A spectral-domain OCT study of formerly premature children. Prat Itharat MD May 30, 2008 Vanderbilt Eye Institute Preceptor: Dr.

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1 A spectral-domain OCT study of formerly premature children. Prat Itharat MD May 30, 2008 Vanderbilt Eye Institute Preceptor: Dr. Recchia

2 Background: Optical coherence tomography (OCT) OCT analogous to ultrasound imaging Non-invasive Uses light waves Many applications in ophthalmology

3 Background: OCT Zeiss Stratus OCT Time Zeiss Domain Cirrus HD-OCT (Meditec, Dublin, CA) Acquires 6 linear 200 B-scans linear B- scans Fewer data points sampled More data points sampled Slower Faster scanning scanning time time Better resolution: up to 5 Resolution: up to 10 microns microns Less concern for eccentric More fixation concern and for eccentric technical fixation and skills technical skills Zeiss Cirrus HD-OCT Spectral Domain (Meditec, Dublin, CA) Zeiss Stratus OCT Acquires 200 linear B-scans Acquires 6 linear B- scans Fewer data points sampled Slower scanning time Resolution: up to 10 microns More concern for eccentric fixation and technical skills More data points sampled Faster scanning time Better resolution: up to 5 microns Less concern for eccentric fixation and technical skills

4 Background: SD vs TD OCT Spectral Domain Time Domain Courtesy of Zeiss Whitepaper

5 Background: Prematurity

6 Background: Prematurity Escedy et al (2007) noted increase central retinal thickness in formerly premature children Stratus OCT Mainly due to presence to ROP

7 Recchia et al (2007) showed OCT abnormalities in ROP patients - first to suggest that changes may be vestiges of prematurity

8 Recchia et al (2007) showed OCT abnormalities in ROP patients - first to suggest that changes may be vestiges of prematurity

9 Recchia et al (2007) showed OCT abnormalities in ROP patients - first to suggest that changes may be vestiges of prematurity

10 Limitations Technologically Methodologically

11 Hypothesis: OCT abnormalities are more common in formerly premature children than in full term children.

12 OCT and prematurity Study questions: 1. Is there a difference in macular thickness between premature and full-term children? 2. Is there a difference in foveal contour between these groups? 3. Are the OCT findings correlated to the presence of ROP or another variable?

13 Methods IRB approval for prospective study Records of formerly premature infants born prior to 1/1/2001 (treated in the Vanderbilt NICU) Control group matched for age and refractive error

14 Methods Group I: premature with ROP (<32 weeks gestational age) Group II: premature without ROP (<32 weeks gestational age) Group III: full term (>36 weeks gestational age)

15 Methods Gestational age, birth weight, ROP status obtained from records Cycloplegic refraction Best corrected visual acuity

16 Methods Quantitative primary outcome measures (OCT) -central subfield thickness -inner (ring) macular thickness -outer (ring) macular thickness -total macular volume

17 Methods Qualitative primary outcome measures (OCT) -presence of foveal depression -preservation of retinal layers

18 Methods OCT data were reviewed by a trained physician (FMR) masked to the birth history of the patient Quality of all scans was assessed and any scans with a signal strength less than 8/10 were discarded For each eye, a 6 x 6 mm macular cube and 5-line macular raster line scan were interpreted individually

19 Results: Eyes

20 Results:

21 Results: Central subfield thickness

22 Results: Inner ring retinal thickness

23 Results: Outer ring retinal thickness

24 Results: Total macular volume

25 Results: Foveal contour

26 Results: Central subfield thickness : inner ring thickness

27 Results: Gestational age effect?

28 Discussion: Significant effect of gestational age Non-significant effect of ROP In contrast to prior studies which suggest that ROP is the major determinant of OCT abnormalities

29 Discussion: Foveal development Foveal depression occurs by a reduction of inner (ganglion cell and inner nuclear) layers of the retina Evident by weeks of gestation Continues until four months postnatally Diagram from Provis et al.

30 Discussion: Foveal development Mintz-Hittner et al described smaller foveal avascular zone (FAZ) in formerly premature children Provis et al showed that the formation of the FAZ (vascular border) precedes foveal depression These two processes may be interrelated

31 Discussion: Foveal development Prematurity may change retinal oxygenation Disruption of FAZ and foveal formation -Blunted/absent foveal depression -Thickened central macula -Preservation of retinal layers Interestingly, most of our patients had excellent visual acuity

32 Limitations Selection bias (less severe ROP, less severe neurological disease) Non-matched gestational age Most ROP staging obtained indirectly through NICU discharge summaries Inter-rater variability of ROP

33 Conclusions OCT findings such as increased central macular thickness and foveal depression blunting may represent hallmarks of prematurity These findings can be associated with normal visual acuity

34 Clinical relevance Greater use of OCT in evaluation of patients with decreased visual acuity OCT abnormalities may not represent ocular disease Research studies in which numerical cutoffs are made for inclusion or evaluation of therapeutic response

35 Acknowledgements

36 References Ecsedy M, Szamosi A, Karko C, Zubovics L, Varsanyl B, Nemeth J, Recsan Z. A comparison of Macular Structure Imaged by Optical Coherence Tomography in Preterm and Full-Term Children. Investigative Ophthalmology & Visual Science. November 2007; 48(11), Fleck BW, McIntosh N. Pathogenesis of retinopathy of prematurity and possible preventive strategies. Early Human Development 2008; 84: Fulton AB, Hansen RM, Moskowitz A, Barnaby Am. Multifocal ERG in subjects with a history of retinopathy of prematurity. Doc. Ophthal. 2005; 111:7-13. Hammer DX, Iftimia N, Ferguson RD, Bigelow CE, Ustun TE, Barnaby AM, Fulton AB. Foveal Fine Structure in Retinopathy of Prematurity: An Adaptive Optics Fourier Domain Optical Coherence Tomography Study. IOVS. May 2008; 49(5), Hendrickson AE and Yuodelis C. The morphological development of the huma fovea. Ophthalmology 1984; 91, Leung CKS, Cheung CYL, Weinreb RN, Lee G, Lin D, Pang CP, Lam DSC. Comparison of macular thickness measurements between time domain and spectral domain optical coherence tomography. IOVS 2008 O Conno AR, Wilson CM, Fielder AR. Ophthalmological problems associated with preterm birth. Eye 2007; 21, Provis JM, Diaz CM, Dreher B. Ontogeny of the primate fovea: a central issue in retinal development. Progress in Neurobiology 1998; 54, Provis JM, Sandercoe T, Hendrickson A. Astrocytes and blood vessels define the foveal rim during primate retinal development. IOVS 2000; 41(10), Provis, JM. Development of the Primate Retinal Vasculature. Progress in Retinal and Eye Research 20(6), Recchia FM, Recchia CC. Foveal Dysplasia Evident by Optical Coherence Tomography in Patients with a History of Retinopathy of Prematurity. Retina 2007; Stout AU, South JM. Retinopathy of Prematuirty. Ped Clin N Am 2003; 50,

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