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PURPOSE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The US Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared to monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized. DESIGN: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase 2 Ladder (NCT02510794) and phase 3 Archway (NCT03677934) and Portal (NCT03683251) trials. PARTICIPANTS: Endophthalmitis cases in the pooled all-PDS safety population (N = 555) including PDS patients in Ladder, Archway, or Portal. METHODS: Ladder patients received PDS (10, 40, or 100 mg/mL) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/mL with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day 1. MAIN OUTCOME MEASURES: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications. RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range: 57-853), including 4 before the first refill-exchange (day range: 57-161). Five patients received between 1-11 refill-exchanges before the event (onset: 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥ 20/40; 4 patients experienced vision loss of ≥ 15 ETDRS letters. CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. This limited series of endophthalmitis cases notes most, but not all, cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes.
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Purpose: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy. Design: Phase I, multicenter, prospective, open-label, dose-escalation trial. Participants: Patients with wAMD and evidence of prior anti-VEGF therapy response. Methods: Patients received a single intravitreal injection of EYP-1901. Main Outcome Measures: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates. Results: Seventeen patients enrolled in the 440 µg (3 patients), 1030 µg (1 patient), 2060 µg (8 patients), and 3090 µg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was -1.8 letters and -5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 µm and +2.4 µm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months. Conclusion: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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PURPOSE: Disparities in clinical trials are a major problem because of significant underrepresentation of certain gender, racial, and ethnic groups. Several factors including stringent eligibility criteria and recruitment strategies hinder our understanding of retinal disease. Thus, we aimed to study the various reasons of screen failures and specific patient and study characteristics among screen failures. DESIGN: This is a cross-sectional retrospective study. METHODS: Screening data of 87 trials from 6 centers were analyzed. Study characteristics (disease studied, phase of trial, and route of drug administration) and patient demographics (age, gender, race, ethnicity, and employment status) were compared among different causes of screen failures. Screen failures were broadly classified into 6 categories: exclusion because of vision-based criteria, exclusion because of imaging findings, exclusion because of other factors, patient-related criteria, physician-related criteria, and miscellaneous. Descriptive statistics, Pearson chi-square test, and analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Prevalence of various reasons for screen failures in multiple trials and its trend among different study and patient characteristics. RESULTS: Among 87 trials and 962 patients, 465 (48.2%) patients were successfully randomized and 497 (51.8%) patients were classified as screen failures. The trials were conducted for various retinal diseases. Mean age was 76.50 ±10.45 years and 59.4% were females. Predominantly White patients (93.4%) and unemployed/retired patients (66.6%) were screened. Of the 497 screen failures, most were because of patients not meeting inclusion criteria of imaging findings (n = 221 [44.5%]) followed by inclusion of vision-based criteria (n = 73 [14.7%]), exclusion because of other factors (n = 75 [15.1%]), patient-related (n = 34 [6.8%]), physician-related (n = 28 [5.6%]), and miscellaneous reasons (n = 39 [7.8%]). Reason for screen failure was not available for 27 (5.4%) patients. A higher proportion of patients screened for surgical trials (15%) declined to participate in the study compared with noninvasive trials involving topical drugs and photobiomodulation (0%) (P = 0.02). CONCLUSIONS: Patients not meeting the imaging and vision-cased criteria were the most common reasons for screen failures. White patients and unemployed patients predominantly participated in clinical trials. Patients are more inclined to continue participation in noninvasive clinical trials compared with surgical trials. Better recruitment strategies and careful consideration of study criteria can aid in decreasing the rate of screen failures.
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Importance: Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). Objective: To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. Design, Participants, and Setting: This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Intervention: Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Main Outcomes and Measures: Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. Results: A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 µm; aflibercept, -196.5 µm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. Conclusions and Relevance: In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. Trial Registration: ClinicalTrials.gov Identifier: NCT03917472.
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Humanos , Masculino , Persona de Mediana Edad , Femenino , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/complicaciones , Inhibidores de la Angiogénesis/efectos adversos , Factor A de Crecimiento Endotelial Vascular , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Inyecciones Intravítreas , Proteínas Recombinantes de Fusión/uso terapéutico , Resultado del Tratamiento , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 µL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. FUNDING: Iveric Bio, An Astellas Company.
