Leber`s Hereditary Optic Neuropathy / Clinical testing

Transcription

ARVO 2015 Annual Meeting Abstracts
381 Leber’s Hereditary Optic Neuropathy / Clinical testing
Tuesday, May 05, 2015 3:45 PM–5:30 PM
Exhibit Hall Poster Session
Program #/Board # Range: 3856–3886/C0261–C0291
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Biochemistry/Molecular Biology,
Multidisciplinary Ophthalmic Imaging, Retina, Visual Psychophysics/
Physiological Optics
Program Number: 3856 Poster Board Number: C0261
Presentation Time: 3:45 PM–5:30 PM
Clinically-Significant Cardiac Pathology in Leber’s Hereditary
Optic Neuropathy
Starleen E. Frousiakis6, Rustum Karanjia2, Jeffrey S. Tran1,
Andrew E. Pouw1, Chiara La Morgia4, Milton Moraes3, Solange
R. Salomao5, Peter Quiros2, Valerio Carelli4, Alfredo A. Sadun2.
1
Ophthalmology, University of Southern California, Woodland
Hills, CA; 2Ophthalmology, UCLA, Los Angeles, CA; 3Instituto de
Olhos de Colatina, Colatina, Brazil; 4Department of Ophthalmology,
University of Bologna, Bologna, Italy; 5Federal University of Sao
Paulo, Sao Paulo, Brazil; 6Ophthalmology, Univeristy of Southern
California, Los Angeles, CA.
Purpose: To determine the association of clinically-significant
cardiac pathology with status as a carrier or affected subject, and to
compare previous findings on cardiac conduction in affected patients
with Leber’s hereditary optic neuropathy (LHON), 11778 mutation,
to a distinct pedigree.
Methods: Cardiac pathology was defined by past history of stroke,
myocardial infarction, angina, and/or palpitations. Subjects were
compared based on LHON status: control, carrier, or affected. A
logistic regression model was constructed, controlling for age and
body mass index (BMI). Data from a previously published cohort of
affected Brazilian patients (n1=23) and newly-acquired values from a
distinct Italian cohort (n2=21) were compared to a database of healthy
controls (n2=87). Each population underwent ECG testing, performed
by a cardiologist, with measurement of PR interval and QTc duration.
An unpaired student’s t-test was performed to determine if there was
a difference between affected populations and controls.
Results: The final regression model indicates that LHON status is
not correlated with an increased prevalence of cardiac pathology in
the sample population. Age is a significant predictor, but interaction
between age and status did not yield a significant difference between
groups. BMI was not found to be a significant predictor of cardiac
pathology. Mean PR intervals and standard deviations in the Italian
pedigree, Brazilian pedigree and control population were 140.6±20.6,
127.2±26.1 and 136.9±9.1, respectively. There was no significant
difference detected in mean PR interval between the Italian pedigree
and healthy controls, thereby validating the previously-published
findings in the Brazilian population. However, this study similarly
demonstrated a subgroup of patients within the Italian pedigree
who had a shortened PR interval (n=2). There was no significant
difference in QTc duration between affected and control populations
in either pedigree.
Conclusions: Carrier and affected populations of LHON do not
demonstrate increased prevalence of clinically-significant cardiac
pathology. This study validated the previously published findings
of a non-significant difference in PR interval and QTc duration in
affected patients with LHON and controls. A subgroup of subjects
with shortened cardiac conduction may be indicative of patients at
increased risk for conduction defects.
Commercial Relationships: Starleen E. Frousiakis, None;
Rustum Karanjia, None; Jeffrey S. Tran, None; Andrew E. Pouw,
None; Chiara La Morgia, None; Milton Moraes, None; Solange
R. Salomao, None; Peter Quiros, None; Valerio Carelli, None;
Alfredo A. Sadun, None
Phenotypic Variability in a Pedigree with Leber Hereditary Optic
Neuropathy (LHON)
Sherry J. Bass1, Daniel Epshtein1, Sanjeev Nath2, Jerome Sherman1,
2 1
. Clinical Sciences, SUNY College of Optometry, New York, NY;
2
The Eye Institute, New York, NY.
Purpose: To report typical and atypical serial findings in three
members of a LHON pedigree with an mt3460 mutation
Methods: Three siblings born of a mother with acute onset LHON
at age 20, an mt3460 genotype and 20/1000 VA were examined and
followed over a 5 year period. The 300-year pedigree was noted for a
history of profound vision loss, surprisingly preferential to females.
The youngest sibling studied was a 7 year-old male with an initial
best-corrected visual acuity (BCVA) of 20/20 OD and 20/25 OS.
The second sibling studied was a 14 year-old female with BCVA
20/20 OD/OS. The third sibling was a 16 year-old male with BCVA
20/20 OD/OS. In addition to visual acuity, testing included fundus
examination with fundus photography, OCT of the retinal nerve fiber
layer (RNFL) and ganglion cell analysis (GCA).
Results: The 7 year-old male had an atypical finding of pale discs
OU. RNFL Analysis (Zeiss Cirrus) revealed RNFL loss superiorly,
temporally, and inferiorly in both eyes. GCA revealed a profound
loss of ganglion cells in the macula. Examination of the 14 year-old
female revealed a hyperemic disc with peripapillary telangiectatic
microangiopathy. The RNFL was thickened nasally in both eyes.
GCA was statistically normal. Examination of the 16 year-old
brother revealed mild peripapillary telangiectatic microangiopathy in
both eyes. The right eye’s RNFL was normal but superior temporal
thinning was seen in the left eye. Diffuse GCA thinning was seen
in both eyes with denser loss inferiorly OD and temporally OS.
Examination at 5 year follow-up revealed no change in any of
the above findings in any of the two siblings with peripapillary
telangiectatic microangiopathy. However, in the youngest sibling
with pale discs, there was a one line reduction in visual acuity in both
eyes but no additional changes in the examination findings.
Conclusions: The rare presentation of early onset progressive LHON
has only been reported in mt17778 pedigrees. This pedigree, with a
mutation in the mt3460 locus, presents with characteristic findings of
both typical LHON and rare atypical early-onset progressive LHON.
Fundus photography, GCA, and RNFL analysis reveal varying stages
of optic nerve appearance and optic neuropathy. This pedigree also
reveals the existence of atypical early onset progressive LHON with
good vision and an mt3460 mutation previously (to the authors’ best
knowledge) unreported in the world’s literature.
Commercial Relationships: Sherry J. Bass, None; Daniel
Epshtein, None; Sanjeev Nath, None; Jerome Sherman, None
Leber’s hereditary Optic Neuropathy: cellular pathophysiology,
potential animal model, and cell-based drug screens for potential
therapeutics
Gino Cortopassi, Alfred K. Yu, Lanying Song, Karl Murray.
Molecular Biosciences, University of California, Davis, Davis, CA.
Purpose: Leber’s hereditary Optic Neuropathy (LHON) is
an inherited mitochondrial disease, resulting from mutations
in mitochondrial complex 1, which cause degeneration of
retinal ganglion cells, for which there is no cure. We analyzed
©2015, 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
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pathomechanism in LHON cells, implicating the mitochondrial
complex I defect, and ATF4 and CHOP and inflammatory
markers. We show the ndufs4 complex 1 knockout mouse
has significant depletion of RGC function, and RGC loss,
coincident with a strong rise in multiple inflammatory markers.
We have designed and improved cell-based screening assays
of 6 mitochondrial functions in cybrids bearing the LHON
mutation, and screened through 1600 FDA-approved drugs
to identify those which rescue LHON-specific defects. The
studies of pathomechanism support a model of LHON in which
primary mutations drive complex I structural changes that cause an
inflammatory response and RGC functional loss and death, and the
drug screening studies identify potential therapeutics.
Methods: Microarrays were carried out as published previously.
RNASeq and MicroElectrode Array (MEA) analysis of retinas of
Ndufs4 KO and wild type controls were carried out using standard
procedures.
Results: Cell-based pathomechanism. Results include the
mitochondrial complex-1 dependent induction of ATF4 and CHOP
and potential inflammatory markers. LHON animal model. The
ndufs4 KO mouse has loss of RGC function and RGC cell death as in
human LHON, and a substantial induction of inflammatory markers
in the retina, coincident with RGC functional loss by MEA. Drug
based screening. Partial poisoning of complex I uncovers a LHON
mutation-specific defect in complex I-driven ATP synthesis that can
be screened for drugs that protect from this defect. Such drugs fall
in particular structural and functional categories. Drug secondaries
and mechanistic understanding. Secondary screening is in progress
for hit confirmation, and mechanism of protective effect is being
generated for particular hits. Testing in animal model of LHON.
Top hits are entering animal testing, and preliminary results are likely
to be available by the meeting time.
Conclusions: We have identified a mechanism of LHON, an animal
model of LHON, and are screening therapeutics of potential benefit
in LHON cells.
Commercial Relationships: Gino Cortopassi, None; Alfred K. Yu,
None; Lanying Song, None; Karl Murray, None
Support: R01 EY012245
Evaluation of visual field metrics in patients with central
scotomas from LHON
Alexander F. Chen1, Amitha Ganti1, Youning Zhang1, Tiffany
Hwang1, Adriana Berezovsky2, Milton Moraes2, 3, Jeffrey S.
Tran1, Tana Wagschal5, Rustum Karanjia4, Alfredo A. Sadun4.
1
Ophthalmology, University of Southern California, Los Angeles,
CA; 2Ophthalmology, Universidade Federal de Sao Paulo, Sao Paulo,
Brazil; 3Centro Universitario do Espirito Santo, Colatina, Brazil;
4
Doheny Eye Institute, Pasadena, CA; 5Visual Field Reading Center,
University of Iowa, Coralville, IA.
Purpose: Patients with large and dense central scotomas may be
unable to reliably complete Stimulus size III (Stim III) Humphrey
Visual Fields (HVF). These patients, however, do considerably better
with Stimulus size V (Stim V) HVF. In Leber’s Hereditary Optic
Neuropathy (LHON) the reliability of the HVF varies over the course
of the disease. The purpose of this study was to determine if Stim
III and Stim V mean deviation (MD) calculations are equivalent in
patients with central scotomas from LHON.
Methods: 10 patients with LHON were administered Stim III and
Stim V HVF tests on the same day during multiple patient visits. Stim
III MD values were obtained from the HVF algorithm. In addition,
separate Stim III and Stim V MD values were obtained from an
investigative algorithm (IA). This IA, developed by the University of
Iowa Visual Field Reading Center, was used to derive patients’ MD
from Stim III and Stim V HVF raw numerical data. The MD values
from the HVF and IA were compared using a Pearson’s productmoment correlation coefficient.
