Dr Shrutika Kankariya DNBDr Suganeswari DO,DNBDr 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 Inactive uveitis

Hypoxia surrounding scar + Breach Bruch Membrane

Inflammation

1) Observation2) Laser Photocoagulation3) Local and Systemic steroids4) Photodynamic therapy( PDT5) Transpupillary

thermotherapy(TTT)

6) Anti VEGF ( bevacizumab and ranibizumab)

8) Surgical removal7) Combination therapy9) 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 µ of centre of fovea

Extra-foveal- CNVM > 200 µ 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

Unilateral – 17 patients. Bilateral- 5 patients.

14(38%)

(toxo)-5(14%)

(PU)-10(27%)

(SC)-6(16%)

- 2(5%)

CNVM was uniformly of classic type in all eyes

57%

100%

66%

100%

100%

MFC

MFC TOXOTOXO

SCSCVKHVKH

PUPU

Inactive

InactiveActive

Active

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

12%

41%

32%

9%

3% 3%No.

of

eyes

SS+ IMN

SS+ IMN

Avasti

n

Avasti

nPDTPDT

TTTTTT

Luce

ntis

Luce

ntisLa

ser

PHCLase

r

PHC

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).

44%

29% 26%

ImprovementImprovement StabilizationStabilization DeteriorationDeterioration

40%40%

128.7%128.7%

8.8%8.8%

-42.4%-42.4%

MFCMFC TOXOTOXOSCSC VKHVKHPUPU

38.2%38.2%17.5%17.5%

Active uveitisActive uveitis

40.1%40.1%

56.7%56.7%

-45.2%-45.2%

-1.8%-1.8%

Avastin SS + IMNTTTTTTPDTPDT

Treatment Regression (eyes)/total (eyes)

% Remarks

Systemic steroids (SS)

4/4 100% Severe inflammation,(>4+), PP cnvm,

Bevacizumab + SS

3/6 50% Inadequate control of underlying inflamation.5.2 injections (Avg-3.2)

PDT + SS 5/5 100% 2 eyes - Regression CNVM didn’t translate into visual gain (RPE atrophy).2 eyes- Delayed stabilization of vision

TTT + SS 1/2 50% Excessive Scarring

Regression (eyes)

Total eyes

% Remarks

Bevacizumab

5 7 71 % 2 eyes – Reactivation (inadequate scarring of CNVM)

PDT 6 6 100 % 1 eye- vision deteriorated (RPE atrophy)

TTT 1 1 100 %

Laser PHC 1 1 100 %

Ranibizumab

1 1 100 %

PDT+Bevacizumab

1 1 100 %

Authors No of eyes

Follow up Mean/max

DiseasesUveitis

Treatments studied

Our study(2013)

37 2.5 (22) MFC, SC, PU, Toxo, VKH(Active Vs Inactive)

Bevacizumab, PDT, TTT, SS Ranimizumab, PHC, Combi

Postelmans et al (2005)

16 1.5(2.5) PIC, POHS PDT

Kramar et al(2004)

10 1(2) MFC, POHS, Toxo, PIC, PU

Bevacizumab

Perentes et al(2010)

12 1.5(3) MFC, Sarcoid, Toxo, VKH

SS, PDT, TTT

Parodi et al(2010)

27 1 (1) MFC Bevacizumab vs pdt

Rouvas et al(2011)

15 1.5 (2.5) MFC, SC, PIC Toxo,

Ranibizumab only

Strength of our study1.Active uveitis Vs healed uveitis

2.Longer follow-up(10 eyes >5 years)3.Varied treatment modalities – different uveitic

entities. 4.Largest sample size from single centre .

Strength of our study1.Active uveitis Vs healed uveitis

2.Longer follow-up(10 eyes >5 years)3.Varied treatment modalities – different uveitic

entities. 4.Largest sample size from single centre .

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.

Timely initiation and judicious extension of CNVM targeted Rx (Anti VEGF + / PDT)

Long term + frequent F/U follow up until

complete scarring of cnvm is achieved and beyond ………..

Especially when on low

dose maintenance

RX

Especially when on low

dose maintenance

RX

Good compliance + adequate F/U

Thank You

1. Macular Photocoagulation Study Group. Argon laser photocoagulation for ocular histoplasmosis: results of a randomizedclinical trial. Arch Ophthalmol 1983;101:1347–1357.

2. 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;13:361–366. 

3. 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

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

5. 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, md‡§retina 30:938–944, 2010

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, phd†retina 31:871–879, 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. sharma§retina 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;148:310–316

9. 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, 13:219–224, 2005

10. 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;28:71–80.

11. 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;91:649–654.