ARVO 2014 Annual Meeting Abstracts
374 Myopia
Tuesday, May 06, 2014 3:45 PM–5:30 PM
Exhibit/Poster Hall SA Poster Session
Program #/Board # Range: 3587–3614/A0036–A0063
Organizing Section: Anatomy/Pathology
Program Number: 3587 Poster Board Number: A0036
Presentation Time: 3:45 PM–5:30 PM
Relationship between axial length and 64 cells retinal thickness or
optic disc-to-fovea angle in young healthy eyes
Takehiro Yamashita, Taiji Sakamoto, Yuya Kii, Minoru Tanaka,
Kumiko Nakao. Ophthalmology, Kagoshima University, Kagoshima,
Japan.
Purpose: To determine relationship between axial length and 64 cells
retinal thickness with posterior pole asymmetry scan (PPA) or optic
disc-to-fovea angle (OFA) in young healthy eyes.
Methods: A prospective study of 64 healthy right eyes was
performed. All participants (mean age 25.6 ± 3.5) underwent
comprehensive ophthalmologic examination, including axial length,
color fundus photographs and optical coherence tomography
(OCT). The 64 cells retinal thicknesses were measured by the PPA
of Spectralis SD-OCT. The OFA was calculated using the fundus
photographs. The relationships between the retinal thickness of the 64
cells or the OFA and the axial length were investigated using linear
regression analysis.
Results: Retinal thicknesses of central 4 cells were not significantly
correlated with the axial length (R=-0.07 to 0.01, p >0.05). Retinal
thicknesses of almost other cells (54 cells) were significantly
negatively correlated with the axial length (R=-0.25 to -0.56, p
<0.05). The OFA was not significantly correlated with the axial length
(R=-0.17, p=0.19).
Conclusions: The retinal thicknesses of the central 4 cells and OFA
were constant regardless of the axial length in young healthy eyes.
Commercial Relationships: Takehiro Yamashita, None; Taiji
Sakamoto, None; Yuya Kii, None; Minoru Tanaka, None; Kumiko
Nakao, None
Clinical Trial: UMIN000006040
Program Number: 3588 Poster Board Number: A0037
Presentation Time: 3:45 PM–5:30 PM
Genome-wide scleral micro- and messenger-RNA profiling in the
mouse myopia model
Ravi Metlapally1, Hanna Park2, Kevin Wang1, Christopher C. Tan2,
Jacob G. Light2, Machelle T. Pardue2, 3, Christine Wildsoet1, 4.
1
Optometry, UC Berkeley, Berkeley, CA; 2Ophthalmology, Emory
University, Atlanta, GA; 3Rehab R&D Center of Excellence, Atlanta
VA Medical Center, Atlanta, GA; 4Vision Science Graduate Group,
UC Berkeley, Berkeley, CA.
Purpose: miRNAs (micro-RNAs) play critical roles in normal
physiological as well as disease processes. Recent studies implicated
miRNAs in scleral remodeling and normal ocular growth. Through
the modulation of scleral extracellular matrix genes, miRNAs have
potential to be therapeutic scleral targets for myopia prevention/
retardation strategies. As a first step, genome-wide miRNA and
mRNA (messenger-RNA) expression profiles in myopic and control
eyes of mice were studied using microarray analyses.
Methods: C57BL/6J mice (n=7, P28), reared under a 12 hr lightdark cycle, were form-deprived (FD) unilaterally for 2 weeks.
Refractive error and axial length measurements were made using
photorefraction and 1310nm SD-OCT. Scleral RNA samples from
FD and control eyes were processed for mirBASE version 19 miRNA
(1279 miRNAs) and Affymetrix GeneChip Gene 2.0 ST (>28000
mRNAs) microarrays. Statistical analyses were performed using
the NIA (National Institute on Aging) Array Analysis Tool. Briefly,
raw data were background subtracted, log-transformed, normalized
and average intensities as well as fold differences calculated. Group
comparisons were made using ANOVA. Functional biological
pathways were identified using WebGestalt software.
Results: FD eyes showed myopic shifts in refractive error (mean
interocular difference: -2.90 +/- 0.86D, p<0.05). Comparison of
scleral RNA profiles for FD and control eyes revealed a total of 54
miRNAs and 261 mRNAs differentially expressed (fold change >1.25
fold in either direction, max FC=1.63 for miRNA, 2.7 for mRNA)
(p<0.05, min p=0.0001). miRNAs of the let-7 family, previously
implicated in matrix remodeling in other tissues, were upregulated
in eyes developing axial myopia. Notable statistically significant
(p<0.05) pathways showing over-representation of genes included
intermediate filament organization, scaffold protein binding, detection
of stimuli, calcium ion, G-protein, and photo-transduction pathways.
Conclusions: A number of scleral mi- and m-RNAs showed
differential expression linked to myopia in the mouse model, further
supporting the involvement of miRNAs in scleral remodeling. The
observed general trend of relatively small fold changes is perhaps
indicative of a tightly controlled regulatory mechanism for scleral
gene expression. Further validation and molecular studies aimed at
understanding specific mechanisms related to myopia are planned.
Commercial Relationships: Ravi Metlapally, None; Hanna Park,
None; Kevin Wang, None; Christopher C. Tan, None; Jacob G.
Light, None; Machelle T. Pardue, None; Christine Wildsoet, None
Support: NIH-NEI K08EY022670 to RM, NIH-NEI R01016435 to
MTP, NIH-NEI R01 EY012392 to CFW
Program Number: 3589 Poster Board Number: A0038
Presentation Time: 3:45 PM–5:30 PM
Spatial and temporal mapping of retinal sublayer and choroidal
thicknesses in the chick using 3-dimensional segmentation with
optical coherence tomography imaging
Diane Nava1, 4, Akhila Raman1, Claudia Nieuwenhuis2, Anwar
Nunez-Elizalde3, Christine Wildsoet1, 4. 1Vision Science Group,
UC Berkeley, Berkeley, CA; 2Department of Computer Science,
Technische Universität München, Garching, Germany; 3Helen Wills
Neuroscience Institute, UC Berkeley, Berkeley, CA; 4Center for Eye
Disease and Development, UC Berkeley, Berkeley, CA.
Purpose: Interest in changes in thickness of the retina (RT) and
choroid (CT) has grown in myopia research, yet studies using
animal models typically use A-scan ultrasonography (US), which is
limited to on-axis measurements, and blockface photography, which
precludes longitudinal tracking. This study sought to exploit in vivo
spectral domain optical coherence tomography (SD-OCT) imaging to
cover the latter deficiencies.
Methods: Young chicks were fitted with either monocular +5 D
single vision (SV) lenses or multifocal (MF) lenses with a +5 D
peripheral defocus. For each eye, several overlapping rectangular
and radial SD-OCT scans covering central and peripheral retina and
choroid were collected (14x14 mm FOV, 100 b-scans, Bioptigen,
NC). Scans were segmented to extract RT and CT using a custom
automated algorithm or a manual segmentation software that uses
defined boundaries from points projected from an 11 by 11 grid. The
data were then reconstructed in 3D and smoothed using a pythonbased algorithm. 3D maps of overlapping scans were merged, after
which the absolute nasal, temporal, superior and inferior fields were
redefined using the angle of the pectin and the location of the area
centralis (AC). Interocular and temporal thickness difference maps
were obtained through registration. Data were compared to RT and
CT from US, photographs of embedded blocks and 10 um vertical
sections.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Results: Peripheral choroidal thickening was detected in the MF
group. RT and CT data obtained with our custom method were
comparable to values obtained from manual calipers, US, blockface
photography, and histological sections, with improved interobserver reliability and resolution. The retinal ganglion cell layer
thickness maps show a peak superior and nasal to the tip of the
pectin, consistent with histological data defining the AC, and served
as a useful reference for validating segmentation algorithms and
quantifying lens-induced regional CT changes.
Conclusions: Our new methods for the visualization and
quantification of chick SD-OCT data allows for fast and accurate
characterization of point-to-point regional and temporal differences
in RT and CT in vivo, providing valuable new insight into the effects
of novel optical defocus manipulations, as well as ex vivo, providing
a replacement for photography applied to blockfaces and histological
sections.
Commercial Relationships: Diane Nava, None; Akhila Raman,
None; Claudia Nieuwenhuis, None; Anwar Nunez-Elizalde, None;
Christine Wildsoet, None
Support: NIH Grant EY12392, NIGMS Grant R25GM090110
Program Number: 3590 Poster Board Number: A0039
Presentation Time: 3:45 PM–5:30 PM
Chick Retinal Pigment Epithelium Responds to Imposed Defocus
in Minutes
Yan Zhang, Albert Truong, Feng Zhao, Christine Wildsoet. Center
for Eye Disease & Development, School of Optometry, Univ of
California, Berkeley, Berkeley, CA.
Purpose: We previously reported that gene expression of BMP2, 4,
and 7 in chick RPE show differential regulation by optical defocus
in as little as 2 hours, which suggest their involvement of RPE in
the early stage of eye growth regulation. This study was conducted
to further characterize the temporal profile of these defocus-induced
BMP gene expression changes in the chick RPE
Methods: White-Leghorn chicks wore monocular -10 or +10 D
lenses from 14 days of age for 5, 15, 30 or 60 minutes. At the end of
the lens treatment periods, chicks were sacrificed, eyes enucleated,
RPE isolated and RNA extract. RNA was subjected to cDNA
synthesis and then qPCR. Expression levels for lens-treated eyes
were compared to those of their fellow eyes
Results: As reported previously, differences in BMP gene expression
were detected in chick RPE samples from eyes subjected to positive
(+) versus negative (-) lens treatments. With positive lenses, 5 and
30 min of wear was sufficient to up-regulate the gene expression of
BMP2 and BMP4 in treated eyes respectively, with up-regulation
also detected at the other 3 time points for BMP2 and 60 minutes
treatment for BMP4. For 5, 15, 30 and 60 min of +lens treatment,
BMP2 was up-regulated 2.0-fold (p < 0.05, n = 5), 3.4-fold (p < 0.05,
n = 7), 11.3-fold (p < 0.01, n = 7), and 5.0-fold (p < 0.001, n = 7),
respectively, while BMP4 was up-regulated 7.8-fold (p < 0.05, n =
7) and 2.9-fold (p < 0.05, n = 7) after 30 and 60 minutes of treatment
respectively. In contrast, BMP7 did not show differential expression
with these short 5-60 min +lens treatments, and nor was differential
expression detected with 5, 30, and 60 min of -lens treatment for
these three BMPs. A trend of down-regulation of BMP2 was observed
after 60 minutes of -lens treatment (6 out of 8 birds), but curiously,
this gene showed significant up-regulation at 15 minutes (2.5-fold, p
< 0.05, n = 8)
Conclusions: This study provides further evidence for the
involvement of the RPE in eye growth regulation signaling cascades.