Results: A total of 72 observations, 10 patients and 18 eyes were
analyzed. Stim III HVF and IA: r^2=0.99, HVF mean MD=-26.1 with
standard deviation (STD)=+/-6.72. IA mean MD=24.1 with STD=+/6.30. Mean absolute difference between HVF and IA =1.98 with
STD=+/-0.769. IA Stim III MD and Stim V MD: r^2=0.415, Stim
V mean MD=-21.2 with STD=+/-5.52. Mean absolute difference
between IA Stim III and Stim V MD=1.98 with STD=+/-2.97.
Conclusions: There was near perfect correlation of Stim III MD
between HVF and IA, validating the algorithm. MD values for Stim
III and Stim V, however, were not interchangeable. This may reflect
the variability that comes from visualizing the smaller stimulus in
subjects with a dense central scotoma.
Commercial Relationships: Alexander F. Chen, None; Amitha
Ganti, None; Youning Zhang, None; Tiffany Hwang, None;
Adriana Berezovsky, None; Milton Moraes, None; Jeffrey S. Tran,
None; Tana Wagschal, None; Rustum Karanjia, None; Alfredo A.
Sadun, Edison Pharmaceuticals (F)
Functional Visual Outcome of 1st vs 2nd Affected Eye in Treated
LHON Patients at 1 Year
Michael Ammar1, Jasdeep S. Chahal1, Amitha Ganti1, Jeffrey S.
Tran1, Edward R. Chu3, Alexander F. Chen1, Tiffany Hwang1, Rustum
Karanjia2, 3, Alfredo A. Sadun2, 3. 1USC Eye Institute, University of
Southern California, Los Angeles, CA; 2Ophthalmology, University
of California at Los Angeles, Los Angeles, CA; 3Doheny Eye
Institute, Los Angeles, CA.
Purpose: Leber’s Hereditary Optic Neuropathy (LHON) is
a mitochondrial optic neuropathy with no definitive therapy.
Involvement of the first eye is usually followed by the second eye
within a few months. Thus, the second eye is exposed to systemic
treatment, such as quinone therapy, earlier relative to its onset. We
carried out a retrospective chart review to test our hypothesis that
functional visual outcome is better in the 2nd affected eye at 1 year in
treated LHON patients.
Methods: Charts from 2009 to 2014 were analyzed at a university
affiliated eye institute. Patients were diagnosed with LHON, and
were seen at 1 year ± 2 months after conversion for the 2nd eye. 20
patients were identified and all were given quinone therapy for the
duration of the year. 14 began treatment after both eyes were affected
(hence earlier for 2nd eye) and 6 began after one eye was affected
(hence before visual loss in the 2nd eye). Average time to treatment
after involvement of the 1st eye was 172 days. LogMAR visual acuity
(VA), retinal nerve fiber layer (RNFL) thickness, and mean deviation
(MD) were recorded for 1st and 2nd eyes affected. A two-tailed
Student’s t-test was used for statistical analysis.
Results: At 1 year in the 1st affected eye, patients treated after both
eyes were affected had an average VA of 1.73 ± 1.67, an average
MD of -21.44 ± 7.39, and an average RNFL thickness of 64.75 ±
13.25. In the 2nd affected eye, they had an average VA of 1.78 ± 1.77,
an average MD of -15.82 ± 11.93, and an average RNFL thickness
of 66.13 ± 10.97. At 1 year in patients treated after both eyes were
affected, P values for the 1st vs 2nd affected eye were 0.4546 for VA,
0.1768 for MD, and 0.5342 for RNFL thickness. At 1 year in the 1st
affected eye, patients treated between affected eyes had an average
VA of 2.00 ± 2.08, an average MD of -29.08 ± 3.17, and an average
RNFL thickness of 65.60 ± 11.01. In the 2nd affected eye, they had an
average VA of 1.93 ± 2.10, an average MD of -24.22 ± 4.99, and an
average RNFL thickness of 60.20 ± 9.73. At 1 year in patients treated
between affected eyes, P values for the 1st vs 2nd affected eye were
0.1620 for VA, 0.1556 for MD, and 0.1540 for RNFL thickness.
Conclusions: In this LHON cohort, there was a trend but no
statistically significant difference in visual outcome between the 1st
and 2nd affected eye at 1 year. Hence, the timing of quinone therapy
does not appear to be critical.
Commercial Relationships: Michael Ammar, None; Jasdeep
S. Chahal, None; Amitha Ganti, None; Jeffrey S. Tran, None;
Edward R. Chu, None; Alexander F. Chen, None; Tiffany Hwang,
None; Rustum Karanjia, None; Alfredo A. Sadun, None
Mitochondria haplogroups in patients with dominant optic
atrophy
Isao Nakata, Eric D. Gaier, Daniel Navarro-Gomez, John S.
Borchert, Xiaowu Gai, Louis R. Pasquale, Simmons Lessell, Dean
M. Cestari, Joseph F. Rizzo, Janey L. Wiggs. Ophthalmology,
Massachusetts Eye and Ear Infirmary, Boston, MA.
Purpose: The most common inherited optic neuropathies are
dominant optic atrophy (DOA) caused by mutations in OPA1 and
Leber hereditary optic neuropathy (LHON) caused by mutations in
mitochondrial DNA (mtDNA). Previous studies have suggested that
background mtDNA haplogroups may affect LHON pathogenicity
and expressivity, however, the role of mtDNA halogroups in DOA
remains unexplored. This study aims to identify mtDNA haplogroups
in OPA1-related optic atrophy patients and to investigate the impact
of the haplogroups on the clinical phenotype.
Methods: Fifty-nine patients with the clinical diagnosis of primary
optic atrophy were studied. Genomic DNA was evaluated by next
generation sequencing using the Genetic Eye Disease (GEDi)
diagnostic panel that covers 234 genes (including OPA1) as
well as the entire mitochondrial genome. Patients with apparent
homozygosity based on consecutive single nucleotide polymorphisms
were also evaluated for copy number variation (CNV) using
Multiplex Ligation-dependent Probe Amplification (MLPA)
analysis. The mitochondrial haplogroup was determined using our
custom halplogroup-defining tool Phy-Mer (Navarro-Gomez et al.,
submitted). The difference in clinical phenotype (both ocular and
nonocular) among mtDNA haplogroups was tested with the ANOVA
test for continuous data and with the chi-square test for categorical
data.
Results: In the 59 optic atrophy cases, mtDNA haplogroup analysis
identified 19 cases (32.2%) with haplogroup H, 10 cases (16.9%)
with haplogroup U, and 8 cases (13.6%) with haplogroup J. Next
generation sequencing and CNV analysis identified 21 patients
(35.6%) with OPA1 disease-causing mutations and one patient (1.7%)
with a primary LHON mutation (m.11778G>A). In the overall group
(both with and without OPA1 mutations), significant differences
in age of onset, visual acuity, and visual field among haplogroups
was not observed (P > 0.05) although extra-ophthalmological
abnormalities such as hearing loss and peripheral neuropathy
tended to be more frequent in haplogroup J (42.9%) compared
with haplogroups U/H (16.0%, P = 0.157). In the cases with OPA1
mutations (n = 21), we found significantly more extra-ocular
abnormalities in haplogroup J cases (75.0%) compared to haplogroup
U/H cases (0.0%, P = 0.0140).
Conclusions: This study showed a potential association between
mtDNA haplogroup and extra-ocular findings in DOA with OPA1
mutation.
Commercial Relationships: Isao Nakata, None; Eric D. Gaier,
None; Daniel Navarro-Gomez, None; John S. Borchert, None;
Xiaowu Gai, None; Louis R. Pasquale, None; Simmons Lessell,
None; Dean M. Cestari, None; Joseph F. Rizzo, None; Janey L.
Wiggs, None
Support: JSPS Postdoctoral Fellowships for Research Abroad (IN),
Alcon Research Institute Award (JLW)
Improvements on a Method for Recognizing Colorblind
Malingering
Andrew E. Pouw1, Rustum Karanjia2, Alfredo A. Sadun2. 1Keck
School of Medicine, University of Southern California, Los Angeles,
CA; 2Ophthalmology, Doheny Eye Institute, University of California
Los Angeles, Los Angeles, CA.
Purpose: Standard tests of colorblindness screen for organic disease.
We have developed a method that attempts to recognize malingerers
of colorblindness. The purpose of this study is to validate this test in a
sample population.
Methods: An online survey was distributed to 84 self-reported and
verified colorblind participants and 131 participants instructed to
simulate colorblind malingering. The survey contained three sets of
twelve color-adjusted versions of the standard Ishihara color plates,
as well as one set of twelve unmodified plates. Participants were
asked to identify numbers on these 48 plates. Two tests were then
created, each using six unique plates. A “balanced test” emphasizing
both sensitivity and specificity was assembled by prioritizing test
plates that colorblind participants most often correctly identified, as
well as those test plates which malingering simulators most often
incorrectly identified. A second set of six test plates comprised the
“specific test,” which maximized test specificity. This was assembled
by prioritizing only those plates that colorblind participants most
often correctly identified. Statistical measures of both the “balanced
test” and “specific test” (sensitivity, specificity, and Youden indexes)
were assessed at each possible cut-off threshold, and a receiver
operating characteristic (ROC) function with its area under the curve
(AUC) charted.
Results: For the “balanced test,” colorblind and colorblind simulating
participants had a difference of means of 60.1% (CI: 53.6% to
66.5%). Statistical measures showed an optimal cut-off of at least
1 missed “balanced test” plate to recognize a colorblind malingerer
(Youden index: 0.81, sensitivity: 88.6%, specificity: 92.9%), with
an AUC of the ROC of 0.93. For the “specific test,” colorblind and
colorblind simulating participants had a difference of means of
41.6% (CI: 34.8% to 48.4%). Statistical measures showed a cut-off
of at least 2 missed “specific test” plates to identify a colorblind
malingerer with 100% specificity (sensitivity 51.9%, Youden index
0.52, AUC of 0.85).
Conclusions: Our method for recognizing colorblind malingering
demonstrates a high degree of reliability in a large population, and
can be used to both screen for colorblind malingerers and to identify
them with 100% specificity.
Commercial Relationships: Andrew E. Pouw, None; Rustum
Karanjia, None; Alfredo A. Sadun, None
Clinical Value of Electrophysiology in Determining the Diagnosis
of Visual Dysfunction in Neuro-Ophthalmology Patients
GH Yap1, LY Chen2, R Png2, Loo JL2, Tow S2, Mathur Ranjana2, Chia
A2. 1Singapore General Hospital, Singapore, Singapore; 2Singapore
National Eye Center, Singapore, Singapore.
