Volume 8, Number 4
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.
VEGF Trap-Eye for Macular Edema Secondary to CRVO
In this multicenter, randomized, prospective, controlled trial, investigators assessed the efficacy and safety
of intravitreal vascular endothelial growth factor (VEGF) Trap-Eye in eyes with macular edema secondary to
central retinal vein occlusion (CRVO).
They randomized 189 eyes 3:2 to receive VEGF Trap-Eye 2 mg or sham injection monthly for 6 months. The proportion of
eyes with a ≥15–letter gain or more in best-corrected visual acuity (BCVA) at week 24 (primary efficacy end
point), mean changes in BCVA and central retinal thickness (CRT), and proportion of eyes progressing to neovascularization
of the anterior segment, optic disc, or elsewhere in the retina were the main outcome measures.
At week 24, the investigators observed that 56.1% of VEGF Trap-Eye treated eyes gained 15 letters or more from
baseline versus 12.3% of sham-treated eyes (p<0.001). They found that the VEGF Trap-Eye treated eyes
gained a mean of 17.3 letters versus sham-treated eyes, which lost 4.0 letters (p<0.001). They also noted
that central retinal thickness decreased by 457.2 µm in eyes treated with VEGF Trap-Eye versus 144.8 µm
in sham-treated eyes (p<0.001), and progression to any neovascularization occurred in 0 and 5 (6.8%) of
eyes treated with VEGF Trap-Eye and sham-treated eyes, respectively (p = 0.006). According to the
investigators, conjunctival hemorrhage, reduced visual acuity and eye pain were the most common adverse events (AEs).
Serious ocular AEs were reported by 3.5% of VEGF Trap-Eye patients and 13.5% of sham patients. Incidences
of nonocular serious AEs generally were well balanced between both groups.
At 24 weeks, monthly intravitreal injection of VEGF Trap-Eye 2 mg in eyes with macular edema resulting from CRVO
improved visual acuity and CRT, eliminated progression resulting from neovascularization, and was associated with a
low rate of ocular AEs related to treatment.
Source: Boyer D, Heier J, Brown DM, et al. Vascular endothelial growth factor Trap-Eye for macular
edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS Study.
Ophthalmol. 2012; March 22 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.01.042.
Bevacizumab Used in the Treatment of Macular Edema in CRVO
The authors of this Swedish prospective, randomized, sham injection-controlled, double-masked clinical
trial evaluated the efficacy of intraocular injections with bevacizumab in patients with macular edema (ME)
secondary to central retinal vein occlusion (CRVO).
At baseline, they randomized 60 patients with ME secondary to CRVO 1:1 to receive intraocular injections of bevacizumab
or sham injections every 6 weeks for 6 months. The primary outcome measure was the proportion of patients gaining at least
15 letters at 6 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity
(BCVA), foveal thickness and neovascular glaucoma.
According to the authors, at the end of follow-up, 18 of 30 patients (60.0%) in the study group had gained ≥15
letters compared with 6 of 30 patients (20.0%) in the control group (p=0.003). They noted that the BCVA
improved by 14.1 letters at 24 weeks compared with a decrease of 2.0 letters in the control group (p<0.003)
and that the mean decrease in central retinal thickness (CRT) was significantly greater in the study group (426 µm)
than in the control group (102 µm) at all time points up to week 24 (p<0.001). They found no residual
edema, defined as CRT <300 µm at 24 weeks, in 26 of 30 patients (86.7%) in the treatment group compared with
6 of 30 patients (20%) in the control group (p<0.001). The authors also reported that in the sham group,
5 of 30 patients (16.7%) had developed iris rubeosis at week 24. No patients in the study group had rubeosis at
week 24 (p=0.052). There were no events of endophthalmitis, retinal tear, or retinal detachment during the
24-week treatment period. No serious non-ocular adverse events were reported.
In conclusion, intraocular injections of bevacizumab given every 6 weeks for 6 months improve visual acuity (VA)
and reduce ME significantly compared with sham.
