needed
–Cystoid Macular Edema
Try pre and post-operative topical NSAIDS
–ketoralac – Acular or nepafenac (Nevanac)
Aggressive corticosteorids
–Intravitreal kenalog or triescence 4mg

139. Cataract Extraction for Uveitis
Patients
Summary
–Pre-operatively
Will the patient potentially benefit from surgery?
Set reasonable expectations
Anticipate intra-operative techniques and equipment
Control of inflammation for at least three months
–Intra-operatively
Consider surgical PI, suture
Need for management of pupil, membranes, zonule
Type/location IOL

140. Cataract Extraction for Uveitis
Patients
Summary
–Post-operatively
More frequent follow-
ups
IOP measured at
every visit
Frequent fundus
examination
Aggressive control of
inflammation Photograph courtesy of Debra A. Goldstein, MD.

141. Non-Infectious Scleritis : Long Term Study
1.Retrospective study
a.832 eyes from 4 Uveitis centers with an aggregate follow up of 1906 years
2.Unlike uveitis, scleritis remission takes much longer (almost 8 years)
3.Tapering of IMT should be done only after 7 years or more of disease quiescence.
4.Less Remission Rates in patients with
a.bilateral disease
b.RA
c.systemic vasculitis (GPA),
d.any systemic immunologic disease
5.There was an interesting (possibly spurious) finding of statin therapy being associated with
greater remission incidence.
**This is important information for the practitioner to know how and when to taper IMT in
these difficult cases.
Kempen JH, Pistilli M, Begum H, et al. Remission of Non- Infectious Anterior Scleritis: Incidence and Predictive Factors. Am J Ophthalmol 2021;
223:377-395.(

142. Collaborative Ocular Tuberculosis Study
The Collaborative Ocular Tuberculosis Study (COTS) has consensus guidelines for
starting antitubercular therapy (ATT) in several clinical scenarios.(2-step Modicfied
Delphi Technique) These guidelines include:
**Positive immunologic test and radiologic signs of active or healed pulmonary
tuberculosis:ATT should be initiated in these scenarios.
1.First episode of TBAU:ATT should be initiated if both immunologic and radiologic test
results are positive.
2.Recurrent TBAU:ATT should be initiated depending on the TB endemicity.
3.TBIU:ATT should be initiated depending on the TB endemicity.
4.TBPU:ATT should be initiated depending on the TB endemicity.
5.Active TB Retinal Vasculitis:ATT should be initiated depending on the TB
endemicity.
6.Special Cases : Tuberculous choroiditis or multifocal choroiditis:
1.When is corticosteroid treatment initiated?
2.Is it needed?
Agrawal R, Ludi Z, Betzler BK, Testi I, Mahajan S, Rousellot A, Kempen JH, Smith JR, McCluskey P, Nguyen QD, Pavesio C, Gupta V. The Collaborative Ocular
Tuberculosis Study (COTS) calculator-a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis. Eye (Lond). 2023 May;37(7):1416-
1423.

143. Case 2 - Left Eye

144. Case 2 – ICG Left eye

145. Case 2 -
What next?
Is a work up required?
Management?

146. Case 2
Within 2 weeks
–symptoms resolved
–Vision 20/20
–White spots gone
–No recurrence at 6 months

147. Case 3
67 year old white male with 6 month history of
painless, progressive vision loss in each eye.
PMHx: Negative – never hospitalized;
Meds : None
Exam: Va: HM RE; 20/100 LE
A/C – No cells
Vitreous : 3+ cells in sheets both eyes
Fundus:

148. Case 3

149. Case 3

150. Case 3
Next step in work up?

151. Case 3

152. Case 3

153. Case 3

154. Case 3
Diagnosis: PCNSL
Management:
–Systemic Chemo rx - IV MTX, Ara-C,
–Radiation therapy – low dose fractionated
–Intravitreal therapy – MTX 600mcg + Rituximab 1mg
x3 for 3 months
Patient still alive at 3 years with NLP right eye and
20/70 vision in left eye
Prognosis : Much poorer with CNS symptoms

155. Case 465 year old AA woman presents with sudden, severe, painless vision loss
and floaters in the right eye
PMHx – Hypertension;
POHx – Non-contributory
ROS – non contributory except for nonproductive cough for 1 year, weight
loss >15 lbs in 6 months; No fevers or chills
Ocular Findings
–Vision – RE – HM; LE -20/40
–Ta- 12 OU
–SLE: Fine KP ou; 3+ cells OU; 1+ flare OU; No Synechiae
–Vitreous – 3+ cells RE; 2+ cells LE
–Fundus
RE – massive serous RD and disc hyperemia
LE- Vitritis with some punched out white grey choroidal lesions; serous RD

156. Case 4

157. Case 4
Further ROS – No poliosis, vitiligo,
hearing loss, tinnitus, meningismus
Laboratory Work Up

158. Case 4

159. Case 4

160. Case 4
PPD- Negative
FTA –ABS and VDRL – Negative
ACE – 100; Lysozyme -20
Chest Radiograph: Bilateral Hilar Adenopathy
Pulmonary – Bronchoscopy/Mediastinoscopy –
–Biopsy – Non- caseating granulomata – no FB, no TB
or NTM, no fungi