Purpose: Neuro-ophthalmologists often refer patients for
electrophysiology to distinguish between retinal and post-retinal
pathology, and to aid in diagnosis. We performed a retrospective
review to assess clinical value of visual electrophysiology in
identifying causes of visual dysfunction in patients referred from
neuro-ophthalmology clinics.
Methods: A retrospective review of 410 subjects (0.3 – 88 years,
mean 43.6 +/- SD 20.0) referred for visual electrophysiology from
various neuro-ophthalmologists between 2009-2013 was performed.
Most underwent pattern, full-field and multifocal electroretinography
and pattern visual evoked potential (VEP) tests. Flash and multifocal
VEP were included where indicated. Main outcome measures were
the site of pathology and sensitivities for each test.
Results: 158 were referred for poor vision for investigation, 102
for unexplained visual field defects, 97 for miscellaneous visual
symptoms and 53 for other reasons. Most subjects referred for
poor vision for investigation had electrophysiology findings of
retinopathy (37%) or post-retinal pathology (34%), and those with
vision poorer than 6/24 more likely having abnormal findings (86%
vs 62%, p=0.0020). Among those with unexplained visual field
defects, findings of retinopathy, post-retinal pathology and normality
were noted in 31%, 24% and 28%, respectively. Most subjects with
miscellaneous visual symptoms had normal findings (69%). Among
the tests, multifocal ERG was most sensitive for retinopathy (96%)
and maculopathy (95%) and pattern VEP was most sensitive for postretinal pathology (94%). An indeterminate result was noted in 9%.
Conclusions: Electrophysiology was effective in allowing
differentiation between retinopathy, optic neuropathy and
electrophysiologic normality in 91% of subjects. Pre-testing
provisional diagnoses of retinopathy and post-retinal pathology were
revised in 30% and 42% respectively as a result of electrophysiologic
testing. A clear understanding of the characteristics of each test used
in correlation with the clinical picture and interpretation of all results
in totality are important in localising the site of pathology.
Commercial Relationships: GH Yap, None; LY Chen, None; R
Png, None; Loo JL, None; Tow S, None; Mathur Ranjana, None;
Chia A, None
Factors Predicting King-Devick Test Performance in Adults and
Adolescents
Yi Pang1, Robert J. Steinmetz2, Danielle F. Leong3, 2, Leonard V.
Messner1, Sherry Audycki4, James Fanelli5, Dan McGehee6, Wendy
Stone1, Katherine Lynch1, Heather Moss7. 1Illinois Coll of Optom,
Chicago, IL; 2SoLo Eye Care, Chicago, IL; 3King-Devick Test,
LLC, Oakbrook Terrace, IL; 4Advanced Eye Center, Bedford, MA;
5
Cape Fear Eye Institute, Wilmington, NC; 6Swagel Wootton Hiatt
Eye Center, Mesa, AZ; 7Department of Ophthalmology and Visual
Sciences and Department of Neurology & Rehabilitation, University
of Illinois at Chicago School of Medicine, Chicago, IL.
Purpose: The King-Devick (K-D) test is a rapid number naming test
that has been studied extensively as a marker of neurological disease
and concussion. Potentially confounding variables have not been
studied in a large sample. The purpose of this study was to determine
important confounding variables that are associated with K-D test
performance.
Methods: In this cross-sectional, multi-center study, subjects ≥15yrs
old with binocular near visual acuity < 20/30 completed two trials of
the K-D test protocol. Exclusion criteria included concussion within
3-months, post-concussion syndrome, dyslexia or neuro-degenerative
disorders. History of concussion, amblyopia, strabismus as well
as demographic variables of education, race/ethnicity, gender and
age were assessed by subject interview. Multiple linear regression
analysis was performed. Independent variables were modeled as
categorical (age (< or > 40 years), race/ethnicity, gender, education,
concussion, amblyopia, strabismus) and continuous (age in years
greater than 40 years) terms.
Results: Subjects (n=691, age 39.8±17.7 years) were enrolled across
5 sites. The average best K-D time was 41.2±8.2s. Table 1 shows the
results of multiple regression analysis. The final multiple regression
model included age beyond 40 years, education, black race and
Hispanic race. With other variables held constant, the K-D test time
worsened by 0.27s for each year in age above 40, improved by 1.94s
for each category of higher education level achieved, worsened by
3.67s for black race and improved by 2.38s for Hispanic ethnicity.
Gender, White race, Asian race, amblyopia, strabismus, or history of
concussion was not associated with K-D test performance.
Conclusions: Age greater than 40 years, education, black race
and Hispanic ethnicity were significantly associated with K-D test
performance. Knowledge of these confounding variables is important
for applications of K-D test in neurologically diseased populations
and its development as a clinical measurement tool.
Commercial Relationships: Yi Pang, None; Robert J. Steinmetz,
None; Danielle F. Leong, King-Devick Test, LLC (E); Leonard V.
Messner, None; Sherry Audycki, None; James Fanelli, None; Dan
McGehee, None; Wendy Stone, None; Katherine Lynch, None;
Heather Moss, None
THE MULTIPLE RAREBIT TEST (DIGITSTEP):
FEASIBITILY STUDY IN A PEDIATRIC POPULATION
Danielle Coury1, Julie Racine2, David Rogers1, 2. 1Ophthalmology,
The Ohio State University, Columbus, OH; 2Ophthalmology,
Nationwide Childrens Hospital, Columbus, OH.
Purpose: PURPOSE:
In adult patients, assessment of vision is often measured by visual
acuity alone. Although suitable to detect optical defect, visual acuity
may fail to detect anomalies of the retina and/or the optic nerve.
Alternative tests such as the Humphrey visual field (HVF) and the
contrast sensitivity test (CST) have been used to address the above.
More recently, a new technique was developed, the multiple rarebit
test, to quickly address neuronal damage in patients with optic nerve
anomalies. The multiple rarebit test has been used in adults with
success, but has not been used in pediatric populations. Therefore,
the purpose of this study was to 1- assess the feasibility of this new
method in a pediatric population and 2- to compare the results with
other methods such as the VF and the CST.
Methods: METHODS:
Ten subjects aged between 5 and 10 years of age with no known
ophthalmic pathology were recruited from the Nationwide Children’s
Hospital eye clinic to participate. Four tests were obtained for
all participants: Snellen visual acuity (VA), Humphrey visual
field (HVF), contrast sensitivity (CST) and multiple rarebit test
(Digitstep). All tests were performed monocularly and both eyes were
tested in the same session. Time to complete the test, ‘likeliness’ of
the test and the efforts needed to perform the test were compiled.
Results: RESULTS:
All subjects were able to perform all four tests. The VA, CST and the
Digitstep were well performed by subjects. Each test took less than 5
minutes to complete and subjects enjoyed the tests. On the other hand
HVF was very difficult to perform in younger patients (≤ 6y.o) and it
was time-consuming.
Conclusions: CONCLUSION:
The multiple rarebit test in a pediatric population is feasible. It is
easier for a child to perform the multiple rarebit test than to perform
the HVF. It is a quick test that children enjoyed. We noticed two
downsides of the test, first being the speed at which the numbers
are presented is fixed and can be sometimes too fast for the younger
subjects (≤6 years old) and second the digital numbers 2 and 5 are
similar in morphology and are often mistaken one another in children
younger than 6 years of age. In the future, the multiple rarebit test
could be use to asses the utility of the multiple rarebit test in children
affected with retinal or optic nerve damage.
Commercial Relationships: Danielle Coury, None; Julie Racine,
None; David Rogers, None
Support: The Ohio Lions Eye Research Foundation 319712
Proper ordering and interpretation of studies to avoid diagnostic
delay in optic nerve sheath meningioma
Thomas Ableman, Steven A. Newman. Ophthalmology, University of
Virginia, Charlottesville, VA.
Purpose: Optic nerve sheath meningiomas are often discovered
after substantial delay. The fact that fractionated radiation therapy
may substantially improve the prognosis underlies the importance
of timely diagnosis and treatment. We performed a retrospective
analysis of 7 cases of optic nerve sheath meningiomas with
substantial diagnostic delay to identify the circumstances and pitfalls
which led to the delay.
Methods: Retrospective analysis of 7 cases of optic nerve sheath
meningiomas with substantial diagnostic delay including records,
imaging, and diagnostic studies
Results: In several cases significant progressive visual loss occurred
during the 1-10 year delay in diagnosis. Some of these reversed
with radiation therapy after definitive diagnosis and referral to the
interventional radiology service. : Four potentially preventable
problems resulting in diagnostic delay were identified:
1. Lack of ordering imaging studies often due to an alternative
diagnosis such as AION or papillitis.
2. Lack of appropriately directed imaging (head scans instead of
orbital scans, the lack of employment of fat sat and gadolinium).
3. Miss-reading requiring reinterpretation.
4. Misinterpretation of OCT data because blocked axonal transport
masks development of optic atrophy.
Conclusions: Advances in technology have improved our ability
to identify potentially treatable optic nerve sheath meningiomas.
However, it remains incumbent on the evaluating ophthalmologist
to be familiar with appropriate ordering and interpretation of such
studies to avoid diagnostic delay.
Commercial Relationships: Thomas Ableman, None; Steven A.
Newman, None
Eye movement enhancement in Parkinson’s disease as a result of
CN-NINM intervention: a case study
Yakov Verbny, Kimberly Skinner, Mitchell Tyler, Kurt Kaczmarek, Yuri
Danilov. Biomedical Engineering, University of Wisconsin-Madison,
Madison, WI.
Purpose: The neurorehabilitation of sensory and motor functions
in Parkinson’s disease (PD) patients is undeveloped, and recovery
of eye-movement control is largely unexplored. There are very few
methods that show the possibility of rehabilitation of eye movements
affected by PD. The goal of this research was to investigate how well
cranial-nerve non-invasive neuromodulation (CN-NINM) can reduce
the effects of PD-induced impairments of oculomotor function and
help to recover eye movement control.
Methods: We completed a 4-month intervention with a 66-yearold male 6 years after he was diagnosed with PD symptoms. This
individual demonstrated abnormal gait, poor posture and balance,
occasional tremor and noticeable impairment of oculomotor function.