The differences in the temporal profiles of gene expression changes
induced by positive versus negative lenses, i.e., positive lenses
inducing very rapid changes, suggest different pathways are involved.
Finally, differences in the temporal profiles of the three genes studied
- BMP2, 4 and 7, suggest that they are regulated differently. These
proteins may interact synergistically across time during eye growth
regulation
Commercial Relationships: Yan Zhang, None; Albert Truong,
None; Feng Zhao, None; Christine Wildsoet, None
Support: NIH grants R01EY012392 (CFW), K08EY023609 (YZ),
K12EY017269 (YZ)
Program Number: 3591 Poster Board Number: A0040
Presentation Time: 3:45 PM–5:30 PM
Quantitative analysis of tessellated fundus and its association
with choroidal thickness in healthy eyes
Naoya Yoshihara, Takehiro Yamashita, Yuya Kii, Minoru Tanaka,
Kumiko Nakao, Taiji Sakamoto. Ophthalmology, Kagoshima
University, Kagoshima, Japan.
Purpose: To investigate the relationship between the tessellated
fundus index (TFI) and choroidal thickness (CT) by the objective
method.
Methods: A prospective observational cross-sectional study
comprised 100 right eyes of 100 healthy young Japanese participants.
All participants (mean age 25.8 ± 3.9) underwent comprehensive
ophthalmologic examination, including axial length, color fundus
photograph. The subfoveal choroidal thickness (SFCT) and the
nasal choroidal thickness (NCT) being located 750 μm nasal
from the fovea were measured using enhanced depth imaging of
Spectralis OCT. Fundus color between the fovea and the optic disc
was quantified on digital color fundus photographs as a surrogate
of the degree of the tessellated fundus using Image J. The TFIs was
calculated as the ratio of mean red-green-blue (RGB) intensity. We
used following three formula; TFI1: (R-G)/R, TFI2: R/(R+G+B),
TFI3: (R-G)/(R+G+B). The relationship between the TFIs and the
choroidal thickness and the axial length was investigated using linear
regression analysis.
Results: The mean axial length was 25.3 ± 1.4 mm. The all TFIs
were significantly associated with the SFCT or NCT (R=-0.20 to
-0.24, p<0.05). The correlation coefficients between the TFI2 and
SFCT or NCT were higher than the correlation coefficients between
the TFI1 or TFI3 and SFCT or NCT. However, all the TFIs were not
significantly associated with the axial length.
Conclusions: The degree of tessellated fundus was increased as the
choroidal thickness decreased in young healthy eyes.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Commercial Relationships: Naoya Yoshihara, None; Takehiro
Yamashita, None; Yuya Kii, None; Minoru Tanaka, None;
Kumiko Nakao, None; Taiji Sakamoto, None
Clinical Trial: UMIN000006040
Program Number: 3592 Poster Board Number: A0041
Presentation Time: 3:45 PM–5:30 PM
Is Retinal Shape different in Asians and Caucasians?
Estimation from Peripheral Refraction and Peripheral Eye
Length Methods
Pavan K. Verkicharla1, David A. Atchison1, Marwan Suheimat1,
Katrina L. Schmid1, Ankit Mathur1, Edward A. Mallen2, Xin Wei3,
Noel A. Brennan3. 1School of Optometry & Vision Science, Institute
of Health & Biomedical Innovation, Queensland University of
Technology, Brisbane, QLD, Australia; 2School of Optometry and
Vision Science, University of Bradford, Bradford, United Kingdom;
3
Johnson & Johnson Vision Care, Inc., Jacksonville, FL.
Purpose: Race appears to be associated with myopiogenesis,
with East Asians showing high myopia prevalence. Considering
structural variations in the eye, it is possible that retinal shapes are
different between races. The purpose of this study was to quantify
and compare retinal shapes between racial groups using peripheral
refraction (PR) and peripheral eye lengths (PEL).
Methods: A Shin-Nippon SRW5000 autorefractor and a Haag-Streit
Lenstar LS900 biometer measured PR and PEL, respectively, along
horizontal (H) and vertical (V) fields out to ±35° in 5° steps in 29
Caucasian (CA), 16 South Asian (SA) and 23 East Asian (EA) young
adults (spherical equivalent range +0.75D to −5.00D in all groups).
Retinal vertex curvature Rv and asphericity Q were determined from
two methods:
a) PR (Dunne): The Gullstrand-Emsley eye was modified according
to participant’s intraocular lengths and anterior cornea curvature.
Ray-tracing was performed at each angle through the stop, altering
cornea asphericity until peripheral astigmatism matched experimental
measurements. Retinal curvature and hence retinal co-ordinate
intersection with the chief ray were altered until sagittal refraction
matched its measurement.
b) PEL: Ray-tracing was performed at each angle through the anterior
corneal centre of curvature of the Gullstrand-Emsley eye. Ignoring
lens refraction, retinal co-ordinates relative to the fovea were
determined from PEL and trigonometry.
From sets of retinal co-ordinates, conic retinal shapes were fitted in
terms of Rv and Q. Repeated-measures ANOVA were conducted on Rv
and Q, and post hoc t-tests with Bonferroni correction were used to
compare races.
Results: In all racial groups both methods showed greater Rv for the
horizontal than for the vertical meridian and greater Rv for myopes
than emmetropes. Rv was greater in EA than in CA (P=0.02), with Rv
for SA being intermediate and not significantly different from CA and
EA. The PEL method provided larger Rv than the PR method: PEL:
EA vs CA 87±13 vs 83±11 m-1 (H), 79±13 vs 72±14 m-1 (V); PR: EA
vs CA 79±10 vs 67±10 m-1 (H), 71±17 vs 66±12 m-1 (V). Q did not
vary significantly with race.
Conclusions: Estimates of Rv, but not of Q, varied significantly with
race. The greater Rv found in EA than in CA and the comparatively
high prevalence rate of myopia in many Asian countries may be
related.
Commercial Relationships: Pavan K. Verkicharla, Johnson
& Johnson Vision Care, Inc. (F); David A. Atchison, Johnson &
Johnson Vision Care, Inc. (F); Marwan Suheimat, Johnson &
Johnson Vision Care, Inc. (F); Katrina L. Schmid, Johnson &
Johnson Vision Care, Inc. (F); Ankit Mathur, Johnson & Johnson
Vision Care, Inc. (F); Edward A. Mallen, Johnson & Johnson Vision
Care, Inc. (F); Xin Wei, Johnson & Johnson Vision Care, Inc. (E);
Noel A. Brennan, Johnson & Johnson Vision Care, Inc. (E)
Support: Johnson & Johnson Vision Care, Inc.
Program Number: 3593 Poster Board Number: A0042
Presentation Time: 3:45 PM–5:30 PM
Identification of integrin receptor subunits in the guinea pig
sclera
Kevin Wang1, Ravi Metlapally1, Christine Wildsoet1, 2. 1School of
Optometry, University of California Berkeley, Berkeley, CA; 2Vision
Science Graduate Group, University of California Berkeley, Berkeley,
CA.
Purpose: Treatment for myopia, the result of excessive elongation
of the globe, has been directed mostly at the symptoms and not
at the core issue of elongation. The ocular dimensional changes
reflect increased scleral remodeling, which is also associated with
biomechanical weakening of the sclera. As integrins have been linked
to scleral remodeling previously, they represent potential targets for
myopia treatments aiming to slow ocular elongation. As a first step,
this study aimed to characterize the integrin subunits in the guinea
pig sclera, a common myopia model.
Methods: Primers for α and β integrin subunits were designed using
NCBI entries from a genome sequencing project, Primer3, and UCSC
Genome Browser Bioinformatics. Total RNA was extracted from
both intact scleral samples and fibroblasts cultured from guinea pig
sclera. Reverse transcription was performed to produce cDNA and
PCR used to amplify products of a predetermined size. Finally, PCR
products were sequenced to confirm their identity.
Results: PCR analysis of intact guinea pig scleral samples revealed
twenty-four of the twenty-six known integrin subunits, corresponding
to a possible twenty-two combinations of integrins, while only
twenty-one of the twenty-six known subunits were detected in
cultured scleral fibroblasts, allowing for nineteen potential integrin
combinations. Specifically, scleral tissue expressed all known integrin
alpha subunits except integrin αD and αE, which were also not
expressed in scleral fibroblasts although expression of integrin αD
and αE was confirmed in guinea pig liver. Integrins αL, αM, and
αX were also not expressed in scleral fibroblasts. Both guinea pig
scleral tissue and scleral fibroblasts expressed all known integrin beta
subunits. All results were verified through sequencing.
Conclusions: While the above results are similar to those of a
previous study in the tree shrew, another popular myopia model,
guinea pig sclera expressed all known mammalian beta integrin
subunits while tree shrew sclera did not express β2-, β3-, β6-, and
β7-integrin subunits. However, alpha integrin subunits found in tree
shrew sclera were also found in guinea pig sclera. Data provided from
this study will help guide future studies directed at understanding the
relationship between scleral integrins and myopia.
