Volume 9, Number 2
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.
Risk of AMD in Aspirin Users
Researchers conducted a prospective analysis of data from an Australian population-based cohort with four examinations
during a 15-year period (1992–1994 to 2007–2009) to determine whether regular aspirin use is associated with
a higher risk of developing age-related macular degeneration (AMD).
They had participants complete a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status
and AMD risk factors. The researchers graded AMD by comparing retinal photographs taken at each study visit to assess
the incidence of neovascular, or wet, AMD and geographic atrophy, or dry AMD, according to the international AMD classification.
Of 2,389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users
and 63 of the 2,389 developed neovascular AMD, the researchers reported. They noted that persons who were regular aspirin
users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7%
in nonusers. After adjusting for age, sex, smoking, history of cardiovascular disease, systolic blood pressure and body
mass index, they found that persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds
ratio [OR], 2.46; 95% CI, 1.25–4.83) and that the association showed a dose-response effect
(multivariate-adjusted p=.01 for trend). Furthermore, the study researchers determined that aspirin use was
not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59–1.65).
Source: Liew G, Mitchell P, Wong TY, et al. The association of aspirin use with age-related
macular degeneration. JAMA Intern Med. 2013; Jan 21. [Epub ahead of print]. DOI: 10.1001/jamainternmed.2013.1583.
Commentary on Liew, et al.
The Invited Commentary by cardiologists Sanjay Kaul, MD, and George A. Diamond, MD, takes a closer look at
the prospective, population-based cohort study by Liew and colleagues (above) to determine whether the relationship
of aspirin use with age-related macular degeneration (AMD) has to do with association or causation.
They point out strengths of the study, including the fact that it is the largest prospective cohort with more than five
years of longitudinal evaluation reported to date using objective and standardized ascertainment of AMD, as well as the use
of standardized protocols for determining medication use, the recording of detailed demographic and clinical information
for risk adjustment, and appropriate methodologic approaches, such as multivariate logistic regression and propensity
score adjustment, to minimize the impact of confounding. The key limitation, according to Kaul and Diamond, is the
nonrandomized design of the study, with its potential for residual (unmeasured or unobserved) confounding that cannot
be mitigated by multivariate logistic regression or propensity score analysis. Additional limitations they say deserve
attention include the modest strength of association (odds ratio, 2.0–2.5); incomplete data on other morbidities;
the potential for “overfitting” resulting in biased estimates because of the limited number of incident cases
of AMD (n=63) and 10 or more candidate predictor variables; and the issue of missing data (only 56% of the cohort
eligible for follow-up at >15 years were assessed). These limitations can potentially undermine the interpretation
and threaten the validity of trial results.
Application of the Hill criteria to the Liew study yields instructive insights, according to Kaul and Diamond. These are
useful and time-tested considerations for determining whether an association is causal. They look at strength of
association, consistency, temporality, biological gradient or dose-response relationship, biological plausibility,
specificity, coherence, experiment and analogy.
From a purely science-of-medicine perspective, they indicate that the strength of evidence is not sufficiently robust
to be clinically directive and that at best, these findings are hypothesis-generating that should await validation
in prospective, randomized studies before guiding clinical practice or patient behavior. However, from an
art-of-medicine perspective, based on the limited amount of available evidence, some courses of action are available.
In the absence of definitive evidence regarding whether limiting aspirin exposure mitigates AMD risk, one obvious course
of action is to maintain the status quo; for primary prevention of cardiovascular disease, the decision to prescribe
aspirin should be predicated on the balance of risks and benefits; and for guideline-eligible patients, the presence or
absence of strong risk factors for neovascular AMD might tilt treatment decisions in one direction or the other.
For patients taking long-term aspirin for other indications, such as pain control, caution is warranted in light of
In Kaul and Diamond's final analysis, they state that decisions about aspirin use are best made by balancing the
risks against the benefits in the context of each individual’s medical history and value judgments.
Source: Kaul S, Diamond GA. Relationship of aspirin use with age-related macular degeneration.
JAMA Intern Med. Jan 21. [Epub ahead of print]. DOI: 10.1001/jamainternmed.2013.2530.
