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A spectral-domain OCT study of formerlypremature children.

Prat Itharat MD

May 30, 2008

Vanderbilt Eye Institute

Preceptor: Dr. Recchia

Background: Optical coherence tomography (OCT)

OCT analogous to ultrasound imaging

Non-invasive

Uses light waves

Many applications in ophthalmology

Background: OCT

Zeiss Cirrus HD-OCT(Meditec, Dublin, CA)

Acquires 200 linear B-scans

More data pointssampled

Faster scanning time Better resolution: up to 5

microns Less concern for eccentric

fixation and technicalskills

Zeiss Stratus OCT

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

Zeiss Stratus OCTTime Domain

Zeiss Cirrus HD-OCTSpectral Domain(Meditec, Dublin, CA)

Acquires 6 linear B-scans Acquires 200 linear B-scans

Fewer data points sampled More data points sampled

Slower scanning time Faster scanning time

Resolution: up to 10 microns Better resolution: up to 5 microns

More concern for eccentric fixationand technical skills

Less concern for eccentric fixationand technical skills

Background: SD vs TD OCT

Spectral Domain Time Domain

Courtesy of Zeiss Whitepaper

Background: Prematurity

Background: Prematurity

Escedy et al (2007) noted increase centralretinal thickness in formerly prematurechildren

Stratus OCT

Mainly due to presence to ROP

Recchia et al (2007) showed OCT abnormalities inROP patients - first to suggest that changes may bevestiges of prematurity

Recchia et al (2007) showed OCTabnormalities in ROP patients - first tosuggest that changes may be vestiges ofprematurity

Recchia et al (2007) showed OCTabnormalities in ROP patients - first tosuggest that changes may be vestiges ofprematurity

Limitations

Technologically

Methodologically

Hypothesis:

OCT abnormalities are more common in

formerly premature children than in full term

children.

OCT and prematurity

Study questions:1. Is there a difference in macular thickness

between premature and full-termchildren?

2. Is there a difference in foveal contourbetween these groups?

3. Are the OCT findings correlated to thepresence of ROP or another variable?

Methods

IRB approval for prospective study

Records of formerly premature infantsborn prior to 1/1/2001 (treated in theVanderbilt NICU)

Control group matched for age andrefractive error

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)

Methods

Gestational age, birth weight, ROPstatus obtained from records

Cycloplegic refraction

Best corrected visual acuity

Methods

Quantitative primary outcome measures(OCT)

-central subfield thickness

-inner (ring) macular thickness

-outer (ring) macular thickness

-total macular volume

Methods

Qualitative primary outcome measures(OCT)

-presence of foveal depression

-preservation of retinal layers

Methods

OCT data were reviewed by a trainedphysician (FMR) masked to the birthhistory of the patient

Quality of all scans was assessed and anyscans with a signal strength less than 8/10were discarded

For each eye, a 6 x 6 mm macular cube and5-line macular raster line scan wereinterpreted individually

Results: Eyes

Results:

Results: Central subfield thickness

Results: Inner ring retinal thickness

Results: Outer ring retinal thickness

Results: Total macular volume

Results: Foveal contour

Results: Central subfield thickness : inner ring thickness

Results: Gestational age effect?

Discussion:

Significant effect of gestational age

Non-significant effect of ROP

In contrast to prior studies which suggest thatROP is the major determinant of OCTabnormalities

Discussion: Foveal development

Foveal depression occursby a reduction of inner(ganglion cell and innernuclear) layers of theretina

Evident by 24-25 weeks ofgestation

Continues until fourmonths postnatally

Diagram from Provis et al.

Discussion: Foveal development

Mintz-Hittner et al described smaller fovealavascular zone (FAZ) in formerly prematurechildren

Provis et al showed that the formation ofthe FAZ (vascular border) precedes fovealdepression

These two processes may be interrelated

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 excellentvisual acuity

Limitations

Selection bias (less severe ROP, less severeneurological disease)

Non-matched gestational age

Most ROP staging obtained indirectlythrough NICU discharge summaries

Inter-rater variability of ROP

Conclusions

OCT findings such as increased centralmacular thickness and foveal depressionblunting may represent hallmarks ofprematurity

These findings can be associated withnormal visual acuity

Clinical relevance

Greater use of OCT in evaluation ofpatients with decreased visual acuity

OCT abnormalities may not representocular disease

Research studies in which numericalcutoffs are made for inclusion or evaluationof therapeutic response

Acknowledgements

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. InvestigativeOphthalmology & Visual Science. November 2007; 48(11), 5207-5211.

• Fleck BW, McIntosh N. Pathogenesis of retinopathy of prematurity and possible preventive strategies. EarlyHuman Development 2008; 84: 83-88.

• Fulton AB, Hansen RM, Moskowitz A, Barnaby Am. Multifocal ERG in subjects with a history ofretinopathy of prematurity. Doc. Ophthal. 2005; 111:7-13.

• Hammer DX, Iftimia N, Ferguson RD, Bigelow CE, Ustun TE, Barnaby AM, Fulton AB. Foveal FineStructure in Retinopathy of Prematurity: An Adaptive Optics Fourier Domain Optical CoherenceTomography Study. IOVS. May 2008; 49(5), 2061-2070.

• Hendrickson AE and Yuodelis C. The morphological development of the huma fovea. Ophthalmology 1984;91, 603-612.

• Leung CKS, Cheung CYL, Weinreb RN, Lee G, Lin D, Pang CP, Lam DSC. Comparison of macularthickness measurements between time domain and spectral domain optical coherence tomography. IOVS2008

• O’Conno AR, Wilson CM, Fielder AR. Ophthalmological problems associated with preterm birth. Eye2007; 21, 1254-1260.

• Provis JM, Diaz CM, Dreher B. Ontogeny of the primate fovea: a central issue in retinal development.Progress in Neurobiology 1998; 54, 549-581.

• Provis JM, Sandercoe T, Hendrickson A. Astrocytes and blood vessels define the foveal rim during primateretinal development. IOVS 2000; 41(10), 2827-2836.

• Provis, JM. Development of the Primate Retinal Vasculature. Progress in Retinal and Eye Research 20(6),799-821.

• Recchia FM, Recchia CC. Foveal Dysplasia Evident by Optical Coherence Tomography in Patients with aHistory of Retinopathy of Prematurity. Retina 2007; 27-1221-1226.

• Stout AU, South JM. Retinopathy of Prematuirty. Ped Clin N Am 2003; 50, 77-87.

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