Volume 10, Number 1
January 2014

 

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.



Bioheart to Conduct Dry AMD Study
Bioheart Inc. announced that it will enroll up to 100 patients in a study...

Alimera Ships First Orders of Iluvien to U.K. National Health Service Hospitals
pSivida Corp.'s licensee Alimera Sciences has shipped initial orders of Iluvien...

And More...

Intravitreal Aflibercept Injection for Neovascular AMD

In these two randomized, double-masked, active-controlled, Phase III trials, investigators sought to determine the efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period.

Participants consisted of 2,457 patients with neovascular AMD. From baseline to week 52, they received 0.5 mg intravitreal ranibizumab every four weeks (Rq4), 2 mg aflibercept every four weeks (2q4), 0.5 mg aflibercept every four weeks (0.5q4), or 2 mg aflibercept every eight weeks (2q8) after three monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks. Main outcome measures were the proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA.

According to the investigators, proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. They observed that mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2.q.4. eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9 to 15.9] and 9.0% [95% CI, 3.0 to 15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of –0.64 [95% CI, –0.89 to –0.40] and –0.55 [95% CI, –0.79 to –0.30]; p<0.0001, post hoc analysis). Incidences of Antiplatelet Trialists' Collaboration–defined arterial thromboembolic events were similar across groups (2.4% to 3.8%) from baseline to week 96.

All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks, the investigators concluded. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of five fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing.

Source: Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1):193–201.

IOP of Eyes on Monthly Ranibizumab for AMD

To characterize preinjection intraocular pressure (IOP) in eyes receiving monthly ranibizumab versus sham or verteporfin photodynamic therapy (PDT) for age-related macular degeneration (AMD), this post hoc analysis of IOP data from two Phase III clinical trials, the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial, was conducted.

Participants consisted of all safety-evaluable patients who received one or more injections of sham or PDT or of ranibizumab and had one or more post baseline IOP measurements recorded for the study eye. Preinjection IOP measurements for study eyes (n=1,125) and fellow eyes in MARINA and ANCHOR at baseline and at each monthly visit through month 24 were analyzed. Endpoints evaluated were maximum preinjection IOP during the 24-month treatment period; any occurrence of absolute preinjection IOP of 21 mmHg or more, 25 mmHg or more or 30 mmHg or more; any occurrence of IOP increase of 6 mmHg or more, 8 mmHg or more or 10 mmHg or more from baseline; any combination of IOP increase of 6 mmHg or more or 8 mmHg or more from baseline with concurrent absolute preinjection IOP of 21 mmHg or more or 25 mmHg or more; glaucoma-related adverse events; new glaucoma medications used for 45 days or more; and glaucoma filtration or laser surgeries.

Across treatment groups, 60.1% to 70.9% of study eyes had a maximum preinjection IOP of less than 21 mmHg. Comparing ranibizumab 0.5 mg versus sham or PDT treatment, respectively: 39.9% versus 29.1% and 10.9% versus 5.1% had maximum preinjection IOPs of 21 mmHg or more or 25 mmHg or more, respectively; 44.1% versus 29.9% and 24.2% versus 13.6% had IOP increases from baseline of 6 mmHg or more or 8 mmHg or more, respectively; 26.1% versus 13.6% and 16.8% versus 9.0% had one or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 21 mmHg or more; 9.6% versus 3.7% and 7.5% versus 2.4% had one or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 25 mmHg or more. No differences were observed in fellow eyes.

In conclusion, most ranibizumab-treated eyes did not experience sustained preinjection IOP of 21 mmHg or more (more than two consecutive visits) over 24 months. When evaluating the combined IOP endpoint, more ranibizumab-treated eyes had one or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, with concurrent highest IOPs of 21 mmHg or more and 25 mmHg or more versus sham or PDT. IOP should be monitored in eyes receiving ranibizumab.

Source: Bakri SJ, Moshfeghi DM, Framcom S, et al. Intraocular pressure in eyes receiving monthly ranibizumab in 2 pivotal age-related macular degeneration clinical trials. Ophthalmology. 2014;Jan 6. [Epub ahead of print.]