Realizing the Limitations of Research Data
In an Editor's Note about the Invited Commentary by Kaul and Diamond, Kenneth E. Covinsky, MD, MPH, emphasizes
the need for careful consideration before concluding that an association described in an observational study
truly represents a cause-effect relationship. He noted that while the study by Liew, et al. may provide useful incremental data about an important condition, the data are not definitive enough to suggest changes in clinical practice.
In fact, the purpose of covering such an article is to hopefully stimulate further research on the relationship
between aspirin and macular degeneration. Dr. Covinsky notes that the Liew study provides an opportunity to educate
the public about the subtleties and incremental nature of medical research and that our understanding of disease
etiology advances as evidence accumulates from multiple good studies.
Source: Covinsky KE. The incremental nature of clinical research. JAMA Intern Med. 2013; Jan 21. [Epub ahead
Relationship Between Long-term Aspirin Use and AMD
The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in
Wisconsin, examined the association of regular aspirin use with incidence of age-related macular degeneration
(AMD). Examinations were performed every five years over a 20-year period (1988 to 1990 through 2008 to 2010).
Study participants (n=4,926) were aged 43 to 86 years at the baseline examination. At subsequent
examinations, participants were asked if they had regularly used aspirin at least twice a week for more than
three months. The main outcome measure was the incidence of early AMD, late AMD and two subtypes of late
AMD (neovascular AMD and pure geographic atrophy), assessed in retinal photographs according to the
Wisconsin Age-Related Maculopathy Grading System.
The mean duration of follow-up was 14.8 years and there were 512 incident cases of early AMD (of 6,243 person-visits at
risk) and 117 incident cases of late AMD (of 8,621 person-visits at risk) over the course of the study. Regular aspirin
use of 10 years prior to retinal examination was associated with late AMD (hazard ratio [HR], 1.63 [95% CI,
1.01–2.63]; p=.05), with estimated incidence of 1.76% (95% CI, 1.17%–2.64%) in regular
users and 1.03% (95% CI, 0.70%–1.51%) in nonusers. It was noted that for subtypes of late AMD,
regular aspirin use 10 years prior to retinal examination was significantly associated with neovascular AMD
(HR, 2.20 [95% CI, 1.20–4.15]; p=.01) but not pure geographic atrophy (HR, 0.66 [95% CI,
0.25–1.95]; p=.45). Aspirin use five years (HR, 0.86 [95% CI, 0.71–1.05]; p=.13) or
10 years (HR, 0.86 [95% CI, 0.65–1.13]; p=.28) prior to retinal examination was not associated with
incident early AMD.
Among an adult cohort, aspirin use five years prior to observed incidence was not associated with early or late AMD.
However, regular aspirin use 10 years prior was associated with a small but statistically significant increase in the
risk of incident late and neovascular AMD.
Source: Klein BE, Howard KP, Gangnon RE, et al. Long-term use of aspirin and age-related macular
degeneration. JAMA. 2012;308(23):2469–2478.
Epimacular Brachytherapy in the Treatment of Neovascular AMD
To evaluate the safety and efficacy of epimacular brachytherapy (EMBT) for the treatment of neovascular age-related
macular degeneration (AMD), the authors of this multicenter, randomized, active-controlled, Phase III clinical trial
examined 494 participants with treatment-naïve neovascular AMD.
They randomized participants with classic, minimally classic, and occult lesions in a 2:1 ratio to EMBT or a
ranibizumab monotherapy control arm. The EMBT arm received two mandated, monthly loading injections of 0.5 mg ranibizumab.
The control arm received three mandated, monthly loading injections of ranibizumab, followed by quarterly injections.
Both arms also received monthly as needed (pro re nata) retreatment. The proportion of participants losing fewer
than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline visual acuity (VA) and the proportion
gaining more than 15 ETDRS letters from baseline VA was the main outcome measure.
