FDA Approves Genentech’s Lucentis (Ranibizumab Injection) Prefilled Syringe Genentech announced that the U.S. Food and Drug Administration approved the Lucentis (ranibizumab injection) 0.5 mg prefilled syringe as a new method of administering the medicine... Data Reinforce Efficacy of Voretigene Neparvovec in RPE65-Mediated IRD Spark Therapeutics announced that Albert M. Maguire, MD, professor of ophthalmology at the Perelman School of Medicine of the University of Pennsylvania and principal investigator, presented one-year efficacy data from the crossover group and two-year durability data from the original intervention group... And More...

Ranibizumab and Aflibercept in AMD: Time to Retreatment and Visual Function

In a study funded by Novartis, researchers compared time to retreatment and visual function between individuals with treatment-naïve neovascular age-related macular degeneration treated with either intravitreal ranibizumab or intravitreal aflibercept in routine clinical practice, as part of a retrospective, interventional, comparative case series.

They included 200 eyes of 197 individuals with neovascular AMD for the study, along with 99 individuals in the IVR group and 101 individuals in the IVA group, who met the inclusion criteria with 12 months of follow-up in the present study. All individuals received three consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab or 2 mg/0.05 mL aflibercept as loading doses. Researchers allowed retreatment if they noted evidence of clinical deterioration, or presence of intraretinal edema or subretinal fluid on spectral-domain optical coherence tomography exam performed at the one-month follow-up. Using the Kaplan-Meier analysis, they compared the time to retreatment after the third injection during the loading phase to the first recurrence during the maintenance phase between treatments, and they compared functional and anatomic outcomes between the IVR and IVA groups.

The median time to retreatment after the last induction dose was five months in both groups. The proportion of individuals treated with IVR who required injection retreatment (67.7 percent) was not significantly higher than that of those treated with IVA (63.4 percent) at the 12-month follow-up; log-rank test, p=.554. In both groups, researchers observed significant improvements in postoperative best-corrected visual acuity compared with preoperative VA over the 12-month follow-up period (p<.05 for both). Central foveal thickness decreased from the baseline values in both groups during the follow-up period (p<.001 for both). Although researchers found a trend toward greater BCVA improvements in the IVA group, they found no significant differences in BCVA or CFT between the treatment groups.

Researchers found that both IVR and IVA were well-tolerated and demonstrated efficacy in improving the visual acuity in treatment-naïve AMD. Despite a trend toward greater BCVA improvements in the IVA group, researchers determined a similar injection burden following the loading phases of both ranibizumab and aflibercept.

SOURCE: Inoue I, Yamane S, Sato S, et al. Comparison of time to retreatment and visual function between ranibizumab and aflibercept in age-related macular degeneration. Am J Ophthalmol 2016;169:95-103.

Intravitreal Aflibercept for DME: 148-Week Results From VISTA and VIVID Studies

Researchers compared efficacy and safety of intravitreal aflibercept injection with macular laser photocoagulation for diabetic macular edema over three years, as part of two similarly designed Phase III trials sponsored by Regeneron: VISTA-DME and VIVID-DME. They looked at individuals with central-involved DME (eyes; n=872).

Eyes received IAI 2 mg every four weeks (2q4); IAI 2 mg every eight weeks after five monthly doses (2q8); or laser control. From week 24, if rescue treatment criteria were met, IAI cases received active laser, and laser controls received IAI 2q8. From week 100, laser controls not receiving IAI rescue treatment received IAI as needed according to retreatment criteria. The primary endpoint was the change from baseline in best-corrected visual acuity at week 52. Researchers reported 148-week results.

Mean BCVA gain from baseline to week 148 was 10.4 letters with IAI 2q4; 10.5 with IAI 2q8; and 1.4 letters with laser control (p<0.0001) in VISTA; while the mean BCVA gain was 10.3 with IAI 2q4; 11.7 with IAI 2q8; and 1.6 letters with laser control (p<0.0001) in VIVID. The proportion of eyes that gained ≥15 letters from baseline at week 148 was: 42.9 percent with IAI 2q4; 35.8 percent with IAI 2q8, and 13.6 percent with laser control (p<0.0001) in VISTA; and 41.2 percent with IAI 2q4; 42.2 percent with IAI 2q8; and 18.9 percent with controls (p<0.0001) in VIVID. Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 vs. those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale score in both VISTA (29.9 percent and 34.4 percent vs. 20.1 percent [IAI 2q4: p=0.0350; IAI 2q8: p=0.0052]) and VIVID (44.3 percent and 47.8 percent vs. 17.4 percent [p<0.0001 for both]). In an integrated safety analysis, the most frequent ocular serious adverse event was cataract (3.1 percent for 2q4; 2.1 percent for 2q8; and 0.3 percent for control).