Commercial Relationships: Kevin Wang, None; Ravi Metlapally,
None; Christine Wildsoet, None
Support: T35EY007139 to KW, K08EY022670 to RM,
R01EY012392 to CFW
Program Number: 3594 Poster Board Number: A0043
Presentation Time: 3:45 PM–5:30 PM
Changes in mRNA expression of Endothelial Growth Factor A,
C, D and Vascular Endothelial Growth Factor Receptor 1, 2, 3
during induction of deprivation myopia in chickens
Marita P. Feldkaemper, Frank Schaeffel. Centre for Ophthalmology,
Institute for Ophthalmic Research, Tuebingen, Germany.
Purpose: It was previously reported that the vascular epithelial
growth factor inhibitor Bevacizumab can slow the development of
deprivation myopia in chickens and suppress choroidal thickening
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
that normally occurs during recovery from deprivation myopia
(Mathis and Schaeffel, ARVO 2013). Furthermore, Sheng, Zhu
and Wallman (ARVO 2012) found that VEGF isoform V165 can
transiently thin the choroid in chickens. We have further studied the
role of VEGF in myopia by measuring the choroidal expression of
different VEGF isoforms and their receptors, both after long-term
deprivation and during recovery from myopia.
Methods: 7 days old White Leghorn chicks were treated with (a)
diffusers for 8 days on both eyes but diffusers were removed on
one eye one hour before choroidal tissue analysis, (b) no treatment
except for that one eye was occluded 1 hour before tissue analysis,
(c) unilateral diffuser treatment for 16 days, (d) unilateral diffuser
treatment for 15 days followed by removal of a diffuser for one day
(n= 6 chicks in groups a-d). Semi-quantitative real-time PCR was
used to quantify mRNA levels of VEGFA (transcript variant 1 and 2),
VEGFC, VEGFD, VEGFR1, VEGFR2 and VEGFR3. Beta-actin and
HPRT served as reference genes.
Results: Most mRNA levels of the VEGF isoforms were not
changed during deprivation myopia. Only VEGFD mRNA was
significnatly up-regulated after 16 days of diffuser wear with a 46%
increase in normalized mRNA expression (paired t-test, p=0.02).
Neither recovery for 1 hour or of 1 day had any effect of the mRNA
expression of the various VEGF genes.
Conclusions: Changes in choroidal mRNA expression levels (VEGF
D) were evident only after long-term treatment of the chickens with
diffusers. This growth factor might therefore either play a role in the
maintainance of the myopic state or its induction is related to early
degenerative processes in high myopia.
Commercial Relationships: Marita P. Feldkaemper, None; Frank
Schaeffel, None
Program Number: 3595 Poster Board Number: A0044
Presentation Time: 3:45 PM–5:30 PM
The association between initial choroid thickness and subsequent
ocular growth rate in young chicks: Evidence for different
choroidal mechanisms in growth inhibition vs stimulation
Kristen Totonelly, Xiaoying Zhu, Pearl Thai, Rinita Zanzerkia,
Debora L. Nickla. New England College of Optometry, Boston, MA.
Purpose: Thick choroids are associated with ocular growth inhibition
and thin choroids with growth stimulation. Whether this is relevant to
the mechanisms underlying the signal cascade that mediates scleral
growth in response to visual or pharmacological stimuli is unknown.
These studies asked whether choroid thickness in young chicks
predicts subsequent ocular growth rates under various conditions.
Methods: We determined the correlation between choroid thickness
and subsequent ocular growth rate (scleral GAG synthesis for group
6) under the following conditions. (1) Plus lens-wear for 4 days (d)
(n=14). (2) Minus lens-wear for 5 d (n=16). (3) Diffuser-wear for 5
d (n=16). (4) Fellow untreated eyes (n=53). (5) Daily injections of
quinpirole (n=12), apomorphine (n=17), atropine (n=11), pirenzepine
(n=10), or a single injection of oxotremorine (n=27). (6) Eyecups of
RPE, choroid and sclera cultured for 24 hrs (n=9). Some of these data
are retrospective.
Results: There was a negative correlation between initial choroid
thickness and subsequent ocular growth rate in visual conditions in
which eye growth was inhibited (plus lens: r=-0.662, p<0.01) and
in untreated eyes (r=-0.393, p<0.005), but not when growth was
stimulated (minus lens: r=0.08, p=0.72; diffusers: r=0.036, p=0.9).
In untreated eyes and in eyes wearing diffusers or minus lenses
there was also a correlation between initial choroid thickness and
subsequent thinning (p<0.05); there was no such correlation for plus
lenses. In eyecups, there was a negative correlation between choroid
thickness and scleral GAG synthesis (r=-0.79, p<0.01). Drugs: There
was a negative correlation between choroid thickness and growth rate
in eyes injected with quinpirole (r=-0.72, p=0.008) but the data for
apomorphine did not reach significance. There was no correlation for
eyes injected with muscarinic agents.
Conclusions: That initial choroidal thickness does not predict
ocular growth rate under all conditions implies that thickness is
not correlated with the efficacy of a mechanical barrier to a signal
molecule. This is also supported by the negative correlation between
thickness and quinpirole-mediated growth inhibition. Finally, the
results support different roles for the choroid in growth stimulation vs
inhibition.
Commercial Relationships: Kristen Totonelly, None; Xiaoying
Zhu, None; Pearl Thai, None; Rinita Zanzerkia, None; Debora L.
Nickla, None
Support: NIH EY013636
Program Number: 3596 Poster Board Number: A0045
Presentation Time: 3:45 PM–5:30 PM
Gaze-Induced Axial Length Changes in Highly Myopic Eyes as
Gauged by Magnetic Resonance Imaging
Quan V. Hoang1, Jonathan Tang1, Julie Goldman1, Jane Y. Pan2, 1,
Stanley Chang1. 1Ophthalmology, Harkness Eye Institute, Columbia
University, New York, NY; 2Methodist Girls’ School, Singapore,
Singapore.
Purpose: To determine if axial length changes occur in highly
myopic eyes undergoing the stress and strain of normal eye
movement.
Methods: A prospective imaging study was performed on highly
myopic patients (> 26 mm of axial length) with a clinical diagnosis
of staphyloma. 3-D MRI scans were acquired while subjects gazed in
5 directions (primary, nasal 15°, temporal 15°, superior 10°, inferior
10°). Volume renderings were manually reoriented so that the plane
of the limbus (the cornea-sclera interface) was normal to the plane of
the screen. Four axial length measurements were taken at 90-degree
rotations around the central axis and averaged for each eye in every
gaze. Eye axial lengths at each eccentric gaze were compared to the
axial length in primary gaze using a fixed effects regression allowing
for person-specific and eye-specific effects (n = 40).
Results: Axial lengths were unchanged in temporal gaze when
compared to primary gaze (p = 0.89). Axial lengths shortened in nasal
gaze (-0.07 mm, p = 0.04, 95% CI -0.148 to 0.008) and in superior
gaze (-0.08 mm, p = 0.03, 95% CI -0.163 to 0.003). Axial lengths
increased by +0.12 mm when changing from primary to inferior
gaze (p = 0.001, 95% CI [0.043 to 0.196]). Linear regressions for
individual patients demonstrated that the F-test of the axial length
measured in the four gazes were jointly different from the axial
length measured in primary gaze. This difference was significant at
the p < 0.05 level in 33 out of 40 eyes (82.5%).
Conclusions: Eye lengthening appears to occur only in inferior
gaze, which is of interest given past clinical studies suggesting an
association between excessive near work and myopia development
and progression.
Commercial Relationships: Quan V. Hoang, None; Jonathan
Tang, None; Julie Goldman, None; Jane Y. Pan, None; Stanley
Chang, Alcon (F)
Support: NIH 5 KL2 TR 81-8 (QVH) and an unrestricted grant from
Research to Prevent Blindness (New York, New York)
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Program Number: 3597 Poster Board Number: A0046
Presentation Time: 3:45 PM–5:30 PM
Lack of oblique peripheral astigmatism in the chicken eye,
comparison to the human eye and possible consequences for
emmetropization
Felix Maier1, Arne Ohlendorf2, Siegfried Wahl2, Frank Schaeffel1.
1
Institute for Ophthalmic Research, Section for Neurobiology of
the Eye, Tuebingen, Germany; 2Institute for Ophthalmic Research,
ZEISS Vision Science Lab, Tuebingen, Germany.
Purpose: Primates display considerable off-axis astigmatism. In
humans, its magnitude can be described by a parabolic function:
astigmatism relative to the pupil axis = 3.28*10-3 * angle2
(Howland, 13th IMC in Tuebingen 2010). Howland also proposed
that peripheral astigmatism may represent a cue for emmetropization,
since either its tangential or radial axis are in better focus, depending
on the spherical refractive error. It is known that the chicken eye
emmetropizes independently in the center and the periphery but not
whether it uses peripheral astigmatism.
Methods: Infrared photorefraction was used to map out the
refractions over the horizontal visual field, both in the vertical and
horizontal meridians, in three 43 day old chicks (6 eyes) and three
near emmetropic male human subjects (6 eyes, age 34.7 ± 6.8 years).
Chicks were trained to accept that the operator turned their heads
as desired by holding their beak. Videos were recorded and eye
orientation and refractions were determined from the position of the
first Purkinje image relative to the pupil center and the brightness
slopes in the pupil. Human subjects were measured with a scanning
photorefractor (Tabernero et al. 2009).
Results: There was no significant difference in the amount of
astigmatism in chicks and humans in the center of the visual field
(0 deg: chicks -0.35±0.79 D, humans 0.65±0.60 D, p = 0.30).
Similar to what was found by Howland, astigmatism increased in
our subjects’ eyes to the periphery with the function: astigmatism =
2.21*10^-3*angle^2-0.0245*angle+1.589. Strikingly, in the chick
eye astigmatism did not increase in the periphery. Highly significant
differences were found in the peripheral astigmatism in humans and
chicks (at 40 deg in the temporal visual field: humans 4.21±2.39 D,
chicks -0.63±0.80 D, p < 0.001 (unpaired t-test) and at 20 deg in
the nasal visual field: humans 3.69±1.16 D, chicks 0.74±0.44 D, p
< 0.001; the trend is similar at 20 deg in the temporal visual field:
humans 1.68±1.40 D, chicks 0.30±0.29 D, p = 0.07 and in the nasal
visual field at 40 deg humans 5.17±3.71 D, chicks 0.78±0.11 D, p =
0.12).