The authors reported that at 24 months, 77% of the EMBT group and 90% of the control group lost fewer than
15 letters. This difference did not meet the prespecified 10% noninferiority margin. Additionally, this end point
was noninferior using a 20% margin and a 95% confidence interval for the group as a whole and for classic and
minimally classic lesions, but not for occult lesions. The study authors also noted that EMBT did not meet the superiority
end point for the proportion of participants gaining more than 15 letters (16% for the EMBT group versus 26% for
the control group): this difference was statistically significant (favoring controls) for occult lesions, but not
for predominantly classic and minimally classic lesions. They observed a mean VA change of –2.5 letters in the EMBT
arm and +4.4 letters in the control arm. Participants in the EMBT arm received a mean of 6.2 ranibizumab injections versus
10.4 in the control arm. At least one serious adverse event occurred in 54% of the EMBT arm, most commonly
postvitrectomy cataract, versus 18% in the control arm. Mild, nonproliferative radiation retinopathy occurred
in 3% of the EMBT participants, but no case was vision-threatening.
In conclusion, the two-year efficacy data do not support the routine use of EMBT for treatment-naïve wet AMD,
despite an acceptable safety profile. Further safety review is required.
Source: Dugel PU, Bebchuk JD, Nau J, et al; CABERNET Study Group. Epimacular brachytherapy for
neovascular age-related macular degeneration: a randomized, controlled trial (CABERNET).
Macular Epiretinal Brachytherapy in Treated AMD
Investigators performed this prospective, multicenter, interventional, noncontrolled clinical trial to report the
optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) results of the Macular Epiretinal Brachytherapy
in Treated Age-Related Macular Degeneration study.
Participants consisted of 53 eyes of 53 patients with chronic, active neovascular age-related macular degeneration
(AMD) requiring frequent anti-vascular endothelial growth factor (anti-VEGF) retreatment. Participants underwent pars
plana vitrectomy with a single 24-gray dose of epimacular brachytherapy (EMB), delivered with an intraocular, handheld
cannula containing a strontium 90/yytrium 90 source positioned over the active lesion. The investigators retreated
participants with ranibizumab administered monthly as needed, using predefined retreatment criteria. Patients underwent
FFA at baseline, month one and month 12. They also underwent optical coherence tomography (OCT) at baseline and then monthly
for 12 months. The FFA and OCT images were evaluated by independent, central reading facilities. Change in OCT
centerpoint thickness and angiographic lesion size 12 months after EMB was the main outcome measure.
According to the investigators, mean centerpoint thickness increased by 50 µm, from 186 µm to 236 µm
(p=0.292), but 70% of participants had an increase of less than the mean, with a median increase of only
1.8 µm. They reported that the FFA total lesion size increased slightly by 0.79 mm², from 14.69 mm² to
15.48 mm² (p=0.710) and that the total choroidal neovascularization (CNV) area increased by 1.17 mm²,
from 12.94 mm² to 14.12 mm² (p=0.556). They also found that the classic CNV area decreased substantially
by 3.70 mm², from 3.90 mm² to 0.20 mm² (p<0.01). Predominantly classic lesions showed the
greatest response, with mean Early Treatment Diabetic Retinopathy Study visual acuity improving by 1.5 letters
(versus –4.0 for all participants combined); mean centerpoint thickness decreased by 43 µm (p=0.875).
The angiographic and OCT response did not correlate with lesion size at baseline.
The study investigators concluded that in chronic, active neovascular AMD, EMB is associated with nonsignificant changes
in centerpoint thickness and FFA total lesion size over 12 months.
Source: Petrarca R, Dugel PU, Nau J, et al. Macular epiretinal brachytherapy in treated age-related
macular degeneration (MERITAGE): month 12 optical coherence tomography and fluorescein angiography.
Effect of 2.0 mg Intravitreal Ranibizumab on Recalcitrant Neovascular AMD
To determine whether a higher dose of intravitreal ranibizumab could improve the anatomy and best-corrected visual
acuity (BCVA) in eyes with neovascular age-related macular degeneration (AMD) with persistent disease activity
despite monthly intravitreal anti-vascular endothelial growth factor (VEGF) injections, this Phase I to II
multicenter, open-label, controlled clinical trial was performed.
Participants included 87 patients with recalcitrant neovascular AMD, defined as having leakage on fundus fluorescein
angiography or spectral domain optical coherence tomography (SD-OCT) despite frequent anti-VEGF injections. Each was
treated with 2.0-mg ranibizumab injections monthly for three doses and monitored with Early Treatment Diabetic Retinopathy
Study (ETDRS) 4-m refractions, clinical examinations and SD-OCT. Mean outcome measures were the mean change in baseline
visual acuity (VA), the percentage of patients who experienced a loss or gain of 15 or more letters in ETDRS BCVA, the
mean change in central retinal thickness and the incidence of adverse events.