The CN-NINM intervention used a combination of both physical and
cognitive exercises with electrotactile stimulation to the tongue using
a Portable Neuromodulation Stimulator (PoNStm). Assessment of
oculomotor function was performed before and after the CN-NINM
intervention using special 4-channel binocular eye tracking goggles
(VisualEyes, Micromedical Inc). To evaluate the state of subject’s
eye movements we used three static nystagmus tests (vertical and
horizontal gaze, and spontaneous nystagmus) and three dynamic tests
(random saccade, smooth pursuit and optokinetic). All of the tests
were performed without tongue stimulation.
Results: The CN-NINM intervention resulted in the gradual
enhancement of patient eye movement control in all 6 tests. We
observed improvement of eye fixation, accuracy and stability in
nystagmus and gaze tests, increased eye movement accuracy and
precision, improved gain and velocity of target tracking, and changes
in both smoothness and synchronization of binocular movement
control in oculomotor tests. The most significant improvements in
eye movement control were found during performance of smooth
pursuit and random saccade testing. We also observed improvement
in his gait, posture and balance.
Conclusions: Our study establishes a proof of concept and
effectiveness of a new non-invasive neuromodulation therapy.
The improvements of eye movement control demonstrated by this
individual suggest that rehabilitation using a combination of exercise
and tongue-based neurostimulation may benefit people affected by
PD and would offer a novel treatment option for this disease.
Commercial Relationships: Yakov Verbny, None; Kimberly
Skinner, None; Mitchell Tyler, Advanced Neurorehabilitation
LLC,Madison,WI (I), Advanced Neurorehabilitation
LLC,Madison,WI (P), Advanced Neurorehabilitation
LLC,Madison,WI (S), Helius Medical Technologies, Newtown,
PA (I), Helius Medical Technologies, Newtown, PA (P), Helius
Medical Technologies, Newtown, PA (S), NeuroHabilitation Corp.,
Newtown, PA (P), NeuroHabilitation Corp., Newtown, PA (R); Kurt
Kaczmarek, Advanced Neurorehabilitation LLC,Madison,WI (I),
Advanced Neurorehabilitation LLC,Madison,WI (P), Advanced
Neurorehabilitation LLC,Madison,WI (S), Helius Medical
Technologies, Newtown, PA (I), Helius Medical Technologies,
Newtown, PA (P), NeuroHabilitation Corp., Newtown, PA (C),
NeuroHabilitation Corp., Newtown, PA (P), NeuroHabilitation Corp.,
Newtown, PA (R); Yuri Danilov, Advanced Neurorehabilitation
LLC,Madison,WI (I), Advanced Neurorehabilitation
LLC,Madison,WI (P), Advanced Neurorehabilitation
LLC,Madison,WI (S), Helius Medical Technologies, Newtown,
PA (I), Helius Medical Technologies, Newtown, PA (P), Helius
Medical Technologies, Newtown, PA (S), NeuroHabilitation Corp.,
Newtown, PA (C), NeuroHabilitation Corp., Newtown, PA (P),
NeuroHabilitation Corp., Newtown, PA (R)
Support: University of Wisconsin Foundation and the Jane Bradley
Pettit Foundation
Higher prevalence of visual symptomatology in individuals with
Parkinson’s disease
Helene Kergoat1, 4, Estefania Chriqui1, 4, Caroline Law1, 4, Elizabeth
L. Irving3, Marie-Jeanne Kergoat4, 2, Bernard-Simon Leclerc5,
4
, Michel Panisset2, 6, Sylvain Chouinard2, 6, Ronald Postuma7,
8 1
. Optometrie, Universite de Montreal, Montreal, QC, Canada;
2
Medecine, Universite de Montreal, Montreal, QC, Canada; 3School
of Optometry and Vision Science, University of Waterloo, Waterloo,
ON, Canada; 4Institut universitaire de geriatrie de Montreal,
Montreal, QC, Canada; 5CSSS de Bordeaux-Cartierville–SaintLaurent-CAU, Montreal, QC, Canada; 6Centre hospitalier de
l’Universite de Montreal, Montreal, QC, Canada; 7Montreal General
Hospital, Montreal, QC, Canada; 8McGill University, Montreal, QC,
Canada.
Purpose: We have recently reported that the prevalence of visual
symptoms linked with convergence insufficiency (CI) was higher in a
group of individuals with Parkinson’s disease - PD (27%) compared
to those in an age-matched group without PD (9%). Here, we
investigated the prevalence of visual symptomatology in individuals
with vs without PD who, based on a co-existing oculovisual
condition, were excluded from participation in our original study. We
hypothesize that the prevalence would be higher in those with PD
than those without.
Methods: Two study groups (n= 82 each) were included: 1)
participants having PD (Avg. ± SD: 71.2 ± 10.4 yrs) recruited
from two specialized neurology departments, and 2) age-matched
participants not having PD (70.5 ± 9.2 yrs). These participants
had various oculovisual conditions (eg. strabismus, glaucoma)
excluding them from the CI study. The Convergence Insufficiency
Symptom Survey (CISS-15) was also used here to verify visual
symptomatology in the 2 study groups. A score of ≥ 21 is considered
positive for symptomatology. The CISS-15 and a detailed oculovisual
questionnaire were administered to each participant by a telephone
interview. Confidence intervals and t-tests were performed using
SPSS.
Results: The participants did not differ for age (p = 0.60). The results
indicated that 45.1% of participants with vs 17.1% of those without
PD presented a score of ≥21 on the CISS-15 questionnaire (p < 0.05).
Conclusions: We have previously shown that the prevalence of
visual symptoms is higher in individuals with vs without PD but
without a co-existing oculovisual condition. We demonstrate here that
this prevalence remains higher in individuals with vs without PD who
also have a co-existing oculovisual condition. These results indicate
that PD per se places individuals with the disease at greater risk of
visual symptomatology.
Commercial Relationships: Helene Kergoat, None; Estefania
Chriqui, None; Caroline Law, None; Elizabeth L. Irving, None;
Marie-Jeanne Kergoat, None; Bernard-Simon Leclerc, None;
Michel Panisset, None; Sylvain Chouinard, None; Ronald
Postuma, None
Support: Canadian Institutes of Health Research; Canadian
Optometric Education Trust Fund; Comité aviseur pour la recherche
clinique-Institut universitaire de gériatrie de Montréal
Spectral-domain Optical Coherence Tomography in Huntington
Disease: Potential Biomarker?
Joao N. Beato1, Carlos Andrade2, Ana Monteiro2, Andreia Costa2,
Joana Guimarães2, Carolina Garrett2, Elisete Brandão1, Fernando
Falcão-Reis1, 3, Susana Penas1, 3. 1Ophthalmology, São João Hospital
Center, Porto, Portugal; 2Neurology, São João Hospital Center, Porto,
Portugal; 3Department of Sense Organs, Faculty of Medicine Of
University of Porto, Porto, Portugal.
Purpose: Clinical evaluation, neuroimaging, and biochemical
biomarkers have been extensively investigated in Huntington’s
disease, but none has been established. We performed a prospective
cross-sectional observational study to investigate retinal and
choroidal changes in HD and evaluate any potential correlation with
stage of the disease.
Methods: A thorough neurological evaluation was performed on
HD patients, including Motor Score of the Unified Huntington’s
disease rating scale (TMS-UHDRS), total functional capacity (TFC)
and independency status (IS). Age and sex matched healthy controls
enrolled were collected from the Ophthalmology Department
database. Both groups underwent examination through dilated pupil
using the Spectralis HRA+OCT®, Heidelberg® with the enhanced
depth imaging (EDI). Peripapillary RNFL and choroidal thickness
(PCT), macular and choroidal thickness (MT, CT) and respective
volumes (MV, CV) were evaluated.
Results: A total of 15 eyes of 8 HD patients were included. Sixteen
eyes of 8 healthy sex, age and mean refractive error-matched controls
were selected. Nasal RNFL, temporal PCT, superior peripheral
MT and MV and all macular choroidal thickness and volume
measurements were significantly (p<0.05) reduced in patients when
compared to controls. Several MT and MV measurements, were
positively correlated with TFC and IS and negatively correlated with
TMS-UHDRS, along with PCT measurements.
Conclusions: This findings suggest that both retina and choroid may
be affected in HD. Moreover, macular thickness and volume tend to
decrease with increasing severity of the disease. This could open a
way for the potential role of SD-OCT as a biomarker in HD.
Commercial Relationships: Joao N. Beato, None; Carlos Andrade,
None; Ana Monteiro, None; Andreia Costa, None; Joana
Guimarães, None; Carolina Garrett, None; Elisete Brandão,
None; Fernando Falcão-Reis, None; Susana Penas, None
Alzheimer disease and Mild Cognitive Impairment assessment
using Optical Coherence Tomography
Miguel Castilla Marti1, Octavio Rodriguez Gomez1, Sergi Mojal
García2, Mercé Boada i Rovira1. 1fACE - Barcelona Alzheimer
treatment & research center, BArcelona, Spain; 2IMIM - Hospital del
Mar, BArcelona, Spain.
Purpose: Early markers are needed for experimental and clinical
diagnosis and follow-up of Alzheimer disease (AD) and earlier stages
as Mild Cognitive Impairment (MCI). Retinal Nerve Fiber Layer
(RNFL) thinning have been observed in AD and MCI patients. We
performed a prospective, observational clinical study to ascertain how
RNFL thickness, as measured by Optical Coherence Tomography
(OCT), can be correlated with different grades of cognitive
impairment.
Methods: All patients who came to our center during an open
door initiative carried out between September and October of
2014 were invited to participate in neurological and complete
neuropsychological examination, and then sorted between three
different diagnostic groups: Healthy controls (C), MCI and AD. All
patients who agreed undergone through a complete ophthalmological
examination, including measurements of RNFL and macular
thickness by OCT Model 3D OCT-1 Maestro (Topcon, Japan). All
statistical analyses were performed using the Statistical Package for
the Social Sciences (version 20.0; SPSS, Inc., Chicago, IL, USA)
Results: 200 eyes from 100 patients (38 Healthy controls, 41 MCI
and 21 AD) were included . Mean age for the whole sample was
67 years (SD=10.46) and 59.5 years for Control group, 67.71 for
MCI and 80.52 for AD. Those differences showed to be statistically
significant with a p value <0.001. No differences were observed on
Macular thickness between groups. RNFL measurements showed
to be different for overall thickness (p<0.001), superior (p<0.001),
temporal (p=0.002) and inferior (p=0.003) quadrants. Statistical
significance dissapeared when age adjustment was applied, resulting
the superior quadrant thickness values for each group (C=113.01mm,
MCI=111.67mm, AD=100.95mm) to be marginally significant
(p=0.070). When compared individually, AD group showed to be
statistically different from C (p=0.037) and MCI (p=0.024) on upper
quadrant, with no differences between MCI and Controls.