Conclusions: The chick eye is perhaps the first vertebrate eye
without oblique peripheral astigmatism. While the optical design of
the crystalline lens in the chick eye must be fascinating, the lack of
peripheral astigmatism suggests that emmetropization cannot rely on
it.
Commercial Relationships: Felix Maier, None; Arne Ohlendorf,
Carl Zeiss Vision International GmbH (E); Siegfried Wahl, Carl
Zeiss Vision International GmbH (E); Frank Schaeffel, None
Support: Werner Reichardt Centrum für Integrative
Neurowissenschaften Pool Projekt 2012-12
Program Number: 3598 Poster Board Number: A0047
Presentation Time: 3:45 PM–5:30 PM
Blue light protects against temporal frequency dependent
refractive changes
Stephanie Britton, Stephan Hanowsky, Frances J. Rucker. Biomedical
Science and Disease, New England College of Optom., Boston, MA.
Purpose: A previous experiment indicated that chicks exposed to
luminance flicker without blue light showed a hyperopic shift at
higher temporal frequencies and a myopic shift at lower frequencies.
In this experiment we test the hypothesis that blue light is important
in emmetropization by comparing the response of chicks to
luminance flicker with and without blue light over a range of
temporal frequencies.
Methods: 4-5 day old White Leghorn chicks were exposed daily
for three days (9am to 5pm) to sinusoidal luminance modulation
at 80% contrast, at one of six temporal frequencies: 0, 0.2, 1, 2, 5,
10 Hz. Luminance flicker “without blue” light was created with
in-phase modulation of red and green, while “with blue” flicker was
created with in-phase modulation of red, green and blue light. Mean
illumination was 680 lux. Chicks were maintained in a dark chamber
overnight. Changes in ocular components were measured before and
after the experiment with a non-contact ocular biometer (Lenstar LS
900), and refractive error was measured with a Hartinger Coincidence
Refractometer. Photokeratometry was used to calculate corneal
astigmatism and images were analyzed with Image J.
Results: Refraction, eye length, and choroidal changes were
dependent on temporal frequency (p<0.03 all) and on the interaction
between frequency and blue light (p<0.03 all). Without blue,
refractions were more hyperopic with higher temporal frequencies,
and more myopic at lower temporal frequencies. There was a
hyperopic shift (> 1 D) at 5 and 10 Hz, and a myopic shift (> -0.6 D)
at ≤2 Hz, and an increase in astigmatism along J45 (p=0.04). With
blue light, refraction remained constant (mean change -0.24 D).
Without blue light, there was less eye growth at high frequencies
and more at low frequencies. Eyes were 145 mm shorter at 10 Hz
than they were at 0.2 Hz (p<0.003), while with blue, they were
only 77 mm shorter. Without blue light, anterior chamber depths
were deeper (p=0.006), while choroids were thinner at low and
intermediate temporal frequencies, contributing to the myopic shift at
low frequencies. At 5 Hz, choroids thinned 46 mm more without blue
light, than with blue light (p=0.03).
Conclusions: Emmetropization shows a temporal, blue light
sensitivity. Blue light protects against temporal frequency dependent
refractive changes through modification of eye length, choroidal
thickness, anterior chamber depth and corneal curvature.
Commercial Relationships: Stephanie Britton, None; Stephan
Hanowsky, None; Frances J. Rucker, None
Support: New England College of Optometry Internal Research
Award
Program Number: 3599 Poster Board Number: A0048
Presentation Time: 3:45 PM–5:30 PM
The effect of near additions and prismatic lenses on
accommodative micro-fluctuations in Chinese myopic children
Huiling Lin1, 3, Drobe Björn2, 3, Lin Meng1, 3, Jin Wanqing1, 3, Chen
Yunyun1, 3. 1School of Optometry and Ophthalmology, Wenzhou
Medical University, Wenzhou, China; 2R&D Optics Asia, Essilor
International, Wenzhou, China; 3WEIRC (WMU-Essilor International
Research Centre), Wenzhou, China.
Purpose: To investigate the effects of near additions and prismatic
lenses on accommodative micro-fluctuations and horizontal
heterophoria in Chinese myopic children.
Methods: 14 myopic children (SE: -0.75D to -3.75D) aged from 9
to 13 participated in the study. Accommodative micro-fluctuations
and horizontal heterophoria were measured through multiple lenses
by means of an open-field infrared autorefractor (WAM-5500,
Grand Seiko Co., Ltd., Hiroshima, Japan) and modified Thorington
technique. Tested lenses were additions (-1.00, 0, +1.00, +2.00 and
+3.00D on each eye) and horizontal prisms (3ΔBI, 2ΔBI, 1ΔBI, 0,
1ΔBO and 2ΔBO on each eye). Lens order was randomized. During
accommodation measurements, children were looking at RSVP (rapid
serial verbal presentations) of Chinese characters at 25cm.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Results: RMS (root mean square) of accommodative response
increased significantly in the condition of -1.0D near addition
(0.28±0.11D) compared to plano lens (0.18±0.06D, p<0.001). No
significant difference in RMS was found between plano and positive
addition lenses (p > 0.05), even though smaller RMS were found for
+1.0D and +2.0D lenses (respectively 0.14±0.05D, 0.13±0.15D). No
significant difference in RMS was found between prismatic lenses
(p=0.22). Heterophoria decreased (more exophoric) with plus-power
addition lenses (p<0.001) and increased with base-in prismatic lenses
(p=0.038). RMS was found to be correlated with the phoria state (r =
0.345, p < 0.001).
Conclusions: Over-correction resulted in higher accommodative
micro-fluctuations while plus-power addition lenses and prismatic
lenses had no influence on accommodative micro-fluctuations. Phoria
decreased with plus-power addition lenses and increased with base-in
prismatic lenses.
Commercial Relationships: Huiling Lin, Essilor International
(F); Drobe Björn, Essilor International (E); Lin Meng, Essilor
International (F); Jin Wanqing, Essilor International (F); Chen
Yunyun, Essilor International (F)
Program Number: 3600 Poster Board Number: A0049
Presentation Time: 3:45 PM–5:30 PM
Transient changes in choroidal thickness to different levels of
imposed myopic defocus
Jinhua Bao1, 3, Bjorn Drobe2, 3, Ke Chen1, 3, Hao Chen1, 3. 1School
of Ophthalmology and Optometry, Wenzhou Medical University,
Wenzhou, China; 2R&D Optics Asia, Essilor International, Wenzhou,
China; 3WEIRC, WMU-Essilor International Research Centre,
Wenzhou Medical University, Wenzhou, China.
Purpose: To investigate short-term changes in choroidal thickness
and other ocular biometrics to imposed myopic defocus in young
adults.
Methods: Ocular biometrics of thirteen myopic young adult subjects
was measured before and after 60 minutes of exposure to monocular
defocus (right eye) while watching movies on a 5.5m distant screen.
Choroidal and retinal thicknesses were measured by means of Lenstar
SD-OCT (Heidelberg Spectralis OCT; Heidelberg Engineering,
Heidelberg, Germany) and axial length by Lenstar LS 900 optical
biometer (Lenstar LS 900; Haag Streit AG, Koeniz, Switzerland).
Four different monocular defocus conditions were tested, each on
a separate day: control (no defocus) and myopic defocus (+1D,
+3D and +5D defocus). The fellow eye was optimally corrected for
distance (no defocus).
Results: After 60 minutes, choroidal thickness of the right eye
exhibited a significant increase only for +3D and +5D defocus
conditions (mean change, +1D: +7.53±7.80μm, p>0.05; +3D:
+12.51±11.23μm, p=0.002; +5D: +11.74±8.45μm, p<0.001). Retinal
thickness exhibited no significant change with any myopic defocus
conditions (mean change, +1D: -1.17±2.52μm, +3D: -1.93±1.99μm,
+5D: -1.77±3.49 μm; p>0.1). Optical axial length decreased
significantly only after +5D defocus condition (mean change,
+1D: +2.13±9.67μm, p>0.1; +3D: -1.93±9.05μm, p>0.1; +5D:
-6.56±9.14μm, p=0.024). Choroidal thickness, retinal thickness and
axial length of the left eye showed no significant change (p>0.05).
Conclusions: Significant increase in choroidal thickness occurred in
human subjects after 60 minutes of myopic defocus of 3D or more
but not in axial length. Moreover, there is no evidence to support
the notion that choroidal thickness elongation is proportional to the
degree of myopic defocus.
Commercial Relationships: Jinhua Bao, Essilor International
(F); Bjorn Drobe, Essilor International (F); Ke Chen, Essilor
International (F); Hao Chen, Essilor International (F)
Program Number: 3601 Poster Board Number: A0050
Presentation Time: 3:45 PM–5:30 PM
Comprehensive lesions of the retina surrounding the optic nerve
enhance elongation and cause myopia in the guinea pig eye
Sally A. McFadden, Callan Medcalf, Guang Zeng, John Holdsworth.
Faculty of Science and IT, University of Newcastle, Callaghan, NSW,
Australia.
Purpose: Disruption to detailed vision using form deprivation
(FD) induces excessive eye elongation and myopia. The underlying
mechanisms are local to the eye since FD myopia induces excessive
growth after optic nerve section.1 Surprisingly, foveal photoablation
does not inhibit FD myopia in young monkeys.2 However, the region
around the optic nerve (the peripapillary zone or PPZ) expands early
during myopia development and the overlying retina may carry the
pertinent signals.3 We studied the effect of retinal photocoagulation
lesions of the PPZ on both normal and myopic growth.
Methods: Guinea pigs received FD alone (n = 16) or comprehensive
PPZ lesions using multiple spots (laser strength of 100 mW for 50
ms, n = 9) the day prior to FD. FD involved wearing a diffuser over
one eye from 6 to 13 days of age. PPZ lesions were also administered
at the same age in a group not form deprived (n = 7). Refractive error
(using a Nidek autorefractor after cycloplegia) and eye shape (based
on retinal hemisections4) were assessed at the end of the rearing
period. Results are presented as the relative differences between the
two eyes.