A total of 87 patients with an average of 24 injections before enrollment and a mean of 10.4 injections in the preceding
12 months had a mean refracted VA of 69.2 ETDRS letters (20/41 Snellen) and a mean central subfield of 422 µm at
baseline. Mean VA gain over baseline was +2.5 letters at day seven (n=82), +3.7 letters at month one (n=87), +3.9 letters
at month two (n=87) and +3.3 letters at month three (20/36 Snellen; p=0.001; n=86). Furthermore, anatomic outcomes
showed a mean OCT central subfield thickness improvement from baseline of –48.4 µm at day seven
(n=84), –37.5 µm at month 1 (n=87), –42.4 µm at month two (n=85), and –33.1 µm at
month three (p=0.01; n=86).
Intravitreal injections of 2.0 mg ranibizumab led to statistically significant VA gains and anatomic improvement in
patients with persistent intraretinal, subretinal or subretinal pigment epithelial fluid during a previous regimen of
frequent 0.5-mg ranibizumab injections.
Source: Brown DM, Chen E, Mariani A, Major JC, SAVE Study Group. Super-dose anti-VEGF (SAVE) trial:
2.0 mg intravitreal ranibizumab for recalcitrant neovascular macular degeneration–primary end point.
Progression of Intermediate AMD With Proliferation and Inner Retinal
Migration of Hyper-reflective Foci
Drusen and migrating retinal pigment epithelium have been associated with hyper-reflective foci (HF) detected by
spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF
distribution and its correlation with age-related macular degeneration (AMD) progression.
This prospective, observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT
Study included patients (n=299) with one enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT
imaging at one- and two-year visits. The number and location of HF were scored in SD-OCT scans of all 299 eyes and the
change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise
signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution
(AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with
logistic regression analysis. The main outcome measure was the mean change in number of HF, transverse and axial
distribution of HF in the macula, and AxD per eye.
In 299 study eyes, the two-year increase in the number of HF (p<0.001) and the AxD (p<0.001) per
eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy
(GA) at two years were correlated with the presence of baseline HF (p<0.001; odds ratio [OR], 4.72;
95% confidence interval [CI], 2.43–9.80), greater number of baseline HF (p<0.001; OR, 1.61 per HF;
95% CI, 1.32–2.00) and greater baseline AxD (p<0.001; OR, 1.58 per AxD point; 95% CI,
Proliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD.
These characteristics were associated with greater incidence of GA at year two; therefore, SD-OCT HF proliferation and
migration may serve as biomarkers for AMD progression.
Source: Christenbury JG, Folgar FA, O’Connell RV, et al; Age-Related Eye Disease Study 2 Ancillary Spectral
Domain Optical Coherence Tomography Study Group. Progression of intermediate age-related macular degeneration
with proliferation and inner retinal migration of hyperreflective foci. Ophthalmology. 2013; Jan 24.
[Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.10.018.
ARMS2 and the Risk of Early and Late AMD
In the following population-based, cross-sectional European Eye Study in seven countries in Europe, scientists
examined associations between severity stages of early and late age-related macular degeneration (AMD) and genetic
variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and investigated
potential interactions between smoking and ARMS2.
They recruited 4,750 participants, 65 years of age and older, through random sampling. They classified participants on the
basis of the more severely affected eye into five mutually exclusive AMD severity stages ranging from no AMD, three
categories of early AMD and late AMD. History of cigarette smoking was available and allowed classification into never,
former and current smokers, with the latter two groups combined into a single category of ever smokers for analysis.
The scientists also performed genotyping for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170
in CFH and analyzed these associations by logistic regression. Main outcome measures consisted of odds ratios (ORs) for
stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
Early AMD was present in 36.4% and late AMD was present in 3.3% of participants, the study scientists found.
