Volume 8, Number 4
April 2012

 

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.



iCO Therapeutics and JDRF Support Phase II Clinical Trial for DME Treatment
iCo Therapeutics and charitable funder JDRF have joined forces to investigate a potential new treatment for diabetic macular edema (DME)...

Bascom Palmer Eye Institute to Serve as a Site for Phase I/II AMD Clinical Trial
Advanced Cell Technology, Inc. reported that the Bascom Palmer Eye Institute in Miami has received institutional review board (IRB) approval as a site for...

And More...

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 clinical trial.

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 be considered.

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]. DOI: 10.1016/j.jcjo.2012.01.005.


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]. DOI: 10.1097/IAE.0b013e31824f91e8.


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 outcome measures.

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.






iCO Therapeutics and JDRF Support Phase II Clinical Trial for DME Treatment

iCo Therapeutics and charitable funder JDRF have joined forces to investigate a potential new treatment for diabetic macular edema (DME). The iDEAL study is a Phase II clinical trial to evaluate whether the drug iCo-007 could help to treat DME in people with either type 1 or type 2 diabetes. It explores whether varying combinations and concentrations of iCo-007 are effective in improving visual acuity in people with DME. The iDEAL study, which is in the process of recruiting participants, follows patients for a 12-month period, during which, patients are randomized into one of the following four groups: either one of two mono-therapy arms using repeated intravitreal dosing of two different concentrations of iCo-007; or one of two combination arms using iCo-007 with laser photocoagulation or iCo-007 and ranibizumab. To be eligible for the trial, participants must have type 1 or type 2 diabetes, baseline visual acuity between 20/32 and 20/320 on the Early Treatment Diabetic Retinopathy Study ETDRS chart, and DME with central subfoveal thickness > 250 µm on OCT. Read more here.

Source: iCo Therapeutics, March 2012.




Bascom Palmer Eye Institute to Serve as a Site for Phase I/II AMD Clinical Trial

Advanced Cell Technology, Inc. reported that the Bascom Palmer Eye Institute in Miami has received institutional review board (IRB) approval as a site for the company’s prospective, open-label Phase I/II clinical trial for dry age-related macular degeneration using human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells. The trial is designed to determine the safety and tolerability of the hESC-derived RPE cells following sub-retinal transplantation into patients with dry AMD. It will ultimately enroll 12 patients, with cohorts of three patients in each in an ascending dosage format.

Source: Advanced Cell Technology, Inc., April 2012.




New LED Light Source Enhances Intra-ocular Illumination During Vitreo-retinal Surgery

Swiss company Oertli Instrumente AG recently introduced the new highly advanced Goodlight LED light source. According to the company, it enables excellent viewing and combines the advantages of healthy light with those of the latest LED technology. Goodlight LED is available with any Oertli OS3 (dual light source) and faros. Oertli says that compared with traditional light sources, light intensity is increased by up to 60%; and this without renouncing healthy light. Additionally, with Goodlight LED, the danger of photoretinitis is minimized without using additional filters.

Source: Oertli Instrumente AG, March 2012.




FDA Clears Heidelberg for Spectralis Anterior Segment Module

The FDA has granted Heidelberg Engineering GmbH clearance for the new, Spectralis Anterior Segment Module (ASM), which provides high-resolution images of cornea, anterior chamber angle and sclera utilizing unique Heidelberg Noise Reduction technology for enhanced detail. Heidelberg says that with the ASM, clinicians can assess both chamber angles at the same time using a 16-mm-wide angle-to-angle OCT scan.

Source:Heidelberg Engineering GmbH, March 2012.




Lpath to Continue iSONEP Trials in August

Lpath, Inc. plans to manufacture new antibody drug substance in preparation for the continuation of its PEDigree and Nexus trials, which are testing iSONEP as a treatment for wet AMD (Nexus) and pigmented epithelial detachment (PEDigree). The company plans to submit the necessary documentation regarding the new drug material to the FDA by June and expects both trials will be open for enrollment in August.

Source: Lpath, Inc., March 2012.




Digital Imaging System Program for Infants Implemented in Russian Federation

Clarity Medical Systems, Inc. recently reported that it has implemented a significant RetCam digital imaging system program in the Russian Federation. Russian President Dmitry Medvedev approved the initial purchase of RetCam Systems for 42 of the country's 83 states to be used in care centers handling prematurely born infants at risk for eye diseases such as retinopathy of prematurity.

Source: Clarity Medical Systems, Inc., March 2012.




pSIVIDA and Neuron Systems to Collaborate on Durasert Technology

pSivida Corp. has entered into a technology evaluation agreement for its bioerodible Durasert drug delivery technology in ophthalmology with Neuron Systems, Inc. Under the terms of the agreement, the companies will evaluate the use of pSivida's technology as a delivery system for a treatment for dry AMD.

Source: pSivida Corp., March 2012.




Optos Delivers First Shipments of Daytona Retinal Imaging Devices

Optos plc has delivered the first Daytona devices to customers in line with expectations. The company says the Daytona represents the next generation of Optos ultra-widefield retinal imaging technology and has been scaled to accommodate smaller office spaces while providing high-resolution imaging and adding new auto-fluorescence capabilities. Daytona’s new ergonomic body weighs only about 25 kg and is designed to increase patient comfort, as well as make it easier to correctly position the eye. It also features an improved user interface with intuitive, workflow-based software.

Source: Optos plc, March 2012.




 

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