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Biosimilars have recently emerged into the vitreoretinal pharmaceutical market. This review defines biosimilars, discusses the approval process, and reviews the benefits, risks, and controversies regarding biosimilars. This review also discusses ranibizumab biosimilars that have recently received United States Food and Drug Administration approval in the United States and discusses anti-vascular endothelial growth factor biosimilars that are in development. [Ophthalmic Surg Lasers Imaging Retina 2023;54:362-366.].
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Biosimilares Farmacéuticos , Enfermedades de la Retina , Humanos , Estados Unidos , Biosimilares Farmacéuticos/uso terapéutico , Aprobación de Drogas/métodos , Ranibizumab/uso terapéutico , Enfermedades de la Retina/tratamiento farmacológico , United States Food and Drug AdministrationRESUMEN
In rare instances, immunotherapy associated with hypotony and uveitis has been documented. We report the case of a 72-year-old man treated with 2 months of ipilimumab and nivolumab for metastatic melanoma who developed bilateral hypotony maculopathy and serous choroidal detachments without prominent initial uveitis. Despite treatment with topical, periocular, and intraocular corticosteroid injection, hypotony persisted 18 months after immunotherapy cessation. The patient's unresponsiveness to corticosteroids indicates the need to further explore the mechanism behind immune checkpoint inhibitor-associated hypotony. We hypothesize that immunotherapy significantly decreased aqueous humor production through ciliary body inflammation, disruption, or shutdown. [Ophthalmic Surg Lasers Imaging Retina 2023;54:301-304.].
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Degeneración Macular , Enfermedades de la Retina , Uveítis , Masculino , Humanos , Anciano , Nivolumab/efectos adversos , Ipilimumab/efectos adversos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/tratamiento farmacológico , Corticoesteroides/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVE: To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States. MATERIALS AND METHODS: Using the modified Delphi method, a list of 12 consensus statements were generated by the coauthors based on short-answer responses to an initial survey. In total, 56 retina specialists completed the entire consensus survey. Except for two multiple-choice questions, there were 10 consensus statements that used a modified Likert scale to indicate their level of agreement to the statement: Agree = 3, Mostly Agree = 2, Mostly Disagree = 1, Disagree = 0. Percentage agreement and 95% confidence intervals (CIs) were calculated, and a consensus threshold was set at > 80% agreement for each statement. RESULTS: Seven of 10 consensus statements using the modified Likert scale reached consensus, including those on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. The remaining three statements displayed high agreement with average scores > 80%, but the 95% CIs were below threshold. These included the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. Two multiple-choice questions focused on clinical situations in which corticosteroids would be used as baseline therapy for DME (pseudophakic eye [73%], recent stroke/myocardial infarction [66%], and pregnancy/breastfeeding [66%]) and which delivery route satisfies the steroid challenge for the FAc implant (intravitreal [100%], sub-tenon/periocular [73%], and topical [57%]). CONCLUSIONS: Physicians highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. [Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173.].
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Humanos , Fluocinolona Acetonida , Glucocorticoides , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Implantes de Medicamentos , Inflamación/tratamiento farmacológico , Inyecciones Intravítreas , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. Neovascular AMD (nAMD) is a subtype of AMD most frequently treated with intravitreal anti-vascular endothelial growth factor (aVEGF) injections, which has allowed for patients to maintain vision that would have otherwise been lost. However, the need for frequent intravitreal injections for optimal results poses a risk for undertreatment in nAMD patients due to the high treatment burden associated with current aVEGF therapy. Many novel agents and pathways are being explored and targeted for less burdensome treatment options, one of which is the ranibizumab port delivery system (PDS). The PDS is a surgically implanted, refillable device that allows for the sustained release of ranibizumab, a widely used aVEGF agent, into the vitreous cavity. Positive results non-inferior to monthly ranibizumab injections in both phase II and phase III clinical trials allowed for FDA approval of the device with refill intervals of 6 months, which represents the longest approved treatment interval to date for nAMD therapy. This article reviews the need for a durable nAMD treatment option in real-world practice, the clinical trial and extension study data for the PDS, the risk of adverse events and safety profile of the PDS and the potential clinical role of the PDS in answering the real-world needs of nAMD treatment. In addition, other pipeline sustained-treatment modalities are discussed in the context of ongoing clinical trials.