Data on both genotype and AMD were available for 4,276 people. The ORs for associations between AMD stage and ARMS2
increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential
confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase
in risk of late AMD (p<3×10–20). The ORs for associations with CFH were similar for stage three
early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted
and adjusted models (p=0.001). The scientists noted that the highest risk was observed in those doubly homozygous
for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16–242), with p values for trend
ranging from 0.03 (early AMD, stage 1) to 1×10–26 (late AMD).
A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a
significant gene-environment interaction with cigarette smoking was confirmed.
Source: Chakravarthy U, McKay GJ, de Jong PT, et al. ARMS2 increases the risk of early and late age-related
macular degeneration in the European Eye Study. Ophthalmology. 2013;120(2):342–348.
Argon Laser With and Without Anti-VEGF Therapy for Extrafoveal PCV
In Singapore, the following prospective cohort, noninterventional study sought to describe the clinical characteristics
and outcome of eyes with extrafoveal polypoidal choroidal vasculopathy (PCV) treated with argon laser.
This was a prospective study of Asian patients with extrafoveal PCV, confirmed on indocyanine green angiography and treated
with argon laser with and without anti-vascular endothelial growth factor (VEGF) therapy. Patients were followed over
12 months with visual, angiographic and structural outcomes recorded.
Of the 93 eyes with PCV at baseline, 33 eyes (35.5%) in 31 patients had extrafoveal involvement and were treated with
argon laser. Foveal involvement with fluid or blood at baseline was apparent in 23 eyes (69.7%), despite the
extrafoveal location of one or more polyps. Of these 33 eyes, 12 (36.4%) also received anti-VEGF injections (median,
2.5 injections) over the 12-month period. Two eyes received photodynamic therapy rescue during subsequent follow-up and
were excluded for visual outcome analysis. In the remaining 31 eyes, mean visual acuity improved from 0.57 logarithm
of the minimal angle of resolution (logMAR) units (range, 0.00 to 2.0 logMAR; standard deviation, 0.51 logMAR) at baseline
to 0.39 logMAR (range, 0.00 to 2.0 logMAR; standard deviation, 0.43 logMAR) at month 12 (p=.01), with a mean gain
in visual acuity of 9.0 letters at month 12. Stable or improved vision (defined as losing five letters or fewer) was achieved
in 28 eyes (90.3%). Use of anti-VEGF was associated with significantly thicker central subfield at baseline (347.6 vs.
258.1 µm; p=.02) and resulted in similar vision and OCT results at month three and 12 compared with eyes that
did not receive anti-VEGF.
It was concluded that argon laser treatment with selected use of anti-VEGF therapy achieves stable or improved visual
outcome in most eyes with extrafoveal PCV, including eyes with fluid or blood affecting the fovea at presentation.
Source: Cheung CM, Yeo I, Li X, et al. Argon laser with and without anti-vascular endothelial growth factor
therapy for extrafoveal polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013;155(2):295–304.
Treatment of Myopic CNV With Intravitreal Pegaptanib Sodium (Macugen)
The authors of the following open-label, nonrandomized, prospective clinical trial reported the morphologic and
functional outcomes resulting from the use of intravitreal pegaptanib sodium (Macugen) in patients with myopic
choroidal neovascularization (CNV).
They assessed morphologic outcome, such as foveal thickness, by optical coherence tomography (OCT), and functional outcomes
by best-corrected visual acuity (BCVA) and microperimetry. Their treatment protocol consisted of three consecutive doses
of intravitreal pegaptanib (0.3 mg/0.05 mL; baseline, sixth week, and 12th week). Follow-up checks were scheduled at
baseline, 18, 24, 36 and 48 weeks.
The authors studied 20 eyes from 20 patients; all patients completed follow-up at 48 weeks. After intravitreal pegaptanib,
a significant decrease in foveal thickness occurred (–20%), and at the end of follow-up, CNV closure was obtained
in all eyes. The study authors recorded an improvement of functional parameters in all patients (BCVA from 25.5 ±
8.09 letters to 45.5 ± 8.16 letters, p<0.0001; microperimetry from 8.40 ± 2.14 dB to 10.8 ±
2.05 dB, p<0.01). They noted that the mean number of intravitreal pegaptanib doses was three, and that none
of patients met the re-treatment criterion during the entire follow-up period. Neither ocular nor systemic side effects
The findings demonstrate that the selective inhibition of VEGF-165 isoform by IVP is an effective treatment for myopic
Source: Rinaldi M, Chiosi F, Dell'omo R, et al. Intravitreal pegaptanib sodium (Macugen) for treatment
of myopic choroidal neovascularization: a morphologic and functional study. Retina. 2013;33(2):397–402.