Source: Epstein DL, Algvere PV, von Wendt G, et al. Bevacizumab for macular edema in central retinal
vein occlusion: a prospective, randomized, double-masked clinical study. Ophthalmol. 2012; Mar. 19 [Epub
ahead of print]. DOI: 10.1016/j.ophtha.2012.01.022.
Evaluation of Ranibizumab Treatment for Macular Edema Due to RVOs
To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema
after retinal vein occlusion (RVO), researchers conducted an open-label extension trial of the 12-month Ranibizumab
for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO)
and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials.
They included 304 patients who completed BRAVO and 304 patients who completed CRUISE and saw patients at least every
3 months and gave them an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria.
Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes
included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic
Retinopathy Study protocol and central foveal thickness.
According to the researchers, in patients who completed month 12, the mean number of injections (excluding month
12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5
(central RVO), respectively. They also noted that the incidence of study eye ocular serious AEs (SAEs) and SAEs
potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to
9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch
RVO patients was 0.9 (sham/0.5 mg), –2.3 (0.3/0.5 mg), and –0.7 (0.5 mg), respectively. Additionally, the
mean change from baseline BCVA at month 12 in central RVO patients was –4.2 (sham/0.5 mg), –5.2 (0.3/0.5 mg),
and –4.1 (0.5 mg), respectively.
No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment
were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year
of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients
remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up
and injections should be individualized and, on average, central RVO patients may require more frequent follow-up
than every 3 months.
Source: Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for macular edema due to retinal vein
occlusions: long-term follow-up in the HORIZON trial. Ophthalmol. 2012;199(4):802–809.
Efficacy and Safety of Verteporfin Plus Ranibizumab for CNV in AMD
In the following prospective, multicenter, double-masked, randomized, active-controlled trial, investigators
compared the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal
ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration (AMD).
They included 255 patients with all types of active subfoveal choroidal neovascularization (CNV) and randomized them 1:1
to as-needed (pro re nata; PRN) combination (standard-fluence verteporfin 6 mg/m² PDT and ranibizumab 0.5 mg)
or PRN ranibizumab monotherapy (sham infusion [5% dextrose] PDT and ranibizumab 0.5 mg). They also administered
3 consecutive monthly injections to patients, followed by PRN retreatments based on protocol-specific retreatment
criteria. Mean outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline to month 12,
and the proportion of patients with treatment-free interval ≥3 months at any timepoint after month 2.
The study investigators reported that the mean change in BCVA at month 12 was +2.5 and +4.4 letters in the combination
and monotherapy groups, respectively (p = 0.0048; difference: –1.9 letters [95% confidence
interval, –5.76 to 1.86], for having achieved noninferiority with a margin of 7 letters). They also noted that
the proportion of patients with a treatment-free interval of ≥3 months at any timepoint after month 2 was high,
but did not show a clinically relevant difference between the treatment groups. Secondary efficacy endpoints included
the mean number of ranibizumab retreatments after month 2 (1.9 and 2.2 with combination and monotherapy,
respectively [p = 0.1373]). The time to first ranibizumab retreatment after month 2 was delayed by 34 days
(about 1 monthly visit) with combination (month 6) versus monotherapy (month 5), the investigators observed. At month
12, mean ± standard error central retinal thickness decreased by 115.3 ± 9.04 µm in the combination group
and 107.7 ± 11.02 µm in the monotherapy group. The mean number of verteporfin/sham PDT treatments was comparable
in the 2 groups (combination, 1.7; monotherapy, 1.9). The safety profiles of the 2 groups were comparable, with a
low incidence of ocular serious adverse events.
The combination PRN treatment regimen with verteporfin PDT and ranibizumab was effective in achieving BCVA gain
comparable with ranibizumab monotherapy; however, the study did not show benefits with respect to reducing the number
of ranibizumab retreatment over 12 months. The combination therapy was well tolerated.
