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Dr Shrutika Kankariya DNB Dr Suganeswari DO,DNB Dr Jyotirmay Biswas MS

Sankara Nethralaya, Chennai

No financial disclosures.

Inflammatory Choroidal Neovascular Membrane (CNVM) is a well documented sight threatening complication of ocular inflammation.

Active uveitis Inflammation Inflammatory mediators + VEGF


Chemokines Complement production Myeloid cell accumulation

Inactive uveitis Hypoxia surrounding scar + Breach Bruch Membrane Predominantly VEGF

Angiogenesis

CNVM

1) Observation 2) Laser Photocoagulation 3) Local and Systemic steroids 4) Photodynamic therapy( PDT 5) Transpupillary thermotherapy(TTT)

6) Anti VEGF ( bevacizumab and ranibizumab) 8) Surgical removal 7) Combination therapy 9) Intravitreal injection triamcinolone

To characterize inflammatory CNVM in various underlying uveitic disease entity

To prognosticate the treatment outcome of inflammatory CNVM in various uveitic diseases

To postulate treatment strategy for inflammatory CNVM in active and inactive uveitis.

Design : Retrospective chart review


Period : 1995 to 2011 (16 years) Setting : Tertiary care eye institute Inclusion criteria Clinically diagnosed inflammatory CNVM CNVM presenting in eyes with active uveitis(posterior uveitis and panuveitis) or occuring adjacent to the healed retino-choroiditis lesion. Confirmation Optical coherence tomography (OCT) and Fundus fluorescein angiography (FFA) Follow-up > 1 year with Regular follow-up

Exclusion criteria
CNVM due to other causes were judiciously excluded (ARMD, myopia,

angioid streak, idiopathic)

Definitions Location of CNVM

Subfoveal-CNVM beneath fovea Juxta-foveal- CNVM within 200 of centre of fovea Extra-foveal- CNVM > 200 from centre of fovea. Peripappilary CNVM within 1 DD of ONH.

Size
Large - > 3.5 DD

37 eyes (32 patients). Mean Age 34 years Mean follow up of 29 month Laterality
15 (47%) 17 (53%)

Male Female

Unilateral 17 patients. Bilateral- 5 patients.

Multifocal Choroiditis (MFC)


2, (5%) 6 (16%) 14(38%)

14(38%)

Toxoplasma (toxo)-5(14%) Panuveitis (PU)-10(27%)

10 (27%) 5 (14%)

Serpiginous (SC)-6(16%) Vogts Koyanagi Haradas Disease (VKH) - 2(5%)

CNVM was uniformly of classic type in all eyes

57%

100%

66% 100% 100%

Inactive Active

MFC TOXO

SC

PU

VKH

Juxtafoveal CNVM - 16 eyes (43.3%)

Subfoveal CNVM -11 eyes (29.7%)

Peripapillary CNVM - 10 eyes (27%)

All 10 EYES -ACTIVE UVEITIS 8 eyes - Panuveitis

Inflammation stimulated angiogenesis in active uveitis ( panuveitis) has propensity for peripapillary region

41% 32%

No. of eyes

12% 9% 3% 3%

44%

29%

26%

Improvement

Stabilization

Deterioration

Mean visual acuity demonstrated improvement from initial visual acuity of (logmar = 0.643 0.385) to final visual acuity of (logmar = 0.574 0.442).

0.7

-42.4%

0.6

128.7%
0.5 Mean Values (Decimal)

40%
0.4

8.8%

23.2%
0.3

0.2

0.1

Multifocal choroiditis

MFC

Serpiginous choroiditis

SC

Toxoplasma

TOXO

Panuveitis

PU

VKH VKH

Initial Visual Acuity

Final Visual Acuity

0.45

17.5%
0.4 0.35 0.3 0.25 0.2 0.15 0.1

38.2%

0.05
0

Inactive Uveitis Inactive uveitis


Initial Visual Acuity

Active uveitis Active Uveitis


Final Visual Acuity

56.7%
6

40.1%
4

-1.8%
3

-45.2%

Avastin A

PDT PDT
Initial Visual Acuity

TTT

TTT

SSNO + IMN

Final Visual Acuity

Treatment

Regression (eyes)/total (eyes) 4/4

Remarks

Systemic steroids (SS)

100%

Severe inflammation,(>4+), PP cnvm,

Bevacizumab + 3/6 SS
PDT + SS

50%

Inadequate control of underlying inflamation. 5.2 injections (Avg-3.2)


2 eyes - Regression CNVM didnt translate into visual gain (RPE atrophy).2 eyes- Delayed stabilization of vision Excessive Scarring

5/5

100%

TTT + SS

1/2

50%

Regression Total eyes % (eyes)

Remarks

Bevacizumab

71 %

2 eyes Reactivation (inadequate scarring of CNVM)


1 eye- vision deteriorated (RPE atrophy)

PDT TTT Laser PHC

6 1 1

6 1 1

100 % 100 % 100 %

Ranibizumab
PDT+Bevacizu mab

1
1

1
1

100 %
100 %

Authors Our study (2013) Postelmans et al (2005)

No of eyes 37

Follow up Mean/max 2.5 (22)