Results: FD alone resulted in –3.1D of relative myopia and 100 mm
of relative eye elongation in the PPZ area with relative eye shrinkage
(–47 mm) in the temporal retina. Greater myopia was observed after
PPZ lesions combined with FD (–7.35D, 150 mm) and unlike normal
FD, excessive growth also occurred in the mid periphery, particularly
in nasal retina. PPZ lesions also induced relative myopia in animals
not form deprived (–3.8D, p < 0.001).
Conclusions: Retinal signals from the PPZ may be critical for normal
refractive development and when eliminated, cause exaggeration of
the central elongation so characteristic of myopic eyes. Without these
signals, the eye also grows excessively in the periphery suggesting
they are necessary for relative growth inhibition.
1. Smith EL et al. IOVS (2007), 48(9), 3914-3922.
2. Wildsoet CF, McFadden SA. IOVS (2010) 51 ARVO E-Abstract
1737.
3. Zeng G, McFadden SA. IOVS (2011) 52 ARVO E-Abstract 3923.
4. Zeng G et al. Vision Res. (2013), 76, 77-88.
Commercial Relationships: Sally A. McFadden, None; Callan
Medcalf, None; Guang Zeng, None; John Holdsworth, None
Support: Port Waratah Coal Services, HMRI 13-23, UN NM
G1300470, Ellex Medical Pty. Ltd.
Program Number: 3602 Poster Board Number: A0051
Presentation Time: 3:45 PM–5:30 PM
Longitudinal changes in corneal power and axial length in the
Correction of Myopia Evaluation Trial (COMET) Cohort
Mitchell Scheiman1, Li Deng3, Jane E. Gwiazda3, Qinghua
Zhang2, Ruth E. Manny4, Karen D. Fern4, Eric Weissberg3. 1Coll
of Optometry, Salus University, Elkins Park, PA; 2Department of
Preventive Medicine, Stony Brook University Medical Center, Stony
Brook, NY; 331 New England College of Optometry, Boston, MA;
4
College of Optometry, University of Houston, Houston, TX.
Purpose: To describe changes in corneal power and axial length
(AL) in the COMET cohort followed for 14 years, and explore the
relationship between AL and corneal radius (CR) over this time
period.
Methods: 469 ethnically diverse, 6-11 year old children with -1.25
to -4.50 D of myopia were enrolled in COMET. Children wore
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
either single vision (SVLs) or progressive addition lenses (PALs)
for 5 years and were followed for an additional 9 years wearing
PALs, SVLs, or contact lenses. Additionally, 206 non-myopic young
adults matched by gender, ethnicity, and age with COMET myopes
were recruited at the 12-year visit. Refractive error (cycloplegic
autorefraction), corneal curvature (CC, auto-keratometry), and ocular
component dimensions (A-scan ultrasound) were measured annually
for COMET children, and once for the non-myopic, matched youngadult subjects. Linear mixed model was used to evaluate longitudinal
changes based on all available records adjusting for covariates
(gender, ethnicity, lens type, baseline age and baseline refraction).
Unpaired t-test was used to compare myopes and non-myopes at the
12-year visit. The Pearson correlation coefficient (PCC) between
AL and CC was computed at each visit. The comparison of PCCs
between myopes and non-myopes at the 12-year visit was conducted
using Fisher’s transformation.
Results: Longitudinally, COMET girls had significantly steeper CC
than boys (p<0.0001). Caucasians had the steepest CC, and Hispanics
the flattest (p=0.001). The correlation between AL and CC was -0.70
(p<0.0001) at baseline and decreased to -0.53 (p<0.0001) at the 14year visit. The average AL to CR ratio (AL/CR) was 3.15 at baseline
and increased to 3.31 at the 14-year visit. In the cross-sectional
analysis, the correlation between AL and CC for the COMET myopes
at the 12-year visit was lower than for the matched non-myopes (r
=-0.57 vs.-0.76; p<0.0001). In addition, the AL/CR in myopes was
significantly higher than in non-myopes (3.30 vs. 3.00; p<0.0001).
Conclusions: These data demonstrate significant gender and ethnicity
differences in average corneal curvature as myopia progresses.
In addition, our findings suggest that as axial length continues to
increase in myopic children the cornea may be incapable of further
flattening, contributing to myopia progression.
Commercial Relationships: Mitchell Scheiman, None; Li Deng,
None; Jane E. Gwiazda, None; Qinghua Zhang, None; Ruth E.
Manny, None; Karen D. Fern, None; Eric Weissberg, None
Support: EY11756, EY11754, EY11805, EY11752, EY11740, and
EY11755
Clinical Trial: NCT00000113
Program Number: 3603 Poster Board Number: A0052
Presentation Time: 3:45 PM–5:30 PM
The effects of the relative strength of simultaneous competing
defocus signals on emmetropization in infant rhesus monkeys
Baskar Arumugam1, 2, Li-Fang Hung1, 2, Chi-ho To3, Earl L. Smith1, 2.
1
College of Optometry, University of Houston, Houston, TX; 2Vision
CRC, Sydney, NSW, Australia; 3Center for Myopia Research School
of Optometry, Hong Kong Polytechnic University, Hung Hom, Hong
Kong.
Purpose: The aim of this study was to investigate the effect of dual
focus lenses with unequal areas devoted to competing defocus signals
on emmetropization in infant monkeys.
Methods: The subjects were infant rhesus monkeys that, beginning
at 3 weeks of age, were reared with Fresnel lenses that had unequal
areas devoted to the two power zones. The treatment lenses had
central 2 mm zones of zero power and concentric annular zones that
had 33:66 area ratios for alternating powers of +3.0 D and 0 D (n=6;
+3D/pl) or 66:33 ratios for powers of -3.0 D and 0 D (n=6; -3D/pl).
The monkeys wore the treatment lenses over both eyes continuously
until 153±3.4 days. Comparison data were obtained from monkeys
reared with either dual focus lenses with approximately equal power
areas (50:50 area ratios) or full field single vision lenses over both
eyes (FF+3 D, n=6; FF-3 D, n=6). Refractive status, corneal power
and axial dimensions were assessed every 2 weeks throughout the
lens rearing period. Control data were obtained from 33 monkeys
reared with unrestricted vision.
Results: At the end of the treatment period, the median refractive
error and average vitreous chamber depth for the +3D/pl lensreared monkeys were similar to those for animals reared with FF+3
D lenses (OD: +5.19 D vs +4.63 D, p=0.23 and 9.44±0.60 mm vs
9.58±0.32 mm, p=0.65) or similarly powered Fresnel lenses that
had equal areas devoted to each power (OD: +5.25 D, p=1.0), but
axially more hyperopic than those for control monkeys (OD: +2.50
D, p=0.0002; VC: 9.82±0.30 mm, p=0.03). On the other hand, for the
-3D/pl monkeys, refractive development was dominated by the zeropowered portions of the lenses. The median refractive error for the
-3D/pl monkeys was more hyperopic than that found in the FF-3D
monkeys (OD: +2.94 D vs -1.19 D, p=0.02), but similar to that for
monkeys reared with Fresnel lenses that had equal areas devoted to
each power (OD: +3.13 D, p=0.94) and that observed in the control
animals (p=0.24).
Conclusions: The results demonstrate that even though the least
hyperopic/most myopic power zones made up only about 1/3 of the
surface area of the treatment lenses, their associated image planes
dominated refractive development. Overall, the results indicate that
imposing relative myopic defocus over a large part of the retina
provides a strong signal for slowing eye growth.
Commercial Relationships: Baskar Arumugam, None; Li-Fang
Hung, None; Chi-ho To, Inventor (P); Earl L. Smith, Zeiss (P)
Support: NIH Grants EY03611 and EY07551; Vision CRC
Program Number: 3604 Poster Board Number: A0053
Presentation Time: 3:45 PM–5:30 PM
Both Lens Induced Hyperopia and Recovery Increase the
Amplitude of Diurnal Rhythm in Refractive Error
Melanie C. Campbell1, 2, Kaitlin Bunghardt1, Marsha L. Kisilak1, 2,
Elizabeth L. Irving2. 1Physics & Astronomy, University of Waterloo,
Waterloo, ON, Canada; 2School of Optometry and Vision Science,
University of Waterloo, Waterloo, ON, Canada.
Purpose: We have reported a larger amplitude of circadian variation
in mean ocular refraction (MOR) in the previously goggled eye
compared with the control eye on removal of positive or negative
lenses. Here we compare the circadian rhythm present during lens
induction of hyperopia in the goggled and control eyes with that
following goggle removal.
Methods: Short term changes in MOR were measured immediately
before and after goggle removal following 6 days of emmetropization
to lens induced hyperopia. Eleven birds, unilaterally treated with
a +10D goggle on the day of hatching, were raised on a 14h/10h
light dark cycle. On day 6, beginning at 8:30 am, Hartmann-Shack
refractive error and A scan ultrasound axial length (to the retina)
were measured every 4 hours, ending on day 9. The goggle was
permanently removed after the 8:30am measurement on day 7.
MOR was analyzed for the largest common pupil. Linear variations
were subtracted and residual sinusoidal variations were fitted before
and after goggle removal. Comparisons were made to previously
presented results. Paired t tests were used, p≤0.05 for significance and
if normalcy or equal variance tests failed, a Wilcoxon Signed Rank
Test was performed.
Results: On day 6 after partial emmetropization (+5.5D), sinusoidal
amplitudes in goggled eyes vs control eyes were significantly larger
for MOR and smaller for length. This implies a difference in the
amplitude of power variation between goggled and control eyes.
Control eyes were not different from eyes of control birds on day 6.
Day 7 diurnal amplitudes for length and MOR after goggle removal
were significantly larger than before removal. The eyes’ amplitudes
no longer differed for length but MOR amplitude was larger in
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
previously goggled eyes than in control eyes. Acrophases on days 6
and 7 for MOR of goggled eyes were significantly clustered, while
those for control eyes were not (Rayleigh test).
Conclusions: Unlike in previously reported emmetropization to -15D
lenses, after 6 days, following incomplete emmetropization to +10D
lenses, the amplitude of circadian rhythms differed in the control
and goggled eyes. Nonetheless, following goggle removal, as for the
-15D lenses, the amplitude of oscillation of mean ocular refraction
in the treated eye increased. Circadian rhythms could provide
enhanced signals to the direction of defocus both during goggling and
following goggle removal.
Commercial Relationships: Melanie C. Campbell, None; Kaitlin
Bunghardt, None; Marsha L. Kisilak, None; Elizabeth L. Irving,
Visioneering (F)
Support: NSERC Canada
Program Number: 3605 Poster Board Number: A0054
Presentation Time: 3:45 PM–5:30 PM
Macrophage Activation Pattern in Human Myopic Choroidal
Neovascular Membranes
Khaled Nassar, El Shaymaa El Far, Julia Luke, Matthias Luke,
Swaantje Grisanti, Salvatore Grisanti. Ophthalmology, Luebeck
University, Luebeck, Schleswig-Holstein, Germany.
Purpose: A little is known about the role of macrophages in myopic
choroidal neovascular membrane (CNV) pathogenesis. The present
study aimed to characterize the pattern of macrophage activation in
CNV caused by degenerative myopia compared to that caused by age
related macular degeneration (AMD).
Methods: 20 surgically excised CNV derived from 15 AMD (5
classic and 10 occult CNV) patient and 5 patient with degenerative
myopia were stained using CD68, CCR7 and CD163 antibodies
staining for pan macrophages, classically activated macrophage
(M1 macrophages) and alternatively activated macrophage (M2
macrophages); respectively. The immunopositive cell density was
calculated per mm2 in 400x images.
Results: All CNVs were untreated and subfoveally located.
Macrophage infiltration was higher in the myopic CNV with a cell
density of M: 268.4±117.78; M1: 137.8 ±189.5; M2: 453.6±313
cell/mm2. In classic AMD related CNV, the cell density of M
macrophages were 251.6±72.8 cell /mm2, M1 macrophages: 131.4±
94.38, and M2 macrophages: 122.8±64.10 cell/mm2. In occult AMD
related CNV, the cell density of M macrophages were 301± 159 cell
/mm2, M1 macrophages: 167 ± 90 cell/mm2 and M2:167 ± 89 cell/
mm2. Alternatively activated macrophages were the dominant type
in myopic CNV (p value: 0.043) and differ significantly from both
classic and occult AMD CNV, (p value: 0.008, 0.01) respectively.
Conclusions: Alternatively activated macrophages might play an
important role in the myopic CNV pathogenesis. The identification of
different activation patterns may be important for distinct therapeutic
strategies.
Fig. 1 Macrophage polarized activation.
A simplified view of immune and tissue-derived signals inducing
classical (M1) and alternative (M2) macrophage polarized activation.
The main functional effects on macrophage functions, molecular
markers and effector molecules are schematically represented in both
cases.
Fig. 2 Immunohistochemical detection of macrophage phenotypes
(M1 and M2).
A) Photomicrographs of myopic CNV depicting CD 163 (M2)
positive macrophages (black arrow). Vascular channels are seen
within the fibrous part of the membrane. B) Photomicrographs of
occult CNV depicting CCR7 (M1) positive macrophages (black
arrow),in close relation to RPE cells, scale bare 20mm.
Commercial Relationships: Khaled Nassar, None; El Shaymaa
El Far, None; Julia Luke, None; Matthias Luke, None; Swaantje
Grisanti, None; Salvatore Grisanti, None
Support: This study was supported in part by the “Jung-Stiftung Für
Wissenschaft und Forschung” Foundation, Hamburg; Germany. The
authors indicate no financial conflict of interest.
Program Number: 3606 Poster Board Number: A0055
Presentation Time: 3:45 PM–5:30 PM
Eye Dimensions during Lens Induced Myopia (LIM) and
Recovery in the Chick
Zheng Shao1, 2, Kaitlin Bunghardt1, Marsha L. Kisilak1, 2, Melanie
C. Campbell1, 2. 1Physics and Astronomy, University of Waterloo,
Waterloo, ON, Canada; 2School of Optometry and Vision Science,
University of Waterloo, Waterloo, ON, Canada.
Purpose: The chick eye refocuses out of focus images, primarily
through changes in ocular growth rates. We reported changes in
eye power during recovery from lens induced myopia (LIM) in the
chick eye. Here we analyze changes in eye dimensions in LIM and
recovery.
Methods: Nine Ross Ross chicks were unilaterally goggled
(-15D) on the day of hatching. The goggle was removed on day
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
7. Retinoscopy and ultrasound were performed; measurements
continued up to day 10 at 10 time points. Mean ocular refraction
(MOR), axial length, the distance from the cornea to the back of the
lens (CBL), lens thickness, and vitreous chamber depth (VCD) were
measured; power changes were calculated. All data were fitted with
linear functions of age, and paired t tests were performed.
Results: During LIM, MOR of the goggled eye partially
emmetropized (-11.3 D) to the goggle by day 7, primarily due to
faster increases in VCD. The lengths and MORs predicted a -3.2 D
power difference between treated and control eyes on day 7. The lens
and CBL were significantly thicker in treated versus control eyes.
After goggle removal, axial length, CBL, and lens thickness for the
treated eye didn’t change significantly between days 7 and 8, while
VCD decreased. Dimensions continued to increase in the control
eye. Lens thickness was still significantly larger in the treated eye
on day 8. Recovery from LIM was complete by day 9 and resulting
dimensions did not differ significantly from the control eye for both
days 9 and 10. Power decreased significantly between days 7 and 8 in
the treated eye and relative to the control eye. After day 8, power of
the treated eye didn’t change significantly while power of the control
eye decreased, and they were not significantly different by day 9.
Conclusions: By day 7 in LIM, the differences in axial length and
MOR between eyes predict a slightly lower power in the goggled eye.
The thicker lens and CBL are consistent with a small power decrease.
During recovery, lens thickness and eye power, as well as length,
are significantly different between treated and control eyes. Days 7
to 9, these properties do not change significantly in the treated eye
but continue to change in the control eye. Differences between the
treated and control eyes, in power and in dimensions, in addition to
length, are present during LIM and recovery. After emmetropization
is complete in recovery, none of the properties considered differ
between the two eyes.
Commercial Relationships: Zheng Shao, None; Kaitlin
Bunghardt, None; Marsha L. Kisilak, None; Melanie C.
Campbell, None
Support: NSERC Canada
Program Number: 3607 Poster Board Number: A0056
Presentation Time: 3:45 PM–5:30 PM
Phase-dependent effects of brief periods of myopic defocus on the
rhythms in axial length and choroid thickness in chicks
Debora L. Nickla, Rinita Zanzerkia, Pearl Thai, Kristen Totonelly.
Biosciences, New England College of Optometry, Boston, MA.
Purpose: We have shown that the eye growth inhibition caused by
2-hr periods of myopic defocus is more effective when given during
the mid-day than during the mid-night (Nickla & Totonelly, ARVO
2013). In this study we examined the effects of myopic defocus given
at 4 times of day on the diurnal rhythms in eye length and choroid
thickness.
Methods: 12-d-old chicks wore monocular +10 D lenses for 2 hr
periods at 5:30 am (“dawn”; n=11), 12:00 pm (“day”; n=8), 7:30 pm
(“dusk”; n=11) or 12:00 am (“night”; n=6) for 5 d. Lights were on
from 7:30 am-7:30 pm. Eyes were measured using ultrasound at the
start, and at 6-hr intervals over 24 hrs on the last day (12pm, 6pm,
12am, 6am, 12pm). Refractions (RE) were measured on a Hartinger’s
refractometer. To determine phase and amplitude, data from each
eye was fit with a sine wave. Circular statistics were used for
comparisons of phase. ANOVAs and Bonferroni post-hoc tests were
used to determine between-group significance for growth changes.
Results: Defocus during the day was more effective at inhibiting eye
growth than at dawn or night (change/5d, X-C: ANOVA p=0.014;
-174 mm vs -84 mm and -82 mm; p=0.042, p=0.075 respectively; RE:
3.8 D vs 1.1 and 2.8 D; p<0.05). This was associated with a phase-
delay in the rhythm in axial length compared to normal (6:30 pm
vs 2:45 pm; p<0.05; 1-tailed t-test). By contrast, defocus at night
caused a phase-delay in the rhythm in choroid thickness (compared
to dusk and day: 3:15 am vs 12:45 am (p=0.05) and 1:00 am (p<0.05,
1-tailed t-test)). It also abolished the diurnal rhythm in axial length
due to an “acute” growth stimulation from 12 am to 6 am (night vs
day, dawn and dusk, respectively: 119 mm vs -18 mm, -15 mm, 10
mm; ANOVA p<0.001; p<0.01). This effect did not occur in eyes
receiving “normal” vision at night (27 vs 119 mm; p=0.005), in which
growth was inhibited (629 vs 774 mm/7d; p<0.0001). In exp. eyes,
the amplitude of the choroid rhythm was larger than controls in 3
groups (day: 110 vs 51 mm; night: 91 vs 46 mm; dawn: 131 vs 69 mm;
p<0.05).
Conclusions: The greater efficacy of myopic defocus at mid-day is
associated with a phase shift in the axial length rhythm, moving it
towards the choroid rhythm. The lesser efficacy of defocus at night
results from an acute stimulation of eye growth. These results have
implications for future behavioral therapies involving light exposure
to prevent myopia.
Commercial Relationships: Debora L. Nickla, None; Rinita
Zanzerkia, None; Pearl Thai, None; Kristen Totonelly, None
Support: NIH-EY013636
Program Number: 3608 Poster Board Number: A0057
Presentation Time: 3:45 PM–5:30 PM
Predicting refractive error from ocular biometrics using
structural equation modeling
Christopher A. Clark, Ann E. Elsner, Benjamin J. Konynenbelt.
School of Optometry, University of Indiana, Bloomington, IN.