Source: Larsen M, Schmidt-Erfurth U, Lanzetta P, et al; MONT BLANC Study Group. Verteporfin plus ranibizumab
for choroidal neovascularization in age-related macular degeneration: Twelve-month MONT BLANC study
results. Ophthalmol. 2012;Mar. 19 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.02.002.
A 12-Month Review of Verteporfin Plus Ranibizumab for CNV in AMD
To demonstrate noninferiority of ranibizumab in combination with verteporfin photodynamic therapy (PDT)
versus ranibizumab monotherapy in patients with subfoveal choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD) 321 patients were randomized to receive either ranibizumab 0.5 mg monotherapy
(n = 112), standard fluence (SF) verteporfin PDT combination therapy (n = 104) or reduced fluence (RF) verteporfin
PDT combination therapy (n = 105) in this prospective, multicenter, double-masked, randomized, phase IIIb
Ranibizumab was administered monthly in the monotherapy group and in both combination therapy groups, ranibizumab
was initiated with 3 consecutive monthly injections, followed by retreatment as needed (pro re nata) with
monthly monitoring. All patients were evaluated monthly for 12 months. Main outcome measures were the mean change
in best-corrected visual acuity (BCVA) from baseline at month 12 and proportion of patients randomized to either
combination therapy with a ranibizumab treatment-free interval of 3 months or longer.
A total of 268 patients (89.1%) completed the 12-month study. It was reported that mean BCVA change at month 12
was +5.3 and +4.4 letters with verteporfin SF (n = 103) or verteporfin RF (n = 105) plus ranibizumab, respectively,
compared with +8.1 letters with ranibizumab monotherapy (n = 110; adjusted 97.5% confidence interval [CI], (–7.90
to infinity); p = 0.0666; and 97.5% CI, (–8.51 to infinity); p = 0.1178; for combination regimens
vs. monotherapy, respectively). Noninferiority of either combination regimen to monthly ranibizumab monotherapy was
not demonstrated (primary end point). It was noted that a ranibizumab treatment-free interval of 3 months or longer was achieved in 92.6% and 83.5% of the patients randomized to verteporfin SF or verteporfin RF groups, respectively,
with a mean of 5.1 and 5.7 ranibizumab injections, respectively, and patients in the ranibizumab monotherapy arm
received 10.5 injections. At month 12, mean central retinal thickness decreased by 151.7 µm and 140.9 µm
for the verteporfin SF and RF groups, respectively, and by 172.2 µm with ranibizumab monotherapy. Safety
and tolerability of all 3 regimens were similar to and consistent with previous studies in neovascular AMD. The number
of ocular serious adverse events was low and occurred largely as single cases.
Ranibizumab monotherapy or combined with verteporfin PDT improved BCVA at month 12; however, noninferiority
(7-letter margin) of combination regimens to ranibizumab monotherapy was not demonstrated. Verteporfin RF did not
confer clinical benefits over verteporfin SF. All treatments were well tolerated.
Source: Kaiser PK, Boyer DS, Cruess AF, et al.; DENALI Study Group. Verteporfin plus ranibizumab for
choroidal neovascularization in age-related macular degeneration: twelve-month results of the DENALI
Study. Ophthalmol. 2012;March 23 [Epub ahead of print]. DOI: 10.1016/j.ophtha.2012.02.003.
180-Degree Rotation of the Choroid as a Novel Surgical Treatment for AMD
The objective of this U.K. study was to examine the feasibility of rotating choriocapillaris, Bruch's membrane (BM)
and retinal pigment epithelium (RPE) through 180 degrees 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.
Surgery was performed in six rhesus macaque monkeys, which have a similar choroidal blood supply to humans. After
inducing a retinal detachment, the recurrent branch of the long posterior ciliary artery was used as a pedicle around
which a graft stretching to the temporal equator was rotated. Retina was reattached over the rotated graft and eyes
were followed up for up to 6 months with repeated angiography and optical coherence tomography (OCT). The morphology
of retinal cells and BM were assessed by immunohistochemistry and electron microscopy.
