Volume 9, Number 1
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.
Subretinal Drusenoid Deposits in Non-Neovascular AMD
The authors of this study sought to characterize the morphology, prevalence and topography of subretinal
drusenoid deposits, a candidate histological correlate of reticular pseudodrusen, with reference to basal linear
deposit (BlinD), a specific lesion of age-related macular degeneration (AMD), and to propose a biogenesis model
for both lesions.
They postfixed donor eyes with median death-to-preservation of 2:40 hours in osmium tannic acid paraphenylenediamine
and prepared them for macula-wide high-resolution digital sections. They determined annotated thicknesses of
21 chorioretinal layers standard locations in sections through the fovea and the superior perifovea.
According to the authors, in 22 eyes of 20 white donors (83.1 ± 7.7 years), subretinal drusenoid deposits
appeared as isolated or confluent drusenoid dollops punctuated by tufts of retinal pigment epithelium apical
processes and associated with photoreceptor perturbation. They detected subretinal drusenoid deposits and BlinD in
85% and 90% of non-neovascular AMD donors, respectively, and reported that subretinal drusenoid deposits
were thick (median, 9.4 µm) and more abundant in the perifovea than in the fovea (p<0.0001).
Furthermore, BlinD was thin (median, 2.1 µm) and more abundant in the fovea than in the perifovea
The study authors concluded that subretinal drusenoid deposit and BlinD prevalence in AMD eyes are high.
Subretinal drusenoid deposits organized morphology, topography and impact on surrounding photoreceptors imply
specific processes of biogenesis. Contrasting topographies of subretinal drusenoid deposits and BlinD
suggest relationships with differentiable aspects of rod and cone physiology, respectively. A two-lesion,
two-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented.
Source: Curcio CA, Messinger JD, Sloan KR, et al. Subretinal drusenoid deposits in
non-neovascular age-related macular degeneration: morphology, prevalence, topography and biogenesis
model. Retina. 2012; Dec 21. [Epub ahead of print]. DOI: 10.1097/IAE.0b013e31827b6324.
Predictors for Visual Outcomes with Ranibizumab or Bevacizumab
for Neovascular AMD
To determine the baseline predictors of visual acuity (VA) outcomes one year following treatment with
ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD), a cohort study within
the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) was conducted.
A total of 1,105 participants with neovascular AMD, baseline VA 20/25 to 20/320 and VA measured at one year
were included. Participants were randomly assigned to ranibizumab or bevacizumab on a monthly or as-needed
schedule. Masked readers evaluated fundus morphology and features on optical coherence tomography (OCT). VA was
measured using electronic VA testing and independent predictors were identified using regression techniques. Main
outcome measures were the VA score, VA score change from baseline and a gain of three lines or more at one year.
At one year, the mean VA score was 68 letters, mean improvement from baseline was seven letters and 28%
of participants gained three or more lines. Older age, larger area of choroidal neovascularization (CNV) and elevation
of retinal pigment epithelium (RPE) were associated with worse VA (all p<0.005), less gain in VA
(all p<0.02) and a lower proportion gaining ≥3 lines (all p<0.04). It was noted that
better baseline VA was associated with better VA at one year, less gain in VA, and a lower proportion gaining ≥3
lines (all p<0.0001). Additionally, predominantly or minimally classic lesions were associated with
worse VA than occult lesions (66 vs. 69 letters; p=0.0003), retinal angiomatous proliferans (RAP) lesions
were associated with more gain in VA (10 vs. seven letters; p=0.03) and a higher proportion gaining ≥3
lines (odds ratio, 1.9; 95% confidence interval, 1.2–3.1), and geographic atrophy (GA) was associated with
worse VA (64 vs. 68 letters; p=0.02). Moreover, eyes with total foveal thickness in the second quartile
(325–425 µm) had the best VA (p=0.01) and were most likely to gain ≥3 lines (p=0.004).
Predictors did not vary by treatment group.
For all treatment groups, older age, better baseline VA, larger CNV area, predominantly or minimally classic
lesion, absence of RAP lesion, presence of GA, greater total fovea thickness and RPE elevation on OCT were
independently associated with less improvement in VA at one year.