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Ranibizumab , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/efectos adversos , Preparaciones de Acción Retardada , Factores de Crecimiento Endotelial , Humanos , Ranibizumab/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda/inducido químicamenteRESUMEN
BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.
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Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Biespecíficos/administración & dosificación , Retinopatía Diabética/tratamiento farmacológico , Edema/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Angiopoyetina 2/antagonistas & inhibidores , Anticuerpos Biespecíficos/efectos adversos , Retinopatía Diabética/diagnóstico , Método Doble Ciego , Esquema de Medicación , Edema/etiología , Femenino , Humanos , Inyecciones Intravítreas , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/efectos de los fármacos , Masculino , Persona de Mediana Edad , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/efectos de los fármacosRESUMEN
AIM: To quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases. METHODS: The validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden. RESULTS: Of 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4-5 weeks (40%). The mean TBS was 16.1±9.2 (range 1-48; scale of 1-54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0-6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0-6) with the care of their diseases. CONCLUSIONS: The mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.
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Retinopatía Diabética , Degeneración Macular , Edema Macular , Enfermedades de la Retina , Humanos , Femenino , Anciano , Masculino , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Inyecciones Intravítreas , Enfermedades de la Retina/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológicoRESUMEN
The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.
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The real-world performance of a home telemonitoring strategy (ForeseeHome AMD Monitoring System®, Notal Vision, Inc.,Manassas VA, USA) was evaluated and compared to the device arm of the AREDS2-HOME study among patients with intermediate AMD (iAMD) who converted to neovascular AMD (nAMD). All patients with confirmed conversion to nAMD who used the home monitoring system from 10/2009 through 9/2018 were identified by Notal Vision Diagnostic Clinic's medical records. Selected outcome variables were evaluated, including visual acuity (VA) at baseline and at conversion, and change in visual acuity (VA) from baseline to time of conversion. In total, 8991 patients performed 3,200,999 tests at a frequency of 5.6 ± 3.2 times/week. The 306 eyes that converted from iAMD to nAMD over the study period (a 2.7% annual rate) were included in the analyses. There was a median (interquartile range) change of -3.0 (0.0-(-10.0)) letters among converted eyes, 81% [95% confidence interval (72-88%)] maintained a VA ≥ 20/40 at the time of conversion, while 69% of the conversion detections were triggered by system alerts. The real-world performance of an at-home testing strategy was similar to that reported for the device arm of the AREDS2-HOME study. The home telemonitoring system can markedly increase early detection of conversion to nAMD.
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IMPORTANCE: Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). OBJECTIVE: To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. EXPOSURES: Treatment with brolucizumab IVI, 6 mg. MAIN OUTCOMES AND MEASURES: Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. RESULTS: A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) µm and was 269.8 (66.5) µm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. CONCLUSIONS AND RELEVANCE: In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.
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Retinopatía Diabética , Degeneración Macular , Vasculitis Retiniana , Uveítis , Degeneración Macular Húmeda , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados , Retinopatía Diabética/tratamiento farmacológico , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inyecciones Intravítreas , Degeneración Macular/inducido químicamente , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Masculino , Ranibizumab/uso terapéutico , Vasculitis Retiniana/diagnóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Uveítis/diagnóstico , Degeneración Macular Húmeda/inducido químicamente , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológicoRESUMEN
PURPOSE: To review evidence and provide guidelines on intracameral (ICM) injection techniques and monitoring. MATERIALS AND METHODS: A review of published literature on ICM injection and intravitreal injections formed the basis for roundtable deliberations by an expert panel of ophthalmologists. RESULTS: ICM injection as a way to deliver medications is growing in popularity. However, there is limited published literature and no standard approach to best practices for ICM injections, particularly when not accompanying another surgical procedure. Fortunately, there is long clinical experience with ICM manipulation and a large body of evidence surrounding intravitreal injections that has provided important guidance. The expert panel formulates several concrete guidelines and many suggested techniques to help physicians safely and effectively employ ICM injections. CONCLUSIONS: This committee addressed the many considerations surrounding ICM injection of drugs or implants and agree that it is a safe and effective surgical procedure when performed with appropriate training and according to established safe practices.