It was reported that revascularization of the choroid was limited, with reestablishment of drainage to the vortex veins
seen in only one case. Furthermore, there was a secondary loss of the RPE and outer retina evident on histological
analysis three months after surgery; however, the underlying BM remained intact.
To conclude, pedicled choroidal rotation surgery is technically feasible but re-establishing blood flow remains
challenging, despite good apposition of transplanted and host tissues. The ability to rotate autologous BM from the
equator to the macula, may provide a viable substrate to support submacular RPE replacement in combination with other
cell therapy approaches.
Source: Lee E, Singh MS, Jones HE, et al. Assessment of 180 degree rotationof the choroid as a novel
surgical treatment for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2012; Mar. 16 [Epub
ahead of print]. DOI: 10.1167/iovs.11-8674.
Hemorrhagic Complications Following Intravitreal Ranibizumab Injection for PCV
The authors of this Korean retrospective case series evaluated clinical features and risk factors for
hemorrhagic complications in eyes with polypoidal choroidal vasculopathy (PCV) after intravitreal ranibizumab injection.
They conducted the study as a retrospective chart review of 54 patients with PCV who had received intravitreal
ranibizumab 0.5 mg and based their analysis of 2 groups on mean PCV lesion size: <15mm² (n = 24);
or ≥15mm² (n = 32). They also documented and analyzed the occurrence of fresh postoperative subretinal
hemorrhage, best-corrected visual acuity, systemic disease and medication history.
The study authors reported that the mean injection number was 3.3 ± 0.7 (range, 1 to 6), with a mean follow-up
of 7.4 ± 2.8 months (range, 4 to 14 months). During the follow-up period, they observed postoperative
subretinal hemorrhage in 5 (8.9%) of 56 eyes. They also noted that the occurrence of postoperative hemorrhage
was significantly increased in the group with large PCV size (p = 0.01). Pars plana vitrectomy was performed
for postoperative bleeding that resulted in vitreous hemorrhage in 1 eye (1.8%). Moreover, various systemic
diseases and medication with an anticoagulant had no correlation with occurrence of hemorrhagic complications.
Subretinal hemorrhage after ranibizumab injection can occur in patients with PCV, the authors concluded. When
considering ranibizumab injection for treatment of a large PCV lesion, the risk for hemorrhagic complications should
Source: Cho JH, Lee DW, Cho SW, et al. Hemorrhagic complications after intravitreal ranibizumab injection
for polypoidal choroidal vasculopathy. Can J Ophthalmol. 2012; Mar. 15 [Epub ahead of print].
Verteporfin PDT in Combination with Ranibizumab or Alone Versus
Ranibizumab Monotherapy in Patients with Symptomatic Macular PCV
Researchers assessed the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone
versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). They
determined that verteporfin PDT combined with ranibizumab 0.5 mg or alone was superior to ranibizumab monotherapy
in achieving complete regression of polyps in this 6-month study in patients with symptomatic macular PCV.
In this multicenter, double-masked, primarily indocyanine green angiography-guided trial, the study researchers randomized
61 Asian patients to verteporfin PDT (standard fluence), ranibizumab 0.5 mg, or the combination. They then
administered verteporfin PDT/placebo to patients and initiated three consecutive monthly ranibizumab/sham
injections starting Day 1, and re-treated (Months 3–5) as per predefined criteria. The primary endpoint was
the proportion of patients with indocyanine green angiography-assessed complete regression of polyps at Month 6.
Secondary endpoints included mean change in best-corrected visual acuity at Month 6 and safety.
At Month 6, the researchers found that verteporfin combined with ranibizumab or alone was superior to ranibizumab
monotherapy in achieving complete polyp regression (77.8% and 71.4% vs. 28.6%; p<0.01); mean
change ± standard deviation in best-corrected visual acuity (letters) was 10.9 ± 10.9 (verteporfin
PDT + ranibizumab), 7.5 ± 10.6 (verteporfin PDT), and 9.2 ± 12.4 (ranibizumab). There were no new safety
findings with either drug used alone or in combination. All treatments were well tolerated over 6 months.