Role of Posterior Vitreous Detachment on Outcome of Anti-VEGF Treatment in AMD

The aim of this study was to determine the effect of posterior vitreous detachment on the outcome of anti-vascular endothelial growth factor (anti-VEGF) injection.

A total of 61 eyes with age-related macular degeneration (AMD) that had received intravitreal bevacizumab or ranibizumab injections were retrospectively reviewed. The vitreomacular interface was evaluated, and eyes were grouped according to the presence of posterior vitreous detachment (group one, n=25) or vitreomacular adhesion (group two, n=36). All patients received three loading doses of intravitreal anti-VEGF injections at monthly intervals, and subsequently, pro re nata regimen was performed. Best-corrected visual acuity (BCVA) and central foveal thickness measurement at follow-up were evaluated. The development of posterior vitreous detachment during the follow-up was also reported.

It was noted that the BCVA changes at each visit compared with baseline were significantly better in group one (p=0.01, 0.02, 0.02, 0.009, 0.009, respectively at third, sixth, ninth, 12th month and last visit). When BCVA was classified according to the change in visual acuity of 10 letters or more, the rate of improved or stable BCVA was greater in group one (p=0.02). During the follow-up, five eyes (14.3%) developed posterior vitreous detachment.

Vitreomacular adhesion seems to have an adverse effect on the visual prognosis of anti-VEGF treatment for AMD.

Source: Üney GÖ, Ünlü N, Acar MA, et al. Role of posterior vitreous detachment on outcome of anti-vascular endothelial growth factor treatment in age-related macular degeneration. Retina. 2014;34(1):32–37.


SD-OCT vs. TD-OCT in the Detection of Neovascular AMD Activity

Scientists sought to compare the sensitivity of commonly used time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT) platforms and scanning modalities in the management of neovascular age-related macular degeneration (AMD) in a population with a high prevalence of exudative disease activity.

They enrolled 50 consecutive patients within the prospective Super-dose Anti-Vascular Endothelial growth factor (SAVE) trial, which analyzed the utility of 2.0 mg intravitreal ranibizumab for the treatment of recalcitrant neovascular AMD, in a comparison trial of three different OCT platforms. Stratus TD-OCT radial scan (Carl Zeiss Meditec Inc.) was compared with three Heidelberg Spectralis Heidelberg Retinal Angiograph+OCT (Heidelberg Engineering) acquisition settings (radial, seven-line raster, volumetric) and two Cirrus high-definition (HD)-OCT (Carl Zeiss Meditec Inc) acquisition settings (five-line raster, volumetric).

Using every imaging platform and acquisition setting, scientists positively identified evidence of exudative disease activity in 163 of 191 patient visits (85.3%). They identified intraretinal cysts in 83 of 191 visits (43.5%), and subretinal fluid in 116 of 191 visits (60.7%). Of these positive visits, the Stratus TD-OCT radial scanning technology demonstrated a significantly lower rate of detection (71.8%) when compared with the Spectralis HRA+OCT spectral domain scanning modalities (radial 87.1%, p<0.001; seven-line raster 92.0%, p<0.001; volumetric 94.5%, p<0.001) or the Cirrus HD-OCT spectral domain scanning modalities (five-line raster 81.6%, p=0.001; volumetric 92.0%, p<0.001). The scientists also identified intraretinal cysts and subretinal fluid in 83 visits (43.5%) and 116 visits (60.7%), respectively, with 36 eyes (18.8%) having fluid in both locations. No individual imaging modality demonstrated a diagnostic advantage for detecting subretinal fluid versus intraretinal cysts (e.g., Cirrus volume detected 86.7% of intraretinal cysts and 88.8% of subretinal fluid, p=0.33).

In this neovascular AMD patient population, SD-OCT was a superior diagnostic tool when compared with TD-OCT, with each spectral-domain platform and acquisition setting identifying significantly more exudative disease activity. The scientists did not directly compare the two spectral-domain platforms (Cirrus and Spectralis) because identical image acquisition parameters were not used. No individual imaging modality demonstrated a diagnostic advantage for detecting subretinal fluid versus intraretinal cysts.

Source: Major JC, Wykoff CC, Mariani AF, et al. Comparison of spectral-domain and time-domain optical coherence tomography in the detection of neovascular age-related macular degeneration activity. Retina. 2014;34(1):48–54.


GA Risk in the Comparison of AMD Treatment Trials

To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT), the authors of this cohort within a randomized clinical trial analyzed 1,024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment.

They assigned eyes to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a two-year monthly or pro re nata (p.r.n.) injection regimen, or monthly injections for one year and p.r.n. for one year. They evaluated demographic, genetic and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) as risk factors for GA through two years of follow-up. The authors also used time-dependent Cox proportional hazard models to estimate adjusted hazard ratios (aHRs). Development of GA was the main outcome measure.

By two years, GA developed in 187 of 1,024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43 to 4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16 to 2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40 to 3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34 to 3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29 to 0.82), OCT measurements of subretinal fluid thickness of >25 µm (aHR, 0.52; 95% CI, 0.35 to 0.78), subretinal tissue complex thickness of >275 compared with ≤75 µm (aHR, 0.31; 95% CI, 0.19 to 0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31 to 0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06 to 1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17 to 2.16) than p.r.n. dosing. The study authors reported that there were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3 or TLR3.

They determined that approximately one-fifth of CATT patients developed GA within two years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.

Source: Grunwald JE, Daniel E, Huang J, et al; CATT Research Group. Risk of geographic atrophy in the comparison of age-related macular degeneration treatment trials. Ophthalmology. 2014;121(1):150–161.


Change in Drusen Volume as a Novel Clinical Trial Endpoint for the Study of Complement Inhibition in AMD

In the following single-center, prospective, randomized, double-masked clinical trial, researchers evaluated the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component 5.

They randomized patients 2:1 to receive intravenous eculizumab or placebo over 26 weeks. The main outcome measure was a decrease in drusen volume of at least 50% at 26-week follow-up.

The researchers reported that mean drusen cube root volumes were 0.49 mm and 0.47 mm (p=0.64) at baseline and 0.51 mm and 0.42 mm (p=0.17) at 26 weeks in the eculizumab and placebo groups, respectively. They also found that in the placebo group, one eye had a decrease in drusen volume of at least 50% and two eyes developed neovascularization through 26 weeks.

To conclude, systemic complement inhibition with eculizumab did not significantly reduce drusen volume. Drusen growth was dependent on the number of complement at-risk alleles. Future trials should consider the use of a composite clinical trial endpoint in which efficacy is defined by the treatment's ability to prevent drusen growth, neovascularization and the formation of geographic atrophy over one year.

Source: Filho CA, Yehoshua Z, Gregori G, et al. Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration. OSLIRetina. 2013; Dec 19. [Epub ahead of print]. DOI: 10.3928/23258160-20131217-01.


Follow-Up of AMD Over 10 Years

Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials. In this study, investigators aimed to describe 10-year progression rates to intermediate or advanced AMD.

They observed the Age-Related Eye Disease Study (AREDS) participants for an additional five years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. The study investigators followed participants aged 55 to 80 years with no AMD or AMD of varying severity (n=4,757) up in the AREDS trial for a median duration of 6.5 years. When the trial ended, they followed 3,549 of the 4,203 surviving participants for five additional years. Exposure was defined as treatment with antioxidant vitamins and minerals.

Development of varying stages of AMD and changes in visual acuity were the main outcome measures. The investigators evaluated the rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy [GA]) using annual fundus photographs assessed centrally. They also measured best-corrected visual acuity at annual study visits.

They found that the risk of progression to advanced AMD increased with increasing age (p=0.01) and severity of drusen. They also noted that women (p=0.005) and current smokers (p<0.001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central GA by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200.

The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.