Purpose: Previous work has shown that retinal differences may exist
due to refractive error. As an example, total retinal thickness has been
shown to be relatively thicker centrally and thinner peripherally for
myopes compared to emmetropes. These differences may be due
to effects from axial elongation or potential variables influencing
refractive development. If these changes are correct, they should be
able to predict refractive error in subjects.
Methods: Eighty subjects had a battery of tests performed including
axial length, corneal topography, anterior chamber depth, peripheral
refraction, peripheral partial coherence interferometry, and SD OCT
for retinal thickness. The group was randomly split into two groups
of forty subjects, one for model development and the other for model
testing. Two designs were developed to predict central refractive
error. The first group was the complete model using all available
data. The second model was completed using only retinal thickness
changes including thicknesses from the total retina (TRT), outer
nuclear layer (ONL), outer plexiform, inner nuclear layer (INL),
and the inner plexiform layer/ganglion cell layer. The second model
had no data from axial length, corneal topography, etc. Structured
equation modeling was done through SPSS (IBM, Endicott, NY.)
Results: Structural equation modeling using retinal layer thickness
only to predict refractive error had an R2 = 0.273, P = 0.008. Layers
contributing significantly to the model included the TRT, INL and
ONL both centrally and peripherally. Using the full model, including
the axial length, the model improved R2 = 0.698, P = 0.001. As
expected, axial length was the primary contributor to the full model.
Conclusions: Differences in retinal thickness can be used to predict
refractive error. This suggests that these differences are associated
with refractive error and are real changes being detected. It appears
like both central and peripheral retinal thickness differences may be
important. Longitudinal work is needed to determine whether these
differences are due to changes in refraction or if they may directly be
influencing refractive development.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Commercial Relationships: Christopher A. Clark, None; Ann E.
Elsner, None; Benjamin J. Konynenbelt, None
Support: EY022064
Program Number: 3609 Poster Board Number: A0058
Presentation Time: 3:45 PM–5:30 PM
Quality of life of patients suffering from pathological myopia:
overview of their social and emotional environment
David Gaucher1, 2, Claire Chartier3, Michel Weber4, Francois
Malecaze5, Salomon Y. Cohen6, Eric H. Souied7, Nicolas Leveziel8.
1
NHC, University Hospital, Strasbourg, France; 2Strasbourg
university, Strasbourg, France; 3Novartis Pharma, Rueil Malmaison,
France; 4Ophthamic department, University hospital of Nantes,
Nantes, France; 5Toulouse University, Toulouse, France; 6CIL, Paris,
France; 7Paris Est University, Creteil, France; 8Poitiers Université,
Poitiers, France.
Purpose: Pathological myopia may affect 2 to 4% of the French adult
population.
The aim of this survey is to better understand patients suffering
from pathological myopia through their experiences, the impact of
the condition on their daily lives, their attitudes and beliefs. This
exploration will enable us to better meet the needs and expectations
of those suffering from this debilitating condition, which we assume
has a significant impact on quality of life and social integration.
Methods: This qualitative survey was conducted in France from
November to December 2013. Twenty patients suffering from
pathological myopia, i.e. patients with myopia over -8 dioptres
were interviewed. The sample is representatively split by sociodemographic criteria such as gender, age and region. A quantitative
survey in 75 patients is planned in January 2014 to assess the
impact of complications in the personal and professional life. Semistructured interviews lasting approximately one hour allowed patients
to speak freely about their experiences. A discussion guide has been
devised, covering the daily lives of patients as well as their care and
the history of their condition.
Results: The first inference is that pathological myopia is a “nonvisible” disease with professional and personal impact, which is
underestimated in circles. The second is the difficult everyday reality
faced by myopic patients, owing to a lack of understanding on the
part of the public and the depreciation of the skills and abilities of
those suffering from pathological myopia. Such are the inferences
drawn from the first interviews conducted. Consequently, patients
are using strategies to conceal the disease in professional and
personal circles, so as to avoid isolation, and rejection and stigma
exist. Possible adaptation strategies are emerging as a result of the
initial interviews, such as research by key resource persons and
development of other senses, such as touch.
Conclusions: This is the first in-depth study into the daily lives
of people suffering from pathological myopia. It aimed to analyse
their social and emotional environment. The results allow health
professionals and general public to be alerted to the emotional and
social difficulties experienced by these patients, which are perhaps
underestimated by ophthalmologists.
Commercial Relationships: David Gaucher, NOVARTIS (C);
Claire Chartier, Novartis Pharma (E); Michel Weber, Novartis (C);
Francois Malecaze, Novartis (C); Salomon Y. Cohen, Allergan (C),
Bausch and Lomb (C), Bayer (C), Novartis (C), Théa (C); Eric
H. Souied, Novartis (C); Nicolas Leveziel, Bayer (C), Novartis (C),
Théa (C)
Program Number: 3610 Poster Board Number: A0059
Presentation Time: 3:45 PM–5:30 PM
Right eyes are longer than left eyes: axial length findings from a
large cataract cohort with consistent refractive findings from a
large twin cohort
Omar A. Mahroo1, 2, Pirro G. Hysi3, Obeda Kailani4, Juliet
Thompson4, Christopher J. Hammond1, 3. 1Ophthalmology,
King’s College London, London, United Kingdom; 2Physiology,
Development and Neuroscience, University of Cambridge,
Cambridge, United Kingdom; 3Twin Research and Genetic
Epidemiology, King’s College London, London, United Kingdom;
4
West Kent Eye Centre, Princess Royal University Hospital, London,
United Kingdom.
Purpose: Small inter-ocular differences exist in the incidence of
certain conditions; for example, retinal detachments affect right eyes
slightly more frequently. This cross-sectional study explored, in two
large cohorts, whether right and left eyes differ in terms of axial
length or myopia (both linked risk factors for retinal detachment).
Methods: For the cataract cohort, axial lengths previously measured
for 12,766 eyes of 8,195 consecutive patients over a 6.5 year period
were analysed. Right and left eyes were compared (t test: paired
for patients with measurements for both eyes; unpaired for those
with measurements available for one eye). For the twin cohort,
refractive error was compared between right and left eyes (paired t
test) for 5,755 twin subjects from 3,199 families from the TwinsUK
database. To adjust for relatedness within families, re-sampling
was performed with one random member of each family (running
10,000 permutations). For 1,186 twins, eye dominance data were also
available.
Results: For 4,571 patients for whom axial lengths were available
for both eyes, mean (SD) axial lengths were 23.55 (1.40) mm and
23.50 (1.40) mm for right and left eyes respectively (p=4.7x10-20).
For 3,624 patients undergoing unilateral surgery, mean axial lengths
were 23.56 (1.28 mm) and 23.47 (1.23) mm respectively (p=0.04).
For twin subjects, right eyes were significantly more myopic than left
eyes (p = 0.04). 65% of twin subjects for whom eye dominance data
were also available were right-eye dominant. Although right eyes
were on average more myopic for right eye dominant subjects, the
laterality was reversed for left eye dominant subjects, but differences
did not reach significance.
Conclusions: Right eyes appear to be, on average, slightly, but
significantly, longer than left eyes. Longer eyes tend to be more
myopic and our refractive data were consistent with this. This
represents a novel finding and, in terms of clinical significance,
may explain the slight laterality imbalance in retinal detachments.
An understanding of mechanisms underlying small differences
in development of the two eyes would shed important light on
the development of myopia; our finding that differences might
be reversed for left eye dominant subjects suggests an interesting
interaction with mechanisms driving eye dominance.
Commercial Relationships: Omar A. Mahroo, None; Pirro G.
Hysi, None; Obeda Kailani, None; Juliet Thompson, None;
Christopher J. Hammond, None
Support: Fight for Sight UK grants (OAM, PH); Wellcome Trust
(CJH). TwinsUK also receives support from the National Institute for
Health Research (NIHR) BioResource Clinical Research Facility and
Biomedical Research Centre based at Guy’s and St Thomas’ NHS
Foundation Trust and King’s College London.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Program Number: 3611 Poster Board Number: A0060
Presentation Time: 3:45 PM–5:30 PM
Replication analysis of myopia-associated genes in Japanese
cohort and in highly myopic patients using genome-wide
association study
Munemitsu Yoshikawa1, Kenji Yamashiro1, Masahiro Miyake1, 2, Maho
Oishi1, Yugo Kimura1, Kyoko Kumagai1, Yumiko Akagi-Kurashige1,
2
, Hideo Nakanishi1, 2, Norimoto Gotoh1, 2, Nagahisa Yoshimura1.
1
Department of Ophthalmology and Visual Sciences, Kyoto
University Graduate School of Medicine, Kyoto, Japan; 2Center for
Genomic Medicine/Inserm U.852, Kyoto University Graduate School
of Medicine, Kyoto, Japan.
Purpose: Recently, two large consortium for myopia, Consortium for
Refractive Error and Myopia (CREAM) and 23andMe, reported the
results of genome-wide association analysis (GWAS) on spherical
equivalent (SE) refractive error and myopia age of onset and
found that 29 SNPs and 35 SNPs were associated with myopia in
Caucasians, respectively. In this study, we analyzed the associations
of these myopia-associated genetic loci on axial length (AL) and SE
in Japanese.
Methods: We included 3,248 Japanese healthy volunteers from
the Nagahama Study and 500 Japanese unrelated highly myopic
(AL^26mm) patients from Kyoto University Hospital. From
the results of above two GWAS, 50 genes were seemed to have
associations with myopia. To investigate and replicate these
associations in Japanese, we conducted 2 quantitative trait locus
(QTL) analyses using the Nagahama cohort and 1 GWAS using both
cohorts. The QTL analyses were conducted on AL and SE and GWAS
was conducted on the existence of high myipia. We genotyped
3,248 healthy volunteers using either Illumina OmniExpress2.5M or
HumanHap610K, and GWAS was conducted on the existence of high
myopia using either HumanHap550K or HumanHap660K. For each
analyses, VEGAS (Versatile Gene-based Association Study) program
were applied to perform gene-based association tests on myopiarelated 50 genes.