Source: Ying GS, Huang J, Maguire MG, et al; Comparison of Age-related Macular Degeneration
Treatments Trials Research Group. Baseline predictors for one-year visual outcomes with ranibizumab
or bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;
Long-Term Safety of Ranibizumab 0.5 mg in the Treatment of Neovascular AMD
In this 24-month, open-label, multicenter, phase IV extension study, investigators evaluated long-term safety
of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (AMD).
They included 234 patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Ranibizumab
0.5 mg administered at the investigator's discretion as per the European summary of product characteristics
2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss
of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA]
value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression
of active nAMD in the investigator's opinion). Incidence of ocular or nonocular adverse events (AEs) and serious
AEs, mean change in BCVA from baseline over time and the number of injections were the main outcome measures.
The study investigators reported that of 234 enrolled patients, 210 (89.7%) completed the study. They observed
that patients received 6.1 (mean) ranibizumab injections over 24 months and that approximately 42% of patients
had seven or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more
than five letters, indicating either an undertreatment or that factors other than VA loss were considered for
retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage
(12.8%; one event related to study drug), cataract (11.5%; one event related to treatment procedure)
and increased IOP (6.4%; one event related to study drug). Cataract reported as serious due to hospitalization
for cataract surgery occurred in 2.6% of patients, but none was suspected to be related to study drug or
procedure, the investigators noted. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each).
Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during
the study, but none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from
the SECURE baseline.
In conclusion, the SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing
regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well-tolerated over
two years. No new safety signals were identified in patients who received ranibizumab for a total of three years,
and on average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression
or possible undertreatment.
Source: Silva R, Axer-Siegel R, Eldem B, et al; SECURE Study Group. The SECURE Study: Long-term safety
of ranibizumab 0.5 mg in neovascular age-related macular degeneration. Ophthalmology.
Intravitreal Ranibizumab Used to Treat PED with Subfoveal Occult CNV
The investigators in the following prospective, interventional case series sought to assess the effects
of intravitreal ranibizumab injection in patients affected by pigment epithelial detachment (PED) associated
with occult subfoveal choroidal neovascularization (CNV).
The considered 40 eyes of 40 patients for the purpose of the study and recruited consecutive patients for a
24-month study. All patients underwent a complete ophthalmic examination, including best-corrected visual acuity
(BCVA) on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. After a three-month loading phase,
the investigators administered further intravitreal ranibizumab injections on the basis of detection of any type
of fluid on optical coherence tomography (OCT). Primary outcome measures included any changes in mean BCVA at 12 and
24 months and the proportion of eyes losing fewer than 15 letters (corresponding to three ETDRS lines) from
baseline visual acuity. Secondary outcome measures included changes in central macular thickness on OCT and variation
in mean area of the entire lesion.
The investigators reported that 40 patients were included in their study. They also noted that mean BCVA decreased
from 20/66 (58 ETDRS letters) to 20/83 (53 letters) at 12 months and 20/112 (489 ETDRS letters) at 24 months
(p=.003). They observed that 80% and 67.5% of eyes lost fewer than three lines at 12 and 24
months, respectively. Furthermore, mean central macular thickness passed from 545 µm to 428 µm at
12 months and 426 µm at 24 months. Mean lesion area changed from 6,826 µm² to 6,312 µm² at
12 months and 6,010 µm² at 24 months.
The treatment of PED associated with occult subfoveal CNV with intravitreal ranibizumab injection after a
three-month loading phase and pro re nata strategy can lead to partial results over a 24-month follow-up,
the study investigators determined. Further investigations are warranted to establish the best therapeutic approach
to this disease.
Source: Parodi MB, Iacono P, Papayannis A, et al. Intravitreal ranibizuamb for pigment epithelium
detachment with subfoveal occult choroidal neovascularization: a prospective 24-month case series.
Am J Ophthalmol. 2013;155(1):103–108.
Treatment Results of Ranibizumab for Neovascular AMD and Causes
Danish researchers conducted a retrospective, single-center chart review to evaluate four-year treatment
results of neovascular age-related macular degeneration (AMD) with ranibizumab using a variable dosing regimen.
