EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

PURPOSE: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). METHOD: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. RESULTS: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. CONCLUSION: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.

Impact of insulin treatment in diabetic macular edema therapy in type 2 diabetes.

OBJECTIVE: To evaluate the impact of insulin therapy on the outcomes of diabetic macular edema (DME) treatment with vascular endothelial growth factor (VEGF) inhibitors in people with type 2 diabetes. METHODS: A retrospective consecutive case series of 95 patients with type 2 diabetes and DME who were treated with anti-VEGF therapy. We examined 2 cohorts: patients taking only oral antidiabetic agents and patients on insulin therapy. The main outcome measures were change in visual acuity and change in central subfield macular thickness measured by spectral-domain optical coherence tomography. The additional variables analyzed included glycated hemoglobin (A1C), creatinine, blood pressure and body mass index and their correlations with clinical findings. RESULTS: Both groups had a statistically significant improvement in visual acuity (oral antidiabetic agents group: 20/61 to 20/49, p=0.003; insulin therapy group: 20/76 to 20/56, p=0.005). There was no difference between groups at initial or 12-month examination (p=0.239 and p=0.489, respectively). From an anatomic standpoint, central subfield macular thickness also improved significantly in both groups: from 454.7 µm to 354.9 µm (p<0.001) in the oral antidiabetic agents group and from 471.5 µm to 368.4 µm (p<0.001) in the insulin therapy group. Again, there was no significant difference between groups at initial or 12-month follow-up examinations (p=0.586 and p=0.591, respectively). Mean A1C levels remained relatively stable during the follow up in both groups. CONCLUSION: Anti-VEGF therapy is a useful treatment for DME. This study suggests that chronic insulin therapy, compared with oral antidiabetic agents, does not modify the anatomic or functional effectiveness of DME treatment.

The impact of metabolic parameters on clinical response to VEGF inhibitors for diabetic macular edema.

AIMS: Evaluate the role of systemic factors on the functional and anatomic outcomes of anti-VEGF therapy for diabetic macular edema (DME). METHODS: A retrospective consecutive case series of 124 patients with DME treated with anti-VEGF therapy was collected. The main outcome measures were change in best corrected visual acuity (BCVA) and change central subfield macular thickness (CST) measured with spectral-domain ocular tomography coherence (SD-OCT); and their correlation with clinical findings. RESULTS: Patients with serum hemoglobin A1c values (HbA1c) ≤ 7.0% had a statistically significant improvement in BCVA (20/66 to 20/43, p < 0.001), and those patients with HBA1c > 7.0% also had a significant but less robust improvement in BCVA (20/78 to 20/62, p = 0.024). CST improved significantly in both groups, but showed a larger magnitude of improvement in the group with better DM control [-140.7 microns (p < 0.001) and -83.3 microns (p < 0.001)]. Mean HBA1c levels remained relatively stable during the follow-up in both groups, but patients with improved glucose control during the study duration had a significantly lower retinal thickness than patients that had a stable or worsening HbA1c (mean final CST of 324.3 versus 390.0 µm, respectively, p = 0.042). Other systemic parameters were not correlated with changes in OCT thickness or BCVA. There was not a significant difference related to number of intravitreal injection in the HbA1c ≤ 7.0% group compared to HbA1c > 7.0% group, mean of 5.48 and 6.0 intravitreal injections respectively (p = 0.362). CONCLUSION: This study suggests that glucose regulation can impact the response to anti-VEGF therapy in the management of DME.

24-Gy low-voltage x-ray irradiation with ranibizumab therapy for neovascular AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 24-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage x-ray irradiation at a dose of 24 Gy was administered in one session through three locations in the inferior pars plana in a consecutive series of patients with neo-vascular AMD (treatment naïve and previously treated). Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity examinations were performed at 1 week, 1 month, and monthly thereafter with quarterly fluorescein angiography. RESULTS: Nineteen patients completed 6 months of follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 38.3 ± 19.5 letters. At 6 months, the corresponding ETDRS score was 44.7 ± 16.8 letters. At 6 months, the mean change in visual acuity was 6.4 ± 9.8 ETDRS letters. Patients received an average of 0.4 additional ranibizumab injections following the initial two mandated injections. CONCLUSION: A single treatment of external 24-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement in visual acuity in patients with neovascular AMD at 6 months, with no radiation-related adverse effects.

16-Gy low-voltage x-ray irradiation with ranibizumab therapy for AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 16-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage 16-Gy x-ray irradiation was administered in one session through three locations in the inferior pars plana. Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) examinations were performed at 1 week, 1 month, and monthly thereafter, with quarterly fluorescein angiography (FA). After the two initial ranibizumab injections, subsequent injections were administered according to the following criteria: VA decline of 10 ETDRS letters compared with baseline, increase of 100-µm central foveal thickness on OCT compared with baseline, the development of new submacular hemorrhage, and the development of a new area of classic choroidal neovascularization on FA. RESULTS: Twenty-six patients completed a 6-month follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 46.6 letters (range: 5 to 80; standard deviation [SD]: 21.5). At 6 months, the corresponding ETDRS score was 55.6 letters (range: 25 to 80; SD: 18.9) and the mean change in VA was 9.5 ETDRS letters (SD: 10.3). On responder analysis, 96% lost 15 or fewer ETDRS letters, 81% gained 0 or more ETDRS letters, and 50% gained 15 or more ETDRS letters. Patients received a total of 13 ranibizumab injections following two initial injections. At 6 months, patients received an average of 0.5 additional injections following the initial two mandated injections. CONCLUSION: A single treatment of externally applied, non-invasive 16-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement of VA in patients with neovascular AMD at 6 months with no radiation-related adverse effects.

Optical coherence tomography enhanced depth imaging of choroidal tumors.

PURPOSE: To describe the spectral-domain optical coherence tomography (SD-OCT) features of choroidal tumors imaged using enhanced depth imaging (EDI) technique. DESIGN: Prospective observational case series. METHODS: One tumor each from 23 eyes of 23 patients was included. All the patients underwent clinical fundus photography, ultrasonography, and EDI SD-OCT. Qualitative characteristics (tumor outline, reflectivity and/or shadowing of choroidal layers, and detection of inner sclera) and quantitative characteristics (measurement of maximum tumor thickness and the largest tumor diameter) were assessed. RESULTS: Patients (male=12) were categorized as: amelanotic choroidal nevus (4), melanotic choroidal nevus (9), choroidal melanoma (3), circumscribed choroidal hemangioma (3), and choroidal metastasis (4). In all cases, EDI SD-OCT was able to identify the tumor distinctly from the surrounding normal choroid. Qualitative analysis revealed: amelanotic nevi, homogenous and medium reflective band with visible choroidal vessels; melanotic nevi and choroidal melanomas, high reflective band in the anterior choroid with shadowing, and nonvisualization of choroidal vessels and inner sclera; choroidal hemangiomas, medium/low reflective band without shadowing; and choroidal metastasis, low reflective band in the deep choroid with enlargement of the suprachoroidal space. Maximum tumor diameter and thickness was measurable by EDI SD-OCT only in 10 cases that were <9.0 mm in diameter and <1.0 mm in thickness (undetectable by ultrasonography). CONCLUSIONS: It is possible to obtain cross-sectional views of a variety of choroidal tumors using EDI SD-OCT. Small choroidal tumors nondetectable by ultrasonography can be objectively measured by this technique.

Optical coherence tomography 3: Automatic delineation of the outer neural retinal boundary and its influence on retinal thickness measurements.

PURPOSE: To investigate the automatic delineation of the outer limits of the macular neural retina, by using the optical coherence tomography (OCT)-3 built-in software, and to determine its influence in assessing retinal thickness in the normal macula. METHODS: Retrospective analysis of the OCT3 data at a tertiary-care referral center was performed to study the automatic delineation of the outer neural retina boundary generated by the OCT built-in software. In parallel, a cross-sectional study was designed to compare retinal thickness measurements obtained at specific macular regions of nine normal eyes by the automatic measurement tool with those obtained using a manual-caliper-assisted technique. RESULTS: OCT data from 121 eyes were evaluated. Two parallel, linear highly reflective layers (HRL) were visible at the level of the outer retinal boundary in normal macular regions. Disappearance of the inner and maintenance of the outer HRL was noted in the presence of eye conditions affecting the external retinal layers. The automated software delineation for the outer retinal border was primarily guided by the presence of the inner HRL, whereas the correlation of the OCT findings with the expected clinical and angiographic features on eyes presenting specific macular conditions pointed toward a deeper retinal pigment epithelium-retina interface occurring at the level of the outer HRL. There was a statistically significant difference between the retinal thickness in specific normal macular regions obtained by the automatic measurement tool and the caliper-assisted technique in which the outer retinal border delineation was based on the outer HRL (P = 0.008, Wilcoxon signed rank test). CONCLUSIONS: Incorrect delineation of the outer neural retina boundary is occurring with the automated retinal thickness measurement tool of the OCT3 software. At specific regions of the normal macula, retinal thicknesses were significantly underestimated due to such misalignment.