Editorial: Spending Money to Save Money on Patient Care—Development of OCT An editorial in the Dec. 5 online edition of the American Journal of Ophthalmology discussed the findings of an associated AJO paper titled “Estimating Public and Patient Savings From Basic Research—A Study of Optical Coherence Tomography in Managing Antiangiogenic Therapy”... FDA Accepts Regeneron’s SBLA Filing for 12-Week Dosing of Eylea The U.S. Food and Drug Administration accepted for review Regeneron Pharmaceuticals’ supplemental biologics license application for a 12-week dosing interval of Eylea ... And More...

Estimating Public & Patient Savings From Basic Research—A Study of OCT in Managing Antiangiogenic Therapy

Researchers compared patient and Medicare savings from the use of optical coherence tomography in guiding therapy for neovascular age-related macular degeneration with the research investments made by the National Institutes of Health and the National Science Foundation in developing OCT, as part of an observational cohort study. Several of the authors have a financial interest in OCT devices and/or companies.

Main outcome measures were spending by Medicare, as tracked by Current Procedural Terminology codes on intravitreal injections (67028), retinal OCT imaging (92134) and anti-vascular endothelial growth factor treatment–specific J-codes (J0178, J2778, J9035, J3490 and J3590). Researchers identified claims using the Medicare provider utilization and payment data from the Centers for Medicare and Medicaid Services among fee-for-service Medicare beneficiaries from 2012 to 2015; 2008 claims were acquired from the 100-percent FFS Part B Medicare claims file. Researchers determined OCT research costs by searching for grants awarded by the NIH and NSF from inception to 2015. They discounted all costs and savings by 3 percent annually and adjusted for inflation to 2015 dollars.

The researchers wrote that, between 2008 and 2015, the U.S. government accrued an estimated savings of $9 billion, while nvAMD patients saw an estimated savings of $2.2 billion, from the use of OCT to guide personalized anti-VEGF treatment. The $9 billion represents a 21-fold return on government investment into developing the technology through NIH and NSF grants, they added.

The researchers wrote further that, although an overall cost-benefit ratio of government-sponsored research is difficult to estimate because the benefit may be diffuse and delayed, their findings reveal that the investment in OCT over two decades was recouped many times over in a few years through better personalized therapy.

Source: Windsor MA, Sun SJJ, Frick KD, et al. Estimating public and patient savings from basic research-a study of optical coherence tomography in managing antiangiogenic therapy. Am J Ophthalmol 2017; Dec 1. [Epub ahead of print].

Baseline Predictors for Five-year VA Outcomes in AMD Treatment Trials

Researchers determined baseline predictors of visual acuity outcomes at five years after initiating treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration, as part of a secondary analysis of data from a cohort study.
Participants included individuals enrolled in the Comparison of AMD Treatments Trials who completed five-year follow-up visits.

They were randomly assigned to ranibizumab or bevacizumab and to one of three dosing regimens. After two years, individuals were released from the clinical trial protocol and assessed at five years. Trained readers evaluated baseline lesion features, fluid and thickness. Baseline predictors were determined by univariate and multivariate regression analyses.

The main outcome measures were VA score and change from baseline, ≥3-line gain, and VA 20/200 or worse at five years.

Among 647 people with VA measured at five years:
• mean VA scores in the study eye was 58.9 letters (≈20/63);
• mean decrease from baseline was 3.3 letters;
• 17.6 percent eyes gained ≥3 lines; and
• 19.9 percent had VA of 20/200 or worse.

In multivariate analyses, worse baseline VA was associated with:
• worse VA;
• more VA gain;
• higher percentage with ≥3-line gain; and
• higher percentage with 20/200 or worse at five years (all p<0.001).

Larger baseline choroidal neovascularization lesion area was associated with:
• worse VA;
• greater VA loss; and
• a higher percentage of patients with 20/200 or worse at five years (all p<0.05).

Absence of baseline subretinal fluid was associated with:
• worse VA (p=0.03); and
• more VA loss (p=0.03).

Female gender, bevacizumab treatment in the first two years and absence of retinal pigment epithelium elevation were associated with higher percentages of ≥3-line gain. Cigarette smoking was associated with a higher percentage with 20/200 or worse. None of the 21 single nucleotide polymorphisms evaluated were associated with VA outcomes.

Researchers determined that worse baseline VA, larger baseline CNV lesion area and the presence of baseline RPE elevation remained independently associated with worse VA, five years after initiating treatment with ranibizumab or bevacizumab. They also found that male gender, cigarette smoking, absence of subretinal fluid and treatment with ranibizumab in the first two years were independently associated with worse vision outcomes at five years.

SOURCE: Ying G, Maguire MG, Pan W, et al. Baseline predictors for five-year visual acuity outcomes in the comparison of AMD treatment trials. Ophthalmology Retina 2017; Nov 23. Epub ahead of print].

