Diabetic maculopathy: multicolour and SD-OCT versus fundus photography

Objective The English Diabetic Eye Screening (DES) programme recommends patients with M1 diabetic maculopathy to be referred to hospital eye services. DES uses flash fundus photography as the reference standard for maculopathy grading. We compared multicolour versus non-stereoscopic fundus photography at identifying M1 maculopathy, with spectral domain optical coherence tomography (SD-OCT) identifying macular thickening. Methods and analysis This cross-sectional study included 345 patients with R1M1 referred from DES and reviewed in secondary care with fundus photographs, multicolour and SD-OCT. Maculopathy was graded based on DES exudate criteria on both multicolour and fundus photography in a blind fashion by two independent graders. Macular thickness was ascertained on SD-OCT. Results Intergrader agreement on grading maculopathy using fundus photography (Cohen’s κ=0.91) and multicolour (Cohen’s κ=0.82) was ‘almost perfect’. Agreement between fundus photography and multicolour on grading maculopathy (Cohen’s κ=0.76) was ‘substantial’. Compared with fundus photography, multicolour had sensitivity of 87% (95% CI 81% to 93%) and specificity of 90% (95% CI 87% to 94%) in detecting M1 maculopathy. SD-OCT identified 84 eyes with macular thickening, 47 of which were graded as M0 by fundus photography. 5 eyes with exudates and severe macular oedema requiring urgent intervention were also missed on fundus photography but not on multicolour. Multicolour, when complemented by SD-OCT, did not miss any clinically significant macular oedema. Conclusion Multicolour integrates synergistically in a single platform with SD-OCT providing effective monitoring of M1 diabetic maculopathy. The need for fundus photography is eliminated by multicolour/SD-OCT in dedicated R1M1 virtual clinics not requiring parallel diabetic retinopathy grading.Publisher PDFPeer reviewe

Clinical Study A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study

properly cited. Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%-1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, -1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration

Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. Main Outcome Measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references

Diabetic maculopathy: multicolour and SD-OCT versus fundus photography

Objective The English Diabetic Eye Screening (DES) programme recommends patients with M1 diabetic maculopathy to be referred to hospital eye services. DES uses flash fundus photography as the reference standard for maculopathy grading. We compared multicolour versus non-stereoscopic fundus photography at identifying M1 maculopathy, with spectral domain optical coherence tomography (SD-OCT) identifying macular thickening.Methods and analysis This cross-sectional study included 345 patients with R1M1 referred from DES and reviewed in secondary care with fundus photographs, multicolour and SD-OCT. Maculopathy was graded based on DES exudate criteria on both multicolour and fundus photography in a blind fashion by two independent graders. Macular thickness was ascertained on SD-OCT.Results Intergrader agreement on grading maculopathy using fundus photography (Cohen’s κ=0.91) and multicolour (Cohen’s κ=0.82) was ‘almost perfect’. Agreement between fundus photography and multicolour on grading maculopathy (Cohen’s κ=0.76) was ‘substantial’. Compared with fundus photography, multicolour had sensitivity of 87% (95% CI 81% to 93%) and specificity of 90% (95% CI 87% to 94%) in detecting M1 maculopathy. SD-OCT identified 84 eyes with macular thickening, 47 of which were graded as M0 by fundus photography. 5 eyes with exudates and severe macular oedema requiring urgent intervention were also missed on fundus photography but not on multicolour. Multicolour, when complemented by SD-OCT, did not miss any clinically significant macular oedema.Conclusion Multicolour integrates synergistically in a single platform with SD-OCT providing effective monitoring of M1 diabetic maculopathy. The need for fundus photography is eliminated by multicolour/SD-OCT in dedicated R1M1 virtual clinics not requiring parallel diabetic retinopathy grading

A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study

Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%–1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, –1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated