Volume 8, Number 5
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.
Two-Year Results of Treatment of Neovascular AMD with Ranibizumab and Bevacizumab
Researchers sought to describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years
and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment in the
following multicenter, randomized clinical trial.
They included 1,107 patients who were followed up during year 2 among 1,185 patients with neovascular age-related
macular degeneration (AMD) who were enrolled in the clinical trial. At enrollment, the researchers assigned patients to
4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, they
randomly reassigned patients initially assigned to monthly treatment to monthly or as-needed treatment, without changing the
drug assignment. The main outcome measure was mean change in visual acuity.
The researchers noted that among patients following the same regimen for 2 years, mean gain in visual acuity was similar for
both drugs (bevacizumab-ranibizumab difference, –1.4 letters; 95% confidence interval [CI], –3.7 to 0.8;
p = 0.21). They also determined that mean gain was greater for monthly than for as-needed treatment
(difference, –2.4 letters; 95% CI, –4.8 to –0.1; p = 0.046). The proportion without fluid ranged from
13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, p = 0.0003; regimen,
p < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2
(–2.2 letters; p = 0.03) and a lower proportion without fluid (–19%; p < 0.0001), the
researchers noted. They also reported that the proportion of study eyes with geographic atrophy (GA) at 2 years among eyes
without apparent GA at enrollment, ranging from 25.8% in the ranibizumab-monthly group to 12.9% in the
bevacizumab-as-needed group, was greater among patients treated monthly (p=0.007). Rates of death and
arteriothrombotic events were similar for both drugs (p > 0.60). The proportion of patients with 1 or more
systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio,
1.30; 95% CI, 1.07–1.57; p = 0.009). Most of the excess events have not been associated previously with
systemic therapy targeting vascular endothelial growth factor (VEGF).
To conclude, ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted
in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no
differences between drugs in rates of death or arteriothrombotic events. Moreover, the interpretation of the persistence of
higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions
associated with inhibition of VEGF. On the other hand, after 2 years, the ranibizumab monthly treated group had the
highest proportion in which GA developed of any the 6 treatment groups. What’s more, the development of GA was higher in
both monthly treated groups than in the p.r.n. groups, which may be important to consider when weighing the risks and
benefits of monthly versus p.r.n. treatment and in the selection of drug.
Source: Martin DF, Maguire MG, Fine SL, et al.; Comparison of Age-related Macular Degeneration Treatments Trials
(CATT) Research Group Writing Committee. Ranibizumab and bevacizumab for treatment of neovascular age-related
macular degeneration: two-year results. Ophthalmol. 2012;May 2. [Epub ahead of print].
Treatment of Neovascular AMD with Ranibizumab Versus Bevacizumab
Investigators compared the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat
neovascular age-related macular degeneration (AMD) in the following multicenter, noninferiority factorial trial.
The trial gave equal allocation to groups and the noninferiority limit was 3.5 letters. It included people ɬ50 years of age
with untreated neovascular AMD in the study eye who read ≥25 letters on the Early Treatment Diabetic Retinopathy Study chart.
The investigators randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as
needed (discontinuous), with monthly review. The primary outcome is at 2 years; this paper reports a prespecified interim analysis
at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure.
Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion
morphology, serum vascular endothelial growth factor (VEGF) levels and costs.
Between March 27, 2008 and October 15, 2010, the investigators randomized and treated 610 participants. One year after randomization,
they found that the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab –1.99 letters,
95% confidence interval [CI], –4.04 to 0.06). They reported that discontinuous treatment was equivalent to continuous
treatment (discontinuous minus continuous –0.35 letters; 95% CI, –2.40 to 1.70). According to the investigators, foveal
total thickness did not differe by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI,
0.86 to 0.97; p=0.005). They also noted that fewer participants receiving bevacizumab had an arteriorthrombotic event or
heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; p=0.03). There was no difference between drugs in the
proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; p=0.25). Additionally, serum
VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; p<0.0001) and higher with discontinuous treatment
(GMR, 1.23; 95% CI, 1.07 to 1.42; p=0.004). The study investigators determined that continuous and discontinuous treatment
costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizuamb; bevacizumab
was less costly for both treatment regimens.
