Volume 9, Number 12
WELCOME to Review
of Ophthalmology's Retina
Online e-newsletter. Each month, Medical Editor Philip Rosenfeld,
MD, PhD, and our editors provide you with this timely and easily
accessible report to keep you up to date on important information
affecting the care of patients with vitreoretinal disease.
Comparison of Ranibizumab and Bevacizumab for Neovascular AMD
French investigators evaluated the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for
the treatment of neovascular age-related macular degeneration (AMD) in this multicenter, prospective, noninferiority,
double-masked, randomized clinical trial performed in 38 ophthalmology centers. The noninferiority limit was five letters.
Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA)
in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion
area of <12 optic disc areas (DA).
Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital
pharmacies were responsible for preparing, blinding and dispensing treatments. The investigators followed patients for one year,
with a loading dose of three monthly intravitreal injections, followed by an as-needed regimen (one injection in case of active
disease) for the remaining nine months with monthly follow-up. Mean change in visual acuity at one year was the main outcome measure.
Between June 2009 and November 2011, the study investigators randomized 501 patients. They noted that in the per protocol
analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval
[CI], –1.16 to +4.93, p<0.0001). They also reported that intention-to-treat analysis was concordant. The mean
number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (p=0.39). Both drugs reduced the
central subfield macular thickness, with a mean decrease of 95 µm for bevacizumab and 107 µm for ranibizumab
(p=0.27). The study investigators found no significant differences in the presence of subretinal or intraretinal fluid at
final evaluation, dye leakage on angiogram or change in choroidal neovascular area. The proportion of patients with serious
adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (p=0.88). The proportion of
patients with serious systemic or ocular adverse events was similar in both groups.
To conclude, bevacizumab was noninferior to ranibizumab for visual acuity at one year with similar safety profiles. Ranibizumab
tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies.
Source: Kodjikian L, Souled EH, Mimoun G, et al; GEFAL Study Group. Ranibizumab versus bevacizumab for
neovascular age-related macular degeneration: results from the GEFAL noninferiority randomized trial.
Seven-Year Outcomes of Ranibizumab-Treated Patients in ANCHOR, MARINA and HORIZON
To assess long-term outcomes seven to eight years after initiation of intensive ranibizumab therapy in exudative
age-related macular degeneration (AMD) patients, scientists conducted this multicenter, noninterventional cohort study.
Participants consisted of 65 AMD patients originally treated with ranibizumab in the Phase III Anti-VEGF Antibody for the Treatment
of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial, Minimally Classic/Occult Trial of the Anti-VEGF
Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) trial, and Open-Label Extension Trial of Ranibizumab for
Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON). Fourteen clinical trial sites recruited
their original subjects for a return evaluation. Individual subject comparisons were obtained from the ANCHOR, MARINA and
HORIZON databases. The primary endpoint was percentage with best-corrected visual acuity (BCVA) of 20/70 or better; secondary
outcomes included mean change in letter score compared with previous time points and anatomic results on fluorescein
angiography, spectral-domain ocular coherence tomography (OCT) and fundus autofluorescence (FAF).
The study scientists reported that at a mean of 7.3 years (range, 6.3 to 8.5 years) after entry into ANCHOR or MARINA, 37% of
study eyes met the primary endpoint of 20/70 or better BCVA, with 23% achieving a BCVA of 20/40 or better. They noted that
another 37% of study eyes had BCVA of 20/200 or worse and 43% of study eyes had a stable or improved letter score
(≥0-letter gain) compared with ANCHOR or MARINA baseline measurements, whereas 34% declined by 15 letters or more, with
overall a mean decline of 8.6 letters (p<0.005). Since exit from the HORIZON study, study eyes had received a mean of
6.8 anti-vascular endothelial growth factor (VEGF) injections during the mean 3.4-year interval; a subgroup of patients who received
11 or more anti-VEGF injections had a significantly better mean gain in letter score since HORIZON exit (p<0.05).
Active exudative disease was detected by spectral-domain OCT in 68% of study eyes, and 46% were receiving ongoing
ocular anti-VEGF treatments. Macular atrophy was detected by FAF in 98% of eyes, with a mean area of 9.4 mm²; the area
of atrophy correlated significantly with poor visual outcome (p<0.0001).
Approximately seven years after ranibizumab therapy in the ANCHOR or MARINA trials, one-third of patients demonstrated good
visual outcomes, whereas another third had poor outcomes. Compared with baseline, almost half of eyes were stable, whereas
one-third declined by 15 letters or more. Even at this late stage in the therapeutic course, exudative AMD patients remain at risk
for substantial visual decline.
Source: Rofagha S, Bhisitkul RB, Boyer DS, et al.; SEVEN-UP Study Group. Seven-year outcomes in ranibizumab-treated
patients in ANCHOR, MARINA, and HORIZON: a multicenter cohor study (SEVEN-UP). Ophthalmology. 2013;120(11):2292–2299.
CFH and ARMS2 Genetic Polymorphisms Predict Response to Antioxidants and Zinc in
Patients with AMD
The Age-Related Eye Disease Study (AREDS) demonstrated that antioxidant and zinc supplementation decreases progression to
advanced age-related macular degeneration (AMD) in patients with moderate to severe disease. This genetic analysis of
a randomized, prospective clinical trail evaluated the interaction of genetics and type of nutritional supplement on
progression from moderate to advanced AMD.
Participants included white patients with AREDS category three AMD in one eye and AREDS categories one through four AMD in the fellow
eye enrolled in the AREDS with available peripheral blood-derived DNA (995). Subjects were evaluated for known AMD genetic risk
markers and treatment category. The progression rate to advanced AMD was analyzed by genotypes and AREDS treatment group using
Cox regression. Additionally, the main outcome measure was the effect of inherited gene polymorphisms on treatment group–specific
rate of progression to advanced AMD.
Over an average of 10.1 years, individuals with one or two complement factor H (CFH) risk alleles derived maximum benefit
from antioxidants alone. In these patients, the addition of zinc negated the benefits of antioxidants. Treatment with zinc
and antioxidants was associated with a risk ratio (RR) of 1.83 with two CFH risk alleles (p=1.03E-02), compared with
outcomes for patients without CFH risk alleles. Patients with age-related maculopathy sensitivity two (ARMS2) risk alleles
derived maximum benefit from zinc-containing regimens, with a deleterious response to antioxidants in the presence of ARMS2 risk
alleles. Treatment with antioxidants was associated with an RR of 2.58 for those with one ARMS2 risk allele and 3.96 for those with
two ARMS2 risk alleles (p=1.04E-6), compared with patients with no ARMS2 risk alleles. Individuals homozygous for CFH and
ARMS2 risk alleles derived no benefit from any category of AREDS treatment.
In conclusion, individuals with moderate AMD could benefit from pharmacogenomic selection of nutritional supplements. In this
analysis, patients with no CFH risk alleles and with one or two ARMS2 risk alleles derived maximum benefit from
zinc-only supplementation. Patients with one or two CFH risk alleles and no ARMS2 risk alleles derived maximum benefit
from antioxidant-only supplementation; treatment with zinc was associated with increased progression to advanced AMD.
These recommendations could lead to improved outcomes through genotype-directed therapy.
Source: Awh CC, Lane AM, Hawken S, et al. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and
zinc in patients with age-related macular degeneration. Ophthalmology. 2013;120(11):2317–2323.
Systemic Cytokines and Complement Factor H Y402H Polymorphism in Dry AMD
To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load
and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD), researchers in Canada
performed the following cross-sectional study.
They enrolled 44 dry AMD patients under care of the Retina Service at the University of British Columbia. They measured drusen load
with an automated software algorithm in spectral-domain optical coherence tomography (SD-OCT) and subfoveal choroidal thickness
manually using enhanced depth imaging (EDI). The researchers also used Bio-Plex suspension assays (Bio-Rad Laboratories) to
analyze cytokines in plasma and genotyped CFH Y402H. Statistical analyses included analysis of covariance and Pearson
correlation, corrected for multiple comparisons.