161. Case 4
Therapy
–Oral and topical corticosteroids and cycloplegics
–Mycophenolate mofetil – non compliant
–Azathioprine – disease control and durable remission for 5 years
–Complicated course –
Cataracts bilateral
 Glaucoma – combined mechanism- Bilateral Baerveldt Tube Shunt
CNVM left eye – Bevacizumab injections – scar – 20/200
Subretinal fibrosis right eye – LP ( due to glaucoma and fibrosis)

162. Case 4

163. Case 4

164. Case 5
39 year old white male with 2 week history of
blurred vision in left eye.
POHx- NC
PMHx – NC
Va : 20/25 RE; 20/400 LE
Anterior Segment – 1+ Flare/ 1+ cells no KPs OU
No posterior synechiae
Vitreous – rare cells OD; 1+ cells OS

165. Case 5

166. Case 5

167. Case 5

168. Case 5

169. Case 5

170. Case 5
Next Step?
–Historical details :
 Has male partner, monogamous
 No arthritis,
2009 – HIV negative
Testing
–FTA-ABS, VDRL
–HIV serology
– Quantiferon TB, ACE, Lysozyme, CXR

171. Case 5
Results :
–FTA+ (1:64); VDRL neg
–Quantiferon TB- neg,
–ACE- neg, Lysozyme- neg, CXR – Neg
Diagnosis – Syphilitic placoid chorioretinitis
Therapy – 2.4 MU IV PEN G x 2 weeks
–10 days of therapy- Va – 20/25

172. Case 5
69 year old white female with painless
subacute vision loss over 1 week in both eyes
Symptoms : Metamorphopsia and a few
floaters; no photopsias
PMHx: Hypertension
POHx : Noncontributory
ROS: Dyspnea; weight loss; arthralgias

173. Case 5
Ophthalmologic Exam
–Va -20/60 OU
–Ta- 14 OD; 12 OS
–Conjunctiva – no injection
–Anterior Chamber : 0.5 cells in each eye; no synechiae
–Vitreous – 1+ cells
–Retina : Subtle disc hyperemia and serous retinal
detachment of posterior pole in each eye; no peripheral
choroidal lesions seen; no vasculitis

176. Case 5 – Right Eye

177. Case 5

178. Case 5
Laboratory Work- up
–FTA-Abs – Negative; PPD – Negative; ACE and
Lysozyme – normal; ANA > 1:4000+; +dsDNA
–Chest X- ray – Bilateral pleural effusions
–Pleural Fluid – High positive ANA titer >1:4000
–Urinalysis – no WBC casts; Mild Proteinuria
–Serum :BUN and Creatinine - nomral

179. Case 5
Diagnosis : SLE – lupus choroidopathy
–Diagnostic criteria - >4/11 met
Therapy :
–Systemic corticosteroids and Imuran
–Ocular findings resolved in 3 months
–Disease free for 10 years
–Durable remission off all meds except low dose
plaquenil for last 5 years

180. Case 6
45 year AA F presents with painful skin ulcers and pain and vision loss in
left eye of 2 months duration.
PMHx – Bronchitis for 3 months – multiple courses of antibiotics – no
imporovement
Meds : None
POHx – Non-Contributory
ROS: Dyspnea, Dry-non-productive cough, low grade fevers, weight loss,
headaches
Va- 20/16 OD; CF 1m OS
No RAPD
Anterior Segment: Normal OD; Fine KP and 2+ cells, No granuloma OS
Vitreous Clear OD; 3+ Haze OS

182. Case 6

183. Case 6

184. Case 6

185. Case 6
Lab Work up
–Quantiferon TB – Negative, Anti-Treponamal IgG – Negative
–Chest Radiograph: Paratracheal LN enlargement : TBBx -
Blastomycosis Granuloma
–MRI of Brain – Multiple Cortical Lesions
–Diagnosis: Disseminated Blastomycosis
–Treatment : Systemic (oral) Fluconazole (6-12 months)
–Treatment Ocular : PPV , Cultures ( All Neg), Intravitreal
Ampho B (5 mcg)

186. Case 6 – 1 week Post Op

187. Case 6 – 1 Week Post Op

188. Case 6 – OCT – 1 week Post
Op

189. Case 6 – 2 week Post Op

190. Case 6 – 1 month Post Op

191. Case 6 – 6 week Post Op

192. Case 6

193. Case 6
Dx: Blastomycosis Endogenous Endophthalmitis
Rx: Long term Fluconazole
Demographics:
–Endemic Regions : Midwestern and Northern United States and Southern Canada
Pathogenesis
–Dimorphic Fungus
–Aerosolized to lungs from soils
–Pulmonary Infection -Most common - Severity based on Inoculum and Host Immune
status
–Cutaneous Infection – 2
nd
most common
–Genitourinary – Epididymitis
–CNS involvement from hematogenous dissemination - <5%
–Increased incidence possibly due to climate change

194. Case 6
Other Dimorphic Pathogenic Fungi
–Histoplasma capsulatum
–Coccidioides immitis
–Paracoccidioides brasiliensis
–Sporothrix schenkii (Cutaneous)

195. Case 6

196. Case 6

197. Case 6
Blastomycosis
–Endogenous Endophthalmitis rare (only 2)
Can occur with orbital cellulitis
–Therapy:
Itraconazole , Ketoconazole, Fluconazole – all effective
for systemic disease
Voriconazole may be better for CNS infection –
expensive
Amphotericin B IV for – severe CNS Meningitis