They concluded that the comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities
with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens
having similar efficacy and safety.
Source: Chakravarthy U, Harding SP, Rogers CA, et al.; The IVAN Study Investigators. Ranibizumab versus bevacizumab
to treat neovascular age-related macular degeneration. Ophthalmol. 2012;May 11. [Epub ahead of print].
Use of Ranibizumab in Treatment-Naïve Patients with Exudative AMD and Relatively Good Baseline VA
In Spain, the authors of the following study investigated the safety and efficacy of a combined fixed-interval and
pro re nata regimen of ranibizumab (FUSION regimen) for treatment of exudative age-related macular degeneration (AMD)
in patients with good visual acuity at baseline. They also aimed to establish whether similar efficacy to monthly regimens can
be achieved with fewer injections, even in patients with good visual acuity.
This was a prospective, open-label, consecutive interventional case series in treatment-naïve patients with exudative AMD. The
FUSION regimen consists of three phases: 1) a loading phase of two or three injections, depending on presence or absence of
choroidal neovascularization activity at first follow-up, 2) administration of one injection on disappearance of exudation,
and 3) subsequent administration of two separate injections at intervals 2 months apart, and then an injection every 3 months.
Endpoints included visual acuity, presence of fluid, adverse events and number of injections administered.
The authors included 17 eyes of 17 Caucasian patients. Mean patient age was 76 years, and 15 patients were female. Mean baseline
visual acuity was 67.5 letters (median 67), with Snellen equivalent 20/50++, ranged between 45 (20/125) and 83 (20/20−−). They noted
that at 3 months, mean change in best-corrected visual acuity (BCVA) was +2.3 letters (median +9) compared with baseline
(p = 0.3). They also found that at 6 months, mean change in BCVA was +4.2 letters (median +9) compared with baseline
(p = 0.02). At 12 months, one patient had discontinued the study. Mean change in BCVA was 5.6 (median +10) compared with baseline
(p = 0.04). No patient lost ≥15 letters, and 14 patients (87.5%) lost <5 letters. The mean number of injections was
6.9. One patient experienced a retinal pigment epithelium tear; no other complications were observed.
The FUSION regimen for ranibizumab has the potential to maintain visual gains achieved during the loading phase, as reported in
studies with monthly injections, even in eyes with a relatively good visual acuity at baseline. These 12-month results warrant
validation in a larger, randomized controlled trial.
Source: Monés J, Biarnés M, Trindade F, Casaroli-Marano R. FUSION regimen: ranibizumab in
treatment-naïve patients with exudative age-related macular degeneration and relatively good baseline visual acuity.
Graefes Arch Clin Exp Ophthalmol. 2012; Apr 15; [Epub ahead of print]. DOI: 10.1007/s00417-012-2009-5.
Targeting Exudative AMD with Ranibizumab Combined with Proton Beam Irradiation
To investigate the safety and tolerability of ranibizumab combined with proton beam irradiation in treating exudative
age-related macular degeneration (AMD), six eyes (6 subjects) with exudative AMD (4 newly diagnosed; 2 previous treated with
ranibizumab) were treated with 4 monthly ranibizumab and 24 GyE proton beam irradiation (2 fractions, 24 hours apart) and seen
monthly thereafter and retreated with ranibizumab for decrease in best-corrected visual acuity (BCVA) of ≥2 lines, new
macular hemorrhage or fluid noted on optical coherence tomography (OCT).