The levels of three of four studied cytokines were significantly different among patients with CC, CT or TT variants of the CFH
Y402H polymorphism (p<.01), the researchers reported. They also found that patients with the at-risk CC variant had
higher systemic levels of interleukin-6, interleukin-18 and tumor necrosis factor α than those with the CT variants, the TT variant,
or both (p<.01). Furthermore, they noted that interleukin-1β did not reach significance (p=.02), but did demonstrate
a consistent trend. They found no correlation between plasma cytokines and drusen load or choroidal thickness
The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome
activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate
the inflammatory status in dry AMD patients. These data support the central role of inflammation in the pathogenesis of AMD and
provide further evidence of a systemic involvement in AMD etiology.
Source: Cao S, Ko A, Partanen M, et al. Relationship between systemic cytokines and complement factor H Y402H
polymorphism in patients with dry age-related macular degeneration. Am J Ophthalmol. 2013;156(6):1176–1183.
AMD and Proportion of CD56+ T Cells in Peripheral Blood
The authors of this case-control study sought to examine the association between age-related changes in the T-cell compartment
and prevalence of age-related macular degeneration (AMD).
They included 117 AMD cases and 106 controls prospectively and processed fresh-drawn peripheral blood samples for flow
cytometric analysis of T-cell populations. They also analyzed plasma samples for anti-cytomegalovirus (CMV) immunoglobulin
(Ig)G and complement factor H (CFH) Y402H genotype. The diagnosis of AMD was made according to the Clinical Age-Related
Maculopathy Staging System. Association between frequency of aged T cells and prevalence of AMD was the main outcome measure.
According to the authors, the prevalence of AMD was associated with distinct age-related changes in the T-cell compartment.
Specifically, they found that the patients with AMD had an increased frequency of CD28- T cells that expressed the
CD56 surface marker (patients, 34.9% vs. aged controls, 25.8%; p=0.002). They also noted that participants in the
highest tertile of CD56+ CD28- T cells had an odds ratio (OR) for the presence of AMD of 3.2 (95%
confidence interval [CI], 1.2 to 8.8) after adjustment for CFH genotype, anti-CMV IgG positivity, age, sex and smoking history.
The adjusted OR of the presence of AMD for persons having at least 1 CFH H402 risk allele increased from 3.5 (95% CI, 1.5 to 8.1)
to 13.3 (95% CI, 3.3 to 53.6) for persons with at least one CFH H402 risk allele and above the median level of CD56+
CD28- T cells.
The authors of this study found increased levels of circulating aged CD56+ CD28- T cells in patients with AMD. Although this supports
the notion of AMD as a systemic disease, it also suggests that the adaptive immune system is implicated in its pathogenesis.
Source: Faber C, Singh A, Falk MK, et al. Age-related macular degeneration is associated with increased proportion of
CD56+ T cells in peripheral blood. Ophthalmology. 2013;120(11);2310– ;2316.
VMA's Impact on Anti-VEGF Treatment for PCV
To evaluate the effect of posterior vitreomacular adhesion (VMA), documented by optical coherence tomography (OCT), on the
outcome of anti-vascular endothelial growth factor (VEGF) treatment of polypoidal choroidal vasculopathy (PCV),
researchers retrospectively reviewed the medical records of 102 patients (104 eyes) with PCV and categorized them according
to the presence of posterior VMA into two subgroups: VMA positive (+) group (23 eyes) and VMA negative (−) group (81 eyes).
They compared best-corrected visual acuity (BCVA) and central macular thickness after anti-VEGF treatment between the two groups
at baseline and at one month, three months, six months and 12 months.
At the last follow-up, average number of injections was 4.82 ± 1.27 in the VMA (+) group and 4.92 ± 1.45 in the VMA (−)
group. After injection, the researchers noted that the mean logarithm of the minimum angle of resolution of BCVA improved from
0.81 ± 0.53 (Snellen equivalent, 20/129) to 0.67 ± 0.52 (Snellen equivalent, 20/93) in the VMA (+) group (p=0.01)
and from 0.79 ± 0.50 (Snellen equivalent, 20/123) to 0.64 ± 0.58 (Snellen equivalent, 20/91) in the VMA (−) group
(p=0.02). They also found that average central macular thickness decreased from 354.4 ± 124.5 μm to 249.6 ± 112.5
µm in the VMA (+) group (p=0.01) and from 361.2 ± 140.2 µm to 267.3 ± 103.5 µm in the VMA (−) group
(p=0.01). Furthermore, polyp regression rate was 21.7% (five eyes of 23 eyes) in the VMA (+) group and 22.2% (18 eyes
of 81 eyes) in the VMA (−) group. There was no statistically significant difference in the BCVA improvement, central macular
thickness improvement, and polyp regression rate between the groups.
Unlike typical age-related macular degeneration, posterior VMA was not associated with a worse visual outcome following
intravitreal anti-VEGF for PCV.
Source: Cho HJ, Baek JS, Lee DW, et al. Effects of vitreomacular adhesion on anti-vascular endothealial growth
factor treatment for polypoidal choroidal vasculopathy. Retina. 2013;33(10):2126–2132.
Effects of Choroidal Vascular Hyperpermeability on Anti-VEGF Treatment for PCV
The authors of the following South Korean retrospective comparative series evaluated the effect of choroidal
vascular hyperpermeability, as determined using indocyanine green angiography (ICGA), on the outcome of anti-vascular
endothelial growth factor (anti-VEGF) treatment for polypoidal choroidal vasculopathy (PCV).
Based on the presence of choroidal vascular hyperpermeability on ICGA, they categorized 103 eyes (101 patients) with PCV into
two subgroups: choroidal vascular hyperpermeability (+) group (41 eyes) and choroidal vascular hyperpermeability (−) group (62 eyes).
All subjects were treatment-naïve and treated by anti-VEGF with initial three loading injections per month, followed by an
as-needed reinjection. The authors compared best-corrected visual acuity (BCVA) and central macular thickness after treatment between
the two groups at baseline and at three, six, nine and 12 months.
At 12 months after treatment, they reported that mean BCVA was significantly improved from 0.68 logarithm of the minimal angle
of resolution (logMAR) (20/95 Snellen equivalent) to 0.50 logMAR (20/63 Snellen equivalent) in the choroidal vascular
hyperpermeability (−) group (p=0.01); however, there was no significant improvement, from 0.79 logMAR (20/123 Snellen
equivalent) to 0.74 logMAR (20/109 Snellen equivalent), in the choroidal vascular hyperpermeability (+) group. In paired comparisons
of BCVA between baseline and each follow-up visit, the choroidal vascular hyperpermeability (−) group showed significant improvement
of BCVA at every follow-up visit (p<0.05); however, the choroidal vascular hyperpermeability (+) group did not
show significant visual improvement after nine months (p>0.05).
To conclude, the therapeutic response to anti-VEGF treatment for PCV in patients with choroidal vascular hyperpermeability decreased
over time. Choroidal vascular hyperpermeability was associated with an inferior visual outcome after intravitreal anti-VEGF treatment
Source: Cho HJ, Kim HS, Jang YS, et al. Effects of choroidal vascular hyperpermeability on anti-vascular endothelial
growth factor treatment for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013;156(6):1192–1200.
Prognostic Factors of Eyes with Naïve Subfoveal Myopic CNV Following
South Korean investigators performed a retrospective observational case series to determine the efficacy of one intravitreal
bevacizumab injection followed by pro re nata (one + p.r.n.) injection in cases of subfoveal myopic choroidal
neovascularization (CNV) and to identify CNV-recurrence–related prognostic factors.
They included 103 eyes of 89 consecutive naïve patients who had subfoveal myopic CNV and had been followed-up for at least
two years. Of those eyes, 24 had recurrences. The remaining eyes were stable after the initial treatment.