The study included 855 patients with neovascular AMD receiving treatment with ranibizumab during a four-year
period. Included in the study were patients with a minimum follow-up of 15 months and all patients who
terminated treatment regardless of follow-up.
The researchers noted that 1,321 patients were treated over the four-year period, and 855 patients were eligible
for inclusion. Of those, 456 patients were still receiving active treatment, whereas 399 patients had
discontinued treatment. Overall treatment results showed a significant decrease in vision from 53.2 Early
Treatment Diabetic Retinopathy Study letters (range, 1 to 85 letters) to 50.5 letters (range, 1 to 87 letters;
p<.001). According to the study researchers, mean follow-up was 23.3 months (range, four to 48 months).
The reason for discontinuing treatment in 181 patients was no signs of activity, whereas 113 patients were judged
to be non-treatable. A total of 36 patients declined further treatment for various reasons.
This report shows that when follow-up extends beyond two to three years, visual acuity does seem to decrease.
Our data show that different responder groups can be identified: bad or nonresponders (approximately 15% of
all patients) and good responders (approximately 21% of all patients). These two groups in general can be
identified within the first two years of treatment, whereas the third group of regular responders
(approximately 64% of all patients) require continuous monitoring and treatment for years.
Source: Falk MK, Kemp H, So/rensen TL. Four-year treatment results of neovascular age-related
macular degeneration with ranibizumab and causes for discontinuation of treatment. Am J
Changes in VA of Wet AMD Patients Treated with Intravitreal Ranibizumab
A retrospective, descriptive, observational study in patients with subfoveal wet age-related macular
degeneration (AMD) treated with ranibizumab was conducted to survey compliance with recommended
intravitreal ranibizumab treatment protocols in daily clinical practice in France, with reference to outcomes.
All historical data for the study period, including demographic, treatment and disease details and visual
acuity measurements (baseline, month three, and month 12), were recorded retrospectively at least 12 months
after the beginning of treatment.
It was observed that in 551 patients followed by 16 ophthalmologists, 12 months of intravitreal ranibizumab
treatment induced a mean visual acuity gain of 3.2 ± 14.8 Early Treatment Diabetic Retinopathy
Study-equivalent letters. It was also noted that less than 40% of patients received the recommended
treatment of initial three monthly injections. More than 50% had to wait more than eight days between
diagnosis and treatment. At month three, visual acuity gain was greater in patients who had received
recommended induction and in whom treatment was initiated quickly. At month 12, the induction-related effect
had largely disappeared, but the time-to-treatment effect persisted. Patients had an average of 5.1 injections
(2.6 during induction period). No patients were monitored monthly as stipulated in the guidelines.
To conclude, although poor compliance with recommendations has been reflected in mediocre outcomes, there is
evidence that practice is improving.
Source: Cohen SY, Mimoun G, Oubraham H, et al; for the LUMIERE Study Group. Changes in visual
acuity in patients with wet age-related macular degeneration treated with intravitreal ranibizumab
in daily clinical practice: the LUMIERE Study. Retina. 2013; Dec 21. [Epub ahead of print].
Variants in the VEGFA Gene and Outcome of Treatment Following
Anti-VEGF Treatment for Neovascular AMD
The authors of the following Australian prospective cohort study sought to determine the association of
genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment
in neovascular age-related macular degeneration (AMD).
They included 201 consecutive patients receiving anti-VEGF injection for neovascular AMD, whom they followed over
12 months. Patients were treated with three initial monthly ranibizumab or bevacizumab injections. Thereafter,
the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven
tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined and multivariate
data analysis was used to determine the role of each tSNP in treatment outcome. The influence of selected VEGFA
tSNPs on visual acuity (VA) outcome at six months was the main outcome measure.
Mean baseline VA was 51 ± 17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores, the authors
reported. Overall, they found that the mean change in VA from baseline was +6.5 ± 12, +4.4 ± 13.4, and
+2.3 ± 14.6 letters at three, six and 12 months, respectively. The tSNP rs3025000 was the only SNP
significantly associated (p<1 × 10–4) with visual outcome at six months with multiple correction.
The presence of the T allele (TC or TT genotypes) at this tSNP predicted a better outcome of +7 letters at six
months compared with the CC genotype. In a subgroup analysis, presence of the T allele predicted a significantly
higher chance of the patients belonging to the responder group (gain of ≥5 letters from baseline) after three,
six and 12 months treatment (odds ratio, 2.7, 3.5 and 2.4; 95% confidence interval, 1.46 to 5.07,
1.82 to 6.71 and 1.27 to 4.57, respectively) than any other outcome group.
Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD, the
authors concluded. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome
at six months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at
three, six and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with
those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective
in certain subgroups of patients.
Source: Abedi F, Wickremasinghe S, Richardson AJ, et al. Variants in the VEGFA gene and treatment
outcome after anti-VEGF treatment for neovascular age-related macular degeneration.
An Association of Transferrin Gene Polymorphism and Serum
Transferrin Levels with AMD
Oxidative stress has been proven to play a key role in age-related macular degeneration (AMD) pathogenesis, and
because iron accumulation has been found in AMD maculae, it may accelerate the oxidative processes in this tissue.
In the present work, scientists in Poland investigated the association between four polymorphisms of the transferrin
gene (rs8177178; rs8177179; rs4481157; rs1130459) and AMD in dependence on the transferrin protein and iron serum levels.
They employed polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) for
genotype determination, ELISA assay for serum transferrin evaluation and colorimetric assay for measurement
of iron concentration in the serum and found that advanced age and AMD family history may be independent risk
factors for AMD (1.02, p<0.05 and 8.88, p<0.001, respectively).
At the rs4481157 site, the GG genotype of the rs4481157 polymorphism decreased the risk of dry AMD (OR 0.50;
p<0.05), while the GA increased this risk (OR 1.07; p<0.05). Moreover, the GA genotype of
this polymorphism decreased the risk of progression to the wet form (OR 0.63; p<0.05). The
scientists' analysis of the gene-environment interactions showed that the rs4481157 polymorphism modulates
the AMD risk among obese (BMI above 30) individuals.
In the former smokers group, they observed a moderate association between rs4481157 polymorphism and AMD risk,
while this association in current smokers was stronger. They found also that the serum level of transferrin was
higher in the AMD group (p<0.001) than in the control, but the total serum iron levels did not differ
between both groups. Furthermore, they found that the serum transferrin was associated with the rs8177178
(p<0.001) and rs4481157 (p<0.01) polymorphisms, and the common variant (GG) of both sites
was related to a lower level of transferrin. Presented data may contribute to the involvement of iron homeostasis
in AMD risk.
Source: Wysokinski D, Danisz K, Blasiak J, et al. An association of transferrin gene polymorphism
and serum transferring levels with age-related macular degeneration. Exp Eye Res. 2013;106:14–23.
Letter Reanalyzes AREDS Data
In the Age-Related Eye Disease Study (AREDS), the growth of geographic atrophy (GA) over four years was shown to
be dependent on the baseline area of GA; however, three articles have demonstrated that the square root transformation
of lesion area measurements eliminates the dependence on baseline lesion size for both the test-retest variability
and the growth rates.
Area measurements of GA collected from 181 eyes of 181 AREDS study patients and followed up longitudinally for up
to four years were analyzed using the square root transformation strategy. The correlations between growth of the
lesion area over four years and baseline lesion size were performed on the original area scale and on the square
root area scale with both Pearson and Spearman correlation analyses. A second analysis divided lesions into the
published categories of baseline lesion size expressed as disc areas (<0.75, 0.75 to <4 and ≥4 disc
areas), and lesion growth was calculated and compared using the standard area of measurements (millimeters squared)
and the square root of these same measurements (millimeters). The influences of the assigned treatments (zinc
and antioxidants) were also analyzed using the square root transformation strategy and these analyses were
performed using generalized estimating equations with correlation structure modeled as first-order autoregressive.