Source: Chew EY, Clemons TE, Agrón E, et al., for the Age-Related Eye Disease Study Research Group. Ten-year follow-up of age-related macular degeneration in the Age-Related Eye Disease Study. AREDS Report No. 36. JAMA Ophthalmol. 2014;Jan 2. [Epub ahead of print.] DOI:10.1001/jamaophthalmol.2013.6636/.


Relationship Between Polymorphism of the DNA Repair SMUG1 and UNG Genes and AMD

The authors of the following study investigated the association between the g.4235T>C (rs2337395) polymorphism of the UNG gene and the c.–31A>G (rs3087404) polymorphism of the SMUG1 gene and the risk of age-related macular degeneration (AMD), as well as modulation of this association by some environmental and lifestyle factors.

They enrolled 272 AMD patients and 105 control subjects in this study, and genotyped both polymorphisms by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP).

The study authors reported that C/C genotype of the g.4235T>C polymorphism of the UNG gene was associated with an increased risk of dry AMD (odds ratio, 2.54), whereas the T/T genotype of this polymorphism decreased such risk (odds ratio, 0.41). They noted that the presence of the T allele of the g.4235T>C polymorphism and the A allele of the c.–31A>G polymorphism of the SMUG1 gene (odds ratio, 2.17 and 2.18, respectively) was associated with an increased risk of AMD severity, expressed by the comparison of the frequencies of genotypes in the group of patients with wet AMD versus those with dry AMD. Conversely, the C/C genotype of the g.4235T>C polymorphism, the G/G genotype of the c.–31A>G polymorphism, and the C/C-G/G combined genotype of both polymorphisms had a protective effect (odds ratio, 0.48, 0.46, and 0.18; respectively).

In conclusion, the results obtained suggest the potential role of the g.4235T>C and the c.–31A>G polymorphisms in AMD pathogenesis.

Source: Synowiec E, Wysokinski D, Zaras M, et al. Association between polymorphism of the DNA repair smug1 and ung genes and age-related macular degeneration. Retina. 2014;34(1):38–47.


SD-OCT Predictors of Visual Outcome in Diabetic CME Following Injection with Bevacizumab

The retrospective cohort study below examined prognostic spectral-domain optical coherence tomography (SD-OCT) parameters in diabetic cystoid macular edema (CME) after anti-vascular endothelial growth factor (anti-VEGF) therapy.

It included 49 eyes with the new onset diabetic CME that had to have a macular SD-OCT and fluorescein angiography at presentation. The baseline OCT scans were analyzed for variables indicative of the extent of retinal involvement by the cystoid change and its location about the center. Univariate and multivariate analyses were performed comparing the OCT findings between the two groups of eyes: the “no improvement” and the “improvement” groups, based on at least two Snellen lines improvement after treatment.

There were 30 and 19 eyes in the no improvement and improvement groups, respectively. In the univariate analysis, the baseline OCT parameters associated with visual improvement included the photoreceptor inner segments thickness centrally (p=0.009) and within the central 1-mm subfield (p<0.0001), and the presence of bridging retinal processes centrally (p=0.004). Multivariate analysis showed both presence and central location of bridging retinal processes within the central 1-mm subfield to be significantly associated with visual improvement (p=0.041 and 0.005, respectively), with an odds ratio of 13.4 (95% confidence interval, 1.336-636.18; p=0.010) for their central location.

In diabetic CME, visual improvement after anti-VEGF therapy is more likely to occur in eyes with residual central retinal processes on baseline macular SD-OCT. This finding may be helpful in patient counseling, case selection and clinical trial planning.

Source: Al Faran A, Mousa A, Al Shamsi H, et al. Spectral domain optical coherence tomography predictors of visual outcome in diabetic cystoid macular edema after bevacizumab injection. Retina. 2013; Dec 23. [Epub ahead of print].