The average patient age was 51.1 ± 15.2 years and the average follow-up duration was 44.1 ± 12.7 months. According to
the study investigators, at baseline and at the one-year, two-year and final visits, the average best-corrected visual acuities
(BCVAs) were 0.57 ± 0.45, 0.38 ± 0.51, 0.40 ± 0.52 and 0.41 ± 0.41 logMAR, respectively. The recurrence rate
during follow-up was 23.3%. The BCVA improved by 0.2 logMAR after 2.7 injections in the eyes without recurrence but by only
0.08 logMAR after 6.9 injections in the eyes with recurrence. In univariate analysis, recurrence was associated with older age,
more myopic refraction, thinner choroid, larger CNV lesions and subfoveal hemorrhage at baseline. In multivariate analysis, only
baseline CNV lesion size associated significantly with CNV recurrence (p=0.002). Recurrence, baseline BCVA, choroidal
thickness and CNV size associated significantly with final BCVA (p=0.026, <0.0001, 0.007 and 0.002, respectively).
Furthermore, baseline choroidal thickness, CNV size, age and presence of lacquer cracks associated significantly with injection number
(p<0.0001, <0.0001, 0.026 and 0.035, respectively).
The investigators determined that one + p.r.n. intravitreal bevacizumab monotherapy effectively stabilized subfoveal myopic CNV.
The CNV size, the baseline BCVA, and the choroidal thickness were the main prognostic factors of subfoveal myopic CNV after one +
p.r.n. injection of bevacizumab.
Source: Yang HS, Kim JG, Kim JT, Joe SG. Prognostic factors of eyes with naive subfoveal myopic choroidal
neovascularization after intravitreal bevacizumab. Am J Ophthalmol. 2013;156(6):1201–1210.
Localized Changes in Retinal Vessel Caliber After Focal/Grid Laser Treatment
in Patients with DME
The study below compared retinal vessel caliber changes at the macula region and surrounding the optic disk after focal/grid
laser treatment for diabetic macular edema (DME).
It included 69 eyes from 46 patients treated with focal/grid laser for DME. Retinal photographs were taken less than six months
before and two months and 12 months after focal/grid photocoagulation treatment. The diameters of retinal vessels around macula
and the optic disk were measured separately before and after treatment. Optic disk and macular diameters were summarized into
central retinal arteriolar and venular equivalent and macular retinal arteriolar and venular equivalent.
Median age and duration of diabetes was 60 years and 13 years. There was a statistically significant decrease in diameter of the
macular arterioles (macular retinal arteriolar equivalent 73.5 vs. 72.0 µm, p=0.04) and venules (macular retinal
venular equivalent 63.5 vs. 62.4 µm, p=0.02) after treatment but no difference in central retinal arteriolar equivalent
or central retinal venular equivalent before and after treatment. Additionally, retinal vascular calibers in control eyes did not
change throughout the study.
In conclusion, the diameters of macular vessels decreased after focal/grid laser treatment in most eyes. In contrast, vessel calibers
at the optic disk did not change. Quantitative measurement of macular vessels may allow physicians to monitor the progress and
success of diabetic macular edema treatment.
Source: Lundberg K, Kawasaki R, Sjølie A, et al. Localized changes in retinal vessel caliber after focal/grid laser
treatment in patients with diabetic macular edema: a measure of treatment response? Retina. 2013;33(10):2089–2095.
Residual ILM Following ERM Peeling
To determine the degree of residual internal limiting membrane (ILM) after idiopathic epiretinal membrane (ERM) peeling and
the usefulness of staining with brilliant blue G, a prospective, multicenter, observational study of 98 eyes undergoing pars
plana vitrectomy and membrane peeling for idiopathic ERM was conducted. All eyes underwent core vitrectomy (20, 23 or 25 gauge)
followed by intravitreal triamcinolone to verify that the posterior hyaloid had been removed. Brilliant blue G (0.2 mL of 0.25 mg/mL)
was injected into the vitreous cavity and washed out immediately. The ERM was peeled and then the surgeon observed and recorded
the characteristics of the underlying ILM. The posterior pole was restained with brilliant blue G (0.2 mL of 0.25 mg/mL), and the
same observations on the characteristics of the ILM were recorded. Peeling of the remaining ILM was performed. The main outcome
measured was the status of the ILM after ERM peel. Secondary outcomes included best-corrected visual acuity and central macular
thickness at six months postoperatively.