Follow-up ranged from 12 months to 36 months (mean, 28 months) and baseline BCVA ranged from 20/40 to 20/250. It was reported that
final BCVA ranged from 20/25 to 20/400 and no radiation retinopathy was noted in any eye. Calculated radiation distribution dose
curves indicate that ≤10% of retina received ≥90% of radiation dose in all eyes. Two subjects lost ≥3 lines of BCVA
during follow-up, 1 subject in both eyes from enlarging geographic atrophy and the other from worsening fibrovascular pigment
epithelial detachment, which was refractory to multiple ranibizumab treatments before enrollment. Among 4 eyes with newly
diagnosed exudative AMD, 3 had no fluid on OCT at month 12 without further treatment.
No safety concerns were noted after 3 years in eyes with exudative AMD treated with ranibizumab combined with proton beam irradiation
in this small pilot study. A larger randomized prospective study is under way to further evaluate this combination therapy.
Source: Park SS, Daftari I, Phillips T, Morse LS. Three-year follow-up of ranibizumab combined with proton beam irradiation
as treatment for exudative age-related macular degeneration. Retina. 2012;32(5):956–966.
Treatment Success of VEGF Polymorphisms in Patients with Wet AMD
Along with environmental risk factors such as smoking, hypertension and atherosclerosis, genetic susceptibility is a
primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial
growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for
the progression of exudative AMD. In this prospective cohort study, researchers in Austria tested the hypothesis that VEGF
gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD.
They included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally
administered bevacizumab in this trial. All patients were aged >50 years and had angiographically verified exudative AMD.
The researchers collected blood from the finger pad on blood cards for genotyping for the VEGF polymorphisms rs1413711,
rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, they reassessed visual acuity and
performed an ophthalmic examination. They also analyzed visual acuity outcome, number of retreatments and overall time of treatment
in dependence of the VEGF polymorphisms. Main outcome measures were mean change in visual acuity at the end of the treatment period.
According to the researchers, the included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment
period of 42 to 1182 days. In univariate analysis, only the G/G genotypes of rs3024997 and rs2010963 compared with all other
5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate
analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a
The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.
Source: Boltz A, Ruij M, Jonas JB, et al. Role of vascular endothelial growth factor polymorphisms in the treatment success
in patients with wet age-related macular degeneration. Ophthalmol. 2012;Apr 23. [Epub ahead of print].
Effects of Subretinal Coapplication of rtPA and Bevacizumab Followed by
Repeated Intravitreal and Anti-VEGF Injections for Neovascular AMD with Submacular Hemorrhage
German investigators evaluated short-term and long-term outcomes of subretinal coapplication of recombinant tissue
plasminogen activator (rtPA) and bevacizumab followed by intravitreal injections of bevacizumab or ranibizumab for
neovascular age-related macular degeneration (AMD) with submacular hemorrhage (SMH) in this retrospective, consecutive,
interventional case series of 41 eyes of 40 patients.
All patients underwent pars plana vitrectomy with subretinal coapplication of rtPA and bevacizumab and intravitreal gas
tamponade. Postoperatively, repeated intravitreal injections of bevacizumab or ranibizumab were applied following a flexible,
predominantly visual acuity-driven re-treatment regimen.
The investigators reported that mean diameter of SMH was 4.5 disc diameters (range 1.5–12) and that complete displacement of
SMH was achieved in 35 of 41 eyes. They also noted that large and prominent SMH extending beyond the vascular arcades were
completely displaced in six of eight eyes and that SMH recurred in eight eyes after a mean of 9.1 months (2–19). The
study investigators applied a mean of 4.5 (2–9) intravitreal anti-vascular endothelial growth factor injections during
12 months postoperatively. Short-term (3 months, n=41), mean best-corrected logMAR visual acuity (BCVA) improved significantly from
the preoperative value 1.7 (3.0–0.5) to 0.8 (1.6–0.2). Furthermore, 12 eyes had reading ability (≥logMAR 0.4) and 29 eyes
had gained ambulatory visual acuity (≥logMAR 1.6). Long-term (mean 17 months (12–32), n=26) BCVA was 0.9 (1.6–0.1).
Compared with short-term, BCVA had decreased in 12 of 26 eyes.