10-year Incidence and Risk Factors for RVO
The researchers in this population-based, longitudinal study sought to assess the 10-year incidence of retinal
vein occlusions (RVOs) and associated factors in adult Chinese subjects.
Participants consisted of 2,695 subjects from the 2001 Beijing Eye Study (66.4% of the survivors), when repeated
in 2011. The study participants underwent a detailed ophthalmic examination. The researchers reviewed the fundus
photographs for the new development of RVOs and differentiated these into branch RVOs (BRVOs) and central RVOs (CRVOs).
The main outcome measure was incidence of RVOs.
The study researchers detected incident RVOs in 51 eyes (49 subjects) with an incidence of 1.9 ± 0.1 per 100 persons
and 1.0 ± 0.1 per 100 eyes. They reported that the incidence of BRVO was 1.6 ± 0.1 per 100 subjects (43 subjects
[88% of patients with RVO]; 44 eyes), and incidence of CRVO was 0.3 ± 0.1 per 100 persons. Of 61 patients with an
RVO in 2001 and 25 subjects reexamined in 2011, at least four subjects (7%) developed a second RVO. Incident BRVOs
were located more often in the superior temporal quadrant and inferior temporal quadrant (32% and 34%,
respectively) than in the superior nasal quadrant and inferior nasal quadrant (21% and 14%, respectively),
the researchers noted. They also determined that in 35 eyes (80% of the BRVO eyes), the BRVO was located at an
arteriovenous crossing. At the crossing sites, they found arterioles superficial to venules in 28 eyes (64% of the
BRVO eyes) and they detected macular edema in 18 (37%) of all RVO eyes, including 13 (30%) of BRVO eyes.
In multivariate logistic analysis, they associated incident RVOs with higher systolic blood pressure (p=0.01; odds
ratio [OR], 1.04), hypertension (p=0.03; OR, 4.62), lower cognitive function score (p=0.007; OR, 0.88),
blood concentration of cholesterol ≥5.72 mmol/L (p=0.007; OR, 3.29) and status after cerebral infarction/hemorrhage
(p=0.02; OR, 1.19). Incident RVOs were not significantly related to the intake of aspirin (p=0.37).
The 10-year incidence of RVOs in Greater Beijing (1.9 ± 0.1 per 100 persons) was similar to that in other studies
on Caucasian populations. The 10-year incidence of RVOs was related to the known risk factors of arterial
hypertension, hypercholesterolemia and status after cerebral infarction/hemorrhage, as well as with a lower cognitive
function score. Incident BRVO was approximately six times more frequent than incident CRVO and macular edema was detected
in approximately 30% of BRVO eyes.
Source: Zhou JQ, Xu L, Wang S, et al. The 10-year incidence and risk factors of retinal vein occlusion:
The Beijing Eye Study. Ophthalmology. Jan 24. [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.09.033.
Natural Course, Intravitreal Triamcinolone, and Intravitreal Bevacizumab
for Treatment of Macular Edema Secondary to BRVO
To evaluate the natural course of the eyes with macular edema secondary to branch retinal vein occlusion (BRVO) and
to compare the visual outcome and macular thickness with eyes treated with intravitreal injection of triamcinolone
acetonide (IVTA) and intravitreal injection of bevacizumab (IVB), the authors of this Korean study reviewed the
medical records of patients with macular edema secondary to BRVO who were followed over 12 months.
They evaluated the best-corrected visual acuity (BCVA) and central macular thickness (CMT) of the patients who have had
no treatment for macular edema (natural course group) and compared the BCVA and CMT of the patients who had been treated
with IVTA or IVB.
BCVA and CMT of the natural course group improved in a slow, but steady manner, the authors found. They also noted that
the IVTA and the IVB group showed temporary improvement after injection, but macular edema recurred and there was no
significant difference in the visual outcome and macular thickness after six months.
To conclude, although IVTA and IVB were effective to decrease the macular edema at one month after the injection in BRVO,
BCVA and CMT of the natural course group were not inferior to both the IVTA and the IVB groups at 12 months.
Source: Kwon SI, Kim YW, Bang YW, et al. Comparison of natural course, intravitreal triamcinolone, and
intravitreal bevacizumab for treatment of macular edema secondary to branch retinal vein occlusion. J Ocul
Pharmacol Ther. 2013;29(1):5–9.
Analysis of Risk Factors Linked to CRVO
To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients
throughout the United States, investigators conducted this longitudinal cohort study.
In their study, they included all beneficiaries aged ≥55 years who were continuously enrolled in a managed care network
for at least two years and who had two or more visits to an eyecare provider from 2001 to 2009.
The investigators used insurance billing codes to identify individuals with a newly diagnosed CRVO. They performed
multivariable Cox regression to determine the factors associated with CRVO development. Adjusted hazard ratios (HRs) with
95% confidence intervals (CIs) of being diagnosed with CRVO served as the main outcome measures.
Of the 494,165 enrollees who met the study inclusion criteria, 1,302 (0.26%) were diagnosed with CRVO over
5.4 (± 1.8) years. After adjustment for known confounders, the investigators found that blacks had a 58%
increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25–1.99), and that women had a 25%
decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66–0.85). A diagnosis of stroke increased the
hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23–1.68), and hypercoagulable state was associated with a
145% increased CRVO risk (HR, 2.45; 95% CI, 1.40–4.28). Individuals with end-organ damage from hypertension
(HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52–2.42) and 53% (HR, 1.53; 95% CI,
1.28–1.84) increased risk of CRVO, respectively, relative to those without these conditions.
This study confirms that HTN and vascular diseases are important risk factors for CRVO. The study investigators also
identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, they show
that, compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO,
whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation
for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as
this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO.
Source: Stem MS, Talwar N, Comer GM, Stein JD. A longitudinal analysis of risk factors associated with
central retinal vein occlusion. Ophthalmology. 2013; 120(2):362–370.
Efficacy of Intravitreal Bevacizumab for Acute CSCR
The following study investigated the efficacy of intravitreal bevacizumab injection in patients with acute central
serous chorioretinopathy (CSCR).
Between six weeks and three months, 13 eyes of 22 patients with acute CSCR received an intravitreal bevacizumab injection
(2 mg/0.08 mL); nine eyes had no medical treatment as a control. At baseline and follow-up visits, patients had
best-corrected visual acuity (BCVA), intraocular pressure assessment, dilated fundus examination and spectral domain
optical coherence tomography (SD-OCT) imaging. Outcome measures were the resolution of neurosensory detachment, improvement
in visual acuity and symptoms.
All patients showed prompt improvements of visual acuity and symptoms until the third month and recovered from
neurosensory detachment gradually following treatment in the study group. It was reported that the vision of control
subjects recovered later and that the regression of serous retinal detachments was fairly slow. It was also noted that
the mean BCVA improved from 0.39 ± 0.16 at first visit (at baseline) to 0.73 ± 0.17 at the sixth month in the
study group and from 0.25 ± 0.17 at first visit (at baseline) to 0.67 ± 0.13 at the sixth month in the control
group, which was statistically significant (p=0.0001; p=0.0001, respectively). Mean retinal thickness for
the study group was decreased from 414.38 ± 102.79 at first visit (at baseline) to 256.46 ± 84.77 at the third
month and 198.30 ± 29.81 at the sixth month (p=0.0001, p=0.0001). For the control group, mean
retinal thickness was decreased from 510.33 ± 80.59 at first visit (at baseline) to 336.33 ± 127.83 at the
third month and 205.66 ± 19.65 at the sixth month (p=0.004, p=0.0001, respectively). Furthermore,
one of the patients in the control group revealed recurrence at the sixth month and the patient was given intravitreal
injection of bevacizumab.
It was concluded that intravitreal bevacizumab injection for acute CSCR can lead to remarkable improvements of visual
acuity within three months follow-up compared to controls. These results demonstrated that intravitreal bevacizumab
injection may be a promising option for selected patients in the treatment of acute CSCR.
Source: Aydin E. The efficacy of intravitreal bevacizumab for acute central serous chorioretinopathy.