According to the authors of this letter, application of the square root transformation to the area
measurements eliminated the statistical significance of the correlations between growth and baseline area.
Four-year growth rates were significantly correlated with baseline lesion size using the original area
measurements (Pearson r=0.53, p<.001; Spearman r=0.49, p<.001), but there was not
statistically significant correlation once the area measurements underwent the square root transformation
strategy (Pearson r=0.10, p=.30; Spearman r=0.17, p=.08). When the baseline lesions were divided
into different size categories, there was a statistically significant difference in the growth of GA using the
original area measurements (p<.001), but no statistically significant difference after applying the
square root transformation strategy (p=.34). Zinc and antioxidant treatment and their interaction were
not associated with decreased lesion growth using either the original area or square root area measurements
The square root transformation strategy reduced the association between growth rates and baseline area measurements
in AREDS, which confirmed the recent reports. Additionally, the square root strategy simplifies the design and
enrollment of clinical trials by eliminating the need to either specify a range of lesion sizes or adjust for lesion
size in the analysis. While this reanalysis of the AREDS data did not alter the conclusion about the lack of
efficacy when using zinc and antioxidants for the treatment of GA, the square root strategy did eliminate the
artifactual dependence of growth on baseline size within the range of lesion sizes enrolled in AREDS. However,
very small lesions when GA first appears and very large lesions nearing the end of their growth cycle are expected
to grow more slowly based on the natural history of GA in AMD.
Source: Feuer WJ, Yehoshua Z, Gregori G, et al. Square root transformation of geographic atrophy
area measurements to eliminate dependence of growth rates on baseline lesion measurements: a reanalysis
of Age-Related Eye Disease Study Report No. 26. JAMA Ophthalmol. 2013; 131(1):110–111.
Retinal Sensitivity Following Intravitreal Triamcinolone
Acetonide Injection for ME Secondary to BRVO
To evaluate the effect of intravitreal triamcinolone acetonide (IVTA) on retinal sensitivity in cases of macular
edema (ME) secondary to branch retinal vein occlusion (BRVO), Turkish investigators conducted this prospective
study, which included 14 eyes of 14 cases of BRVO.
In each eye, at baseline and one, three and six months after IVTA injection, they assessed logMAR visual acuity,
central 4° retinal sensitivity by MP-1 microperimetry and optical coherence tomography (OCT) foveal thickness.
The investigators reported that ages ranged from 60 to 79 years (mean 68 ± 8 years). At one, three and six
months, the logMAR visual acuity had increased from 0.71 ± 0.21 to 0.42 ± 0.21, 0.46 ± 0.30 and
0.46 ± 0.27; the mean foveal thickness had decreased from 540 ± 88 µm to 254 ± 51 µm,
288 ± 84 µm and 280 ± 91 µm; and the mean retinal sensitivity had increased from 4.7 ±
2.5 dB to 7.9 ± 2.7 dB, 8.2 ± 3.6 dB and 8.3 ± 4.6 dB, respectively.
In eyes with ME secondary to BRVO, IVTA injections result in a significant increase in not only the visual acuity,
but also the central 4° retinal sensitivity in six months follow-up.
Source: Senturk F, Ozdemir H, Karacorlu M, et al. Retinal sensitivity improvement after
intravitreal triamcinolone acetonide injection for macular edema secondary to branch retinal vein
occlusion. Indian J Ophthalmol. 2013;61(1):3–7.
Link Between Morphologic and Functional Changes in Retinal
Vessels and BRVO
The authors of the following Japanese prospective, observational, cross-sectional study examined the morphologic
and functional changes in retinal veins of eyes affected with branch retinal vein occlusion (BRVO) by thin
sectioning with optical coherence tomography (OCT).
They included 25 consecutive patients (25 eyes) with acute BRVO and examined major retinal veins, arteries
and arteriovenous (A/V) crossing by sequential thin sectioning by Spectralis HRA+OCT (Heidelberg
Engineering, Heidelberg). The retinal blood flow was mimicked in vitro and scanned with Spectralis HRA+OCT.
