Maturation of the Human Fovea: Correlation of Spectral-Domain Optical Coherence Tomography Findings With Histology

Vajzovic, Lejla; Hendrickson, Anita E.; O’Connell, Rachelle V.; Clark, Laura A.; Tran-Viet, Du; Possin, Daniel E.; Chiu, Stephanie J.; Farsiu, Sina; Toth, Cynthia A.

doi:10.1016/j.ajo.2012.05.004

Cited by 196 publications

(187 citation statements)

References 34 publications

(50 reference statements)

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“…Consistent with previous reports, we found that the OS and ISE cannot always be visualized in the central fovea before 46 weeks GA. 5,8 This contrasts with histological findings, where the IS and OS can always be visualized at the fovea from birth in term infants. The IS and OS may be too short and immature perinatally to form a visible band on OCT. 8 Possibly, the photoreceptors are undergoing centripetal migration and elongation at different rates in individual infants, explaining why bands corresponding to the IS and OS on OCT are not visible in all newborns at the central fovea.…”

Section: Discussionmentioning

confidence: 41%

“…The IS and OS may be too short and immature perinatally to form a visible band on OCT. 8 Possibly, the photoreceptors are undergoing centripetal migration and elongation at different rates in individual infants, explaining why bands corresponding to the IS and OS on OCT are not visible in all newborns at the central fovea.…”

Section: Discussionmentioning

confidence: 99%

“…This included a study of foveal development after premature birth, which included 4 term infants aged between 1 and 9 months and 4 children aged between 2 and 5 years, and a second study that described human foveal maturation using OCT and histology, which included 30 term infants and 16 children. 5,8 The developmen- tal trajectories described in this study follows on directly from those described previously in premature infants. 5,8 A direct comparison of the mean retinal layer thickness values reported in our study with those previously reported is limited by the differences in the age ranges used to calculate mean retinal layer thickness values.…”

Section: Discussionmentioning

confidence: 99%

“…5,8 The developmen- tal trajectories described in this study follows on directly from those described previously in premature infants. 5,8 A direct comparison of the mean retinal layer thickness values reported in our study with those previously reported is limited by the differences in the age ranges used to calculate mean retinal layer thickness values. For example, in the study by Maldonado et al, 5 a mean value of 10 lm for inner retinal layer thickness was reported for infants aged between 1 and 9 months.…”

Section: Discussionmentioning

confidence: 99%

“…1). 7,8 Each of these layers on OCT corresponds to its histologically named equivalent with the exception of the ONL and OPL. 7 The axons of the photoreceptors (Henle fiber layer) that are part of the OPL on histology have similar reflectivity as the ONL on OCT.…”

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confidence: 99%

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In Vivo Foveal Development Using Optical Coherence Tomography

Lee

Purohit

Patel

et al. 2015

Invest. Ophthalmol. Vis. Sci.

110

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PURPOSE.To characterize the time course of normal foveal development in vivo in term infants and young children using handheld spectral-domain optical coherence tomography (HH-SDOCT). METHODS.We obtained 534 HH-SDOCT scans from 261 infants, children, and young adults with a mean age of 4.9 years (range, 0-27 years). Each retinal layer was manually segmented in ImageJ and correlated with gestational age (GA) and visual acuity (VA). The developmental trajectories of each retinal layer at the fovea, parafovea, and perifovea were calculated using fractional polynomial modeling.RESULTS. The central macular thickness (CMT) increases logarithmically between birth and 48.6 months GA. The foveal ganglion cell (GCL), inner plexiform, inner nuclear (INL), and outer plexiform layers decrease in thickness exponentially until 18 months GA. Interestingly, the parafoveal and perifoveal GCL and INL thicknesses initially decrease until 17 months GA and then increase in thickness until 65.5 GA. The foveal outer nuclear layer, inner segment, and outer segment of the photoreceptors increase in thickness logarithmically until 32.4, 26.9, and 45.3 months GA, respectively. The parafoveal and perifoveal outer retinal layers increase in thickness more gradually until 146 months GA. The thickness of the outer retinal layers and CMT were strongly correlated with VA, with r ¼ 0.54 (P < 0.0001) and r ¼ 0.52 (P < 0.0001), respectively. CONCLUSIONS.We have modeled for the first time the complex, nonlinear developmental trajectories for each retinal layer and demonstrate that development continues until adolescence. Our description of normal development will be helpful in diagnosing, monitoring, and understanding pediatric retinal disease.