The operation effectively displaces small and large SMHs, the investigators concluded. In the long-term, a predominantly
visual acuity-driven re-treatment regimen puts the initial functional improvement at risk. More sensitive re-treatment parameters
may help to improve long-term functional outcome.
Source: Treumer F, Roider J, Hillenkamp J. Long-term outcome of subretinal coapplication of rtPA and bevacizumab followed
by repeated intravitreal anti-VEGF injections for neovascular AMD with submacular haemorrhage. Br J Ophthalmol.
Comparison of Combination Therapy with Low-Dose Transpupillary Thermotherapy
and Intravitreal Ranibizumab for Neovascular AMD
Scientists in Sweden sought to compare the effect of combined low-dose transpupillary thermotherapy (TTT) and intravitreal ranibizumab
with sham TTT and intravitreal ranibizumab in patients with neovascular age-related macular degeneration (AMD) in the following
24-month, double-masked, randomized, active-controlled clinical trial.
They randomly assigned 100 patients with primary neovascular AMD (1:1) to receive intravitreal ranibizumab and sham TTT or
intravitreal ranibizumab and low-dose TTT. After an initial loading phase of ranibizumab, they assigned patients to receive
quarterly low-dose TTT (136 mW/mm) or sham TTT for 24 months. The scientists allowed retreatment with ranibizumab in both treatment
groups using a variable dosing regimen. The primary endpoint was the number of intravitreal injections with ranibizumab.
Secondary endpoints included change in best-corrected visual acuity (BCVA), central retinal thickness (CRT) and lesion area.
In the per protocol (PP) population (78 patients), the mean number of ranibizumab injections was 8.0 in the sham TTT group versus
6.3 in the TTT group (p<0.05). The mean number of injections between 0–12 months and 13–24 months was 4.8 versus
4.6 (p<0.05) and 3.2 versus 1.7 (p<0.01) in the sham TTT and TTT groups, respectively. There was no
statistically significant difference in BCVA (+4.0 vs +0.9 ETDRS letters), CRT (–49.9% vs –36.4%) or lesion area
(–0.3% vs –10.6%) between the treatment groups at the final examination. The results of the intent-to-treat
population (92 patients) were similar to the PP population.
In conclusion, treatment with low-dose TTT significantly reduced the number or intravitreal injections of ranibizumab over 24 months.
The results suggest that low-dose TTT can serve as an adjuvant in combination with intravitreal ranibizumab for neovascular AMD.
Source: Söderberg AC, Algvere PV, Hengstler J, et al. Combination therapy with low-dose transpupillary thermotherapy
and intravitreal ranibizumab for neovascular age-related macular degeneration: a 24-month prospective randomised clinical
study. Br J Ophthalmol. 2012;96(5):714–18.
Rotation of the Choroid as Surgical Treatment for AMD
In the following study, the researchers sought to examine the feasibility of rotating choriocapillaris, Bruch's membrane (BM)
and retinal pigment epithelium (RPE) through 180° on a vascular pedicle and to assess revascularization and tissue
preservation postoperatively. Such an approach could be used in the treatment of age-related macular degeneration (AMD), where
there is focal disease at the macula with healthy tissues located peripherally.
Successful surgery was performed in six rhesus macaque monkeys, which have a very similar choroidal blood supply to humans. After
inducing a retinal detachment, the researchers used the recurrent branch of the long posterior ciliary artery as a pedicle around
which they rotated a graft stretching to the temporal equator. They reattached the retina over the rotated graft and followed up
on eyes for up to 6 months with repeated angiography and optical coherence tomography (OCT). Additionally, they assessed morphology
of retinal cells and BM by immunohistochemistry and electron microscopy.
The study researchers noted that revascularization of the choroid was limited, with reestablishment of drainage to the vortex veins
seen in only one case. There was a secondary loss of the RPE and outer retina evident on histological analysis three months after
surgery. The underlying BM however remained intact.
They concluded that pedicled choroidal rotation surgery is technically feasible in vivo with intraoperative control of bleeding.