Combined Cataract Surgery and Ranibizumab Injection in Postoperative Macular Edema in Nonproliferative Diabetic Retinopathy

To evaluate whether intravitreal ranibizumab injection at cataract surgery prevents postoperative diabetic macular edema (PME) in patients with stable diabetic retinopathy without significant macular edema, researchers randomized 80 patients with cataract, stable diabetic retinopathy and no significant macular edema to a sham group (cataract surgery only) or a group undergoing cataract surgery plus intraoperative ranibizumab injection. They assessed best-corrected visual acuities (BCVAs), central subfield thickness and total macular volume at baseline and one week, one, three and six months postoperatively by spectral-domain optical coherence tomography (SD-OCT). Additionally, they computed clinically meaningful PME (central subfield thickness increase >60 µm relative to baseline).

The researchers noted that the groups did not differ in baseline BCVA, central subfield thickness and total macular volume. They also reported that compared with the ranibizumab injection group, the sham group had significantly larger central subfield thickness increases relative to baseline at one week and one month; larger total macular volume increases at all time points (p=0.012, p=0.005, p<0.001, p<0.001, p=0.005, p=0.017, respectively); higher PME frequency at one month (p=0.019); and poorer BCVA improvement from baseline to six months after surgery (p=0.046).

In conclusion, in patients with stable diabetic retinopathy without significant macular edema, intravitreal ranibizumab injection at cataract surgery may prevent the postoperative worsening of macular edema and may improve the final visual outcome without affecting safety.

Source: Chae JB, Joe SG, Yang SJ, et al. Effect of combined cataract surgery and ranibizumab injection in postoperative macular edema in nonproliferative diabetic retinopathy. Retina. 2014;34(1):149–156.


Intravitreal Aflibercept Injection for Macular Edema Resulting from CRVO

This randomized, multicenter, double-masked Phase III study evaluated the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO).

A total of 177 treatment-naïve patients with macular edema secondary to CRVO were randomized in a 3:2 ratio. Patients received either 2-mg intravitreal aflibercept or sham injections every four weeks for 20 weeks. From week 24 to 48, the aflibercept group received aflibercept as needed (pro re nata [p.r.n.]), and the sham group continued receiving sham injections. The primary efficacy endpoint was the proportion of patients who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24. This study reports week 52 results including the proportion of patients who gained 15 letters or more in BCVA and the mean change from baseline BCVA and central retinal thickness. Efficacy end points at week 52 were all exploratory.

At week 52, the mean percentage of patients gaining 15 letters or more was 60.2% in the aflibercept group and 32.4% in the sham group (p=0.0004). Aflibercept patients, compared with sham patients, had a significantly higher mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and reduction in central retinal thickness (–423.5 µm vs. –219.3 µm, respectively) at week 52 (p<0.0001 for both). Aflibercept patients received a mean of 2.5 injections (standard deviation, 1.7 injections) during p.r.n. dosing. The most common ocular adverse events in the aflibercept group were related to the injection procedure or the underlying disease, and included macular edema (33.7%), increased intraocular pressure (17.3%) and eye pain (14.4%).

To conclude, treatment with intravitreal aflibercept provided significant functional and anatomic benefits after 52 weeks as compared with sham. The improvements achieved after six monthly doses at week 24 largely were maintained until week 52 with as-needed dosing. Intravitreal aflibercept generally was well-tolerated.

Source: Korobelnik JF, Holz FG, Roider J, et al; GALILEO Study Group. Intravitreal aflibercept injection for macular edema resulting from central retinal vein occlusion: one-year results of the Phase III GALILEO study. Ophthalmology. 2014;121(1):202–208.


Intravitreal Ranibizumab vs. Standard Grid Laser for Macular Edema Resulting from BRVO

Scientists recruited 36 patients from five institutions to assess the efficacy of intravitreal 0.5 mg ranibizumab for the treatment of center-involving macular edema secondary to branch retinal vein occlusion (BRVO) over one year compared with standard-of-care grid laser.

In this prospective, randomized controlled clinical trial, patients with vision loss in one eye attributable to macular edema following BRVO were randomized 1:1 to a treatment group that received six monthly injections of 0.5 mg ranibizumab and thereafter monthly as needed based on best-corrected visual acuity (BCVA) and central foveal thickness (CFT) assessments on optical coherence tomography scans or a standard-of-care group that received monthly sham injections for the one-year duration of the study. The scientists administered grid laser at 13 and 25 weeks in both groups if criteria for laser treatment were met. Main outcome measures included mean change in BCVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores from baseline to month 12. Secondary outcomes included anatomic outcomes and the percentage of patients requiring grid laser in both groups.