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Cámara Anterior/efectos de los fármacos , Inyecciones Intraoculares , Preparaciones Farmacéuticas/administración & dosificación , Guías de Práctica Clínica como Asunto , Oftalmopatías/tratamiento farmacológico , Humanos , Presión IntraocularRESUMEN
OBJECTIVE: To investigate if the mean central retinal thickness (CRT) amplitude, measured between visits, is consistently decreased when switching from discontinuous to continuous therapy for diabetic macular oedema (DME) following fluocinolone acetonide (FAc) administration. METHODS AND ANALYSIS: In this retrospective cohort study, all patients with DME treated with FAc at a single centre were included. The primary outcome was CRT amplitude changes measured at each visit prior to and after FAc administration. Secondary outcomes included average number of DME treatments before and after FAc injection, visual acuity and intraocular pressure changes. RESULTS: Nineteen eyes were included. The mean (SD) follow-up after FAc was 399 (222) days. The mean (SD) CRT amplitude before FAc was 194.6 (114.90) µm, and following FAc administration, the amplitude decreased to 70.8 (94.23) µm (95% CI -189.5 to -58.1; p≤0.001). After FAc, the number of treatments required per month significantly decreased from an average of 1 treatment every 2.7 months to every 6 months (p=0.009). CONCLUSION: In patients with DME, the CRT amplitude values and number of treatments significantly decrease following FAc administration while maintaining vision. Further studies are needed to evaluate the significance of these interesting findings.
RESUMEN
Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.
RESUMEN
BACKGROUND AND OBJECTIVE: Compare fixed monthly dosing of ranibizumab to treat-and-extend (T&E) ranibizumab during a period of 24 months for diabetic macular edema (DME) treatment. PATIENTS AND METHODS: Single-center, randomized, prospective pilot study that included 20 eyes of 20 subjects. Patients' best-corrected visual acuity (BCVA) was less than or equal to 20/40 and central foveal thickness on spectral-domain optical coherence tomography was greater than 325 µm. Intravitreal ranibizumab was dosed monthly or by protocol-specified treat-and-extend. Primary outcome was mean change in mean BCVA. Institutional review board approval was obtained. RESULTS: At month 24 (M24), there was a mean 8.3-letter gain in the monthly treatment group and an 8.5-letter gain in the T&E group (P = .082; 90% confidence interval). The average change from baseline BCVA was not statistically significantly different at any timepoint. At M24, the median number of injections in the monthly and T&E groups were 22.5 and 18.5, respectively (P = .287). CONCLUSIONS: Visual acuity with monthly dosing appears equivalent to T&E dosing during the course of 24 months. There was a trend toward a lower injection burden in the T&E arm. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e191-e197.].
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Retinopatía Diabética/tratamiento farmacológico , Mácula Lútea/patología , Edema Macular/tratamiento farmacológico , Ranibizumab/administración & dosificación , Agudeza Visual , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
In the United States, diabetic macular edema (DME) is the leading cause of vision loss among people with diabetic retinopathy. Despite the availability of different therapies for DME, up to half of patients with DME show some persistent edema after anti-vascular endothelial growth factor (VEGF) treatment alone, leaving these patients at high risk for vision loss. However, dosing in a similar fashion to that of pivotal anti-VEGF trials is difficult because of real-life challenges faced in clinical practice. This is particularly true for DME, in that the frequency and burden of anti-VEGF injections are a major challenge to patient care. Research evaluating anti-VEGF therapies has shaped the treatment paradigms for patients with DME, and similar benefits have also been noted in clinical trials evaluating the use of intravitreal steroids. Treatment with a long-term intravitreal corticosteroid, which requires fewer injections than treatment with most short-acting therapies, has been found to reduce inflammation and improve vision in a percentage of patients. This roundtable discussion, which took place during the 2018 annual meeting of the Vit-Buckle Society, reviews the current treatment paradigms for DME and evaluates how to customize and optimize treatment strategies geared toward individualized patient care. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S15.].