Conclusions: Data suggests a tendency to RNFL thinning on AD
patients. Nevertheless, age revealed to be the main factor related with
RNFL thinning in our series. If OCT is an appropriate method for
AD and MCI assessment, capable to discriminate between disease
and normal age related changes on retinal thickness layers, need to be
further evaluated.
Commercial Relationships: Miguel Castilla Marti, None; Octavio
Rodriguez Gomez, None; Sergi Mojal García, None; Mercé Boada
i Rovira, None
Examination of retinal structure and visual function in civilian
patients with Traumatic Brain Injury
Jakaria Mostafa1, Divya Narayanan2, Suzanne Wickum1, Kassaundra
Johnston1, Nimesh B. Patel1, Laura J. Frishman1, Jason Porter1.
1
College of Optometry, University of Houston, Houston, TX;
2
Department of Ophthalmology, University of Texas Health Science
Center at San Antonio, San Antonio, TX.
Purpose: Recent reports suggest that veterans with traumatic brain
injury (TBI) may have optic nerve head (ONH) and inner retinal
damage in addition to reduced visual performance. We seek to (1)
quantify the extent to which abnormalities exist in retinal/ONH
structure and visual function in civilian TBI patients and (2) correlate
structural and functional measurements in the same eyes.
Methods: Spectral domain optical coherence tomography
volume scans of the ONH and macula were acquired in 14 eyes
of 7 TBI patients (36 ± 12 years). Peripapillary retinal nerve fiber
layer [RNFL] and macular retinal ganglion cell-inner plexiform
layer [GCIPL] thicknesses were quantified globally and in
sectors, and compared with instrument-based normative data.
Functional measurements were acquired with the full-field flash
electroretinogram (to quantify photopic negative response [PhNR]
amplitude) and 30-2 standard automated perimetry (to quantify mean
deviation [MD] and mean sensitivity). The percentage of agreement
between global structural and functional measures (i.e., whether
compared measures were both normal or abnormal) was calculated,
as was the probability of agreement when corrected for chance (AC1
statistics). Structural and functional measures were correlated on
global and local scales via regression analyses.
Results: GCIPL and RNFL thickness abnormalities were detected in
8/14 and 5/14 eyes, respectively. Abnormalities in PhNR amplitude
compared to normative values were found in 12/14 eyes and in MD
in 10/14 eyes. The strongest agreements occurred between PhNR
and MD (64% of eyes, AC1=0.42), GCIPL and RNFL thickness
(64%, AC1=0.31), and RNFL thickness and MD (64%, AC1=0.29).
Significant linear relationships (P<.05) were found across eyes
between GCIPL and RNFL thicknesses (R2 =0.62), MD and GCIPL
thickness (R2 =0.49), and MD and RNFL thickness (R2 =0.63). Only
9/56 comparisons were statistically significant when using published
structure-function correspondence maps to correlate sector measures
of GCIPL/RNFL thickness with corresponding local measures of
visual field sensitivity.
Conclusions: While structural abnormalities exist in some eyes, our
data indicate a high prevalence of functional abnormalities in TBI
patients. A better understanding of retinal/ONH structure, visual
function and their correlation in TBI patients may enable more
effective diagnosis, classification and treatment of injury.
Commercial Relationships: Jakaria Mostafa, None; Divya
Narayanan, None; Suzanne Wickum, None; Kassaundra
Johnston, None; Nimesh B. Patel, None; Laura J. Frishman,
None; Jason Porter, None
Support: NIH Grant P30 EY007551, Fight for Sight Summer
Student Fellowship, University of Houston College of Optometry
Imaging of optic disc drusen: Swept-Source (SS)-OCT versus
B-scan ultrasound
Michelle Ahn1, Andrew W. Eller2, Bo Wang2, Ellen Mitchell2, Joel S.
Schuman2, Chen D. Lu3, Ireneusz Grulkowski3, James G. Fujimoto3,
Gadi Wollstein2, Gabrielle R. Bonhomme2. 1University of Pittsburgh
School of Medicine, Pittsburgh, PA; 2UPMC Eye Center, Eye and
Ear Institute, Ophthalmology and Visual Science Research Center,
Department of Ophthalmology, University of Pittsburgh School of
Medicine, Pittsburgh, PA; 3Department of Electrical Engineering
and Computer Science, and Research Laboratory for Electronics,
Massachusetts Institute of Technology, Cambridge, MA.
Purpose: Optic disc drusen are currently diagnosed by B-scan
ultrasonography, but this modality is difficult to maneuver,
uncomfortable to patients, and operator-dependent. The aim of this
prospective study was to determine whether an alternative imaging
technology, the Swept-Source (SS)-OCT, improves the ability to
identify optic disc drusen compared to the gold standard of B-scan
ultrasonography.
Methods: We recruited patients who were of 5 years of age or more
and diagnosed with anomalous optic nerve heads. Subjects received a
complete ophthalmologic exam of the anterior and posterior segments
as well as a B-scan ultrasound and SS-OCT. The prototype SS-OCT
system was operated at 1060nm wavelength with 100kHz axial
scan rate. Images from each of the two imaging technologies were
then independently and qualitatively assessed for the presence and
visibility of drusen.
Results: A total of 13 patients (4 males and 9 females) were
recruited. The average age was 47.6 years. Among these subjects,
there were 21 eyes with optic disc drusen. Drusen were confirmed
in B-scans by hyper-reflectance of the calcium deposits at low
gain. In the SS-OCT, they were hypo-reflective bodies that could
be visualized in a 3D cube, making it possible to also pinpoint their
locations. Optic disc drusen were identifiable through SS-OCT in
all 21 eyes (100%), had well-demarcated borders in 19 (90.5%), and
were seen along their entire depths in 16 (76.2%).
Conclusions: While the B-scan tests for the hyper-reflective
properties of the calcified bodies, the SS-OCT allows anatomic
visualization of the actual deposits. Here, we were able to identify
optic disc drusen in all of the eyes that were diagnosed with this
condition through B-scan. The SS-OCT therefore has equal ability to
detect drusen compared to B-scan ultrasonography, and the additional
benefits of ease of conducting the exam, patient comfort, data
standardization, and potential quantification of drusen size make it
more clinically useful.
Commercial Relationships: Michelle Ahn, None; Andrew W.
Eller, None; Bo Wang, None; Ellen Mitchell, None; Joel S.
Schuman, Zeiss (P); Chen D. Lu, None; Ireneusz Grulkowski,
None; James G. Fujimoto, Optovue (I), Zeiss (P); Gadi Wollstein,
None; Gabrielle R. Bonhomme, None
Support: NIH R01-EY013178, R01-EY011289, P30 EY008098; Eye
and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness
(New York, NY)
Macular Edema Associated with Anterior Ischemic Optic
Neuropathy: An OCT Study
Christopher Weaver, Steven A. Newman. Ophthalmology, University
of Virginia, Charlottesville, VA.
Purpose: Thickening of nerve fiber layer is characteristic of anterior
ischemic optic neuropathy. Disc edema, if severe enough, can track
into the macula. This may be responsible for some of the decreased
vision seen in acute anterior ischemic optic neuropathy. To study the
incidence of effect of macular swelling, a retrospective study was
undertaken of patients with anterior ischemic optic neuropathy that
had OCT of both nerve fiber layer and macula.
Methods: A retrospective chart review was performed of longitudinal
data from the University of Virginia from December 2005- January
2014 with inclusion criteria consisting of the diagnosis of AION
and exclusion criteria of pre-existing macular edema from other
comorbidities (n=127).
Results: Of the 127 patients reviewed in this study, 14 had macular
edema as demonstrated on macular OCT (11%), which invariably
resolved over the course of approximately three months. These
patients had improved mean outcomes in visual acuity relative to
those without macular edema, in comparison to baseline visual acuity
in both groups (p<0.05).
Conclusions: Macular edema associated with AION was found in
11% of patients, with these patients demonstrating improvement
in visual acuity at three months compared to those patients who
presented without macular edema. Further studies investigating the
possible correlation between retinal nerve fiber layer thickness and
presence of macular edema are warranted given the uncertainty of the
inciting factors in the development of macular edema in AION.
Commercial Relationships: Christopher Weaver, None; Steven A.
Newman, None
Multicolour Imaging in Acute Macular Neuro-retinopathy
Rashi Arora4, 2, Sara Vaz-Pereira1, 3, Gabriella De Salvo2. 1Hospital
de Santa Maria, Lisbon, Portugal, Lisbon, Portugal; 2University
Hospital of Southampton, Southampton, United Kingdom; 3Faculty
of Medicine, University of Lisbon, Portugal, Lisbon, Portugal;
4
Moorfields Eye Hospital, London, United Kingdom.
Purpose: To evaluate the role of multicolor imaging (MC) in the
diagnosis and follow up of acute macular neuroretinopathy (AMN)
and to compare its features to fundus color photograph, near-infrared
reflectance (NIR) and spectral domain optical coherence tomography
(SD-OCT).
Methods: Color fundus photographs, MC, NIR and SD-OCT were
performed in 5 patients who presented with central scotoma and
without any specific visible fundus features.
Results: AMN was identified as an area of hypo-reflectance in NIR
in 8 eyes of 5 patients. SD-OCT confirmed its location in the outer
retina below the outer plexiform layer in 7 eyes (type 2) and above
the outer plexiform layer in 1 eye (type 1). Additional MC was
performed at baseline in 5 eyes (3 patients) and at follow-up in all
eyes. Subsequent follow up demonstrated improvement of symptoms
and this was objectively confirmed on both NIR and MC by gradual
decrease of hypo-reflectance, with the latest showing higher contrast
between the affected and the physiologic areas. SD-OCT showed a
partial recovery of the ellipsoid zone in type 2 and inner nuclear layer
thinning in type 1.
Conclusions: MC is a new non invasive imaging modality which
allows the detection of fine anatomic retinal details. In our patients,
MC imaging emerged as a very useful tool in the detection and
follow-up of AMN. We believe that, when available, MC should be
routinely used to complement SD-OCT in the diagnosis and follow
up of this rare inflammatory condition.