According to the study scientists, mean BCVA change from baseline was significantly greater in the treatment compared with the standard-of-care group at 12 months (12.5 ETDRS letters vs. –1.6 ETDRS letters, p=0.032). The mean CFT was significantly reduced in the treatment compared with standard-of-care group (361.7 µm vs. 175.6 µm, p=0.025). At 13 and 25 weeks, more patients in the standard-of-care group (68.4%, 50.0%) received grid laser than in the treatment group (6.7%, 8.3%). No new ocular or systemic adverse events were observed.

Compared with standard grid laser, intravitreal ranibizumab provided significant and sustained benefits in visual acuity gain and anatomic improvement in eyes with macular edema secondary to BRVO, the scientists concluded.

Source: Tan MH, Mcallister IL, Gillies ME, et al. Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion. Am J Ophthalmol. 2014;157(1):237–247.


Long-Term Outcomes of RVO Treated with Ranibizumab

To determine long-term outcomes of patients with ranibizumab-treated retinal vein occlusion (RVO), the authors of this prospective follow-up of a subset of patients from two Phase III trials looked at 34 patients with branch RVO (BRVO) and 32 with central RVO (CRVO) who completed the Genentech-sponsored ranibizumab study RVO trials.

Patients seen every month in year one and at least every three months in year two were treated with ranibizumab for intraretinal fluid. Patients requiring injections on consecutive visits were treated with ranibizumab plus scatter photocoagulation. The main outcome measure was mean improvement in best-corrected visual acuity (BCVA) and percentage of patients with edema resolution.

With a mean follow-up of 49.0 months, 17 of 34 BRVO patients (50%) had edema resolution defined as no intraretinal fluid for six months or more after the last injection. According to the study authors, the last injection was given within two years of treatment initiation in 76%. They also noted that the mean number of injections required in unresolved patients in year four was 3.2. In patients with resolved edema, mean improvement in BCVA was 25.9 letters versus 17.1 letters (p=0.09) in unresolved patients, and in both groups, approximately 80% had a final BCVA of 20/40 or better, the authors reported. With a mean follow-up of 49.7 months, 14 of 32 CRVO patients (44%) had edema resolution, with 71% receiving their last injection within two years of treatment initiation. The mean number of injections in unresolved patients in year four was 5.9. Compared with patients with unresolved CRVO, patients with resolved disease had greater improvement in BCVA (25.2 vs. 4.3 letters; p=0.002), and a greater percentage had a final BCVA of 20/40 or better (64.3% vs. 27.8%; p=0.04). Nine patients with BRVO and nine with CRVO received scatter photocoagulation, and with mean follow-up of nine months (BRVO) and 11 months (CRVO) after last laser, only one in each group had resolution of edema.

Long-term outcomes in BRVO patients treated with ranibizumab were excellent, and although half still required occasional injections after four years, they maintained good visual potential. The authors of this study determined that a substantial minority (44%) of patients with ranibizumab-treated CRVO had edema resolution and a good outcome within four years, but most (56%) still required frequent injections, had reduced visual potential, and have a guarded prognosis.

Source: Campochiaro PA, Sohpie R, Pearlman J, et al; RETAIN Study Group. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN Study. Ophthalmology. 2014;121(1):209–219.


Vitrectomy Plus Periocular/Intravitreal Injection of Steroids for Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment

To study the anatomical outcome of rhegmatogenous retinal detachment combined with choroidal detachment after pars plana vitrectomy with periocular/intravitreal injection of steroids, investigators treated 77 eyes that have rhegmatogenous retinal detachment combined with choroidal detachment by pars plana vitrectomy with oral prednisolone (group A) or periocular/intravitreal injection of steroids (group B). They then divided eyes into five subgroups according to different intraocular tamponade agents; group A1: oral steroids and silicone oil; group A2: oral steroids and C3F8; group B1: periocular/intravitreal steroid injections and silicone oil; group B2: periocular steroid injection and silicone oil, and group B3: periocular steroid injection and C3F8. They measured anatomical reattachment of the retina at 12 months after surgery.