Comparing Real-world Acuity After Anti-VEGF Drugs for AMD

Researchers compared real-world visual acuity in individuals with neovascular age-related macular degeneration treated with a single anti-vascular endothelial growth factor drug for one year.

The retrospective, nonrandomized, comparative study included American Academy of Ophthalmology Intelligent Research in Sight Registry participants with nAMD who received only bevacizumab, ranibizumab or aflibercept for one year between 2013 and 2016.

Researchers divided participants into three groups and constructed multivariate analysis of covariance models in a stepwise fashion. Main outcome measures included the logarithm of the minimum angle of resolution VA at one year, and comparison of mean change in logMAR VA between drug types at baseline and one year.

Of 13,859 individuals, 6,723 received bevacizumab, 2,749 received ranibizumab and 4,387 received aflibercept for one year. A total of 84,828 injections were performed. The mean number of injections (SD) at one year was higher in the ranibizumab (6.4 [±2.4]) and aflibercept groups (6.2 [±2.4]) compared with the bevacizumab group (5.9 [±2.4]; p<0.0001). In the age-adjusted model, ranibizumab and aflibercept achieved better logMAR VAs at one year compared with bevacizumab (0.50 [±0.49], 0.49 [±0.44], 0.55 [±0.57]; p<0.0001). However, this difference wasn’t significant after multivariate adjustment (i.e., age, baseline VA, diabetes, posterior vitreous detachment, number of injections, race and insurance). There was no statistical difference in the age-adjusted or multivariate-adjusted mean logMAR VA change (SD) at one year among treatment groups (-0.048 [0.44] bevacizumab, -0.053 [0.46] ranibizumab and -0.040 [0.39] aflibercept; p=0.46). A higher percentage of individuals achieved a ≥3-line VA improvement at one year in the bevacizumab group (22.7 percent) compared with the ranibizumab (20.1 percent; p=0.0093) and aflibercept groups (17.8 percent; p<0.0001). Also, after multivariate adjustment, aflibercept exhibited greater log odds of ≥3-line VA loss compared with bevacizumab-only (1.25 log odds ratio; p<0.0016).

Researchers suggested that all three drugs improved VA similarly over one year of monotherapy.

Source: Rao P, Lum F, Wood K, et al. Real-world vision in age-related macular degeneration patients treated with single anti–VEGF drug type for 1 year in the IRIS Registry. Ophthalmology 2017; Nov 13. [Epub ahead of print].

Dexamethasone & Ranibizumab in Treatment of BRVO or CRVO

Scientists evaluated the therapeutic outcomes for dexamethasone implants or intravitreal ranibizumab injections over six months in individuals with macular edema due to branch or central retinal vein occlusion, in a real-world setting.

They included 107 people with BRVO or CRVO in the retrospective study. Individuals were treated with monotherapy consisting of Dex or three monthly IVR injections following a pro re nata regimen. Scientists compared best-corrected visual acuity, central retinal thickness and intraocular pressure between the two therapy groups after one, three and six months.

Findings included the following:
• Dex-treated individuals with BRVO achieved a statistically significant gain in BCVA measured in logMAR after one month (mean gain, CI: 0.21, 0.08 to 0.34, p=0.001); three months (CI: 0.16, 0.03 to 0.28, p=0.012); and six months (CI: 0.19, 0.07 to 0.32, p=0.002).
• IVR-treated individuals showed a statistically significant BCVA gain in months three (mean improvement, CI: 0.13, 0.01 to 0.26, p=0.039) and six (0.16, 0.03 to 0.29, p=0.018).
• In Dex-treated individuals with CRVO, BCVA worsened slightly at month six (mean worsening, CI: -0.08, -0.24 to 0.08, p=0.305).
• IVR-treated individuals achieved a statistically significant BCVA gain at three months (mean improvement, CI: 0.14, 0.02 to 0.25, p=0.021).
• Both therapies had statistically significant CRT reductions of 150 to 200 μm (median). Adverse events reported were predictable and limited.

Scientists found comparable improvement in BCVA and CRT after Dex and IVR injections for BRVO treatment. They added that CRVO showed greater improvement with IVR.

SOURCE: Winterhalter S, Eckert A, vom Brocke G-A, et al. Real-life clinical data for dexamethasone and ranibizumab in the treatment of branch or central retinal vein occlusion over a period of six months. Graefes Arch Clin Exp Ophthalmol 2017; Nov 28. [Epub ahead of print].

Safety & Efficacy of Dexamethasone for Treatment of Macular Edema Secondary to RVO

Investigators evaluated the safety and efficacy of dexamethasone intravitreal 0.7-mg implants for treatment of macular edema associated with retinal vein occlusion, as part of a six-month, randomized, double-masked, multicenter, Phase III clinical trial with an open-label study extension.

Individuals with branch or central RVO received Dex (n=129) or sham procedures (n=130) in the study eye at baseline; all subjects who met retreatment criteria received Dex at month six. Efficacy measures included Early Treatment Diabetic Retinopathy Study best-corrected visual acuity and central retinal thickness tests.

Time to ≥15-letter BCVA improvement from baseline during the first six months (primary endpoint) was earlier with Dex than in the sham group (p<0.001). At month two (peak effect), the percentage of individuals with ≥15-letter BCVA improvement from baseline was 35 percent with Dex and 12 percent in the sham group. The mean BCVA change from baseline was +10.6 letters with Dex and +1.7 letters in the sham group. The mean CRT change from baseline was -407 μm with Dex and -62 μm in the sham group (all p<0.001). Outcomes were better with Dex than the sham group in BRVO and CRVO. The most common treatment-emergent adverse event was increased intraocular pressure, although increases generally were controlled with topical medication. Mean IOP normalized by month four, and no individuals required incisional glaucoma surgery.

Investigators wrote that Dex had a favorable safety profile and provided clinically significant benefits in a Chinese population with RVO. They added that visual and anatomic outcomes improved with Dex compared with the sham group for three to four months after a single implant.

SOURCE: Li X, Wang N, Liang X, et al. Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in Chinese patients: Randomized, sham-controlled, multicenter study. Graefes Arch Clin Exp Ophthalmol 2017; Nov 8. [Epub ahead of print].

Early Microvascular & Neural Changes in Type 1 & 2 Diabetes Without Signs of DR

Researchers assessed and compared early modifications in inner retinal layer thickness and optical coherence tomography angiography parameters in individuals with diabetes mellitus types 1 and 2 without clinical signs of diabetic retinopathy.

Ninety eyes of 90 subjects (24 type 1 DM, 36 type 2 DM and 30 healthy controls) were prospectively evaluated with spectral-domain OCT, swept-source OCTA and color fundus photography (on the same day). Retinal nerve fiber layer, ganglion cell layer, and nerve fiber layer + GCL thicknesses were automatically determined by the instrument in the central 1, 3 and 6 mm. On OCTA, the following parameters were evaluated:

• area of foveal avascular zone;
• number of focally dilated endings of the capillaries (detected on OCT angiography);
• presence of regular/irregular FAZ;
• capillary loss; and
• capillary network irregularities in the superficial capillary plexus and deep capillary plexus.

Observations included:
• the GCL (p=0.0099) and NFL + GCL (p=0.0367) were significantly thicker in DM type 1 vs. DM type 2 in the central 1 mm after adjustment for age and DM duration;
• the FAZ area was significantly larger in DM type 1 vs. controls in SCP and DCP, and in DM type 1 vs. type 2 in DCP (p<0.05 for all);
• the number of capillary focally dilated endings was higher in DM type 1 vs. controls in SCP and DCP (p<0.01 for all), and in DM type 2 vs. controls only in DCP (p=0.007); and
• perifoveal capillary loss in SCP and inner retinal layer thickness had the highest correlation in both DM types.

Researchers found that specific neural and microvascular modifications occurred before clinical signs of diabetic retinopathy in DM types 1 and 2. They added that perifoveal capillary loss in the SCP was highly correlated with the inner retinal layer, and that these data may help characterize individuals at the preclinical stage of diabetic retinopathy.

Source: Vujosevic S, Muraca A, Alkabes M, et al. Early microvascular and neural changes in patients with type 1 and type 2 diabetes mellitus without clinical signs of diabetic retinopathy. Retina 2017; Dec 4. [Epub ahead of print].

Repeat PPV After Failed Surgery for Proliferative Vitreoretinopathy

Researchers evaluated outcomes of repeat pars plana vitrectomy for proliferative vitreoretinopathy after failed pars plana vitrectomy, as part of a retrospective case series. Subjects included 51 eyes of 50 individuals who underwent repeat surgery after failed previous pars plana vitrectomy for proliferative vitreoretinopathy from 2000 to 2015 at the Kresge Eye Institute.

Researchers assigned individuals to successful and unsuccessful groups. They defined success as retinal reattachment, silicone oil removed and best-corrected visual acuity ≥5/200 at the final follow-up visit.

Forty-three eyes (84.3 percent) were successfully reattached at the last follow-up. Seventeen (33.3 percent) eyes were successful, and 34 (66.7 percent) eyes were unsuccessful according to the criteria. Compared with the successful group, the unsuccessful group had more eyes with preoperative BCVA <5/200 (p<0.001), preoperative BCVA of hand motion or worse (p= 0.002), preoperative flare ≥grade 2+ (p=0.03), preoperative posterior breaks (p=0.02), previous retinectomy (p=0.04) and final postoperative hypotony (intraocular pressure ≤5 mmHg) (p=0.005). Eyes with silicone oil removed were more likely to have BCVA ≥5/200 (p<0.001) at the final follow-up visit. Location of individuals >100 miles (p=0.04) from Detroit and preoperative BCVA of hand motion or worse (p=0.01) were significantly associated with failure in the logistic regression analysis.

Researchers identified preoperative and perioperative factors associated with success after repeat surgery for proliferative vitreoretinopathy in bivariate and logistic analyses relative to ambulatory vision, retinal reattachment and silicone oil removal. They wrote that the decision to perform surgical reoperation should be based on multiple factors, most importantly preoperative BCVA.

Source: Narala R, Nassiri N, Kim C, et al. Outcomes of repeat pars plana vitrectomy after failed surgery for proliferative vitreoretinopathy. Retina 2017; Dec 11. [Epub ahead of print].

FAZ Analysis Using OCTA Before & After Idiopathic Epiretinal Membrane Surgery

Investigators determined the size of the foveal avascular zone by optical coherence tomography angiography before and after idiopathic epiretinal membrane surgery by retrospectively studying 13 consecutive patients (13 eyes) with unilateral epiretinal membrane.

They used OCTA to measure the FAZ area within 3-mm² scans of the superficial and deep plexus layers before and six months after vitrectomy. The unaffected fellow eyes served as controls.

At six months post-vitrectomy, the mean superficial area (0.080 ±0.038) and deep area (0.113 ±0.045 mm²) were significantly larger (p<0.0001, p=0.0035) than the corresponding mean preoperative FAZ areas (0.056 ±0.030 and 0.082 ±0.035 mm²). However, the areas of FAZ expansion were small (0.024 ±0.013 and 0.031 ±0.031 mm²). The mean postoperative superficial and deep FAZ areas were significantly smaller (p<0.0001, p<0.0001) than those of fellow eyes (0.295 ±0.108 and 0.410 ±0.142 mm²). Multiple regression analyses showed that the preoperative FAZ area had the highest correlation with the postoperative FAZ area (p<0.05).

Investigators uncovered horizontal contraction of the FAZ area in eyes with epiretinal membrane. Because preoperative and postoperative FAZ areas correlated, they suggested that the FAZ area might be a useful parameter for determining timing of surgery for epiretinal membrane.

SOURCE: Kitagawa Y, Shimada H, Shinojima A, et al. Foveal avascular zone area analysis using optical coherence tomography angiography before and after idiopathic epiretinal membrane surgery. Retina 2017; Dec 11. [Epub ahead of print].

Correlation of Ultra-Widefield FA and OCTA in Sickle Cell Retinopathy

Scientists aimed to determine whether the degree of peripheral nonperfusion seen on ultra-widefield fluorescein angiography correlated with measures of macular vascular flow as seen on optical coherence tomography angiography in sickle cell retinopathy, as part of a prospective, observational study.

Participants included individuals with sickle cell disease undergoing an eye exam at an urban tertiary medical center.

All individuals underwent dilated fundus exams, UWF FA and macular OCTA imaging on the same day. Scientists measured the peripheral nonperfusion seen on UWF FA to calculate an ischemic index (visualized nonperfusion/total visualized retinal area × 100 percent) and recorded OCTA measurements of macular vessel density. They correlated the degree of peripheral nonperfusion and vessel density. The main outcome measure included the correlation between ischemic index as seen on UWF FA and macular vessel density on OCTA.

Thirty-six eyes of 19 individuals with a mean age of 30.8 years were included. Sickle genotypes included 14 individuals with SS (73.7 percent), four with SC (21.1 percent) and one with β-thalassemia (5.2 percent). The average ischemic index was 4.4 percent for all eyes and was found to be higher in individuals with sickle SC (8 percent) than in those with sickle SS (3.2 percent; p=0.01). The ischemic index also was higher in those with proliferative sickle cell retinopathy (9.3 percent) than in those without (2.8 percent; p<0.01). The ischemic index on UWF FA showed a statistically significant correlation (p<0.05) with vessel density on OCTA in the temporal subfield of the superficial capillary plexus and in all subfields of the deep capillary plexus.

Scientists found that peripheral nonperfusion seen on UWF FA was greater in those with sickle SC disease and proliferative retinopathy, and was correlated with macular vessel density on OCTA, especially in the deep retinal plexus.

SOURCE: Han IC, Linz MO, Liu TYA, et al. Correlation of ultra-widefield fluorescein angiography and OCT angiography in sickle cell retinopathy. Ophthalmology Retina 2017; Dec 9. [Epub ahead of print].