Commercial Relationships: Rashi Arora, None; Sara Vaz-Pereira,
None; Gabriella De Salvo, None
OPA1 sequencing analysis and detailed ophthalmic examinations
including the investigation of microcystic macular edema in 18
patients with bilateral optic atrophy
Shuhei Kameya1, Kiyoko Gocho1, Sachiko Kikuchi1, Kenichi Yoshino2,
Masahiro Miura3, Hiroko Yamazaki4, Kei shinoda5, Atsushi Mizota5,
Kunihiko Yamaki1, Hiroshi Takahashi6. 1Ophthalmology, Chiba
Hokusoh Hosp Nippon Med Sch, Inba, Japan; 2Yoshino Eye Clinic,
Taito-ku, Japan; 3Ophthalmology, Tokyo Medical University Ibaraki
Medical Center, Ami, Japan; 4Ophthalmology, Kohnodai Hospital,
National Center for Global Health and Medicine, Ichikawa, Japan;
5
Ophthalmology, Teikyo University School of Medicine, Itabashi-ku,
Japan; 6Ophthalmology, Nippon Medical School, Bunkyo-ku, Japan.
Purpose: Autosomal dominant optic atrophy (ADOA), also known
as Kjer’s disease, is the most common hereditary ocular neuropathy.
ADOA is characterized by a decrease in the visual acuity that
develops in childhood, temporal palor of the optic discs, centrocecal
scotoma, and color vision defects. The purpose of this study was to
distinguish patients with ADOA and optic atrophy with unknown
origin by comparing the results of OPA1 sequencing analysis and
clinical characteristics of the patients.
Methods: 18 patients with bilateral optic atrophy underwent detailed
ophthalmic examinations. The ophthalmological examinations
included measurements of the best-corrected visual acuity, fundus
photography, perimetry, SD-OCT analysis of nerve fiber layer
thickness, color vision test, differences of severity between right and
left eyes, and investigation of microcystic macular edema (MME)
in SD-OCT. 12 patients underwent an adaptive optics analysis for
detailed examination of MME. Mutational screening of all coding
and flanking intron sequences of the OPA1 gene in 18 patients was
performed by sanger DNA sequencing.
Results: We have identified pathological mutations of OPA1 gene in
7 patients from 5 families. All patients with OPA1 mutation revealed
temporal palor of optic discs, centrocecal scotoma or blind spot
enlargement binoculary. 6 patients with OPA1 mutation showed color
vision deficiency. All patients with OPA1 mutation revealed very thin
retinal nerve fiber layer between optic nerve and macular by a vertical
SD-OCT scan at about 1 mm from the edge of optic disc. Majority
of patients without OPA1 mutation lack some of these observations
commonly found in patients with OPA1 mutation. MME in SD-OCT
was found in 2 patients with OPA1 mutation and 2 patients without
OPA1 mutation. Adaptive optics analysis revealed MME in 2 patients
with OPA1 mutation and 2 patients without OPA1 mutation.
Conclusions: A vertical SD-OCT scan at about 1 mm from the edge
of optic disc is useful way to visualize and evaluate the temporal
palor of optic disc that is a remarkable feature of ADOA. MME
were identified in both groups with and without OPA1 mutation.
Since sanger sequencing could not detect a large deletion of the
gene, further studies such as multiplex ligation-dependent probe
amplification will be needed.
Commercial Relationships: Shuhei Kameya, None; Kiyoko
Gocho, None; Sachiko Kikuchi, None; Kenichi Yoshino, None;
Masahiro Miura, None; Hiroko Yamazaki, None; Kei shinoda,
None; Atsushi Mizota, None; Kunihiko Yamaki, None; Hiroshi
Takahashi, None
Characteristics of microcystic macular edema determined by
adaptive optics scanning laser ophthalmoscopy (AO-SLO) in eyes
with optic neuropathy
Takao Endo1, Takashi Fujikado2, Masakazu Hirota2, Hiroyuki Kanda2,
Takeshi Morimoto2, Shinichi Usui1, Kohji Nishida1. 1Department
of Ophthalmology, Osaka Univ Grad School of Med, Suita, Japan;
2
Applied Visual Science, Osaka Univ Grad School of Med, Osaka,
Japan.
Purpose: Microcystic macular edema (MME) is detected as an
arcuate-shaped low reflectance area in the macula in the infrared
fundus photographs and in the adaptive optics scanning laser
ophthalmoscopic (AO-SLO) images. The low reflectance area
corresponds to the area of microcystic changes in the inner nuclear
layer (INL) detected by optical coherence tomography (OCT), and
they have been reported in a variety of optic nerve diseases. The
purpose of this study was to determine whether MME was present in
eyes with optic neuropathy and to determine their characteristics.
Methods: This was a retrospective study of 41 eyes of 25 patients
with optic neuropathy or glaucoma. There were 7 eyes with traumatic
optic neuropathy, 3 eyes with ischemic optic neuropathy, 4 eyes with
ethambutol optic neuropathy, 4 eyes with Leber’s optic neuropathy,
5 eyes with optic neuritis, 6 eyes with optic nerve atrophy and 12
eyes with glaucoma. All of the patients were examined by AO-SLO
and OCT at the Osaka University Hospital between August 2013
and October 2014. The visual acuity and incidence of MME were
determined in these patients.
Results: Low-reflectance areas in the AO-SLO image with
microcysts in the OCT images were observed in 11 eyes (26.8%). The
visual acuity was significantly poorer in eyes with MME (1.9±1.2
logMAR units) than in eyes without MME (0.42±0.73 log units;
P<0.0). Eight of the 11 eyes with MME had arcuate low reflectance
area but 3 eyes with glaucoma had a nerve fiber layer defect
(NFLD)-like low reflectance area by AO-SLO. This NFLD-like low
reflectance area did not correspond to the scotoma in the Humphery
visual fields, which were different from the ordinal NFLD.
Conclusions: The presence of MME may be related to an advanced
stage of optic neuropathy. The shape of the MME in the AO-SLO
images is not only arcuate but can also be NFLD-like.
Commercial Relationships: Takao Endo, None; Takashi Fujikado,
None; Masakazu Hirota, None; Hiroyuki Kanda, None; Takeshi
Morimoto, None; Shinichi Usui, None; Kohji Nishida, None
A Decade Of Diagnosing Inherited Retinal Dystrophies and Optic
Atrophies: The Evolution Towards An Advanced Standardized
Retinal Imaging and Molecular Genetic Approach
Ulrich Kellner1, 2, Heidi Stöhr3, Susanne Kohl4, Bernhard H. Weber3,
Bernd Wissinger4, Teresa Neuhann5, Silke Weinitz1, 2, Ghazaleh
Farmand1, Simone Kellner1, 2. 1Rare Retinal Disease Center,
AugenZentrum Siegburg, MVZ ADTC Siegburg GmbH, Bonn,
Germany; 2RetinaScience, Bonn, Germany; 3Institute for Genetics,
Regensburg, Germany; 4Molecular Genetics, Institute for Ophthalmic
Research, Tübingen, Germany; 5Molekulargenetisches Zentrum
(MGZ), München, Germany.
Purpose: An early diagnosis of inherited retinal or optic nerve
disorders (IROD) is frequently delayed due to unspecific clinical
signs, variability of clinical manifestations and the underlying genetic
defects. The present study evaluates the impact of non-invasive
retinal imaging techniques (fundus autofluorescence (FAF), nearinfrared autofluorescence (NIA), spectral domain OCT (SD-OCT),
three wavelength MultiColor spectral reflectance imaging (MC)) and
molecular genetic analysis on the diagnostic process of IROD.
Methods: In a single specialized center 1045 patients with IROD
were examined and confirmed based on electrophysiological, retinal
imaging or molecular genetic data between 2004 and 2014. Followup was available in 378 patients (median 3.9 y.). In addition to the
basic ophthalmological examination electrophysiological testing
(ERG n=358; EOG n=53; VEP n=102; mfERG n=283) and noninvasive retinal imaging (FAF n=947; NIA n=698; SD-OCT n=621;
MC n=242) were performed at least once. Molecular genetic analysis
was performed in 545 patients.
Results: The combination of non-invasive retinal imaging
with molecular genetic analysis has continuously replaced
electrophysiological testing as a primary tool for the diagnosis of
IROD. Multiple novel imaging phenomena have been observed
specific for IROD, although frequently not specific for certain
associated genes. Early phenomena in retinal imaging modalities
frequently precede ophthalmoscopic visible alterations and therefore
facilitate early diagnosis. Mostly in cone dysfunction and congenital
stationary night blindness ERG is superior to retinal imaging.
Molecular genetic testing confirmed disease-causing mutations (1
in dominant or x-linked disorders, 2 in recessive disorders) in 229
patients (44.4%).
Conclusions: Non-invasive retinal imaging techniques advanced
towards the primary tool for the diagnostic approach in suspected
IROD and serve as the basis for planning of molecular genetic
analysis. Multiple novel characteristic retinal imaging phenomena
have been observed and increased our understanding of IROD.
Patients have the advantage that imaging techniques are more
widespread available than electrophysiological testing. A targeted
diagnostic strategy reduces the diagnostic delay, enables an earlier
counselling and therapy and avoids unnecessary diagnostic tests.
Commercial Relationships: Ulrich Kellner, None; Heidi Stöhr,
None; Susanne Kohl, None; Bernhard H. Weber, None; Bernd
Wissinger, None; Teresa Neuhann, None; Silke Weinitz, None;
Ghazaleh Farmand, None; Simone Kellner, None
LSFG-measured reduction of temporal optic disc circulation in
ADOA patients
Maki Inoue, Noriko Himori, Takayuki Takeshita, Naoko Aizawa,
Kazuko Omodaka, Yukihiro Shiga, Kazuichi Maruyama, Koji
Nishiguchi, Toru Nakazawa. Tohoku university, Sendai, Japan.
Purpose: To evaluate optic nerve head microcirculation in autosomal
dominant optic atrophy (ADOA) patients with laser speckle
flowgraphy (LSFG), a recently introduced method to assess blood
flow.
Methods: This study comprised 14 eyes of 8 ADOA patients
(mean age: 37.7 ± 14.0 years; spherical equivalent: -3.66 ± 2.15 D;
LogMAR visual acuity: 0.51 ± 0.39). Clinically, the ADOA patients
were diagnosed by low visual acuity, pallid temporal optic nerve
discs, visual field defects, a family history consistent with autosomal
dominant inheritance and the presence of mutations in the OPA1
gene. Eighteen normal eyes of 9 age-matched subjects served as
controls (mean age: 41.6 ± 12.7 years; spherical equivalent: -3.11 ±
1.75 D; LogMAR visual acuity: -0.14 ± 0.05). Blood flow in the optic
nerve head was assessed with LSFG, and the mean blur rate (MBR)
ratio was calculated for each optic nerve head quadrant (superior,
temporal, inferior and nasal) by dividing tissue MBR in that quadrant
by the entire tissue MBR in the optic nerve head. We then compared
the MBR ratio in each quadrant in the two groups.