Source: Koh A, Lee WK, Chen LJ, et al. EVEREST study: efficacy and safety of verteporfin photodyanmic
therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with
symptomatic macular polypoidal choroidal vasculopathy. Retina. 2012; Mar. 15 [Epub ahead of print].
Efficacy and Safety of Ranibizumab in the Treatment of DME
The authors of two parallel, methodologically identical, phase III, multicenter, double-masked, sham
injection-controlled, randomized studies sought to evaluate the efficacy and safety of intravitreal ranibizumab
in diabetic macular edema (DME) patients.
Participants were adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40–20/320
Snellen equivalent) and central subfield thickness ≥275 µm on time-domain optical coherence tomography
(OCT). Intervention was monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was
available per-protocol-specified criteria. The main outcome measure was the proportion of patients gaining ≥15 letters
in BCVA from baseline at 24 months.
In RISE, the authors randomized 377 patients (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). They reported that at
24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (p<0.0001; difference
vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8–34.8)
and 39.2% of 0.5-mg ranibizumab patients (p<0.001; adjusted difference, 20.9%; 95% CI,
10.7–31.1). In RIDE, the authors randomized 382 patients (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). They observed
that significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus
33.6% of 0.3-mg patients (p<0.0001; adjusted difference, 20.8%; 95% CI, 11.4–30.2) and
45.7% of 0.5-mg ranibizumab patients (p<0.0001; adjusted difference, 33.3%; 95% CI,
23.8–42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen
and more likely to improve in ranibizumab-treated patients. The study authors also noted that ranibizumab-treated
patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months
in the sham groups vs 0.3–0.8 in ranibizumab groups). They also found that ocular safety was consistent with
prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular
or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects
from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to
8.8% of ranibizumab patients.
In conclusion, ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and
improved macular edema in patients with DME, with low rates of ocular and nonocular harm.
Source: Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from
2 phase III randomized trials: RISE and RIDE. Ophthalmol. 2012;119(4):789–801.
A Look at Early Neurodegeneration in the Retina of Type 2 Diabetic Patients
To determine whether diabetes type 2 causes thinning of retinal layers as a sign of neurodegeneration and to
investigate the possible relationship between this thinning and duration of diabetes mellitus, diabetic retinopathy
(DR) status, age, gender and glycemic control (HbA1c), scientists calculated mean layer thickness for retinal
layers following automated segmentation of Spectral Domain Optical Coherence Tomography images of diabetic patients
with no or minimal DR and compared with controls. They used DR status, age, gender and HbA1c a multiple linear
regression analysis to determine the relationship between layer thickness and diabetes duration.
In the pericentral area of the macula, they found that the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL)
and inner plexiform layer (IPL) were thinner in patients with minimal DR compared to controls (respective difference
1.9µm, 95% CI 0.3–3.5µm; 5.2µm, 95% CI 1.0–9.3µm; 4.5µm, 95% CI
2.2–6.7µm). The scientists also noted that in the peripheral area of the macula, the RNFL and IPL were
thinner in patients with minimal DR compared to controls (respective difference 3.2µm, 95% CI
0.1–6.4µm; 3.3µm, 95% CI 1.2–5.4µm). Additionally, multiple linear regression analysis
showed DR status to be the only significant explanatory variable (R= 0.31, p=0.03) for this retinal thinning.
This study demonstrates thinner inner retinal layers in the macula of type 2 diabetic patients with minimal DR than
in controls. The results support the concept that early DR includes a neurodegenerative component.
Source: Dijk HW, Verbraak FD, Kok PH, et al. Early neurodegeneration in the retina of type 2 diabetic
patients. Invest Ophthalmol Vis Sci. 2012; Mar. 16 [Epub ahead of print]. DOI: 10.1167/iovs.11-8997.
Age-Related Changes in the RNFL as Imaged by SD-OCT
To investigate age-related changes of the retinal nerve fiber layer (RNFL) imaged by spectral-domain
optical coherence tomography (SD-OCT), the following prospective, cross-sectional and longitudinal studies
recruited 100 normal individuals for cross-sectional analysis. Thirty-five of these were randomly selected
for longitudinal analysis.
The circumpapillary average and quadrant RNFL thicknesses were measured by the Cirrus HD-OCT and in the longitudinal
study, participants were followed at 4-month intervals for a mean of 30 months (range, 24–41 months) for RNFL and
visual field measurements. Cross-sectional RNFL data were analyzed with multiple linear regression models with adjustment
of spherical error, optic disc area, and signal strength. Longitudinal RNFL measurements were analyzed with linear
mixed models with fixed coefficients on follow-up duration, baseline RNFL thickness, spherical error, optic disc area,
and signal strength. Factors influencing the rate of change of RNFL measurements were analyzed in the interaction terms
with “duration” in the linear mixed models. Rates of change of average and quadrant RNFL thicknesses were the main
In the cross-sectional analysis, significant negative correlations were found between age and average
(–0.33 µm/year; p = 0.011), inferior (–0.45 µm/year; p = 0.037), and temporal
(–0.31 µm/year; p = 0.046) RNFL thicknesses. In the longitudinal analysis, the mean rates of
change of average, superior, and inferior RNFL thicknesses were –0.52 (95% confidence interval [CI], –0.86
to –0.17), –1.35 (95% CI, –2.05 to –0.65) and –1.25 µm/year (95% CI, –1.78
to –0.71), respectively, after adjusting for baseline RNFL thickness, spherical error, disc area, and signal
strength. There was no detectable RNFL reduction in the nasal and temporal quadrants. The only significant factor
influencing the rates of change of RNFL measurements was the baseline RNFL thickness. A greater baseline RNFL thickness
was associated with a faster rate of change.
Progressive, age-related decline of RNFL thickness can be detected with longitudinal OCT imaging. Rate estimates
derived from trend analysis for detection of glaucomatous RNFL progression should be interpreted with reference to
the normal ranges of age-related reduction, particularly when the baseline RNFL measurement is large.
Source: Leung CK, Yu M, Weinreb RN, et al. Retinal nerve fiber layer imaging with spectral-domain
optical coherence tomography: a prospective analysis of age-related loss. Ophthalmol. 2012; 119(4):731–737.
Risk of Retinal Detachment with Oral Fluoroquinolone Use
Fluoroquinolones are commonly prescribed classes of antibiotics, yet despite numerous case reports of ocular
toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not
been performed. Investigators in the following study examined the association between the use of oral
fluoroquinolones and the risk of developing a retinal detachment.
This was a nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an
ophthalmologist between January 2000 and December 2007. The study investigators defined retinal detachment cases as
a procedure code for retinal repair surgery within 14 days of a physician service code. They selected 10 controls for
each case using risk-set sampling, matching on age and the month and year of cohort entry. The association between
retinal detachment and current, recent or past use of an oral fluoroquinolone served as the main outcome measure.
From a cohort of 989,591 patients, the investigators identified 4,384 cases of retinal detachment and 43,840 controls.
They associated current use of fluoroquinolones with a higher risk of developing a retinal detachment (3.3% of cases
vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56–5.70]). Neither recent use (0.3% of
cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45–1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89–1.19]) was associated with a retinal detachment. The absolute increase in
the risk of a retinal detachment was 4 per 10 000 person-years (number needed to harm = 2500 computed for any use
of fluoroquinolones). There was no evidence of an association between development of a retinal detachment
and β-lactam antibiotics (ARR, 0.74 [95% CI, 0.35–1.57]) or short-acting β-agonists (ARR, 0.95
[95% CI, 0.68–1.33]).
To conclude, patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared
with nonusers, although the absolute risk for this condition was small.
Source: Etminan M, Forooghian F, Brophy JM, et al. Oral fluoroquinolones and the risk of retinal
detachment. JAMA. 2012;307(13):1414–1419.