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Section: Discussionmentioning

confidence: 41%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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In Vivo Foveal Development Using Optical Coherence Tomography

Lee

Purohit

Patel

et al. 2015

Invest. Ophthalmol. Vis. Sci.

110

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Structural Abnormalities of the Inner Macula in Incontinentia Pigmenti

et al. 2015

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ncontinentia pigmenti (IP), or Bloch-Sulzberger syndrome, is a rare X-linked dominant disorder mainly seen in females because a single allele in male embryos is usually fatal. 1,2 Incontinentia pigmenti usually presents with a characteristic skin rash that leaves hypopigmented patches on the trunk and limbs. 3 The most serious events involve the retina and central nervous system (CNS) in 18% to 30%. [2][3][4][5] Loss-offunction mutations in IKBKG/NEMO impair nuclear factorkappa B (NF-κB) signaling and are responsible for most cases of IP. 6,7 Although NF-κB signaling is ubiquitous, effects from the IKBKG/NEMO mutation do not manifest in all tissues.Vision loss has been associated with vascular occlusions, secondary extraretinal neovascularization (NV), tractional retinal detachments, 2,5,8 and foveal hypoplasia. 8 Herein, we report findings from spectral-domain optical coherence tomography (SD-OCT) in children with IP examined before age 5 years. Poor visual behavior corresponded with inner retinal structural abnormalities.IMPORTANCE This report presents evidence from spectral-domain optical coherence tomography and fluorescein angiography of inner foveal structural abnormalities associated with vision loss in incontinentia pigmenti (IP).OBSERVATIONS Two children had reduced visual behavior in association with abnormalities of the inner foveal layers on spectral-domain optical coherence tomography. Fluorescein angiography showed filling defects in retinal and choroidal circulations and irregularities of the foveal avascular zones. The foveal to parafoveal ratios were greater than 0.57 in 6 eyes of 3 patients who had extraretinal neovascularization and/or peripheral avascular retina on fluorescein angiography and were treated with laser. Of these, 3 eyes of 2 patients had irregularities in foveal avascular zones and poor vision.CONCLUSIONS AND RELEVANCE Besides traction retinal detachment, vision loss in IP can occur with abnormalities of the inner foveal structure seen on spectral-domain optical coherence tomography, consistent with prior descriptions of foveal hypoplasia. The evolution of abnormalities in the neural and vascular retina suggests a vascular cause of the foveal structural changes. More study is needed to determine any potential benefit of the foveal to parafoveal ratio in children with IP. Even with marked foveal structural abnormalities, vision can be preserved in some patients with IP with vigilant surveillance in the early years of life.

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Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome

et al. 2017

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IMPORTANCE A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS).OBJECTIVE To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. DESIGN, SETTING, AND PARTICIPANTSThis case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. MAIN OUTCOMES AND MEASURESThe SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles.RESULTS Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer. The inner nuclear layer was normal or had borderline thinning. The central retinal degeneration was similar to that of cblC deficiency. CONCLUSIONS AND RELEVANCE CongenitalZika syndrome showed a central retinal degeneration with severe GCL loss, borderline inner nuclear layer thinning, and less prominent photoreceptor loss. The findings provide the first, to date, in vivo evidence in humans for possible retinal maldevelopment with a predilection for retinal GCL loss in CZS, consistent with a murine model of the disease and suggestive of in utero depletion of this neuronal population as a consequence of Zika virus infection.

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Maturation of the Human Fovea: Correlation of Spectral-Domain Optical Coherence Tomography Findings With Histology

Cited by 196 publications

References 34 publications

In Vivo Foveal Development Using Optical Coherence Tomography

In Vivo Foveal Development Using Optical Coherence Tomography

Structural Abnormalities of the Inner Macula in Incontinentia Pigmenti

Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome

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