Morphologic characteristics of normal and BRVO-affected retinal vessels seen in OCT sections were the main
Cross-sectional OCT images revealed physiologic retinal vessels as oval configurations with four
distinctive hyperreflectivities in a line, the authors noted. They also reported that the vessel walls showed
the innermost and outermost hyperreflectivity, and the blood flow showed internal paired hyperreflectivities with
an hourglass shape. According to the authors, no eye with disturbed blood flow due to BRVO showed this
internal hyperreflectivity pattern. They found that, in vitro, OCT sections of the blood within the glass tube
without flow showed homogeneous reflectivities. Increased blood flow velocity resulted in the development
of heterogeneous internal reflectivity and hourglass-shaped hyperreflectivities. In all eyes with acute BRVO,
sequential sectioning with OCT visualized three-dimensional vascular architecture and the intravascular conditions
at the A/V crossing. At the affected A/V crossing, arterial overcrossing was seen in 17 eyes and venous overcrossing
was seen in eight eyes. In eyes with arterial overcrossing, the study authors noted that the retinal vein seemed
to run deep under the artery at the A/V crossing, and the venous lumen often appeared to be preserved even at the
A/V crossing. In all eyes with venous overcrossing, the retinal vein appeared to be compressed and choked between
the internal limiting membrane and the arterial wall at the A/V crossing. Optical coherence tomography sectioning
showed intravenous thrombi in 21 eyes, and the thrombi were detected downstream of the A/V crossing in all the cases.
The detection of thrombus was significantly associated with ischemic pattern in BRVO (p=0.036).
In conclusion, in eyes with BRVO, sequential thin sections with OCT visualized three-dimensional retinal vasculature.
The present OCT findings suggest that BRVO may occur by two different mechanisms, depending on the relative anatomic positions of the crossing vessels.
Source: Muraoka Y, Tsujikawa A, Murakami T, et al. Morphologic and functional changes in retinal
vessels associated with branch retinal vein occlusion. Ophthalmology. 2013;120(1):91–99.
Impact of Subconjunctival Bevacizumab on Corneal NV
London researchers evaluated the off-label use of subconjunctival bevacizumab for corneal neovascularization
(NV) and found that three subconjunctival injections of 2.5 mg bevacizumab are more effective than placebo
at inducing the regression of recent-onset corneal NV.
They randomly assigned 30 patients with recent-onset corneal NV from various causes into a
double-masked, placebo-controlled trial. Each received three 0.1 ml injections containing either 2.5 mg bevacizumab
or 0.9% saline at monthly intervals. The researchers used dexamethasone 0.1% drops four times a day for the
first month, at which time the dose was modified, if clinically indicated. The primary outcome was change in
area of corneal involvement by corneal NV from baseline to three months measured using specialized imaging technology.
The mean area of corneal NV reduced by –36% (range –92% to +40%) in the 15 eyes that
received bevacizumab compared with an increase of 90% (range –58% to +1,394%) in eyes that
received saline placebo (analysis of covariance (ANCOVA); p=0.007), the researchers noted. One outlier
in the placebo arm developed corneal graft rejection with aggressive neovascularization (+1,384%), but even
when this patient was excluded, the mean reduction in corneal NV in the placebo group (–3%,
range –58% to +40%) was still significantly different from the treatment arm
(ANCOVA; p=0.016). Moreover, changes in best-corrected visual acuity, central corneal thickness,
intraocular pressure and endothelial cell counts were similar between groups. The intervention was well
tolerated with no major safety concerns.
Further studies are needed to confirm this effect and our data suggest that a sample size of 40 patients
per treatment group is required.
Source: Petsoglou C, Balaggan KS, Dart JK, et al. Subconjunctival bevacizumab induces regression of
corneal neovascularization: a pilot randomized placebo-controlled double-masked trial. Br
J Ophthlamol. 2013;97(1):28–32.
Sustained Chronic Inflammatory Reaction in RP
This Japanese retrospective, observational study investigated the nature of inflammatory reaction in eyes of patients
with retinitis pigmentosa (RP) and its possible role in the pathogenesis of the disease.