Diseases Uveitis

Treatments studied

MFC, SC, PU, Bevacizumab, PDT, TTT, Toxo, VKH SS Ranimizumab, PHC, (Active Vs Inactive) Combi PIC, POHS PDT

16

1.5(2.5)

Strength of our study Kramar et al 10 1(2) MFC, POHS, Toxo, Bevacizumab 1 .Active uveitis Vs healed uveitis (2004) PIC, PU 2.Longer follow-up(10 eyes >5 years) Perentes et al 12 1.5(3) MFC, Sarcoid, SS, PDT, TTT different uveitic entities. (2010) 3.Varied treatment modalities Toxo, VKH 4.Largest size from singleBevacizumab centre . vs pdt Parodi et al 27 1 (1) sample MFC
(2010) Rouvas et al (2011) 15 1.5 (2.5) MFC, SC, PIC Toxo, Ranibizumab only

Characterization.

Active uveitis - Peri-papillary region.

Prognostication.
-

Inactive uveitis - Better progosis Active uveitis - Relatively poor prognosis Recurrence and reactivation more common. PDT related side-effects more common.

Treatment strategy..
Stringent control of inflammation throughout the course of disease.

Especially when Timely initiation and judicious extension ofdose CNVM on low targeted Rx (Anti VEGF + / PDT) maintenance RX

Long term + frequent F/U follow up until complete scarring of cnvm is achieved and beyond ..

Good compliance + adequate F/U

Development of Inflammatory CNVM in active uveitis

adequate control of inflammation Reactivation of CNVM Recurrenc e of CNVM

Thank You

1.

Macular Photocoagulation Study Group. Argon laser photocoagulation for ocular histoplasmosis: results of a randomizedclinical trial. Arch Ophthalmol 1983;101:13471357. Postelmans L, Pasteels B, Coquelet P, et al. Photodynamic therapy for subfoveal classic choroidal neovascularization related to punctate inner choroidopathy (PIC) or presumedocular histoplasmosis-like syndrome (POHS-like). Ocul Immunol Inflamm 2005;13:361366. Inflammatory choroidal neovascular membrane in posterior uveitis- pathogenesis and treatment.. Narendra Dhingra, Susan Kelly,mohammed A majid, claire b bailey, Andrew D Dick. Indian J Ophthalmol: 2010: 58:3-10

2.

3.

4.

Bevacizumab vs Photodynamic Therapyfor Choroidal Neovascularizationin Multifocal Choroiditis Maurizio Battaglia Parodi, MD; Pierluigi Iacono, MD; Dimitrios Stelyos Kontadakis, MD; Arch Ophthalmol. 2010;128(9):1100-1103Ilaria Zucchiatti, MD; Maria Lucia Cascavilla, MD; Francesco Bandello, MD
bevacizumab for choroida neovascularization related to nflammatory diseases michal kramer, md,* ruth axer-siegel, md,* tareq jaouni, md, ehud reich, md,* itzhak hemo, md, ethan priel, fops, edward averbukh, md, rita ehrlich, md,*itay chowers, md, dov weinberger, md,* radgonde amer, mdretina 30:938944, 2010

5.

6.

Intravitreal ranibizumab for the treatment of inflammatory choroidal neovascularizationalexander rouvas, md, phd,* petros petrou, md,* maria douvali, md,* amalia ntouraki, md,* ioannis vergados, md, phd,* ilias georgalas, md, phd, nikolaos markomichelakis, md, phdretina 31:871879, 2011

7.

ocular photodynamic therapywith verteporfin for choroidal neovascularization secondary to ocular histoplasmosis syndrome m.a. busquets,* g.k. shah,* j. wickens, d. callanan, k.j. blinder,* d. burgess,* m.g. grand,* n.m. holekamp,* i. boniuk,* d.p. joseph,*m.a. thomas,* e. fish, j. bakal, h. hollands, s. sharmaretina 23:299 306, 2003

8.

long-term visual outcomes of intravitreal bevacizumab in inflammatory ocular neovascularization ahmad m. mansour, j. fernando arevalo, fockeziemssen, abla mehio-sibai,friederike mackensen, alfredo adan, wai-man chan, thomas ness, alay s. banker,david dodwell, thi ha chau tran, christine fardeau, phuc lehoang,padmamalini mahendradas, maria berrocal, zuheir tabbarah, nicholas hrisomalos,frank hrisomalos, khalil al-salem, and rainer guthoffam j ophthalmol 2009;148:310316 subretinal neovascular membranes complicating uveitis: frequency,treatments, and visual outcome yannis perentes ab; van t. tran a; michel sickenberg c; carl p. herbort ab a inflammatory eye diseases, la source eye center, lausanne, and university of lausanne, lausanne,switzerland b university of lausanne, lausanne, switzerland c ouchy angiography and laser center,lausanne, switzerlandocular immunology and inflammation, 13:219224, 2005

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chan wm, lai ty, lau tt, lee vy, liu dt, lam ds. combined photodynamic therapy and intravitreal triamcinolone for choroidal neovascularization secondary to punctuate inner choroidopathy or of idiopathic origin: one-year results ofa prospective series. retina2008;28:7180.
essex rw, tufail a, bunce c, aylward gw. two-year results of surgical removal of choroidal neovascular membranes related to non age-related macular degeneration. br jophthalmol 2007;91:649654.

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