After ERM peel, all of the eyes had residual ILM. In 74 eyes, the ILM was present and damaged, whereas in 24 eyes, the ILM was
present and undamaged. In 37 eyes, the operating surgeon was unable to determine the status of the ILM before brilliant blue G
staining. At six months, the logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.75 ± 0.39
at baseline to 0.31 ± 0.26 (p<0.0001). The central macular thickness also improved from 460 ± 91 µm at
baseline to 297 ± 102 µm (p<0.003).
ILM is frequently still present after ERM peeling. Staining with brilliant blue G facilitates its identification.
Source: Carpentier C, Zanolli M, Wu L, et al. Residual internal limiting membrane after epiretinal membrane peeling:
results of the Pan-American Collaborative Retina Study Group. Retina. 2013;33(10):2026–2031.
Incidence, Characteristics, Evolution and Preventive Risk Factors of ERM Recurrence
Scientists evaluated the incidence, evolution, clinical characteristics, possible risk factors or preventive factors and visual
outcomes of epiretinal membrane (ERM) recurrence in this retrospective study of 440 consecutive patients (440 eyes) who underwent
pars plana vitrectomy for ERM. The internal limiting membrane (ILM) was peeled in 266 cases, with the help of indocyanine green in
27 cases and brilliant blue in 45 cases. Cases of symptomatic ERM recurrence were re-operated.
According to the scientists, the incidence of ERM recurrence was 5% (22/440), and 2% of the patients were reoperated
(nine/440). They noted that epiretinal membrane recurrence was symptomatic in nine cases (41%) and asymptomatic in 13 cases
(59%). They also found that ILM peeling was the only factor preventing ERM recurrence (adjusted odds ratio=0.33, p=0.026).
Furthermore, the use of staining dyes did not prevent recurrence (adjusted odds ratio=0.35, p=0.338). In the case of
ERM reproliferation, the absence of ILM peeling, the existence of ERM on the fellow eye, and poor visual acuity before surgery seemed
to be associated with a high risk of symptomatic recurrence and reoperation. The mean duration for follow-up was 3.5 ± 1.7 years.
The study scientists concluded that ILM peeling not only reduces the likelihood of reproliferation of ERM, but also seems to improve
the visual prognosis of recurrent ERMs. The use of dyes did not reduce the rate of recurrence compared with when ILM was peeled
Source: Sandali O, El Sanharawi M, Basli E, et al. Epiretinal membrane recurrence: incidence, characteristics,
evolution, and preventive risk factors. Retina. 2013;33(10):2032–2038.
In Vivo Detection of Acute Ischemic Damages in Retinal Arterial Occlusion with OCT
The authors of this study sought to describe characteristic findings of acute retinal ischemic damage in optical coherence
They reviewed 18 cases of acute retinal arterial occlusion with available fundus photography, OCT and/or fluorescein angiography
in the early phase (less than one month) with more than two months follow-up. They also performed a site-to-site analysis between
OCT morphology and correlating fundus images on each visit.
The authors reported that retinal opacities at first presentation were vague to mild opacity in four eyes, moderate (affecting
visibility of underlying choroidal vessels) in seven, severe (yellow to whitish) in five, and very severe (chalky white) in two.
They observed that these changes eventually disappeared within one month (eight of nine eyes). They also consistently noticed
inner retinal hyper-reflectivity and a “prominent middle limiting membrane” in OCT up to one month showing
regional correlation with the retinal opaque areas and readily identified them even in areas with vague or disappeared retinal
opacities. Later, inner retinal atrophic changes replace these ischemic OCT signs.
A prominent middle limiting membrane sign is a useful indicator of acute ischemic retinal damage, especially in cases showing
subtle or resolved retinal opacities before the onset of atrophic changes.
Source: Chu YK, Hong YT, Byeon SH, Kwon OW. In vivo detection of acute ischemic damages in retinal arterial occlusion
with optical coherence tomography: a ‘prominent middle limiting membrane sign’. Retina.