The study investigators found no significant difference in retinal reattachment rate between eyes in group A and eyes in group B (77.4% vs. 73.9%, p=0.726). The retinal reattachment rates were 83.3% in group A1, 69.2% in group A2, 82.4% in group B1, 73.3% in group B2, and 64.3% in group B3. There was no statistical difference in the retinal reattachment rates between any of the groups.

For the treatment of rhegmatogenous retinal detachment combined with choroidal detachment, pars plana vitrectomy with periocular/intravitreal corticosteroids was comparable in reattachment rate to pars plana vitrectomy with systemic steroids, suggesting an acceptable alternative for patients with this condition who cannot tolerate systemic steroids.

Source: Wei Y, Wang N, Chen F, et al. Vitrectomy combined with periocular/intravitreal injection of steroids for rhegmatogenous retinal detachment associated with choroidal detachment. Retina. 2014;34(1):136–141.




 



Bioheart to Conduct Dry AMD Study

Bioheart Inc. announced that it will enroll up to 100 patients in a study to determine the safety and efficacy of adipose-derived stem cells or AdipoCell in patients with dry age-related macular degeneration (AMD). The company says that the study has been reviewed and approved by the Institutional Review Board of the International Cellular Medicine Society.

Source: Bioheart Inc., December 2013.




Alimera Ships First Orders of Iluvien to U.K. National Health Service Hospitals

pSivida Corp.'s licensee Alimera Sciences has shipped initial orders of Iluvien to several U.K. National Health Service (NHS) facilities. The company also noted that the first NHS patient has received Iluvien for the treatment of chronic macular edema (DME) insufficiently responsive to available therapies. In November, the National Institute for Health and Care Excellence published final guidance recommending Iluvien as a treatment option for pseudophakic patients with chronic DME insufficiently responsive to available therapies, subject to a patient access scheme.

Source: pSivida Corp., January 2014.




Researchers Seek to Characterize Development of Retinal Detachment After Open Globe Trauma

Researchers from the Massachusetts Eye and Ear, Harvard Vanguard Medical Associates and Harvard Medical School Department of Ophthalmology have reported on the first study in 35 years that reviews the circumstances around retinal detachment following open globe injuries (OGI). The case-control study looked at 892 patients (893 OGIs), of whom 255 were ultimately diagnosed with retinal detachments, with the remaining eyes serving as controls. They used Kaplan-Meier analysis to estimate the time to detachment, and multivariable logistic regression to define the clinical factors associated with retinal detachment after OGI.

The researchers concluded that retinal detachment is common after open globe trauma, though it often doesn't appear until days to weeks after the initial traumatic event. Several clinical variables at the time of initial presentation can predict the future risk of detachment. Additionally, the study researchers created a new screening tool: the Retinal Detachment after Open Globe Injury score. For additional details on the study, click here.

Source: Stryjewski TP, Andreoli CM, Eliott D. Retinal detachment after open globe injury. Ophthalmology. 2014;121(1):327–333.




MIT Researchers Create Retinal Disease Screening Instrument

A team of researchers has created an ultra high-speed, handheld swept-source optical coherence tomography ophthalmic imaging instrument using a 2-D micro-electro-mechanical systems (MEMS) mirror to enable screening applications to identify early retinal disease before irreversible vision impairment or loss occurs. The device scans a patient's retina in seconds and corrects for movement by averaging and registering 25 B-scans obtained over the same position in 0.57 seconds. Check out the paper published by the researchers in Biomedical Optics Express.

Source: Lu CD, Kraus MF, Potaid B, et al. Handheld ultrahigh speed swept-source optical coherence tomography instrument using a MEMS scanning mirror. Biomedical Optics Express. 2014; 5(1):293–311.


 

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