Results: In all quadrants, MBR was significantly lower in the ADOA
patients than in the controls (superior: 8.23 ± 1.50 vs. 13.84 ± 3.28;
temporal: 5.12 ± 1.02 vs. 10.33 ± 2.48, inferior: 7.04 ± 1.31 vs. 13.65
± 2.46, nasal: 8.70 ± 1.13 vs. 13.94 ± 2.32, respectively, p < 0.01).
Only in the temporal quadrant, the MBR ratio was significantly lower
in the ADOA patients (0.74 ± 0.09 vs. 0.82 ± 0.07, respectively, p <
0.05).
Conclusions: In ADOA, the temporal optic disc generally appears
pale in fundus imaging. This suggests that blood flow on the temporal
side of the optic disc should be reduced compared to other disc areas,
but precise measurements of blood flow in the optic nerve head of
ADOA patients have not yet been reported. Here, we found that blood
flow in the optic disc, particularly on the temporal side, was indeed
significantly lower in ADOA patients than in normal controls. Due to
the anatomical characteristics of the optic nerve, the papillomacular
bundle is susceptible to damage caused by mitochondrial dysfunction,
which occurs in ADOA. Thus, our results suggest that reduced
blood flow in the temporal optic disc in ADOA patients is caused by
damage to the papillomacular bundle.
Commercial Relationships: Maki Inoue, None; Noriko Himori,
None; Takayuki Takeshita, None; Naoko Aizawa, None; Kazuko
Omodaka, None; Yukihiro Shiga, None; Kazuichi Maruyama,
None; Koji Nishiguchi, None; Toru Nakazawa, None
Peripapillary and subfoveal choroidal thickness in non-arteritic
anterior ischemic optic neuropathy (NA-AION)
Libin Jiang. Eye Center, Beijing Tongren Hospital, Beijing, China.
Purpose: To study whether peripapillary and subfoveal choroidal
thicknesses of NA-AION patients is normal or not.
Methods: The study involved 44 unilateral NA-AION patients
(23 men and 21 women), whose mean age was 50.84±9.95 years
(mean±SD), and 60 normal subjects (60 eyes) with similar age
(50.30±1.18 years) and diopter. The patients were divided into
two groups: 19 patients with optic disc edema in group 1 and 25
patients with optic disc edema resolution in group 2. Peripapillary
and subfoveal choroidal thicknesses in all the eyes studied were
measured by enhanced depth imaging Heiderberg Spectralis optic
coherence tomography (EDI-OCT, Heidelberg engineering, Software
Version:5.3.2). Peripapillary choroidal thickness was measured at the
nasal superior (NS), nasal (N), nasal inferior (NI), temporal inferior
(TI), temporal (T) and temporal superior (TS) segments. Choroidal
thicknesses in the suffering eyes and the unaffected fellow eyes of
the patients were compared with that of normal subjects. Choroidal
thicknesses of the patients in Group 1 and Group 2 were also
compared. The correlation between choroidal thickness and retinal
nerve fiber layer (RNFL) thickness, logMAR visual acuity (logMAR
VA), and the mean defection (MD) of Humphrey static perimetry (242) in the NA-AION suffering eyes were analyzed.
Results: It was only found that peripapillary choroidal thickness
at the nasal, nasal inferior and temporal inferior segments in the
suffering eyes in group 1 were significantly thicker than that of
normal subjects (P<0.05). We found no difference in choroidal
thickness (1) between the suffering eyes and the unaffected fellow
eyes of the NA-AION patients, (2) between the unaffected fellow eye
of the NA-AION patients and normal eyes of healthy subjects, (3)
between group 1 and group 2 (all P>0.05). There were no correlations
between choroidal thickness and RNFL thickness in both two groups
(all P>0.05). Neither logMAR VA nor MD correlated with choroidal
thickness in the eyes affected by NA-AION (all P>0.05).
Conclusions: Although peripapillary choroidal thickness in some
segments become thicker in the eyes with optic disc edema caused by
NA-AION, there are no evidences to prove that choroidal thickness is
abnormal in NA-AION compared with normal subjects with similar
age and diopter.
Commercial Relationships: Libin Jiang, None
Serum Level of Vascular Endothelial Growth Factor and
Opening Lumbar Pressure Significantly Correlated with Optic
Disc Edema in Patients with POEMS Syndrome
Takehito Iwase, Hirotaka Yokouchi, Takayuki Baba, Toshiyuki
Oshitari, Shuichi Yamamoto. Japanese Ophthalmological Society,
Chiba, Japan.
Purpose: It has been shown that the intracranial pressure (ICP) can
induce optic disc edema (ODE), and high serum levels of vascular
endothelial growth factor (VEGF) can also induce ODE in patients
with polyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changes (POEMS) syndrome. We performed
a cross sectional observational study to determine whether there is
a significant correlation between the peripapillary retinal nerve fiber
layer (RNFL) thickness and the serum level of VEGF and the spinal
lumbar pressure (LP).
Methods: We studied 32 eyes of 16 treatment-naïve patients (11
men, 5 women) with the POEMS syndrome at the Chiba University
Hospital from September 2012 through October 2014. The diagnosis
of POEMS was made by the criteria established by Dispenzieri in
2007. The peripapillary RNFL (pRNFL) thickness was determined
by optical coherence tomography (OCT: RTVue-100 Optovue, Inc.).
The serum level of VEGF was measured by enzyme-linked immune
sorbent assay (ELISA). The opening (LP) pressure was measured
instead of the ICP. The correlation between the pRNFL thickness and
the serum level of VEGF and opening LP pressure was determined by
the Spearman’s rank-correlation coefficient.
Results: The mean serum level of VEGF was 5130 ± 3590 pg/
ml with a range of 1330 to 11900 pg/ml. The mean opening LP
pressure was 179.1 ± 56.4 mmH2O. There was a significant positive
correlation between the pRNFL thickness and the opening LP
pressure (r=0.67, P=0.0002), and also between the pRNFL thickness
and the serum level of VEGF (r=0.37, P=0.03). In addition, there
was a strong positive correlation between the pRNFL thickness
of the right and left eyes (r = 0.81, P=0.0001). On the other hand,
the correlation between the serum level of VEGF and opening LP
pressure was not significant (r=0.32,P=0.32).
Conclusions: The significant positive correlation between the pRNFL
thickness and the opening LP and also with the serum levels of VEGF
are in accord with previous studies reporting that the ICP and the
serum levels of VEGF can affect the ODE in POEMS patients. These
results suggest that both the higher LP and the serum levels of VEGF
can account for the development of ODE in patients with POEMS
syndrome.
Commercial Relationships: Takehito Iwase, None; Hirotaka
Yokouchi, None; Takayuki Baba, None; Toshiyuki Oshitari, None;
Shuichi Yamamoto, None
Characterizing optic disc edema in the setting of neurosyphilis
John J. Chen1, Matthew Thurtell2. 1Ophthalmology, Mayo Clinic,
Rochester, MN; 2Ophthalmology, University of Iowa, Iowa City, IA.
Purpose: Syphilis can affect any part of the eye, including the optic
nerve. Patients can have disc edema without visual compromise,
which has been attributed to papilledema from raised intracranial
pressure or optic perineuritis from optic nerve sheath inflammation.
However, these attributions were proposed before MRI was largely
available. We performed a retrospective, clinical observational
study to better understand the mechanism of optic disc edema in
neurosyphilis.
Methods: We reviewed all patients seen at the University of Iowa
from 2010 to 2014 with a diagnosis of neurosyphilis affecting the
optic nerve, which revealed three patients with optic disc edema. The
visual acuity, fields, OCT, fundus photos, lumbar puncture, and MRI
results were examined to determine the mechanism of the optic disc
edema. Neurosyphilis was confirmed with reactive VDRL in the CSF.
Results: One patient had unilateral optic disc edema and two patients
had bilateral optic disc edema. The visual fields showed enlargement
of the blind spots only, except for one eye of a patient who had
concomitant chorioretinitis and trace optic disc edema resulting
in a cecocentral scotoma. All three patients denied symptoms of
raised intracranial pressure. The opening pressure was normal in
the two patients who had it measured; the opening pressure in the
patient with unilateral disc edema was not measured. MRI of the
orbits demonstrated no optic nerve sheath enhancement in any of the
patients.
Conclusions: With modern diagnostic imaging, we were able to
demonstrate a lack of optic nerve sheath enhancement in three
patients with optic disc edema and preserved visual function,
suggesting papillitis may be a better term than optic perineuritis in
many cases of isolated disc edema from neurosyphilis.
62 year-old male with bilateral optic disc edema in the setting of
neurosyphilis. The right eye has severe optic disc edema with normal
visual fields other than enlargement of the blind spot. The left eye
has a cecocentral scotoma due to chorioretinitis in conjunction with
trace optic disc edema. OCT shows an elevated retinal nerve fiber
layer thickness in both eyes, right greater than left, and photoreceptor
disruption in the macula of the left eye confirming chorioretinitis.
Magnetic resonance imaging of the orbit demonstrates no optic nerve
or sheath enhancement.
Commercial Relationships: John J. Chen, None; Matthew
Thurtell, None
Current intensity-dependent neuroprotection in eyes with
traumatic optic neuropathy by transcorneal electrical stimulation
Takeshi Morimoto1, Takao Endo2, Kohji Nishida2, Takashi Fujikado1.
1
Applied Visual Science, Osaka Univ Graduate Sch of Med, Suita,
Japan; 2Ophthatmology, Osaka University Graduate School of
Medicine, Suita, Japan.
Purpose: To determine whether the improvement of the visual acuity
in eyes with traumatic optic neuropathy (TON) is associated with the
current intensity of transcorneal electrical stimulation (TES).
Methods: This was a prospective, randomized, partially blinded,
clinical trial of 27 patients at the Osaka University Hospital. All
patients had TES (10 ms, biphasic pulses, 20 Hz) for 30 min once a
month in their TON eyes for 6 months. The patients were randomly
divided into two groups; 1.0 mA (n = 17) or 0.3 mA (n = 9). The
primary outcome measurement was the change in the best-corrected
visual acuity (BCVA) at 3 and 6 months after the start of the TES
treatment. An improvement in visual acuity was defined as a change
of ≥0.2 logarithm of the minimum angle of resolution (logMAR)
units. The changes in the BCVA in the two groups were compared.