Results: In our 2 QTL analyses and 1 GWAS, only 4 genes
(RASGRF1, BMP4, GJD2, and CACNA1D) showed statistical
significance in all three analyses and 7 genes (B4GALNT2, SH3GL2,
SETMAR, ADAMTSL1, BICC1, SFRP1, and TOX) showed
statistical significance in two of the three analyses, whereas 27 genes
did not show significance in any of our study. In GWAS on high
myopia, 17 genes showed statistical significance. However, only 6
genes showed statistical significance in QTL analyses on AL and SE
among these 17 genes, respectively. On the other hand, QTL analyses
on AL and SE showed statistically significant 11 genes each, and as
many as 8 genes had statistical significance among these 11 genes in
common.
Conclusions: For previously reported myopia-related genes, we
showed the results of gene-based tests on AL, SE, and existence of
high myopia in our study cohort in Japan. Our data suggests that the
genetic background of Caucasians and that of Japanese for myopia,
and that of myopia and high myopia, could be different.
Commercial Relationships: Munemitsu Yoshikawa, None; Kenji
Yamashiro, None; Masahiro Miyake, None; Maho Oishi, None;
Yugo Kimura, None; Kyoko Kumagai, None; Yumiko AkagiKurashige, None; Hideo Nakanishi, None; Norimoto Gotoh, None;
Nagahisa Yoshimura, None
Program Number: 3612 Poster Board Number: A0061
Presentation Time: 3:45 PM–5:30 PM
Guinea pig optic nerve head
Lisa A. Ostrin1, Christine Wildsoet2. 1College of Optometry,
University of Houston, Houston, TX; 2School of Optometry,
University of California Berkeley, Berkeley, CA.
Purpose: The guinea pig is becoming an increasingly popular model
of human myopia. The goal of this study was to characterize and
compare the optic nerve head (ONH) and sclera of the guinea pig
with other animal models of human myopia and glaucoma. Myopia
carries an increased risk of glaucoma. The lamina cribrosa (LC) of
the ONH has been implicated as a site of axon damage in glaucoma
and in many species, is continuous with the sclera. It is plausible that
it is also abnormal in myopia.
Methods: Pigmented and albino guinea pig eyes (n=18, ages
2-3 months) were enucleated and the ONH and surrounding
sclera dissected. After formalin fixation, four eyes were paraffin
embedded for hematoxylin and eosin (H&E) staining. Four eyes
were cryoprotected and frozen for immunostaining. Primary
antibodies included collagen types I-V, elastin, fibronectin and glial
fibrillary acidic protein (GFAP). Remaining eyes were fixed in 2%
gluteraldehyde. Two ONHs were stained with osmium tetroxide
(OsO4) and embedded in resin for transmission electron microscopy
(TEM). Eight ONHs underwent alkali maceration with 10% NaOH
to remove cellular tissue, before staining with OsO4 and dehydration
for scanning electron microscopy (SEM) to evaluate the fiber
organization.
Results: H&E-stained sections showed retinal ganglion cell axons
organizing into fascicles in the prelaminar and laminar region.
Immunostained sections revealed collagen types I, III, IV and V in
the ONH, as well as elastin, GFAP and fibronectin. SEM revealed
the scleral canal to have a well-defined LC with radially-oriented
collagen beams, with spaces between presumably occupied by
ganglion cell axons and other support cells in the intact ONH. TEM
images confirmed the latter, revealing collagen fibrils surrounding
non-myelinated nerve bundles in the LC region, with myelination
and decreased collagen posterior to the LC. Adjacent sclera was
composed of crimped collagen fibers in a crisscross arrangement. The
sclera and LC were qualitatively similar in structure in pigmented and
albino guinea pigs.
Conclusions: Unlike mice, another rodent model for myopia and
glaucoma, the ONH of guinea pig includes a radially-organized,
collagen-based LC, similar to that of the tree shrew, but different
from primates in which organization is a porous collagenous
meshwork. Nonetheless, the overall structural similarity of the LC
suggests that the guinea pig is a suitable model for investigating the
relationship between myopia and glaucoma.
Commercial Relationships: Lisa A. Ostrin, None; Christine
Wildsoet, None
Support: NIH 5K08 EY022696, NIH R01 EY12392
Program Number: 3613 Poster Board Number: A0062
Presentation Time: 3:45 PM–5:30 PM
Spectral-domain optical coherence tomography imaging
of the retinal pigment epithelium in myopic choroidal
neovascularization
Laura Dell’Arti1, 2, Diego Vezzola1, Giulio Barteselli1, 3, Chiara
Mapelli2, Eleonora Benatti1, 2, Francesco Viola1, 2, Roberto Ratiglia1, 2.
1
University of Milan, Milan, Italy; 2Ophthalmology, clinical sciences
and community health, Fondazione IRCCS Ca Granda Ospedale
Maggiore Policlinico, Milan, Italy; 3Ophthalmology, Shiley Eye
Center UCSD, San Diego, CA.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.
ARVO 2014 Annual Meeting Abstracts
Purpose: To analyze the retinal pigment epithelium (RPE)
appearance of inactive myopic choroidal neovascularization (CNV)
with spectral-domain optical coherence tomography (SD-OCT) and
to evaluate its association with the lesion size and the treatment
duration.
Methods: We retrospective reviewed imaging studies of eyes with
inactive myopic CNV after successful treatment. Imaging included
infrared reflectance (IR), fundus autofluorescence (FAF), fluorescein
angiography (FA), indocyanine green angiography, and spectraldomain optical coherence tomography (SD-OCT). Patients were
divided into two groups. Group 1 showed uniformity of the RPE
(defined as continuous and highly reflective layer on SD-OCT)
over the CNV, while group 2 showed an irregular RPE (defined as
disrupted and poorly reflective layer on SD-OCT). The presence
of perilesional hyper-reflective ring (PHR) in IR imaging was
determined; the major diameter (MajD), the minor diameter (MinD)
and the area of the lesion (A2) in early FA images were measured
using the built-in caliper of the SD-OCT device. The number of
treatments performed before CNV stabilization was assessed for
every patient.
Results: Eighty-one eyes of 72 patients were included. Group 1 and
group 2 included 27 and 54 eyes, respectively. MajD, MinD and
A2 of the CNVs were significantly lower in group 1 than in group 2
(p<0.001). Group 2 patients needed greater number of treatments than
group 1 patients (p<0.01). The presence of a PHR was detected more
frequently in group 1 than in group 2 (p<0.01). Binary regression
analysis showed that the only predictor for the presence of a uniform
RPE after successful treatment was the size of the CNV. Conditional
selection of variables showed that the best regression model for the
presence of a regular RPE after successful treatment included size of
the lesion and presence of the PHR.
Conclusions: The uniformity of RPE and the presence of PHR turned
out to be good prognostic factors for myopic CNVs. Size of myopic
CNV influences the development of a uniform RPE over the lesion
and, consequently, can condition the prognosis of the disease.
Commercial Relationships: Laura Dell’Arti, None; Diego Vezzola,
None; Giulio Barteselli, None; Chiara Mapelli, None; Eleonora
Benatti, None; Francesco Viola, None; Roberto Ratiglia, None
Results: Body length increased significantly with age for both
strains (p<0.001). C57BL/6J mice had significantly larger body
length (average at 10 weeks, 8.60 ± 0.21 cm) compared to 129S1/
SvJ (8.31± 0.13 cm) mice (p=0.011). Axial length also increased
significantly during the development period (p<0.001). However, it
was not found to be significantly different between the two strains
across age (average at 10 weeks, 3.24 ± 0.07 and 3.26 ± 0.05 mm for
C57BL/6J and 129S1/SvJ respectively). After normalizing to body
length, 129S1/SvJ exhibited a significantly larger eye/body length
ratio (average at 10 weeks, 0.039 ± 0.001) compared to C57BL/6J
(average at 10 weeks, 0.037 ± 0.001) at all ages (p=0.025). Similar
to body length, crystalline lens thickness normalized to body length
significantly changed across both strains (129S1/SvJ > C57BL/6J,
p<0.05). Four week old 129S1/SvJ (-4.92 ± 2.37 D) mice had
significantly greater myopic refractions than C57BL/6J mice (+3.80
± 1.45 D; p<0.001), but both strains reached similar hyperopic
refractions by 14 weeks of age. A significant negative association
was observed between the eye/body length ratio and refraction for all
mice across both strains (slope = -0.0001, r 2 = 0.16, p<0.001).
Conclusions: Body length significantly influences axial length in
different mouse strains during development. The ratio of eye length
to body length is important to refractive development, but not the
only predictor of refractive error in mice.
Commercial Relationships: Ranjay Chakraborty, None; Hanna
Park, None; Christopher C. Tan, None; Megan Prunty, None;
Machelle T. Pardue, None
Support: NIH EY016435 (MTP), NIH P30 EY006360, Research to
Prevent Blindness, and the Department of Veterans Affairs
Program Number: 3614 Poster Board Number: A0063
Presentation Time: 3:45 PM–5:30 PM
Contribution of body length on axial length during normal
eye development in C57BL/6J and 129S1/SvJ wild-type mouse
strains.
Ranjay Chakraborty1, 2, Hanna Park1, 2, Christopher C. Tan1, 2, Megan
Prunty1, 2, Machelle T. Pardue2, 1. 1Ophthalmology, Emory University
School of Medicine, Atlanta, GA; 2Rehab R&D Center of Excellence,
Atlanta VA Medical Center, Atlanta, GA.
Purpose: To determine the influence of body length on eye length
in two different wild-type (WT) mouse strains during normal eye
development.
Methods: Measurements of body length, axial length, and refraction
were retrospectively analyzed for two different WT mouse strains:
129S1/SvJ (n=6) and C57BL/6J (n=8) from 4 to 16 weeks of age.
Body length, from the tip of the nose to the base of the tail were taken
from digital images using image analysis software (ImageJ). Axial
length (using an average refractive index of 1.433 for the entire eye)
and refractions were measured using a 1310 nm spectral domain
OCT (Bioptigen, Inc.) and an infrared photorefractor, respectively.
To elucidate the effect of body length on eye length between strains,
axial length was divided by the body length (eye/body length ratio)
for all animals.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at pubs@arvo.org.