GenSight Receives EMA Orphan Drug Designation GenSight Biologics announced that the European Commission, based on a favorable recommendation from the European Medicines Agency, granted orphan drug designation to the company’s product candidate, GS030, for treatment of retinitis pigmentosa... RetroSense Signs License With UC San Diego RetroSense Therapeutics signed a worldwide license with the University of California, San Diego, to secure exclusive rights to develop red activatable channelrhodopsin (ReaChR), a next-generation optogene developed by the late Nobel laureate Roger Tsien... And More...

Ranibizumab Treatment for PED Secondary to nAMD

Researchers analyzed the effect of baseline presence and height of pigment epithelial detachments on visual and anatomic outcomes at 24 months in individuals with neovascular age-related macular degeneration treated with ranibizumab, as part of a post hoc analysis of HARBOR—a 24-month, Phase III, randomized, multicenter, double-masked, active treatment-controlled study.

Included in the study were 1,097 individuals with neovascular AMD treated with intravitreal ranibizumab 0.5 mg, 2 mg monthly or pro re nata after three monthly loading doses.

Researchers evaluated the effect of presence and height of baseline PED on several outcomes at 24 months, including best-corrected visual acuity, change in PED height, resolution of PED and number of injections in the p.r.n. arms. They assessed development of macular atrophy at month 24 by presence or absence of PED.

A total of 598 individuals (54.5 percent) showed PED at baseline. In the ranibizumab 0.5-mg p.r.n. group, mean numbers of injections were similar for individuals with PED present or absent at baseline (14 vs. 12.5). Mean BCVA gains from baseline to 24 months were seen in all treatment groups and were comparable in individuals with or without PED at baseline treated with ranibizumab 0.5 mg monthly (PED present at baseline: +9 letters; PED absent at baseline: +11.3 letters); 0.5 mg p.r.n. (present: +8.4; absent: +7.9); 2 mg monthly (present: +7.1; absent: +11.1); or 2 mg p.r.n. (present: +7.2; absent: +8.8). When analyzed by baseline PED height, mean BCVA gains were demonstrated and comparable in all treatment groups at 24 months except for individuals treated with ranibizumab 2 mg monthly in the extra-large group (PEDs ≥352 μm; mean BCVA change: -0.8 letters). At 24 months, 53.2 percent (0.5 mg monthly); 44.5 percent (0.5 mg p.r.n.); 70.4 percent (2 mg monthly); and 57.3 percent (2 mg p.r.n.) of individuals showed complete resolution of PED.

Researchers concluded that ranibizumab 0.5 mg given monthly or p.r.n. effectively treated PEDs in individuals with neovascular AMD and resulted in significant vision gains, regardless of PED status and height at baseline. They found no additional vision benefit with a higher dose of ranibizumab (2 mg).

SOURCE: Sarraf D, London NJ, Khurana RN, et al. Ranibizumab treatment for pigment epithelial detachment secondary to neovascular age-related macular degeneration. Ophthalmology 2016; Aug. 26. [Epub ahead of print].

Ozurdex in Neovascular AMD as Adjunct to Ranibizumab: OARA Study

Researchers evaluated the utility of the dexamethasone intravitreal implant (DXI; Ozurdex; Allergan) in combination with ranibizumab (Lucentis; Novartis Pharma AG) vs. ranibizumab monotherapy relative to visual acuity and anatomical outcomes in a neovascular age-related macular degeneration cohort, as part of a multicenter, single-blinded, pilot, randomized control trial.

They randomized 10 individuals (50 years or older) with subfoveal choroidal neovascularization secondary to AMD to receive DXI in combination with ranibizumab or ranibizumab alone after a three-month ranibizumab loading period.

The combination group received one DXI after the loading phase with the option of retreatment at months four to six. Researchers administered ranibizumab pro re nata for six months in both study arms. Mean VA and central macular thickness reductions from baseline to study endpoint (nine months) were reported in addition to adverse event frequency across study cohorts.

From baseline to the study endpoint, VA improved by 10.8 ±13.2 Early Treatment of Diabetic Retinopathy Study letters in the control arm and 3.0 ±10.5 letters in the intervention arm (p=0.331). CMT decreased by 31.7 ±17.5 percent for the controls and 13.3 ±27 percent for the intervention cohorts (p=0.236). One individual developed intraocular pressure in excess of 30 mmHg three months after DXI administration.

Researchers observed no visual or anatomical benefits for ranibizumab monotherapy when treating with DXI as an adjunct to ranibizumab. DXI-related adverse events were consistent with those previously documented for dexamethasone, they also found.

SOURCE: Chaudhary V, Barbosa J, Lam WC, et al. Ozurdex in age-related macular degeneration as adjunct to ranibizumab (the OARA study). Can J Ophthalmol 2016;51:4:302-5.

Real-Life Study in DME Treated With Dexamethasone Implant: The Reldex Study

Investigators evaluated the efficacy and safety of the Ozurex intravitreal dexamethasone implant in diabetic macular edema in a clinical practice, as part of a bicentric, retrospective study. Two of the investigators are consultants for Allergan.

They reviewed 128 eyes of 89 individuals. Main outcome measures included changes in best-corrected visual acuity; central macular thickness; time to retreatment; and incidence of adverse effects. Investigators used linear, mixed-effects models to study changes in BCVA and central macular thickness over the three-year follow-up.

BCVA increased by a mean of 3.6 letters at month two (p=0.005); 4.2 letters at month 12 (p=0.006); 5.3 letters at month 24 (p=0.007); and 9.5 letters at month 36 (p=0.023). The proportion of eyes achieving at least a 15-letter improvement from baseline was 25.4 percent at month 36. Central macular thickness decreased from 451 µm to 289 µm at month two (p<0.001); 370 µm at month 12 (p<0.001); 377 µm at month 24 (p=0.004); and 280 µm at month 36 (p=0.001). Investigators administered a mean of 3.6 injections over a three-year follow-up period. Ten percent of eyes developed a transient increase in intraocular pressure (IOP ≥25 mmHg), and 47 percent of phakic eyes had cataracts removed.

The case series study showed favorable three-year outcomes when using Ozurdex to treat DME. Investigators concluded that intravitreal Ozurdex provided substantial long-term benefits in treating DME in a clinical setting.

Source: Malclès A, Dot C, Voirin N, et al. Real-life study in diabetic macular edema treated with dexamethasone implant: The Reldex Study. Retina 2016; Jul 28. [Epub ahead of print].

Aqueous Humor Cytokine Levels as Biomarkers of DME Disease Severity

Researchers set out to determine whether aqueous cytokine levels correlated with disease severity in diabetic macular edema, as part of a prospective, cross-sectional study of 49 adults with diabetes mellitus; center-involving DME; and central subfield macular thickness ≥310 µm on spectral-domain optical coherence tomography. The researcher received an unrestricted grant from Novartis.

They conducted clinical exams and aqueous sampling before an initial injection of ranibizumab. Researchers also completed a multiplex immunoassay of the samples for vascular endothelial growth factor; placental growth factor; transforming growth factor beta; intercellular adhesion molecule-1; interleukin-2; IL-3; IL-6; IL-8; IL-10; IL-17; vascular cell adhesion molecule-1; monocyte chemoattractant protein-1; and epidermal growth factor. Researchers constructed multivariate robust regression models, and adjusted for age; lens status; severity of retinopathy; and size of foveal avascular zone.

Researchers determined that SD-OCT macular volume was a strong measure of disease severity, correlating with central subfield macular thickness (p<0.001); best-corrected Snellen visual acuity (p<0.001); and baseline diabetic retinopathy severity (p=0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (p=0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. Researchers detected an association between IL-10 levels and best-corrected Snellen visual acuity (p=0.03).

Researchers found that aqueous intercellular adhesion molecule-1 correlated with disease severity as measured by macular volume on SD-OCT, and IL-10 was associated with BCVA. They concluded that intercellular adhesion molecule-1 may be a clinically useful biomarker for DME severity.

SOURCE: Hillier RJ, Ojaimi E, Wong DT, et al. Aqueous humor cytokine levels as biomarkers of disease severity in diabetic macular edema. Retina 2016; Jul 28. [Epub ahead of print].

Baseline Choroidal Thickness for Predicting Treatment Outcomes in CRVO

Investigators assessed the association between initial subfoveal choroidal thickness and response to anti-vascular endothelial growth factor therapy in central retinal vein occlusion eyes, as part of a retrospective cohort study.

They included 43 eyes from 42 individuals with treatment-naïve CRVO and cases with a standard algorithm of three monthly anti-VEGF injections. They used serial enhanced-depth imaging optical coherence tomography scans to measure subfoveal choroidal thickness and central macular thickness. Investigators assessed baseline predictors (particularly choroidal thickness) for functional response (best-corrected visual acuity gain ≥two lines) at three months follow-up using univariate and multivariate analyses.

Initial choroidal thickness in CRVO eyes (246 ±102 μm) was greater than the fellow eye (197 ±86 μm; p=0.023). In addition, mean choroidal thickness at baseline for functional responders (272.2 ±107.3 μm) was greater than non-responders (209.6 ±85.8 μm; p=0.039). Investigators found a higher baseline choroidal thickness (for every 100-μm increase) to be a positive predictor for functional response (regression coefficient: 0.7; p=0.04) on univariate analysis, whereas age (<70 years old) was the only positive predictor for functional response with an odds ratio of 6.49 (95 percent CI: 1.11-38.1; p=0.03) on multivariate regression analysis.

Investigators suggested that baseline choroidal thickness and age may help predict which individuals with CRVO have favorable visual outcomes following short-term anti-VEGF therapy.

SOURCE: Rayess N, Rahimy E, Ying GS, et al. Baseline choroidal thickness as a predictor for treatment outcomes in central retinal vein occlusion. Am J Ophthalmol 2016; Aug 24. [Epub ahead of print].

Ranibizumab for ME After BRVO: One Injection vs. Three Monthly Injections

Researchers compared the 12-month efficacy of one initial intravitreal ranibizumab injection followed by pro re nata dosing with that of three initial monthly IVR followed by p.r.n. dosing in individuals with macular edema after branch retinal vein occlusion, in a prospective, interventional study. Several of the researchers received grant support from Novartis.

Researchers administered one initial IVR injection (1+PRN group) to 42 eyes and three monthly IVRs (3+PRN) to 39 eyes. They administered p.r.n. injections when fovea exudative changes were evident.

At month 12, visual acuity changes from baseline were -0.245 ±0.227 in the 1+PRN group, and -0.287 ±0.222 in the 3+PRN group, with no significant difference between groups (p=0.728). The stratified analysis showed that individuals with better VA (baseline VA >20/40) had similar significant improvement in VA at month 12 (p<0.001) as that of individuals with poorer VA (≤20/40). Better VA at month 12 was significantly associated with younger age (p=0.003); better baseline VA (p<0.001); and thinner baseline central foveal thickness (p<0.001). Mean total number of IVR injections were 3.8 ±1.8 in the 1+PRN group and 4.6 ±1.4 in the 3+PRN group (p=0.060). In both groups, shorter duration to the first PRN injection was associated with greater total p.r.n. injection number (1+PRN: p=0.006; 3+PRN: p<0.001).

Researchers found that, in IVR treatment for ME after BRVO, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. They suggested that individuals with shorter durations to initial p.r.n. injection may require more p.r.n. treatments.

SOURCE: Miwa Y, Muraoka Y, Osaka R, et al. Ranibizumab for macular edema after branch retinal vein occlusion: One initial injection versus three monthly injections. Retina 2016; Jul 28. [Epub ahead of print].

Serum VEGF After Bevacizumab or Ranibizumab Treatment for ROP

Scientists studied vascular endothelial growth factor levels in the systemic circulation after intravitreal injections of bevacizumab or ranibizumab in individuals with type 1 retinopathy of prematurity.

They enrolled 10 individuals with type 1 ROP who received IVB or IVR, and collected serum samples before and up to 12 weeks after IVB or IVR treatment. The main outcome measurements were serum levels of VEGF up to 12 weeks after anti-VEGF treatment.

All eyes had complete resolution of abnormal neovascularization of ROP after IVB or IVR. In directly comparing IVB with IVR, scientists found serum VEGF was suppressed more in individuals with type 1 ROP who received IVB treatment, compared with those who received IVR treatment two weeks after intravitreal injection (p=0.01); four weeks after the injection (p=0.03); and eight weeks after the injection (p=0.03).

Scientists found that IVB treatment suppressed serum VEGF levels in individuals with type 1 ROP for two months, while IVR treatment had less of an impact on VEGF levels. Scientists suggested that further studies were needed to determine the long-term effects of VEGF changes in individuals with ROP.

SOURCE: Wu WC, Shih CP, Lien R, et al. Serum vascular endothelial growth factor after bevacizumab or ranibizumab treatment for retinopathy of prematurity. Retina 2016; Jul 27. [Epub ahead of print].

Plasmin Enzyme-assisted Vitrectomy in a Pediatric Population

Researchers assessed the efficacy and safety of using plasmin-assisted vitrectomy in a pediatric population with vitreoretinal diseases. They prospectively recruited children ages 16 years or younger presenting with vitreoretinopathies who had undergone plasmin-assisted vitrectomy between 2012 and 2013.

The main outcome measure was induction of posterior vitreous detachment using a suction power of 200 mmHg or less during surgery.

Researchers included 11 eyes of 11 children (mean age: 3.7 years; average follow-up duration: 14.1 months). Cases included: three cases of stage 5 retinopathy of prematurity (27 percent); two cases of persistent fetal vasculature (18 percent); two cases of rhegmatogenous retinal detachment (18 percent); two cases of idiopathic epiretinal membrane (18 percent); one case of traumatic macular pucker (9 percent); and one case of traumatic vitreous hemorrhage (9 percent). PVD was achieved in all cases (100 percent) during surgery using low suction after plasmin treatment (mean: 150 ±39 mmHg; range: 100 to 200). Overall, anatomical success was achieved in eight eyes (73 percent). Visual acuity improved in five children (100 percent) for whom vision could be measured at six months after the operation. Researchers found cataracts in four eyes (36 percent), and a rise in transient intraocular pressure in one eye (9 percent).

Researchers determined that plasmin-assisted vitrectomy may offer an effective and less traumatic intervention for a variety of pediatric vitreoretinal diseases.

SOURCE: Lee YS, Wang NK, Chen YP, et al. Plasmin enzyme-assisted vitrectomy in pediatric patients with vitreoretinal diseases. Ophthalmic Res 2016; Aug 6. [Epub ahead of print].

Retinal & Choroidal Thickness on SS-OCT After Surgery for Idiopathic Macular Hole

Scientists analyzed changes in retinal nerve fiber layer thickness, ganglion cell layer thickness, retinal thickness and subfoveal choroidal thickness in eyes that received pars plana vitrectomy with internal limiting membrane peeling for idiopathic macular hole, and compared the data with that of fellow eyes and healthy controls.

The cross-sectional study included 49 subjects. Eighteen eyes that underwent surgery for IMH were designated as group one; 18 fellow eyes were designated as group two and 31 eyes of the healthy controls were designated as group three. Scientists measured RNFLT, GCLT, RT and SFCT with swept-source optical coherence tomography at the last postoperative visit.

The RNFLT was significantly lower in group one than in groups two and three (p<0.05). The GCLT was significantly reduced in all sectors in group one compared with groups two and three (p<0.05). The RT was significantly lower (except in central field) in group one than in groups two and three (p<0.05), and the SFCT was significantly decreased in group one compared with groups two and three (p<0.05).

Scientists determined that PPV with ILM peeling for IMH yielded a reduction in the RNFLT, GCLT, RT and SFCT, as detected on SS-OCT.

SOURCE: Bardak H, Gunay M, Bardak Y, et al. Retinal and choroidal thicknesses measured with swept-source optical coherence tomography after surgery for idiopathic macular hole. Eur J Ophthalmol 2016; Aug 10. [Epub ahead of print].

Suprachoroidal Buckling for RRD Secondary to Peripheral Retinal Breaks

Investigators looked at functional and anatomical outcomes of eyes undergoing suprachoroidal buckling for the management of peripheral retinal breaks in rhegmatogenous retinal detachment. The retrospective cohort study looked at 41 eyes of 41 individuals undergoing suprachoroidal buckling to manage rhegmatogenous retinal detachment secondary to single or multiple retinal breaks.

The introduction of filler material (Healon5; Abbott Medical Optics) using a 23-gauge (23-ga) olive-tipped, suprachoroidal cannula yielded suprachoroidal indentation, enabling the creation of a suprachoroidal dome and chorioretinal apposition. Combined 25-ga vitrectomy was performed in five eyes; cryopexy was used in 37 eyes; and laserpexy was used in four eyes.

Mean visual acuity gain was the primary outcome measure, with final retinal reattachment rate, single-surgery reattachment rate and complications as secondary outcome measures. Mean best-corrected distance visual acuity improved from 20/1,100 to 20/42. Single surgery reattachment rate was 92.7 percent (38/41 eyes). Final retinal reattachment was achieved in all 41 eyes. Investigators found no statistically significant difference in visual acuity gain or anatomical reattachment relative to retinal break quadrant or extent, and observed no major complications. Two localized suprachoroidal hemorrhages occurred at the entry site of the cannula, but resolved without further intervention.

Investigators suggested that suprachoroidal buckling using a specially designed cannula was a safe and effective procedure for managing rhegmatogenous retinal detachment secondary to peripheral retinal breaks.

SOURCE: El Rayes EN, Mikhail M, El Cheweiky H, et al. Suprachoroidal buckling for the management of rhegmatogenous retinal detachments secondary to peripheral retinal breaks. Retina 2016; Jul 29. [Epub ahead of print].