ROP and Imaging. Deborah M Costakos MD, MS August 12, 2016

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1 ROP and Imaging Deborah M Costakos MD, MS August 12, 2016

Acknowledgements Adam Dubis, Ph.D. Joseph Carroll, Ph.

Alana Trotter, MD Erika Philips Mara Goldberg

2 Acknowledgements Adam Dubis, Ph.D. Joseph Carroll, Ph.D. Ryan Vogel, MD Clinton Warren, MD C Devika Subramaniam, M.D. Fouad Zakla, M.D. Alana Trotter, MD Erika Philips Mara Goldberg CRA, OCT-C Derek Denney, MD Deb Felzer, RN Cathy Brault, RN Becky Baumler, RN Pooja Godora, M.D. Alf Dubra, Ph.D.

Work Supported by Russell and Betty Jane Shaw Fund NIH Grants P30EY001931, T32EY014537, R01EY017607 E.

3 Work Supported by Russell and Betty Jane Shaw Fund NIH Grants P30EY001931, T32EY014537, R01EY E. Matilda Ziegler Foundation for the Blind RD and Linda Peters Foundation Research to Prevent Blindness Research Facilities Improvement Program C06RR016511

4 The Numbers 3.9 million babies born per year in the US 60,000 infants born with birth weight <1500g are blinded each year Preterm births continue to rise (9%(1981) to 13%) Wt (g) ROP % St 3% Pre% Thr % < total

5 Imaging options in ROP RetCam Fluoroscein Angiography OCT Adaptive Optics

6 Imaging in ROP questions How does the macula and retina develop? Can imaging predict ROP in infants? Can findings direct treatment? Can imaging predict vision? What is limiting vision in premature infants?

7 ROP in Milwaukee 1100 Screening exams/year at 5 hospitals 400 exams done at CHW each year Handheld OCT available at Children s Hospital of Wisconsin (CHW) via Dr. Carroll s lab Enrollment for OCT study began in 4/2010

8 OCT SD-OCT imaging was performed on infants during routine ROP exams using Bioptigen Hand Held Probe SD-OCT Consent obtained by ROP coordinators Infants are not sedated Chavala et al. 2009

9 Repeatability

10 Immature versus mature retina 31-weeks PMA 23-year-old Maldonado et al Ophthalmology

11 Foveal pit development Foveal pit depth: average rim thickness / central foveal thickness Images with CME excluded

12 Foveal pit development 32 weeks PMA 40 weeks PMA 17 months Dubis et al Arch Ophthalmol

13 Foveal pit development Increased in depth by 4.05%/week (±2.76 SD) No significant difference between treated and untreated ROP groups (p=0.52) 35 wk PMA 38 wk PMA 41 wk PMA 43 wk PMA

Variation in foveal structure OCT findings in patients with ROP 1-4 Shallow/flat foveal depression Preserved inner retinal layers Thin photoreceptor layer Child born full-term Child with

14 Variation in foveal structure OCT findings in patients with ROP 1-4 Shallow/flat foveal depression Preserved inner retinal layers Thin photoreceptor layer Child born full-term Child with history of ROP 1. Villegas er al Am J Ophthalmol 2. Dubis et al Arch Ophthalmol 3. Wu et al Ophthalmology 4. Maldonado et al Ophthalmology Wu et al Ophthalmology

15 Persistent inner retinal layers Dubis et al Ophthalmology

16 Stage ROP with 1 persistent retinal layer Number Stage ROP A We have found persistent inner retinal layers in 93% of patients Not associated with ROP Does not appear to affect visual acuity in adults

17 Adaptive Optics IOVS 57(2):467-75,2016 Extrafoveal cone packing in patients with a history of ROP Low cone density in treated ROP (laser) but image quality was lower. Otherwise no significant cone loss Are the properties of the cones altered such that imaging and possibly function are altered?

18 CME

19 CME reported with ROP Subclinical CME ROP Stages Dubis et al. 54% (25/46) 0-4 Lee et al. 61% (23/38) 0-4 Maldonado et al. 58% (18/31) 0-2 Maldonado et al. 50% (21/42) 0-3 Vinekar et al. 16% (23/146) 0-2* * CME only seen in Stage 2 ROP [CME cystoid macular edema, ROP retinopathy of prematurity]

20 CME Can resolve spontaneously

21 CME can develop Before or after laser Before or after Bevacizumab Average time to development of CME is 37 weeks Bilateral in all cases

22 Asymmetric CME DC_ weeks PMA Right eye Left eye

23 OD Pre-laser

24 OD 1 week post laser

25 OS Pre- laser

26 OS 1 week post laser

27 Bevacizumab

28 Recurrent ROP s/p Bevacizumab Appear different than treatment naïve ROP Difficult to classify by ETROP guidelines Vascular anomalies terminal bulbs Shunt vessels peripheral plus May not have a ridge Neovascularization (peripheral disease) responds to laser

29 Recurrence of ROP with Bevacizumab

37 Fluoroscein angiography in persistent or recurrent ROP 3.3% (16/487) of our patients had ROP at > 45 weeks (45-64 weeks CGA) 2.4% (12/487) would meet criteria for ROP >50 weeks CGA 1.8% (9 cases) were treatment naïve 1.4% (7 cases) previously treated with bevacizumab FA done in 8 cases 7/8 had leakage on FA

38 Ex 31 week infant with Zone III Stage 2 ROP at 64 weeks CGA. Arborization without leakage.

39 Ex 23 week s/p Bevacizumab at 35 weeks with Zone 3 Stage 3 ROP at 51 weeks CGA. Arborization and leakage

40 Ex 23 week s/p Bevacizumab at 35 weeks now 51 weeks CGA with Zone III Stage 3

41 Fluoroscein Angiography and Persistent or Recurrent ROP 16 patients enrolled 7 previously treated with Bevacizumab Unusual findings on FA 9 treatment naive 45 weeks to 64 weeks 3.3% of patients beyond 45 weeks (1.8% of treatment naïve patients)

42 FA in Zone III ROP RetCam imaging is limited in zone 3 Clinical exam was consistent with FA findings Post bevacizumab findings are outside ETROP classification ETROP guidelines do not address treatment of zone 3 disease

43 Questions or Comments?

44 Thank You!

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