Results: The improvement in the BCVA in the 0.3 mA group was
0.10 ± 0.085 logMAR units and that in the 1.0 mA group was 0.11 ±
0.049 logMAR units at 3 month (P=0.73). The improvement in the
BCVA at 6 month in the 0.3 mA treatment group was 0.04 ± 0.085
logMAR units which was significantly less than that in the 1.0 mA
group of 0.26 ± 0.049 (P=0.039) logMAR units. The improvement
of the BCVA was found in 22.2% of the patients in the 0.3 mA
group and 23.5% of the patients in the 1.0 mA group at 3 months,
and 22.2% in the 0.3 MA group and 47.1% in the 1.0 mA group at 6
months. The differences were not statistically significant (P=0.94 and
P=0.21, respectively).
Conclusions: TES at 1.0 mA can improve the VA in patients with
TON more effectively than at 0.3 mA. These results indicate that
there is probably an optimal neuroprotective current intensity of TES
for eyes with TON. These value will provide a guideline for the use
of TES in patients with TON. Further studies with larger sample sizes
and longer duration are needed to confirm the findings and to define
the optimal stimulation parameters.
Commercial Relationships: Takeshi Morimoto, None; Takao
Endo, None; Kohji Nishida, None; Takashi Fujikado, None
Support: Japanese government grant 22791658
Clinical Trial: UMIN000005049
Diagnostic performance of ganglion cell and retinal nerve fiber
layer thickness in alcoholic optic neuropathy
Stéphanie Michau1, Pascal Perney2, Hélène Donnadieu-Rigolle2,
Max Villain1, Vincent Daien1. 1Ophtalmology, University Hospital of
Montpellier, Montpellier, France; 2Addictology, University Hospital
of Montpellier, Montpellier, France.
Purpose: To explore the diagnostic performance of optic nerve
parameters in early alcoholic optic neuropathy.
Methods: 395 eyes of 200 patients were included prospectively
during hospitalisation for alcohol withdrawal from January 2010
to October 2013 in the University Hospital of Montpellier. The
definition of alcoholic optic neuropathy was the assocation of
alterated visual field with impaired color vision. Optic nerve
variables were assessed by visual-evoked potential, Heidelberg
Retina Tomograph III (HRT-III), spectral-domain optic coherence
tomography (SD-OCT) (ganglion cell layer [GCL] and retinal nerve
fiber layer [RNFL]) and scanning laser polarimetry (GDx). Optic
nerve variables were compared between patients with and without
optic neuropathy by age- and sex-adjusted analysis of covariance.
Diagnostic performance was determined by area under the receiver
operating characteristic curve (AUC), sensitivity and specificity.
Results: In total, 47 (24%) patients presented alcoholic ON (mean
(SD) age of 47 (11) years; 33 men). Peripheral neuropathy was more
frequent in patients with than without alcoholic ON (p<.001) and
GCL and RNFL were thinner (mean (SD) of 12.91 (0.7) vs 14.78
(0.3) mm, p=0.015; and 90.27 (2.1) vs 99.57 (1.08) mm, p<.001,
respectively). The AUC was highest for superior GCL (AUC=0.78;
(95% CI, 0.67-0.89)) and global RNFL thickness from SD-OCT
(AUC=0.72; (95% CI 0.62-0.82)) and had the best sensitivityspecificity pair 82.1–62.0% and 79.4–63.4%, respectively. The AUC
for GDx and HRTIII ranged from 0.52 to 0.68.
Conclusions: Objective examination including GCL and RNFL
thickness on SD-OCT could be useful to improve the diagnostic of
alcoholic ON.
Commercial Relationships: Stéphanie Michau, None; Pascal
Perney, None; Hélène Donnadieu-Rigolle, None; Max Villain,
None; Vincent Daien, None
Comparison of retinal nerve fiber layer thickness measurement
by Stratus and Cirrus OCTs in retrobulbar optic neuritis and
non arteritic anterior ischemic optic neuropathy
Barbara Giambene, Gianni Virgili, Ugo Menchini, Stanislao Rizzo.
University of Firenze, Eye Clinic, Firenze, Italy.
Purpose: To compare retinal nerve fiber layer thickness (RNFLT)
measurement by Stratus and Cirrus OCTs and to evaluate the
agreement between the two instruments in retrobulbar optic neuritis
(RON), non arteritic anterior ischemic optic neuropathy (NAION)
and normals.
Methods: Eighty-nine eyes with RON, ninety-two with NAION
(both in the chronic phase, six to twelve months after diagnosis
of acute disease), and one hundred fifty-five normal eyes were
studied. Average RNFLT was measured by Stratus and Cirrus OCTs.
Comparisons among groups were performed by ANOVA test. The
agreement between the two instruments was assessed using intraclass
correlation coefficient (ICC) with 95% confidence interval (CI), and
Bland-Altman analysis. Statistical significance was set at p ≤0.5.
Results: Average RNFLT was lower in NAION eyes than in RON
and normal ones using both OCTs (60.0 ±1.2, 69.9 ±1.2 and 97.4
±0.9 m, p<0.001 by Cirrus; 49.7 ±1.5, 65.9 ±1.9 and 99.2 ±1.3 m,
p<0.001 by Stratus). RNFLT values were higher with Cirrus than
with Stratus in NAION (+10.30 μ, CI 7.82 – 12.79 μ) and RON
(+4.01 μ, CI 1.32 – 6.70 μ) eyes, and slightly lower in normal ones
(-1.75 μ, CI -3.51 – 0.01 μ). A stronger agreement between the two
instruments was found in normal and RON eyes than in NAION ones
(ICC 0.682, CI 0.566-0.771; 0.635, CI 0.467-0.758; 0.321, CI 0.1320.472, respectively).
Conclusions: Both Stratus and Cirrus OCTs can identify RNFLT
reduction in eyes with RON and NAION in the chronic phase.
Absolute RFNLT values differ between the two instruments, hence
they have not to be considered interchangeable.
Commercial Relationships: Barbara Giambene, None; Gianni
Virgili, None; Ugo Menchini, None; Stanislao Rizzo, None
Predictive Value of Perioperative Circumpapillary Retinal Nerve
Fiber Layer Thickness in Primary Rhegmatogenous Retinal
Detachment Macular Anatomic Outcomes
Julia Kuhn1, Joseph Martel2. 1School of Medicine, University
of Pittsburgh, Pittsburgh, PA; 2Department of Ophthalmology,
University of Pittsburgh, Pittsburgh, PA.
Purpose: Despite successful rhegmatogenous retinal detachment
(RRD) surgery, postoperative macular edema, epiretinal membrane
(ERM) formation, and macular atrophy are difficult to predict, yet
important factors influencing final visual outcome. We performed
a retrospective observational clinical study to examine the
perioperative spectral domain optical coherence tomography (sdOCT)
circumpapillary retinal nerve fiber layer (cpRNFL) thickness as a
predictor for the development of postoperative macular disease in
patients undergoing successful RRD repair surgery.
Methods: A review of longitudinal data from 2009 – 2014 at the
University of Pittsburgh Medical Center identified 36 patients
having undergone successful primary RRD surgery without previous
posterior segment surgery, optic nerve disease, or macular disease,
and availability of preoperative and postoperative cpRNFL and
macular sdOCT imaging data. The nonoperative contralateral eye was
used for all group comparisons as a control. Statistical analyses were
performed using a two-tailed Student’s t test and Wilcoxon rank-sum
test.
Results: Of 36 patients who met inclusion criteria, 28 underwent
RRD repair with vitrectomy and 8 with scleral buckling. Median
follow-up time was 12 months (range 0.5-55 months), and mean
follow-up visits was 2.0 (range 1-10). Mean cpRNFL was 91.97mm
±14.73 in RRD eyes and 85.48mm ±12.09 in control eyes (p<0.0001).
Mean macular central subfield thickness (CST) was 325.51mm
±76.19 and 293.30mm ±59.21 in RRD and control eyes, respectively
(p=0.0076). For RRD patients who developed late postoperative
central macular edema (CST >300mm), median cpRNFL thickness
in the early postoperative period was significantly greater than for
RRD patients who did not develop late postoperative central macular
edema (p=0.0027). In RRD patients who developed late central
subfield macular thinning (CST<250mm), median cpRNFL thickness
was not found to be significantly less than in those patients who did
not develop macular thinning (p=0.9552).
Conclusions: Early perioperative cpRNFL thickening may be a
predictor for late postoperative macular edema in patients undergoing
successful RRD repair surgery. Relative cpRNFL thinning or
thickening was not predictive of central macular thinning.
Commercial Relationships: Julia Kuhn, None; Joseph Martel,
None
Commercial Relationships: Mays El-Dairi, None; Monica B.
Sevilla, None; Adam Rothman, None; Sharon Freedman, None;
Amy Tong, None; Vincent Tai, None; Du Tran-Viet, None
Assessment of retinal nerve fiber layer thickness in healthy, full
term neonates
Mays El-Dairi1, Monica B. Sevilla1, Adam Rothman1, Sharon
Freedman1, 2, Amy Tong1, Vincent Tai1, Du Tran-Viet1.
1
Ophthalmology, Duke University Medical Center, Durham, NC;
2
Pediatrics, Duke University School of Medicine, Durham, NC.
Purpose: To measure average retinal nerve fiber layer (RNFL)
thicknesses in healthy, full term neonates.
Methods: Healthy infants born between 37-42 weeks post-menstrual
age were imaged with handheld spectral domain optical coherence
tomography (Bioptigen, Inc., Research Triangle Park, NC). A custom
MATLAB script (Mathworks, Inc., Natick, MA) segmented the
RNFL; the fovea and optic nerve center were manually selected.
A second script measured the average RNFL thickness along the
papillomacular bundle, defined as the arc from -15° to +15° on the
axis from the optic nerve to fovea, with radii of 1.1, 1.3, 1.5, and 1.7
mm from the center of the optic disc. Shapiro-Wilk W tests assessed
these measurements for normality to determine the age-appropriate
radial distance for subsequent analyses. Average RNFL thicknesses
for four temporal 45° sectors (superior temporal, temporal superior,
temporal inferior, and inferior temporal) as well as the temporal
quadrant were calculated and compared to demographic parameters
for all infants.
Results: Fifty full-term infants were adequately imaged for RNFL
analysis. RNFL thicknesses at 1.5 mm radial distance from the optic
nerve were the most normally distributed. While there was a trend
towards greater mean superior temporal RNFL thickness for both
Black and Hispanic versus White infants (128 ±27, 124 ±30, and 100
±19 μm, respectively, P=0.04 for both comparisons), there were no
other significant differences noted in RNFL thicknesses by race, sex,
gestational age, or birth weight.
Conclusions: We present RNFL thickness measurements for healthy,
full term infants that may serve as normative data for future analyses.

Leber`s Hereditary Optic Neuropathy / Clinical testing

Transcription

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