Long-term (60-month) results for the implantable miniature telescope: efficacy and safety outcomes stratified by age in patients with end-stage age-related macular degeneration

BACKGROUND: The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD). METHODS: A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80-20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to[group 1; n=70] and patient age \u3e/=75 years [group 2; n=127]), with a comparative evaluation of change in best-corrected distance visual acuity (BCDVA), quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD). Follow-up in an extension study was 60 months. RESULTS: Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41+/-2.69 lines in all patients (n=76), with 2.64+/-2.55 lines in group 1 and 2.09+/-2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis \u3e30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema \u3e30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost \u3e/=2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per year. ECD loss was less in group 1 than in group 2 (35% versus 40%, respectively) at 60 months. CONCLUSION: Long-term results show substantial retention of improvement in BDCVA. Chronic ECD loss was consistent with that reported for conventional intraocular lenses. The IMT performed as well in group 1 (the younger group) as it did in group 2 through month 60. Younger patients retained more vision than their older counterparts and had fewer adverse events. Although not a specified outcome for this study, patients younger than 65 years also fared better than those in group 2 and retained more vision with fewer adverse events through month 60

KESTREL and KITE Phase 3 studies: 100-week results with brolucizumab in patients with diabetic macular edema.

PURPOSE To report the 100-week outcomes from KESTREL and KITE. DESIGN Two phase 3, double-masked, active-controlled, randomized trials. METHODS Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N=566) or 1:1 to BRO6 or AFL in KITE (N=360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at Week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. RESULTS At Week 100, change from baseline in BCVA (letters) was +8.8 for BRO6 and +10.6 for AFL in KESTREL; +10.9 for BRO6 and +8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid versus (vs) AFL. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE) of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. CONCLUSION Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through Year 2

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind

PurposeRetinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation.DesignThe study is a multicenter, single-arm, prospective clinical trial.ParticipantsThere were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision).MethodsThe Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina.Main Outcome MeasuresThe primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests.ResultsA total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments.ConclusionsThe 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals

Management of retinal vascular diseases: a patient-centric approach

Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial

Purpose: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. / Design: Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. / Participants: Thirty participants in 10 centers in the United States and Europe. / Methods: The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. / Main Outcome Measures: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. / Results: Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. / Conclusions: The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada