Clinical application of OCT for uveitis

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UVEITIS UPDATE

Thomas A. Albini, MD Bascom Palmer Eye Institute Miami, FL USA

Consultant: Allergan, Bausch & Lomb, Eleven Biotherapeutics, Thrombogenics Research Support: Genentech

Collaborators      

 

Swetangi D. Bhaleeya, MD Ruwan A. Silva, MD Raquel Goldhardt, MD Ninel Gregori, MD Anat Galor, MD Janet L. Davis, MD Harry W. Flynn, Jr., MD Steve Yeh, MD › Emory Eye Center



John Kitchens, MD › Retina Associates of Kentucky

Debra Goldstein, MD – Northwestern University  David Callanan, MD – Texas Retina  Quan Dong Nguyen, MD – University of Nebraska  James Bena – Cleveland Clinic  Sunil Srivastava, MD – Cleveland Clinic 

 1.

Multimodality imaging

 2.

Sustained delivery local steroids

 3.

Anti-VEGF in uveitis

Multimodality imaging

Anatomic localization of disease process  Complication-specific findings  Disease-specific findings 

› Infectious uveitis › Non-infectious uveitis

Assessment disease progression and response to therapy  OCT in multimodality diagnostic imaging 

Easily performed in children

8 year old girl with neuroretinitis associated with intermediate uveitis. CXR and ACE were normal. Bartonella and Toxoplasmosis serology negative.

Cystoid

 

Leading cause of visual morbidity in uveitis Specific subtype may have visual significance

Diffuse

Combination

CME SRD

Serous retinal detachment

CME diagnosis and follow-up

20/100

Methotrexate, Pred 10 mg

HLA-B27-associated anterior uveitis in pediatric patient 20/30 Remicade, Methotrexate, Pred 5 mg

Vitrectomy for Uveitic CME 

If anatomical pathology exists › Traction of ERM › Taught ILM › Vitreomacular Traction

 

Complete separation of hyaloid Consider removal of ILM

OCT Findings in toxoplasmosis chorioretinitis

Posterior hyaloid

Inner retinal thickening

Full-thickness retinitis in toxoplasmosis

Inner Segment – Outer Segment Junction

PIC Reactivation

IS/OS junction attenuation

Subtle RPE elevation



Exudative retinal detachment › Subretinal septations may be

pathognomonic

  

Macular edema Choroidal neovascularization Subretinal fibrosis

Figure 3. Lee et al, Korean J Ophthalmol 2009

OD 2/200 “E”

OS 20/400



Spectrum of OCT findings › Cystoid macular edema, sometimes recalcitrant › › ›

› › 

(Key finding in birdshot) Choroidal neovascularization Epiretinal membrane Vitreomacular traction Foveal/macular atrophy Combination of the above

Correlate with FA and ICG

Serpiginous choroidopathy ERM ELM

IS-OS junction Choroidal atrophy

IS-OS attenuation

Posterior placoid chorioretinitis secondary to syphilis

Intraocular lymphoma

SD-OCT is useful for more common entities (i.e. CME with intermediate uveitis)  Also useful for characterization of rare posterior uveitis syndromes  Expanding use of SD-OCT in multimodal diagnostic imaging 

› Following disease activity › Understanding disease pathogenesis

Sustained delivery local steroids



Compare the relative effectiveness  Systemic corticosteroids plus immunosuppression when indicated (systemic therapy) VERSUS  Fluocinolone acetonide implant (implant therapy)  For noninfectious intermediate, posterior, or panuveitis  Follow-up 24 months

255 Participants (479 eyes with uveitis) were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries).  Both eyes received implant if warranted.  Powered to see a 7.5 ETDRS letter difference 

Uveitic macular edema

Baseline 6 months 24 months

Implant

Systemic Treatment

41% 20%(*) 22%

39% 34%(*) 30%

(*) Statistically significant difference in change from baseline

Complications Implant: Higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001) Treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001) Glaucoma (17%, HR=4.2, P = 0.0008). Systemic therapy: More prescription-requiring infections (P=0.034), without notable long-term consequences.

•

Randomized fluocinolone acetonide to one eye

› Fellow eye served as control › 2 doses examined 2.1 mg and .59 mg

› Randomized patients to either fluocinolone implant

(0.59 mg) in one eye or treatment with standard of care (systemic therapy)



Do eyes with underlying vascular leakage treated with implant have better visual acuity outcomes at two years?



Purpose: To analyze the fluorescein angiogram leakage of eyes from the pooled data from the three fluocinolone acetonide clinical trials

Data were combined into a master dataset, separated into 3 categories: › Implanted eyes with .59 mg (IMP) › Standard of care eyes (SOC) › Fellow eyes of all implanted eyes (FEL)  Outcome measure: fluorescein angiogram leakage 



Area of leakage measured in mm2 at 180, 300 and 600 seconds, denoted as MA180, MA300 and MA600.



Angiograms read at Retinal Diseases Image Analysis Reading Center (REDIARC)

Gender (Women) Race (Caucasian) Intermediate Uveitis Panuveitis

Vision

IMPLANT (IMP) (N=290) 63%

FELLOW (FEL) (N=446) 63%

ST of Care (SOC) (N=133) 68%

51%

50%

90%

30 %

30%

34%

45%

47%

44%

0.53±0.36 (20/63)

0.40±0.60 (20/50)

0.30±0.34 (20/40)

Baseline MA 180 sec MA 300 sec MA 600 sec 24 Months MA 180 sec MA 300 sec MA 600 sec

IMP

FEL

SOC

30.3±45.3 34.2±47.7 35.4±48.7

19.6±39.6 22.1±42.5 24.2±46.3

16.8±34.5 19.9±39.2 19.9±39.3

4.4±11.9 5.1±13.3 5.3±13.5

20.6±40.7 21.3±39.6 21.7±38.1

12.5±26.9 14.2±28.1 14.5±28.5

P<0.01

Baseline No leakage Diffuse or petalloid leakage 24 Months More Leakage Leakage Resolved

IMP

FEL

SOC

27.7%

50%

44.4%

70.8 %

48.9%

55.6%

5.0 %

25.9 %

12.5%

73.2 %

26.5 %

28.9%

ETDRS Lines

*

* *p<0.01

Eyes with implants had significant decrease in fluorescein leakage over 2 years  Eyes with improvement of leakage tended to have improvement of vision  In eyes with macular leakage, the fluocinolone acetonide device may offer superior visual acuity improvement over 2 years in comparison to eyes treated with standard of care therapy. 



   

Intolerant of systemic treatment › Patient prejudice › Complications › Pregnancy Complex immunosuppression (2 or more agents) Unilateral disease Pseudophakia and s/p glaucoma surgery Chronic CME

 Children without cataract  Existing Glaucoma  Well controlled on single agent

immunosuppression  Systemic disease  Possible infectious etiology  Poor compliance  No response to intravitreal steroids

Anti-VEGF in uveitis

    

High levels in experimental autoimmune uveitis (EAU) Potent chemo attractant for monocytes Receptors are present and active on all inflammatory cell subtypes High levels in aqueous of patients with uveitic CME CME and CNVM are common complications of uveitis

 

12 y/o female presents with new onset central scotoma right eye, and recurrent iritis both eyes for one year. Recent exacerbation OS – using pred-forte every 2 hours, cyclopentolate BID BCVA 20/30 OD

BCVA 20/25 OS

10/16/07

10/16/07 BCVA 20/30 OD

OD Horizontal 10/16/07 BCVA 20/30 IVA #1

12/18/07 BCVA 20/25 IVA #3

4/15/08 BCVA 20/25 IVA #6

5/6/08 BCVA 20/20 Observe

Vertical

MTX and Infliximab

BCVA 20/60 OD IVA #10 Horizontal

10/20/09 BCVA 20/60 IVA #12

11/17/09 BCVA 20/25 IVA #13

Vertical

10/20/08

MD 1091255

BCVA 20/20 OD

BCVA 20/50 OS

OS

Horizontal 10/20/08 BVCA 20/50 IVA #1

6/16/09 BCVA 20/30 IVA #3

6/30/09 BCVA 20/30 Observe

MD 1091255

Vertical

96 eyes, 6, 12, 18 and 24 months  Improvement of <2.2 lines at all time points  P<0.05  Complete/partial resolution influenced by pathology  PIC (95.7%), POHS (100%)  MFC (68.4%), VKH (66.7%), Serpiginous (77.8%) 

 Prospective

pilot study

7 patients/eyes  6 months  Mean increase of 13 letters (3 and 6 months)  Mean decrease of 211 microns in CRT  3 monthly injections followed by an average of 0.83 injections over the next 3 months 

72 y/o AAM with a history of recurrent idiopathic anterior uveitis and uveitic CME  POH: OD s/p BGI (6/03), OAG OS s/p trab with MMC (3/08), cataracts OU  BCVA HM 1 ft OD, 20/60 OS  IOP 12 mm Hg OU 

RW 820666

Horizontal OS 10/7/08 BCVA 20/50 IVL#1

11/13/08 BCVA 20/30 1 wk s/p IVL #2 Observe 2/12/09 BCVA 20/80 +1 A/C cell PF Q1 hr 3/17/09 BVCA 20/100 Rare A/C cell IOP 35 BGI/CE/IOL RW 820666

Vertical OS

CIRRUS OCT Resolved Inflammation Prednisone 10 mg daily

Horizontal OS 5/19/09 BCVA 20/100 s/p Healon injection Resolved choroidals PF/Acular QID IVL #6 5/28/09 BCVA 20/50 1 wk s/p IVL #6 PF/Acular QID 8/4/09 BCVA 20/50 10 wks s/p IVL #6 Durezol/Acular QID IVL #7 2/2/10 BCVA 20/25 12 wks s/p IVA #7 Durezol/Acular BID Prednisone 10 mg RW 820666

Vertical OS

Anti VEGF agents clearly work for uveitic CNV and CME  Appropriate immunosupresion is essential  Multiple injections appear to be beneficial and well tolerated  Comparative data are lacking 