Researchers found that visual improvements observed with both IAI regimens (over laser control) at weeks 52 and 100 were maintained at week 148, with similar overall efficacy in the groups. Treatment with IAI also had positive effects on the DRSS score. Over 148 weeks, researchers found that the incidence of adverse events was consistent with the known safety profile of IAI.

SOURCE: Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID Studies. Ophthalmology 2016; Sep 17. [Epub ahead of print].

Outcomes of Ranibizumab for DME: Protocol 3 With High-dose (READ-3) Study

Scientists compared 2 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema, as part of a randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial.

A total of 152 individuals (152 eyes) with DME participated in the trial. Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n=77) or 2 mg (n=75) RBZ. Study eyes received six monthly mandatory injections followed by as-needed injections until month 24.

The primary efficacy endpoint of the study was mean change in best-corrected visual acuity and central foveal thickness at month six. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. Scientists randomized a total of 152 eyes in the study.

At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n=59) and +6.78 letters in the 2 mg RBZ group (n=54) (p=0.02). The mean numbers of RBZ injections through month 24 were 18.4 in the 0.5 mg group, and 17.3 in the 2 mg RBZ groups (p=0.08). The mean change in CFT was -192.53 μm in the 0.5 mg RBZ group and -170.64 μm in the 2 mg RBZ group (p=0.41). By month 24, three deaths had occurred in both the 0.5 mg RBZ group and the 2 mg RBZ group; five of these six deaths occurred secondary to cardiovascular causes, and one death occurred as the result of severe pneumonia. All five patients with a cardiovascular cause of death had a history of coronary heart disease.

At month 24, scientists observed significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Scientists identified no new safety events, and concluded that 2-mg RBZ did not appear to provide additional benefit over 0.5-mg RBZ in this study population.

SOURCE: Sepah YJ, Sadiq MA, Boyer D, et al. Twenty-four–month outcomes of the ranibizumab for edema of the macula in diabetes – protocol 3 with high dose (READ-3) Study. Ophthalmology 2016; Aug. 25. [Epub ahead of print].

Anatomical Relationships Between Retinal Neovascularization & Posterior Vitreous in PDR

Researchers described anatomical relationships of retinal neovascular complexes (NVCs) and the posterior vitreous in proliferative diabetic retinopathy using spectral-domain optical coherence tomography, as part of a cross-sectional study.

They imaged neovascular complexes using SD-OCT in 51 eyes of 37 individuals, and analyzed the relationship of NVCs to the posterior vitreous cortex and posterior vitreous spaces, such as the premacular bursa, prevascular vitreous fissures and perimacular cisterns.

In the 77 NVCs evaluated, 61 (79 percent) had grown along the outer surface of the posterior hyaloid face, with vitreoschisis present in 37 (48 percent). The "wolf's jaw" configuration was present in 9 percent and resulted from NVC arising from the arcades and proliferation along the posterior hyaloid face. By contrast, NVCs that invaded the bursa originated from smaller venous tributaries more distant from the arcades. The NVCs invaded the premacular bursa and prevascular vitreous fissure/perimacular cistern infrequently—in 15 percent and 38 percent of cases, respectively (p=0.137).

Researchers revealed that tomographic analysis of diabetic NVCs showed that most NVCs arose and grew along the posterior hyaloid face and that vitreoschisis was more prevalent than in previous ultrasound studies. Researchers deduced that the wolf's jaw configuration did not seem to result from the invasion of the bursa, as previously suggested.

SOURCE: Vaz-Pereira S, Dansingani KK, Chen KC, et al. Tomographic relationships between retinal neovascularization & posterior vitreous in proliferative diabetic retinopathy. Retina 2016; Sept. 30. [Epub ahead of print].

Using OCTA for Follow-up of RVO Treated With Anti-VEGF

Investigators used optical coherence tomography angiography to evaluate the changes of vascular flow of individuals treated with intravitreal injections of anti-vascular endothelial growth factor for macular edema secondary to retinal vein occlusion.

They retrospectively evaluated individuals with RVO with macular edema and treated with intravitreal injections of anti-VEGF. The following exams were performed before and after treatment: best-corrected visual acuity; spectral-domain optical coherence tomography; fluorescein angiography and OCTA (Optovue). They performed automatic measurements of vascular density of the superficial and deep capillary plexus and compared them with age- and sex-matched healthy subjects.

Twenty-eight eyes of 28 individuals (mean age 66.2 years; males 19 percent) were evaluated, including 13 with central RVO; 11 with branch RVO; and four with hemicentral RVO. After treatment, mean central macular thickness significantly decreased from 644 µm to 326 µm and BCVA increased from 20/125 to 20/63 (p<0.01 for both results). On OCTA, perifoveal capillary disruption (p=0.029) and the number of cysts in the superficial capillary plexus and deep capillary plexus (p<0.002) significantly decreased after treatment. The mean vascular density in the superficial capillary plexus slightly decreased during follow-up from 46.44 percent to 45.01 percent (not significantly). These densities were significantly less than those observed in healthy controls (p<0.001).

Investigators wrote that OCTA revealed regression of macular edema, reduced capillary disruption and cysts, and a slight decrease in mean macular vascular density over time and despite treatment. They concluded that OCTA enabled qualitative and quantitative evaluation during follow-up of individuals treated for RVO.

SOURCE: Sellam A, Glacet-Bernard A, Coscas F, et al. Qualitative and quantitative follow-up using optical coherence tomography angiography of retinal vein occlusion treated with anti-VEGF: Optical coherence tomography angiography follow-up of retinal vein occlusion. Retina 2016; Sept. 28. [Epub ahead of print].

Intravitreal Ziv-Aflibercept for ME Following Retinal Vein Occlusion

Scientists reported the efficacy of intravitreal administration of the anti-cancer drug ziv-aflibercept in eyes with macular edema due to retinal vein occlusions, as part of a prospective study.

They enrolled consecutive cases with persistent or recurrent macular edema (central macula thickness >250 µm) due to RVO. Study eyes received intravitreal injections of ziv-aflibercept (1.25 mg/0.05 mL) at baseline, and researchers reassessed individuals monthly for four months, administering additional injections pro re nata for worsening best-corrected visual acuity, intraretinal edema or subretinal fluid seen on spectral-domain optical coherence tomography, or for central macular thickness measurements >250 µm. The primary endpoint was improvement in mean CMT at four months. Secondary endpoints included improvement in mean BCVA, and ocular and systemic safety signals.

Nine eyes (five central and four branch RVOs) of nine individuals were enrolled. The mean ± standard deviation CMT decreased from 604 ±199 µm at baseline to 319 ±115 µm (p=0.001) at one month and to 351 ±205 µm (p=0.026) at four months. The mean BCVA did not improve significantly from baseline (1 LogMAR) to one month (0.74 LogMAR; p=0.2) or four months (0.71 LogMAR; p=0.13). No safety signals were noted.

In this small, prospective study, intravitreal ziv-aflibercept significantly improved mean CMT in eyes with persistent or recurrent macular edema due to RVOs. Scientists suggested prospective, randomized trials comparing ziv-aflibercept with standard pharmacotherapy were needed to better define efficacy and safety.

SOURCE: Paulose R, Chhablani J, Dedhia CJ, et al. Intravitreal ziv-aflibercept for macular edema following retinal vein occlusion. Clin Ophthalmol 2016:10;1853-8.

Volume-Rendered Angiographic and Structural OCTA of Type 2 Macular Telangiectasia

Scientists evaluated volume-rendered angiographic and structural optical coherence tomography of macular telangiectasia type 2 (MacTel2) for right-angle vein complexes, macular cavitations and signs of deeper retinal vascular invasion, as part of a retrospective review of imaging performed in a community-based retinal referral center.

They scanned 24 eyes of 16 people (mean age: 61.8 years) using OCT and employing split-spectrum amplitude-decorrelation techniques to derive flow information. They extracted data to create volume-rendered images of the retinal vasculature with integrated structural information derived from the component OCT images.

Scientists noted that right-angle veins seemed to be associated with vascular proliferation external to the deep vascular plexus. The origin of a right-angle vein was surrounded by a stellate arrangement of radiating retinal vessels apparently caused by contraction of surrounding tissue in the temporal macula. They found cavitations in the fovea, which varied in size and configuration from one exam to the next. Many smaller cavitations, called microcavitations, were seen in the surrounding macula. Vascular invasion occurred into the subretinal space.

Scientists wrote that contractile features of the tissue in the temporal macula, as well as and the number, size and temporal variations in the cavitations, have not been mentioned in previous published descriptions of MacTel2. They found that vascular invasion of deeper layers occurred in the temporal macula through the outer nuclear layer, and that volume-rendered angiographic and structural OCT offered unprecedented ability to examine vascular interrelationships and associations with cavitations in the macula.

SOURCE: Spaide RF, Mihoko S, Yannuzzi LA, et al. Volume-Rendered Angiographic and Structural Optical Coherence Tomography Angiography of Macular Telangiectasia Type 2. Retina 2016; Sept. 30. [Epub ahead of print].

Risk of Recurrence After Primary Rhegmatogenous RD Repair

Researchers evaluated functional and anatomical outcomes of patients with retinal redetachments (re-RD) after surgery for primary rhegmatogenous retinal detachment. They retrospectively reviewed medical records of eyes with re-RD after rhegmatogenous retinal detachment surgery between 1999 and 2014, at the Department of Ophthalmology, University of Cologne, Germany. Data included preoperative and postoperative clinical findings, best-corrected visual acuity, presence and grade of proliferative vitreoretinopathy, surgical procedures and complication rates.

A total of 328 eyes of 2,457 developed a re-RD (13.3 percent), of which 242 eyes (73.8 percent) had only re-RD, while 86 eyes (26.2 percent) had two or more re-RDs. Visible presence of proliferative vitreoretinopathy during first re-detachment surgery increased risk of re-RD with relative risk ratio of 1.46 (p=0.05). BCVA deteriorated with every additional re-RD (p<0.001). A total of 237 eyes received oil endotamponade at least once. In 91 cases, researchers left oil endotamponade for the long term, until last follow-up.

Researchers concluded that the occurrence of multiple re-RDs (≥2 re-RDs) is an infrequent complication after rhegmatogenous retinal detachment surgery. After a first re-RD, risk for multiple re-RDs doubled compared with the risk of a first re-detachment. Researchers added that mean functional outcome was unfavorable, and predictability remained poor because of the wide range of inter-individual postoperative BCVA.

SOURCE: Enders P, Schick T, Schaub F, et al. Risk of multiple recurring retinal detachment after primary rhegmatogenous retinal detachment repair. Retina 2016; Sep 15. [Epub ahead of print].

Diagnostic Clinical Exam Findings vs. Telemedicine Evaluation of Acute ROP

Investigators aimed to characterize discrepancies in the findings of retinopathy of prematurity between digital retinal image grading and exam results from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity study, conducted from May 2011 to October 2013.

Four experts conducted a post-study consensus review of images to examine discrepancies in findings between image grades by trained non-physician readers and physician exam results in infants with referral-warranted ROP (RW-ROP). Images were obtained from 13 North American neonatal intensive care units from eyes of infants with birth weights less than 1,251 g. For discrepancy categories with more than 100 cases, 40 were randomly selected; in total, 188 image sets were reviewed. The main outcome and measure was consensus evaluation of discrepant image and exam findings for RW-ROP components.

Among 5,350 image set pairs, investigators noted 161 instances of image grading that did not detect RW-ROP noted on clinical exam (G−/E+) and 854 instances in which grading noted RW-ROP when the exam did not (G+/E−). Among the sample of G−/E+ cases, 18 of 32 reviews (56.3 percent) agreed with clinical exam findings that ROP was present in zone I, and 18 of 40 (45 percent) agreed that stage 3 ROP was present, but only one of 20 (5 percent) agreed that plus disease was present. Among the sample of G+/E− cases, 36 of 40 reviews (90 percent) agreed with readers that zone I ROP was present; 23 of 40 (57.5 percent) agreed with readers that stage 3 ROP was present; and four of 16 (25 percent) agreed that plus disease was present. Based on the consensus review results of the sampled cases, investigators estimated that the review would agree with clinical exam findings in 46.5 percent of the 161 G−/E+ cases (95 percent CI, 41.6-51.6) and agree with trained reader grading in 70 percent of the 854 G+/E− cases (95 percent CI, 67.3-72.8) for the presence of RW-ROP.

Investigators wrote that the findings revealed the limitations and strengths of remote evaluation of fundus images and bedside clinical exam of infants at risk for ROP, and highlighted the need for standardized approaches as ROP telemedicine becomes more widespread.

SOURCE: Quinn GE, Ells A, Capone A Jr., et al. Analysis of discrepancy between diagnostic clinical examination findings and corresponding evaluation of digital images in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity study. JAMA Ophthalmol 2016; Sep 22. [Epub ahead of print].