However, lack of graft revascularization with the technique in its current form leads to neuroretinal and RPE tissue loss, and
graft shrinkage. We found no evidence that rotational grafts are likely to improve the outcomes presently achieved with free
Source: Lee E, Singh MS, Jones HE, et al. Assessment of 180° rotation of the choroid as a novel surgical
treatment for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2012;53(6):2523–2532.
Treatment of PCV with Reduced-Fluence PDT Combined with Intravitreal Bevacizumab
This prospective, noncomparative, interventional case series evaluated the efficacy and safety of reduced-fluence photodynamic
therapy (PDT) combined with bevacizumab for polypoidal choroidal vasculopathy (PCV).
Sixteen treatment-naïve patients with polypoidal choroidal vasculopathy were treated with reduced-fluence PDT combined
with bevacizumab and all patients were followed up monthly for 12 months with measurements of best-corrected visual acuity (BCVA)
and central foveal thickness by optical coherence tomography (OCT). Additionally, indocyanine green angiography and fluorescein
angiography were performed every 3 months and patients were re-treated with reduced-fluence PDT combined with bevacizumab or with
sole injection of bevacizumab when indicated.
The mean logMAR BCVA showed significant improvement from 0.76 at baseline to 0.46 at 12 months (p = .002). At 12 months, the
BCVA improved in 9 eyes (56.3%) by 3 lines or more, was stable in 6 eyes (37.5%), and decreased in 1 eye (6.3%) because
of recurrence of polyps. It was reported that during the study period, 3 patients (18.8%) had recurrence of polyps and 2 patients
(12.5%) had persistent polyps. It was also observed that mean episodes of reduced-fluence PDT and mean injections of
intravitreal bevacizumab over 12 months were 1.44 and 2.44, respectively. Although 3 patients had mild choroidal nonperfusion—1
eye after 1 session of PDT and 2 eyes after 2 sessions—no severe complications, including endophthalmitis, uveitis, or
subretinal hemorrhage, developed.
Reduced-fluence PDT combined with bevacizumab for PCV seemed to be effective for improving vision and reducing complications.
Further study to optimize the light dose of PDT in combination therapy is needed in order to achieve better treatment outcomes for PCV.
Source: Sagong M, Lim S, Chang W. Reduced-fluence photodynamic therapy combined with intravitreal bevacizumab for
polypoidal choroidal vasculopathy. Am J Ophthalmol. 2012;153(5):873–882.
Prognostic Factors for Visual Outcome Following Injection of Intravitreal Anti-VEGF for
Naïve Myopic CNV
The aim of this study was to evaluate the prognostic factors of visual outcome after intravitreal anti-vascular endothelial growth
factor (anti-VEGF) injection in patients with myopic choroidal neovascularization (CNV).
A total of 40 eyes of 40 consecutive patients with myopic CNV who had received intravitreal ranibizumab or bevacizumab injections
were retrospectively reviewed. Baseline visual acuity, presence of lacquer crack, dark rim, peripapillary choroidal atrophy size,
and location of myopic CNV were evaluated using fluorescein angiography and indocyanine green angiography.
It was reported that the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 12 months
following treatment was 0.23 ± 0.28, and there was a significant improvement compared with the baseline BCVA (p = 0.001).
After multiple linear regression analysis, baseline BCVA, presence of lacquer crack extending the fovea, and peripapillary
choroidal atrophy size were the factors that significantly correlated with BCVA at 12 months (p = 0.001, p = 0.04, and
p = 0.04). For mean change in BCVA over 12 months, there were also significant correlations with baseline BCVA, lacquer
crack extension to the fovea, and peripapillary choroidal atrophy size (p = 0.001, p= 0.03, and p = 0.03).
The mean number of anti–vascular endothelial growth factor injections was 2.8 ± 2.0 over 12 months. Furthermore, complete
resolution of myopic CNV was noted in 22 eyes (55.0%) after initial first injection, and no additional treatment was required
in 12 eyes (30%).