A total of 371 consecutive patients diagnosed with typical RP were included in this study and an additional 165
patients without active inflammatory diseases, including 20 patients diagnosed with cataract, and 36 patients
diagnosed with idiopathic epiretinal membrane, were included as controls.
Density of the inflammatory cells in the anterior vitreous cavity was measured and graded by slit lamp biomicroscopy.
A multiplex enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the concentration of cytokines
and chemokines in aqueous humor and vitreous fluid of patients with RP and controls. In addition, the
relationship between visual function and anterior vitreous cells in these patients was investigated. Main
outcome measures were slit lamp biomicroscopic analysis, best-corrected visual acuity, visual field analysis
and multiplex ELISA.
In 190 of 509 eyes with RP (37.3%), “1+” (five to nine cells per field) or more cells were
observed in the anterior vitreous cavity. Strong inflammatory reaction with “2+” cells (10–30 cells
per field) was associated with younger age. It was noted that in the elderly patients with RP, significantly
decreased visual function was seen in a group with “1+” or more cells (p<0.05). Moreover,
the levels of a variety of proinflammatory cytokines and chemokines, including monocyte chemotactic protein-1,
were increased both in the aqueous humor and vitreous fluid of RP patients compared with the levels in control patients.
It was determined that sustained chronic inflammatory reaction may underlie the pathogenesis of RP,
suggesting interventions for ocular inflammatory reaction as a potential treatment for patients with RP.
Source: Yoshida N, Ikeda Y, Notomi S, et al. Clinical evidence of sustained chronic inflammatory
reaction in retinitis pigmentosa. Ophthalmology. 2013;120(1):100–105.
Retinal Vessel Caliber and Glaucoma Incidence
To examine associations between quantitatively measured retinal vessel caliber and the 10-year incidence of
primary open-angle glaucoma (OAG), the authors of this population-based cohort study (The Blue Mountains Eye
Study) examined 3,654 persons at baseline and 2,461 persons at either five years, 10 years or both times.
After excluding 44 subjects with OAG at baseline, 2,417 participants at risk of OAG at the five- or 10-year
examinations were included. The authors measured retinal vessel calibers of baseline retinal photographs using
a computer-based program and summarized these as central retinal artery and vein equivalents (CRAE, CRVE). They
defined incident OAG as the development of typical glaucomatous visual field loss combined with matching optic disc
rim thinning and an enlarged cup-to-disc (C:D) ratio of >0.7 or C:D asymmetry between the two eyes (≥0.3)
at either the five- or 10-year examination. The study authors used generalized estimating equation models to account
for correlation between eyes while adjusting for glaucoma risk characteristics including intraocular pressure (IOP)
or ocular perfusion pressure (OPP). For the main outcome measures, they assessed the 10-year incidence of OAG.
According to the authors, 82 persons (104 eyes) developed incident OAG over the 10-year follow-up. After adjusting
for age, sex, family history of glaucoma, smoking, diabetes, hypertension, hypercholesterolemia, body mass
index, spherical equivalent refraction and C:D ratio, they found an associated between narrower CRAE and higher
risk of incident OAG (adjusted odds ratio [OR], 1.77; 95% confidence interval [CI], 1.12 to 2.79, per
standard deviation decrease in CRAE). This association persisted after further adjustment for IOP (adjusted OR,
1.87; 95% CI, 1.14 to 3.05) or OPP (adjusted OR, 1.76; 95% CI, 1.11 to 2.78), and remained significant
when analyses were confined to eyes with IOP <20 mmHg and C:D ratio <0.6 at baseline. There were no
independent associations between CRVE and incident OAG.
Retinal arteriolar narrowing, quantitatively measured from retinal photographs, was associated with long-term risk
of OAG. These data support the concept that early vascular changes are involved in the pathogenesis of OAG and
suggest that computer-based measurements of retinal vessel caliber may be useful to identify people with an
increased risk of developing the clinical stage of glaucoma.
Source: Kawasaki R, Wang JJ, Rochtchina E, et al. Retinal vessel caliber is associated with the
10-year incidence of glaucoma: the Blue Mountains Eye Study. Ophthalmology. 2013;120(1):84–90.