J Ocul Pharmacol Ther. 2013;29(1):10–13.
Choroidal Thickness in CSCR
Researchers studied the choroidal thickness profile of 35 eyes (27 patients) with central serous chorioretinopathy
(CSCR) and 35 healthy, age-matched control eyes using high-penetration optical coherence tomography (OCT).
They observed the choroid using the prototype high-penetration OCT and performed fluorescein angiography and indocyanine
green angiography to identify the CSCR location and activity. They also manually measured choroidal thicknesses in
various conditions or locations. The choroidal thickness maps were obtained from cube scans and calculating software
and composed of nine sectors in the Early Diabetic Retinopathy Study chart.
According to the researchers, the subfoveal choroidal thicknesses in all eyes with CSCR were significantly
(p<0.01) greater than that in the control eyes. They noted that the choroidal thickness at the fovea and
the fluorescein points of leakage were significantly (p<0.01 for both comparisons) greater in eyes with
CSCR than the corresponding locations in the fellow eyes in patients with unilateral disease. They also observed that
dilatation of the choroidal large vessels was significantly (p<0.01) more common in CSCR. The foveal
choroidal thickness was significantly greater in eyes with venous dilatation (p<0.01) than those without,
the study researchers determined. They reported that the mean choroidal thickness was significantly (p<0.05)
greater in all sectors of the Early Diabetic Retinopathy Study chart except for the inner (p=0.087) and outer
(p=0.053) inferior sectors. Moreover, the percent mean choroidal thicknesses compared with the normal controls
in the nasal sector were significantly (p<0.05 and p<0.01, respectively) greater in the inner and
outer circles than in the superior, temporal and inferior sectors.
The choroid is diffusely thickened in CSCR likely because of the choroidal vascular dilatation. The nasal macula undergoes
the greatest alterations in choroidal thickness compared with the other areas.
Source: Kuroda S, Ikuno Y, Yasuno Y, et al. Choroidal thickness in central serous chorioretinopathy.
Use of PDT for Chronic CSCR
In this retrospective, multicenter, interventional case series analysis, scientists evaluated the efficacy and safety
of standard photodynamic therapy (PDT) with verteporfin at 48 months in patients with chronic central
serous chorioretinopathy (CSCR).
They evaluated patients every three months in the first year, every six months in the second year and thereafter annually.
They performed optical coherence tomography (OCT) at all visits but fluorescein angiography and indocyanine green angiography
at baseline and thereafter as necessary. They also manually measured retinal thickness on OCT, evaluating central
macular thickness and neural retina thickness. Main outcomes included the evolution of best-corrected visual acuity (BCVA);
the resolution of subretinal fluid, documented with OCT; the number of treatments; and the evaluation of neural retina
thickness during the 48 months of follow-up.
The study included 46 eyes of 42 patients, 38 men (90.4%) and four women (9.5%), with mean age of 49.19 ±
9.9 years (range, 32–70 years). The minimum follow-up period was 48 months (mean, 56.8 ± 10.3 months).
The scientists observed subretinal fluid in all of the included eyes at baseline and 10 eyes (21.7%) had
intraretinal diffuse or cystoid fluid. Concerning the mean BCVA, they reported that a statistically significant
improvement (p<0.01, Student t-test) was registered from 58.8 ± 18.3 letters at baseline to
66.9 ± 18.6 letters at the 48th month. A complete resolution of subretinal fluid was achieved in 93.4%, and
resolution of intraretinal fluid occurred in all 10 cases at 48 months. Additionally, neural retina thickness remained
stable during the 48 months of follow-up (163.8 ± 47 µm at baseline and 163.8 ± 46 µm at 48 months).
The mean number of treatments was 1.08 ± 0.3 and no systemic or ocular side effects were registered.
In conclusion, standard PDT with verteporfin was effective and safe in chronic CSCR treatment with a significant improvement
in the long term, both anatomic and visual, without inducing additional retinal atrophy or systemic adverse effects.
Source: Silva RM, Ruiz-Moreno JM, Gomez-Ulla F, et al. Photodynamic therapy for chronic central
serous chorioretinopathy: a 4-year follow-up study. Retina. 33(2):309–315.