To conclude, better baseline BCVA, lacquer crack extension to the fovea, and peripapillary atrophy were negative prognostic factors
of visual acuity improvement, and there was quite a promising result of anti-VEGF treatment in patients with myopic CNV.
Source: Yoon JU, Kim YM, Lee SJ, et al. Prognostic factors for visual outcome after intravitreal anti-VEGF injection for
naïve myopic choroidal neovascularization. Retina. 2012;32(5):949–955.
SD-OCT in Anti-VEGF Treatment of Myopic CNV
Investigators in Italy evaluated changes in macular morphology due to myopic choroidal neovascularization (CNV) using
spectral-domain optical coherence tomography (SD-OCT).
In all, 22 eyes with recent-onset untreated CNV underwent 1 intravitreal injection of anti-vascular endothelial growth factor
(anti-VEGF), followed by a pro-re-nata regimen. The investigators performed SD-OCT at baseline (before first administration
of anti-VEGF treatment) and month 1, and 2; macular morphologic changes and outer retina characteristics (SD-OCT findings) associated
with CNV activity were evaluated. They calculated sensitivity and specificity for SD-OCT findings using fluorescein angiography (FA)
as standard reference.
They reported that mean central retinal thickness (CRT) showed no significant reduction from baseline (284 ± 98 µm) to
month 1 (257 ± 74 µm) and month 2 (263 ± 72 µm). The investigators noted that a hyper-reflective lesion with
fuzzy borders (fuzzy area), and ‘absent or altered’ IS/OS junction were the only SD-OCT findings associated with CNV
activity (p<0.0001). Both these SD-OCT findings showed good sensitivity and specificity (95.1 and 96.0%
(95% CI: 0.87–0.89), respectively, for the fuzzy area; 87.9 and 66.7% (95% CI: 0.65–0.87), respectively,
for ‘absent or altered’ IS/OS junction) when compared with FA leakage (standard reference).
Outer retina characteristics (i.e., hyper-reflective lesion with fuzzy borders, and “absent or altered” IS/OS junction)
appear more meaningful than CRT in the evaluation of myopic CNV activity. These SD-OCT findings show overall good sensitivity
and specificity when compared with FA leakage (standard reference), and could be considered as an alternative diagnostic tool to
FA for myopic CNV monitoring.
Source: Introini U, Casalino G, Querques G, et al. Spectral-domain OCT in anti-VEGF treatment of myopic
choroidal neovascularization. Eye. 2012; Apr 27. [Epub ahead of print]. DOI: 10.1038/eye.2012.75.
Assessment of Retinal Sensitivity Following Resolution of the Macular Edema
Associated with RVO
The authors of the following Japanese study examined the correlation of retinal sensitivity with both morphologic changes in
the macula and status of retinal capillary perfusion, after resolution of the macular edema associated with retinal vein
They examined retinal sensitivity in the macular area with the Micro Perimeter 1 in 24 eyes after resolution of the macular
edema associated with RVO. Using spectral-domain optical coherence tomography, they examined 6 mm × 6 mm areas of macula with 256
sequential horizontal scans. They also evaluated the condition of the photoreceptor layer depending upon detection of the junctions
between inner and outer segments of the photoreceptors (IS/OS). Additionally, they performed fluorescein angiography in 19 eyes.
They authors observed that mean retinal sensitivity on the affected side of the retina was significantly decreased
(p – 0.001). They also noted that on the affected side, the mean retinal sensitivity within the area of deteriorated IS/OS
was significantly less (3.8 ± 4.8 dB) than that within areas with complete IS/OS (10.1 ± 6.4 dB, p – 0.001).
Mean retinal sensitivity within nonperfused areas was extremely low (0.3 ± 1.3 dB), compared with that in perfused retina
(10.9 ± 5.9 dB, p – 0.001). Moreover, in eyes with a broken foveal capillary ring (FCR), the marked decline in
retinal sensitivity was seen within the area where the FCR was broken; this was not seen in eyes with an intact FCR.
In conclusion, retinal function was decreased markedly in areas with a damaged photoreceptor layer due to RVO, and was lethally
decreased within nonperfused areas. Due to the various limitations of the current study, including implementation of
fluorescein angiography in limited number of eyes, wide range of follow-up, and heterogeneity of pretreatments, further prospective
studies are necessary to confirm the current findings.
Source: Ota M, Tsujikawa A, Ojima Y, et al. Retinal sensitivity after resolution of the macular edema associated with
retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2012;250(5):635–644.
Relationship Between Outer Retinal Layer Morphology with VA in Patients with RVO
To assess associations between visual acuity (VA) and the status of the photoreceptor inner segment–outer segment
(IS–OS) junction in a subset of patients in the Standard Care vs COrticosteroid for REtinal Vein Occlusion (SCORE)
Study, researchers evaluated high-resolution time domain optical coherence tomography (OCT) scans of study eyes from
a single site participating in the SCORE Study.
They also evaluated the integrity of the IS–OS junction in the central subfield using a three-step scale: absent, abnormal
or normal. The researchers also investigated associations of the IS–OS status with ETDRS VA letter score and center point
They evaluated baseline OCTs of 42 eyes and found that the IS–OS junction was absent in 30 (71%) and abnormal in 12 (29%).
They also noted that at month 12, the IS–OS junction was absent in 18 (43%), abnormal in 12 (28%), and normal in 12
(28%) eyes. According to the researchers, at baseline, IS–OS status was significantly associated with CPT, but not with VA.
They reported that at month 12, IS–OS status was significantly associated with CPT and VA, that is, absent or abnormal
IS–OS was associated with increased CPT and worse VA. Change in IS–OS status was not associated with change in CPT
(p=0.8). Worsening of IS–OS status was associated with loss of VA and improvement in IS–OS status to normal
was associated with gain in VA (p=0.03).
In this data set with long-term follow-up of OCTs as part of the SCORE Study, there is a correlation between change in IS–OS
status and VA. This supports further evaluation of outer retinal morphology in larger data sets.
Source: Domalpally A, Peng Q, Danis R, et al.; the SCORE Study Research Group. Association of outer retinal layer
morphology with visual acuity in patients with retinal vein occlusion: SCORE Study Report 13. Eye. 2012;Apr 27.
[Epub ahead of print]. DOI: 10.1038/eye.2012.59.
Inner Retinal Visual Dysfunction and Non-Proliferative DR
The authors of the following study assessed visual function in 18 adults with normal retinal health, 23 adults with diabetes
and 35 adults with NPDR and normal visual acuity to determine the effect of diabetes on inner and outer retinal function in
persons with diabetes and no clinically detectable retinopathy or with non-proliferative diabetic retinopathy (NPDR).
They used contrast sensitivity and frequency doubling technology (FDT) sensitivity to assess ganglion cell function and they
measured acuity, dark adaptation, light-adapted visual sensitivity and dark-adapted visual sensitivity to evaluate cone and
rod photoreceptor visual function. The study authors also determined the presence and severity of diabetic retinopathy by grading
7-field stereoscopic fundus photographs using the Early Treatment Diabetic Retinopathy Study grading system.
According to them, participants with NPDR exhibited impairment of all measured visual functions in comparison with the normal
participants. They also noted that inner retinal function measured by FDT perimetry was the most impaired visual function for
patients with NPDR, with 83% of patients exhibiting clinically significant impairment. Moreover, rod photoreceptor function was
grossly impaired, with almost half of the patients with NPDR exhibiting significantly impaired dark-adapted visual sensitivity.
To conclude, both inner retinal and outer retinal functions exhibited impairment related to NPDR. FDT perimetry and other visual
function tests reveal an expanded range of diabetes induced retinal damage even in patients with good visual acuity.
Source: Jackson GR, Scott IU, Quillen DA, et al. Inner retinal visual dysfunction is a sensitive marker of
non-proliferative diabetic retinopathy. Br J Ophthalmol. 2012;96(5):699–703.